We present the first results for the dust-scattering rings of GRB 221009A, coined as the gamma-ray bursts (GRBs) of the century, as observed by the Neil Gehrels Swift Observatory. We perform analysis of both time resolved observations and stacked data. The former approach enable us to study the expansion of the most prominent rings, associate their origin with the prompt X-ray emission of the GRB and determine the location of the dust layers. The stacked radial profiles increase the signal-to-noise ratio of the data and allows detection of fainter and overlapping peaks in the angular profile. We find a total of 16 dust concentrations (with hints of even more) that span about 15kpc in depth and could be responsible for the highly structured X-ray angular profiles. By comparing the relative scattered fluxes of the five most prominent rings we show that the layer with the largest amount of dust is located at about 0.44 kpc away from us. We finally compare the location of the dust layers with results from experiments that study the 3D structure of our Galaxy via extinction or CO radio observations, and highlight the complementarity of dust X-ray tomography to these approaches.
We report on NICER observations of the Be X-ray binary 4U 0115+63 during the rise of the source's current historic outburst, which began around 2023 March 28 and is the brightest recorded in 27 years.
On 6 February 2023, East Anatolia was devastated by two major earthquakes resulting in hundreds of thousands of collapses and tens of thousands of human casualties. This paper investigates the factors related to building properties and earthquake environmental effects (EEEs) that contributed to the building damage grade and distribution in southeastern Turkey. In regards to the building construction properties, the loose enforcement of the building code, the random urban planning solutions and the poor construction standards are the main construction deficiencies that led to one of the largest disasters in Turkey’s recent history. Regarding geological factors, the triggering of primary and secondary EEEs largely shaped the grade and distribution of damage. Where coseismic surface ruptures intersected with the built environment, heavy to very heavy structural damage was observed. This was evident in many cases along the ruptured segments of the East Anatolian Fault Zone (EAFZ). Liquefaction observed close to waterbodies caused damage typical of building foundation load-bearing capacity loss. The earthquake-triggered landslides affected mainly mountainous and semi-mountainous settlements characterized with pre-earthquake high related susceptibility. The high susceptibility to generation of EEEs was extensively confirmed in many cases resulting in extensive damage. The provided information highlights the importance of such studies for hazard mitigation and disaster risk reduction.
This paper explores the efficacy of the geoeducational assessment method (GEOAM) in evaluating the geoeducational potential of geosites. Leveraging a case study involving four geotopes on the island of Samos, Aegean Sea, Greece, this study examines the strengths and limitations of the GEOAM approach, aiming to comprehensively elucidate its efficacy. The assessment outcomes illuminate the vital role of targeted strategies in enhancing the educational and sustainable impact of geosites, thereby fostering geological understanding and responsible environmental engagement. A prominent finding is the urgency to address the gap in foundational geological knowledge, underscored by the need for robust geoeducation programs at schools and the augmented presence of geologists. While acknowledging potential limitations, including subjectivity in scoring and data availability constraints, this study underscores the method’s broader contribution to societal goals. By integrating geoethic principles, GEOAM offers a comprehensive framework aligning with the objectives of geological comprehension and environmentally conscious practices.
This paper investigates the relationship between investors' attention, as measured by Google search queries, and equity implied volatility during the COVID-19 outbreak. Recent studies show that search investors' behavior data is an extremely abundant repository of predictive data, and investor-limited attention increases when the uncertainty level is high. Our study using data from thirteen countries across the globe during the first wave of the COVID-19 pandemic (January–April 2020) examines whether the search “topic and terms” for the pandemic affect market participants’ expectations about future realized volatility. With the panic and uncertainty about COVID-19, our empirical findings show that increased internet searches during the pandemic caused the information to flow into the financial markets at a faster rate and thus resulting in higher implied volatility directly and via the stock return-risk relation. More specifically for the latter, the leverage effect in the VIX becomes stronger as Google search queries intensify. Both the direct and indirect effects on implied volatility, highlight a risk-aversion channel that operates during the pandemic. We also find that these effects are stronger in Europe than in the rest of the world. Moreover, in a panel vector autoregression framework, we show that a positive shock on stock returns may soothe COVID-related Google searches in Europe. Our findings suggest that Google-based attention to COVID-19 leads to elevated risk aversion in stock markets.
Pulmonary vein isolation (PVI) is the cornerstone in atrial fibrillation (AF) ablation; yet, the role of arrhythmogenic superior vena cava (SVC) is increasingly recognized and different ablation strategies have been employed in this context. SVC can act as a trigger or perpetuator of AF, and its significance might be more pronounced in patients undergoing repeated ablation. Several cohorts have examined efficacy, safety and feasibility of SVC isolation (SVCI) among AF patients. The majority of these studies explored as-needed SVCI during index PVI, and only a minority of them included repeated ablation subjects and non-radiofrequency energy sources. Studies of heterogeneous design and intent have explored both empiric and as-needed SVCI on top of PVI and reported inconclusive results. These studies have largely failed to demonstrate any clinical benefit in terms of arrhythmia recurrence, although safety and feasibility are undisputable. Mixed population demographics, small number of enrollees and short follow-up are the main limitations. Procedural and safety data are comparable between empiric SVCI and as-needed SVCI, and some studies suggested that empiric SVCI might be associated with reduced AF recurrences in paroxysmal AF patients. Currently, no study has compared different ablation energy sources in the setting of SVCI, and no randomized study has addressed as-needed SVCI on top of PVI. Furthermore, data regarding cryoablation are still in their infancy, and regarding SVCI in patients with cardiac devices more safety and feasibility data are needed. PVI non-responders, patients undergoing repeated ablation and patients with long SVC sleeves could be potential candidates for SVCI, especially via an empiric approach. Although many technical aspects remain unsettled, the major question to answer is which clinical phenotype of AF patients might benefit from SVCI?
Defining efficient families of recurrent neural networks (RNN) models for solving time-varying nonlinear equations is an interesting research topic in applied mathematics. Accordingly, one of the underlying elements in designing RNN is the use of efficient nonlinear activation functions. The role of the activation function is to bring out an output from a set of input values that are supplied into a node. Our goal is to define new family of activation functions consisting of a fixed gain parameter and a functional part. Corresponding zeroing neural networks (ZNN) is defined, termed as varying-parameter improved zeroing neural network (VPIZNN), and applied to solving time-varying nonlinear equations. Compared with previous ZNN models, the new VPIZNN models reach an accelerated finite-time convergence due to the new time-varying activation function which is embedded into the VPIZNN design. Theoretical results and numerical experiments are presented to demonstrate the superiority of the novel VPIZNN formula. The capability of the proposed VPIZNN models are demonstrated in studying and solving the Van der Pol equation and finding the root $$\root m \of {a(t)}$$.
In recent years, advances in science and technology have improved our quality of life, enabling us to tackle diseases and increase human life expectancy. However, longevity is accompanied by an accretion in the frequency of age-related neurodegenerative diseases, creating a growing burden, with pervasive social impact for human societies. The cost of managing such chronic disorders and the lack of effective treatments highlight the need to decipher their molecular and genetic underpinnings, in order to discover new therapeutic targets. In this effort, the nematode serves as a powerful tool to recapitulate several disease-related phenotypes and provides a highly malleable genetic model that allows the implementation of multidisciplinary approaches, in addition to large-scale genetic and pharmacological screens. Its anatomical transparency allows the use of co-expressed fluorescent proteins to track the progress of neurodegeneration. Moreover, the functional conservation of neuronal processes, along with the high homology between nematode and human genomes, render extremely suitable for the study of human neurodegenerative disorders. This review describes nematode models used to study neurodegeneration and underscores their contribution in the effort to dissect the molecular basis of human diseases and identify novel gene targets with therapeutic potential.
Transplant-associated thrombotic microangiopathy (TMA) occurs in a significant percentage of patients after allogeneic stem cell transplantation (allo-SCT) and is associated with significant morbidity and mortality. The aim of the present study was to examine the association of serum angiopoetin-2 (Ang2) levels and the presence of antibodies against angiotensin II type 1 (AT1R) and ndothelin A Recreptor (ETAR) with the outcome of patients with TMA and/or graft-versus-host disease (GVHD) after allo-SCT. Analysis of our data showed that elevated serum Ang2 levels at the time of TMA diagnosis are significantly associated with increased non-relapse mortality and decreased overall survival. To our knowledge, this is the first study demonstrating an association between raised Ang2 levels and poor outcomes in patients with TMA. Antibodies against AT1R (AT1R-Abs) and ETAR (ETAR-Abs) were detected in 27% and 23% of the patients, respectively, but there was no association between the presence of autoantibodies and the outcome of patients with TMA. However, a significant finding was the strong positive correlation between the presence of AT1R-Abs with the occurrence of chronic fibrotic GVHD, such as scleroderma and cryptogenic organizing pneumonia, raising the possibility of the contribution of autoantibodies in the pathogenesis of fibrotic GVHD manifestations
In this study, we developed active substrates consisting of Ag-decorated silicon nanowires on a Si substrate using a single-step Metal Assisted Chemical Etching (MACE) process, and evaluated their performance in the identification of low concentrations of Rhodamine 6G using surface-enhanced photoluminescence spectroscopy. Different structures with Ag-aggregates as well as Ag-dendrites were fabricated and studied depending on the etching parameters. Moreover, the addition of Au nanoparticles by simple drop-casting on the MACE-treated surfaces can enhance the photoluminescence significantly, and the structures have shown a Limit of Detection of Rhodamine 6G down to 10−12 M for the case of the Ag-dendrites enriched with Au nanoparticles.
(1)Introduction: Catheter ablation has become a cornerstone for the management of patients with atrial fibrillation (AF). Nevertheless, recurrence rates remain high. Epicardial adipose tissue (EAT) has been associated with AF pathogenesis and maintenance. However, the literature has provided equivocal results regarding the relationship between EAT and post-ablation recurrence.(2) Purpose: to investigate the relationship between total and peri-left atrium (peri-LA) EAT with post-ablation AF recurrence. (3) Methods: major electronic databases were searched for articles assessing the relationship between EAT, quantified using computed tomography, and the recurrence of AF following catheter ablation procedures. (4) Results: Twelve studies (2179 patients) assessed total EAT and another twelve (2879 patients) peri-LA EAT. Almost 60% of the included patients had paroxysmal AF and recurrence was documented in 34%. Those who maintained sinus rhythm had a significantly lower volume of peri-LA EAT (SMD: -0.37, 95%; CI: -0.58-0.16, I2: 68%). On the contrary, no significant difference was documented for total EAT (SMD: -0.32, 95%; CI: -0.65-0.01; I2: 92%). No differences were revealed between radiofrequency and cryoenergy pulmonary venous isolation. No publication bias was identified. (5) Conclusions: Only peri-LA EAT seems to be predictive of post-ablation AF recurrence. These findings may reflect different pathophysiological roles of EAT depending on its location. Whether peri-LA EAT can be used as a predictor and target to prevent recurrence is a matter of further research.
Inflammation, as assessed by epicardial adipose tissue and serum biomarkers, represents an integral mechanistic link in isolated coronary artery ectasia (iCAE) pathogenesis. This should be further investigated in the context of iCAE management and risk stratification.
Methylation of the fundamental macromolecules, DNA/RNA, and proteins, is remarkably abundant, evolutionarily conserved, and functionally significant in cellular homeostasis and normal tissue/organism development. Disrupted methylation imprinting is strongly linked to loss of the physiological equilibrium and numerous human pathologies, and most importantly to carcinogenesis, tumor heterogeneity, and cancer progression. Mounting recent evidence has documented the active implication of miRNAs in the orchestration of the multicomponent cellular methylation machineries and the deregulation of methylation profile in the epigenetic, epitranscriptomic, and epiproteomic levels during cancer onset and progression. The elucidation of such regulatory networks between the miRNome and the cellular methylation machineries has led to the emergence of a novel subclass of miRNAs, namely "epi-miRNAs" or "epi-miRs." Herein, we have summarized the existing knowledge on the functional role of epi-miRs in the methylation dynamic landscape of human cancers and their clinical utility in modern cancer diagnostics and tailored therapeutics. This article is categorized under: RNA in Disease and Development > RNA in Disease.
Context. During the third all-sky survey (eRASS3), eROSITA, the soft X-ray instrument aboard Spectrum-Roentgen-Gamma, detected a new hard X-ray transient, eRASSt J040515.6 − 745202, in the direction of the Magellanic Bridge. Aims: We arranged follow-up observations and searched for archival data to reveal the nature of the transient. Methods: Using X-ray observations with XMM-Newton, NICER, and Swift, we investigated the temporal and spectral behaviour of the source for over about 10 days. Results: The X-ray light curve obtained from the XMM-Newton observation with an ∼28 ks exposure revealed a type-I X-ray burst with a peak bolometric luminosity of at least 1.4 × 1037 erg s−1. The burst energetics are consistent with a location of the burster at the distance of the Magellanic Bridge. The relatively long exponential decay time of the burst of ∼70 s indicates that it ignited in a H-rich environment. The non-detection of the source during the other eROSITA surveys, twelve and six months before and six months after eRASS3, suggests that the burst was discovered during a moderate outburst which reached 2.6 × 1036 erg s−1 in persistent emission. During the NICER observations, the source showed alternating flux states with the high level at a similar brightness as during the XMM-Newton observation. This behaviour is likely caused by dips as also seen during the last hour of the XMM-Newton observation. Evidence for a recurrence of the dips with a period of ∼21.8 h suggests eRASSt J040515.6 − 745202 is a low-mass X-ray binary (LMXB) system with an accretion disk seen nearly edge on. We identify a multi-wavelength counterpart to the X-ray source in UVW1 and g, r, i, and z images obtained by the optical/UV monitor on XMM-Newton and the Dark Energy Camera at the Cerro Tololo Inter-American Observatory. The spectral energy distribution is consistent with radiation from an accretion disk which dominates the UV and from a cool late-type star detected in the optical to infrared wavelengths. Conclusions: After the discovery of X-ray bursts in M 31, the Magellanic Bridge is only the second location outside of the Milky Way where an X-ray burster was found. The burst uniquely identifies eRASSt J040515.6 − 745202 as an LMXB system with a neutron star. Its location in the Magellanic Bridge confirms the existence of an older stellar population which is expected if the bridge was formed by tidal interactions between the Magellanic Clouds, which stripped gas and stars from the clouds.
The La1-xCaxMnO3 series of compounds with antiferromagnetic ground states (x 1/2) have been extensively studied due to the novel spin, orbital, and charge-ordering states observed when the calcium concentration is a simple fraction (x = 1/2, 2/3, and 3/4). The ground states of these compositions have been explained by the Goodenough charge, orbital, and spin ordering model. An important issue remaining is the elucidation of how the ground state changes when x is not a simple number. Here we study the magnetic structure of La1-xCaxMnO3 for 0.51 x 0.69 using powder neutron diffraction measurements supported by magnetization data. For compositions with 0.51 x 0.56, the magnetic structure, which we term as an incommensurate charge exchange (CE) structure can be described by two propagation vectors kC = [1/2, 0, 1/2] and kE = [6E, 0, 1/2]. In the second one, the component parallel to the a* axis of the reciprocal lattice changes with the Mn4+ concentration x as 6E approximate to x - 1/2 providing, thus, an unambiguous signature of the adoption of an incommensurate magnetic structure. As x gradually increases, the diffraction data reveal that two magnetic phases-one adopting the incommensurate CE, and one adopting the commensurate "2/3" magnetic structure-co-exist in the concentration regime of 0.57 x 0.61. Around the simple fraction x = 2/3, the magnetic structure can be also described by three propagation vectors, the commensurate kE = [0, 0, 1/2], kC = [1/2, 0, 1/2], and an incommensurate k2/3 = [1/3 + 62/3, 0, 1/2] propagation vector with 62/3 taking negative/zero/positive values for x smaller than/equal to/larger than 2/3, respectively. Our experimental results for 0.51 x 0.56 are neither in favor of a stripe structure consisting of a fine mixture of x = 1/2 and x = 2/3 phases (phase separation) nor of a defect structure in which an appropriate amount of Mn3+-O sheets have been replaced by Mn4+-O sheets (defect structure). A sinusoidal modulated structure has been used as a possible candidate in explaining the experimental neutron diffraction magnetic Bragg peaks. This result may be linked to the presence of a mixed orbital state of the manganese ions.
The main contribution of this paper is to develop explicit expressions for the Drazin inverse of two kinds of anti-triangular block complex matrices under new assumptions. Further, we apply our results to obtain new formulae for the Drazin inverse of a 2 × 2 block complex matrix. We present a list of well-known results which are recovered in this paper. We give three examples to illustrate our new explicit expressions.
Previous research findings demonstrate that both savoring ability and the presence of high-quality friendships play a significant role in enhancing one’s overall sense of wellbeing. However, these associations have not been thoroughly investigated within a diverse range of adults across their lifespans, nor have they been explored in the specific cultural context of Greece. Thus, the primary objective of this study was to delve into the relationships between close friendship quality, the utilization of savoring techniques, and wellbeing within the Greek cultural framework. The study involved 771 adults from Greece with an average age of 38.35 years, who completed the McGill Friendship Functions Questionnaire, the PERMA Profiler, and the Abridged Ways of Savoring Checklist. Results revealed that there exists a positive correlation between friendship quality and savoring strategies with overall wellbeing. Moreover, the study identified a significant association wherein a greater employment of savoring strategies was linked to higher levels of friendship quality. While this study contributes valuable insights, it also has limitations that warrant acknowledgment. Furthermore, suggestions for potential future research directions are proposed, and the implications of these findings are discussed in relation to interventions aimed at enhancing both friendships and the practice of savoring across various contexts.
The relationship between humans and the environment in the modern world is challenging. UNESCO Global Geoparks are current holistic approaches for protecting and managing geographical areas that emphasise local communities and sustainability. This paper attempts to review the grey literature of Greek universities through their academic repositories, regarding the research field referred to as Greek UNESCO Global Geoparks from 2000 to 2022 and using the keyword “Geopark” to determine possible future research directions. Through the systematic literature review methodology, from 138 bibliographic sources, 28 were selected, which met the predefined criteria. In general, there is a growing scientific–academic interest in Geoparks, which mainly concerns the aspects of geotourism (n = 7), geology (n = 6), management (n = 4), and education (n = 4). Future research directions may focus on promoting the socio-economic and cultural aspects of Geoparks, investing in collaborative management and governance of Geoparks, facing climate change and environmental challenges in Geoparks, and enhancing Geoenvironmental Education in Geoparks. Such approaches may serve the United Nation’s Seventeen Sustainable Development Goals and cultivate cognitive and emotional bonds between local populations and the geoenvironment.
BACKGROUND: Males with 5$\alpha$-reductase deficiency experience oligospermia or azoospermia, resulting in fertility problems. OBJECTIVE: The aim of the present systemic review was to assess the fertility status of males with 5$\alpha$-reductase type 2 deficiency and explore how reproduction can be achieved in these patients. STUDY DESIGN: An extensive search of two databases (Pubmed and SCOPUS) was performed. Studies with original clinical data in patients with 5$\alpha$-reductase deficiency evaluating the impact of the disease on semen quality and quantity and pregnancy outcomes through assisted or natural conception methods were eligible to be included in this systematic review. RESULTS: A total of nine cases were identified based on the eligibility criteria, all of which included reports of successful reproduction in males with 5$\alpha$-reductase type 2 deficiency. DISCUSSION: In five individuals, assisted reproduction technology was used to achieve conception, highlighting its importance in solving the fertility problems that males with 5$\alpha$-reductase deficiency are facing. Potential future fertility is a further indication for assigning the male gender in diagnosed newborns. CONCLUSION: In order to achieve this, the development of a management plan starting at birth is crucial for these patients, so that spermatogenesis and potential fertility can be preserved. In adulthood, semen analysis and mutation screening may also help in guiding these patients to select the correct fertilization method for their individual genetic and phenotypic characteristics.
The concept of Finite Absorption Time (FAT) for oral drug administration is set to affect pharmacokinetic analyses, Physiologically-based Pharmacokinetics simulations, and Pharmacometrics.
OBJECTIVE: Identification of differentially expressed proteins (DEPs) in first trimester maternal plasma between pregnant women with a subsequent spontaneous moderate/late Preterm Delivery (sPTD) and women who delivered at term. The sPTD group consisted of women who delivered between 32 degrees (/7) and 36(6/7 )weeks of gestation. METHODS: Isobaric tags for relative and absolute quantification (iTRAQ) coupled with LC-MS/MS was used for the analysis of five first trimester maternal plasma samples obtained from women with a subsequent moderate/late preterm sPTD and five women with term deliveries. Enzyme-linked immunosorbent assay (ELISA) was further applied in an independent cohort of 29 sPTD cases and 29 controls to verify the expression levels of selected proteins. RESULTS: 236 DEPs, mainly linked to coagulation and complement cascade, were identified in first trimester maternal plasma obtained from the sPTD group. Decreased levels of selected proteins, namely, VCAM-1, SAA, and Talin-1, were further confirmed using ELISA, highlighting their potential as candidate predictive biomarkers for sPTD at32 degrees (/7) and 36(6/7 )weeks of gestation. CONCLUSION: First trimester maternal plasma proteomic analysis revealed protein changes associated with subsequent moderate/late preterm sPTD.
Gamma-ray flares of blazars may be accompanied by high-energy neutrinos due to interactions of high-energy cosmic rays in the jet with photons, as suggested by the detection of the high-energy neutrino IceCube-170922A during a major gamma-ray flare from blazar TXS 0506+056 at the ~3σ significance level. In this work, we present a statistical study of gamma-ray emission from blazars to constrain the contribution of gamma-ray flares to their neutrino output. We construct weekly binned light curves for 145 gamma-ray bright blazars in the Fermi Large Area Telescope Monitored Source List adding TXS 0506+056. We derive the fraction of time spent in the flaring state (flare duty cycle) and the fraction of energy released during each flare from the light curves with a Bayesian blocks algorithm. We find that blazars with lower flare duty cycles and energy fractions are more numerous among our sample. We identify a significant difference in flare duty cycles between blazar subclasses at a significance level of 5%. Then using a general scaling relation for the neutrino and gamma-ray luminosities, ${L}_{\nu }\propto {({L}_{\gamma })}^{\gamma }$ with a weighting exponent of γ = 1.0-2.0, normalized to the quiescent gamma-ray or X-ray flux of each blazar, we evaluate the neutrino energy flux of each gamma-ray flare. The gamma-ray flare distribution indicates that blazar neutrino emission may be dominated by flares for γ ≳ 1.5. The neutrino energy fluxes for 1 week and 10 yr bins are compared with the decl.-dependent IceCube sensitivity to constrain the standard neutrino emission models for gamma-ray flares. Finally, we present the upper-limit contribution of blazar gamma-ray flares to the isotropic diffuse neutrino flux.
Employee attrition, defined as the voluntary resignation of a subset of a company’s workforce, represents a direct threat to the financial health and overall prosperity of a firm. From lost reputation and sales to the undermining of the company’s long-term strategy and corporate secrets, the effects of employee attrition are multidimensional and, in the absence of thorough planning, may endanger the very existence of the firm. It is thus impeccable in today’s competitive environment that a company acquires tools that enable timely prediction of employee attrition and thus leave room either for retention campaigns or for the formulation of strategical maneuvers that will allow the firm to undergo their replacement process with its economic activity left unscathed. To this end, a weights and structure determination (WASD) neural network utilizing Fresnel cosine integrals in the determination of its activation functions, termed FCI-WASD, is developed through a process of three discrete stages. Those consist of populating the hidden layer with a sufficient number of neurons, fine-tuning the obtained structure through a neuron trimming process, and finally, storing the necessary portions of the network that will allow for its successful future recreation and application. Upon testing the FCI-WASD on two publicly available employee attrition datasets and comparing its performance to that of five popular and well-established classifiers, the vast majority of them coming from MATLAB’s classification learner app, the FCI-WASD demonstrated superior performance with the overall results suggesting that it is a competitive as well as reliable model that may be used with confidence in the task of employee attrition classification.
The present work is an attempt at a bibliographic overview in the field of paleontology and specifically in the field of fossils regarding their value and connection with history and mythology, and how it has been used to teach theory of evolution through natural selection (TENS) in a university course. To make our case, we use as our paradigm two well-known historical locations of Greece, namely Thermopiles and Marathon. The area of Marathon includes the location of Pikermi, which is very well known for its fossils that historically have been one of the first locations rich in fossils that have been studied so extensively. Before we make a short tour of other similar locations of the Greek peninsula that are good cases for teaching evolution using paleontology, we present an example of how fossils can be formed via sedimentation. For that, we are using the case of Thermopile, while in antiquity was chosen as the field of the famous battle as it was a very narrow strip of land between the mountain and the sea, nowadays, due to sedimentary alluvial deposits, has become a rather large field. To make the reader familiar with the fossils found around Greece and their topology, we present a short tour and some history about the fossils found throughout its territory. And finally, we argue about how the fossils and the museum education could be used to prepare the pupils for first contact with TENS.
Genital graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT) is an underdiagnosed manifestation of chronic GVHD. Few articles have been published in pediatric populations, and there are no established guidelines for the management of this condition in children. This study aims to provide a systematic literature review of the published studies and cases of genital (vulvovaginal) GVHD in girls and adolescents post HSCT, with a focus on the time of diagnosis and clinical manifestations. The authors searched for English-language articles published after 1990, which included full patient details. Thirty-two cases of female patients under 20 years of age were identified. The median time of diagnosis was 381 days (IQR: 226-730 days), and 83{%} of patients developed Grade 3 vulvovaginal GVHD. Based on these observations, an early pediatric gynecologic examination of these patients, soon within the first year after HSCT, could be suggested for early diagnosis, treatment initiation and prevention of long-term complications.
A new assessment method named GEOAM (geoeducational assessment method), that will be a useful tool for highlighting the geoeducational and geoethical value of a geosite, is proposed. This method takes into account, initially, 11 criteria, which are grouped into 8 categories. Each criterion addresses a different aspect of the geosite’s potential for promoting sustainable development, environmental management, and education. A simplified scoring system using a scale of 1–5 is used, where each criterion is scored based on the degree to which it is presented or implemented. The method was piloted in eight geotopes of the Kalymnos Island and five geotopes of the Nisyros Island, in the SE Aegean Sea, Greece. The implementation of this assessment method highlighted the geoeducational value of these geosites. Based on the criteria and subcriteria incorporated in GEOAM, this paper discusses GEOAM’s potential to promote sustainable development and rational environmental management by directing educators and stakeholders toward actions that conserve and protect geoheritage for future generations, while also contributing to the economic, social, and cultural development of the surrounding communities. By quantifying the geoeducational potential of geosites and integrating essential concepts such as geoconservation and geoethics, the implementation of this new assessment method can benefit the educational community, tourism industry, and environmental conservation efforts.
The geosites of Lemnos represent local touristic products that, beyond their high aesthetic value, display significant scientific links to the geological past as well as prehistory and history, archaeology, mythology and religious heritage of the island. The unique wealth of Lemnos geosites in combination with the abundance of archaeological sites, cultural monuments and museums composes the basis of what we define here as “Geo-Archaeo-Routes”: certain routes that can be geographically defined, offered, guided and finally followed by the touristic masses. The outcome of the performed quantitative Lemnos geosite assessment enables decision making, thus providing a toolbox useful for sustainable Geo-Archaeo-tourism development at a local level and forms the basis for designing “Geo-Archaeo-Routes”. “Geo-Archaeo-Routes” are particularly favorable of environmentally friendly alternative types of tourism, attracting naturalists, hikers, fans of cultural or religious tourism and many others who represent a major part of the touristic needs of the 21st century. The established hiking and road “Geo-Archaeo-Routes” on Lemnos Island may represent a distinctive touristic product as they offer a high level of “nalture” entertainment, blending “nature with culture” in the framework of a holistic geotouristic approach.
Studies of the upper 447m of the DEEP site sediment succession from central Lake Ohrid, Balkan Peninsula, North Macedonia and Albania provided important insights into the regional climate history and evolutionary dynamics since permanent lacustrine conditions established at 1.36 million years ago (Ma). This paper focuses on the entire 584-m-long DEEP sediment succession and a comparison to a 197-m-long sediment succession from the Pestani site ~5 km to the east in the lake, where drilling ended close to the bedrock, to unravel the earliest history of Lake Ohrid and its basin development. 26Al/10Be dating of clasts from the base of the DEEP sediment succession implies that the sedimentation in the modern basin started at c. 2 Ma. Geophysical, sedimentological and micropalaeontological data allow for chronological information to be transposed from the DEEP to the Pestani succession. Fluvial conditions, slack water conditions, peat formation and/or complete desiccation prevailed at the DEEP and Pestani sites until 1.36 and 1.21 Ma, respectively, before a larger lake extended over both sites. Activation of karst aquifers to the east probably by tectonic activity and a potential existence of neighbouring Lake Prespa supported filling of Lake Ohrid. The lake deepened gradually, with a relatively constant vertical displacement rate of ~0.2 mm/a-1 between the central and the eastern lateral basin and with greater water depth presumably during interglacial periods. Although the dynamic environment characterized by local processes and the fragmentary chronology of the basal sediment successions from both sites hamper palaeoclimatic significance prior to the existence of a larger lake, the new data provide an unprecedented and detailed picture of the geodynamic evolution of the basin and lake that is Europe's presumed oldest extant freshwater lake.
The study area of Rodafnidia on the island of Lesbos (Greece) is considered of archaeological interest, as Paleolithic stone tools have been recovered through excavation and collected from the ground surface in recent years. Geologically, the area is mostly covered by Quaternary post-alpine deposits and volcanic rocks. This paper presents the application of a local geophysical survey to determine the volume of the upper Quaternary deposits in which the Paleolithic artefacts can be found and the identification of their ignimbrite substrates. For this reason, the geoelectrical method was selected as the most appropriate for determining the lithostratigraphic subsurface layers. More specifically, a grid of twenty-one (21) Vertical Electrical Soundings (VES) along with an Electrical Resistivity Tomography (ERT) was carried out. The interpretation of the results of these surveys, in conjunction with the results of older excavation trenches, revealed that the Quaternary deposits have been investigated at depths ranging from 0.5 up to 28.5 meters. Furthermore, the lithological boundary of these post-alpine deposits and their underlying pyroclastic ignimbrite flow (with resistivity 24.0–58.0 Ohm.m) seem to dip to the north. The volume of the Quaternary layer is proposed as the maximum depth for archaeological investigation with high chances to recover more Paleolithic material.
This study investigates the production of the speech act of thanking by L2 learners of Greek from three different proficiency levels (beginner, intermediate, and advanced) and seeks to examine the effect of proficiency on the learners’ competence to express gratitude in symmetrical and asymmetrical situations. The quantitative analysis of the results indicates that no significant development is achieved with proficiency and that, irrespective of their proficiency, learners lag far behind native speakers in regard to expressing gratitude adequately and appropriately. It is maintained here that no aspect of pragmatic development should be taken for granted and that pedagogical intervention is indispensable for the learners’ development of pragmatic competence.
Στο άρθρο διερευνάται η δυνατότητα μιας αφηγηματικής ερευνητικής προσέγγισης να αξιολογεί με επιστημονικό τρόπο τα αποτελέσματα της εκπαίδευσης υποψηφίων εκπαιδευτικών σε ένα πρόγραμμα Πρακτικής Άσκησης. Η έρευνα ήταν ποιοτική και πραγματοποιήθηκε την ακαδημαϊκή χρονιά 2021-2022 σε δύο φάσεις. Συμμετείχαν 73 φοιτητές/τριες από το Τμήμα Θεολογίας, του Εθνικού και Καποδιστριακού Πανεπιστημίου Αθηνών, στο πλαίσιο εφαρμογής του ετήσιου προγράμματος Πρακτικής Άσκησης. Μελετήθηκαν τα αποτελέσματα που έχει η Πρακτική Άσκηση υποψηφίων εκπαιδευτικών σε σχολικό περιβάλλον, όταν αυτή πραγματοποιείται μέσω εξατομικευμένης καθοδήγησης και εποπτείας (mentoring), και εξετάστηκε η χρήση μιας αφηγηματικής ερευνητικής προσέγγισης, της τεχνικής της «πιο σημαντικής αλλαγής» (Most significant change), στην αξιολόγηση των αποτελεσμάτων της εκπαίδευσής τους. Τόσο η συλλογή όσο και η ανάλυση των δεδομένων πραγματοποιήθηκαν σε δύο χρονικές φάσεις στη διάρκεια του προγράμματος, με αξιοποίηση της θεωρητικής βάσης της συγκεκριμένης τεχνικής. Συγκεκριμένα, στο μέσο και στο τέλος της Πρακτικής Άσκησης ζητήθηκε από τους/τις φοιτητές/τριες να καταγράψουν την πιο σημαντική αλλαγή που είχαν βιώσει προσωπικά μέσα από την εμπειρία της Πρακτικής Άσκησης, ενώ στη συνέχεια διενεργήθηκε ανάλυση όλων των αφηγήσεων των αλλαγών με τη συμβολή ανεξάρτητων κριτών, ξεχωριστά για κάθε μία από τις δύο φάσεις της ερευνητικής διαδικασίας. Από την ανάλυση περιεχομένου των δεδομένων προκύπτει ότι τα αποτελέσματα από την Πρακτική Άσκηση των υποψηφίων εκπαιδευτικών σχετίζονται με το ακαδημαϊκό κομμάτι της διδασκαλίας και τη θεωρία της, ενώ ταυτόχρονα προκύπτουν αποτελέσματα που συνδέονται με τη διαμόρφωση εκπαιδευτικής επαγγελματικής ταυτότητας. Η έρευνα επιβεβαιώνει την επιστημονική αξιοπιστία της χρήσης αφηγηματικών ερευνητικών προσεγγίσεων (τεχνική της πιο σημαντικής αλλαγής) στην αξιολόγηση των αποτελεσμάτων μιας παρόμοιας εκπαιδευτικής παρέμβασης, ενώ αναδεικνύει σημαντικά κριτήρια για τον μελλοντικό σχεδιασμό προγραμμάτων Πρακτικής Άσκησης, με σκοπό την εκπαίδευση φοιτητών/τριών και υποψηφίων εκπαιδευτικών.
This work presents and discusses chapter two of Marc Lavoie’s book Post-Keynesian Economics: New Foundations. It begins by analysing the concepts of uncertainty and rationality which are extremely important for the post Keynesian approach, and for economic theorizing in general. The notions of fundamental uncertainty and the closely related concept of procedural rationality, are employed in order to build the foundations of a theory of household choice. It proceeds by investigating the repercussions of the theory in a lexicographic/hierarchical analytical framework. In this framework, groups consume different goods depending on their respective needs, income effects are more important than substitution effects, and price competition has a secondary role. It is also shown that Lavoie’s approach does not only draw from the work of Keynes and other major post-Keynesian theorists, but also utilizes contributions from other strands of heterodox economics, thus providing an agenda for a possible theoretical synthesis.
Blazars are a rare class of active galactic nuclei (AGNs) with relativistic jets pointing towards the observer. Jets are thought to be launched as Poynting-flux dominated outflows that accelerate to relativistic speeds at the expense of the available magnetic energy. In this work, we consider electron-proton jets and assume that particles are energized via magnetic reconnection in parts of the jet where the magnetization is still high (σ ≥ 1). The magnetization and bulk Lorentz factor Γ are related to the available jet energy per baryon as μ = Γ(1 + σ). We adopt an observationally motivated relation between Γ and the mass accretion rate into the black hole $\dot{m}$, which also controls the luminosity of external radiation fields. We numerically compute the photon and neutrino jet emission as a function of μ and σ. We find that the blazar SED is produced by synchrotron and inverse Compton radiation of accelerated electrons, while the emission of hadronic-related processes is subdominant except for the highest magnetization considered. We show that low-luminosity blazars (Lγ ≲ 1045 erg s-1) are associated with less powerful, slower jets with higher magnetizations in the jet dissipation region. Their broad-band photon spectra resemble those of BL Lac objects, and the expected neutrino luminosity is $L_{\nu +\bar{\nu }}\sim (0.3-1)\, L_{\gamma }$. High-luminosity blazars (Lγ ≫ 1045 erg s-1) are associated with more powerful, faster jets with lower magnetizations. Their broad-band photon spectra resemble those of flat spectrum radio quasars, and they are expected to be dim neutrino sources with $L_{\nu +\bar{\nu }}\ll L_{\gamma }$.
Relativistic hadronic plasmas can become, under certain conditions, supercritical, abruptly and efficiently releasing the energy stored in protons through photon outbursts. Past studies have tried to relate the features of such hadronic supercriticalities (HSCs) to the phenomenology of gamma-ray burst (GRB) prompt emission. In this work we investigate, for the first time, HSC in adiabatically expanding sources. We examine the conditions required to trigger HSC, study the role of expansion velocity, and discuss our results in relation to GRB prompt emission. We find multipulse light curves from slowly expanding regions (≲ 0.01c) that are a manifestation of the natural HSC quasi-periodicity, while single-pulse light curves with a fast rise and slow decay are found for higher velocities. The formation of the photon spectrum is governed by an in-source electromagnetic cascade. The peak photon energy is approximately $1 \cdot \frac{\Gamma }{100} \frac{1+z}{3}$ MeV for maximum proton energies $(1-10) \cdot \frac{\Gamma }{100} \frac{1+z}{3}$ PeV, while the peak γ-ray luminosities are in the range $(10^{49}-10^{52}) \cdot (\frac{\Gamma }{100})^4$ erg s-1. HSC bursts peaking in the MeV energy band are also copious neutrino emitters with peak energies $\sim 10 \cdot \frac{\Gamma }{100} \frac{1+z}{3}$ TeV and an all-flavour neutrino fluence $\sim 10~{{\ \rm per\ cent}}$ of the γ-ray one. The hypothesis that long-duration GRBs are powered by HSCs could be applied therefore only to the most luminous GRBs observed assuming bulk Lorentz factors Γ ≤ 100.
Despite the unique position of gold catalysis in contemporary organic synthesis, this area of research is notorious for requiring activators and/or additives that enable catalysis by generating cationic forms of gold catalysts. Cycloisomerization reactions occupy a significant portion of the gold-catalyzed reaction space, while they represent a diverse family of reactions that are frequently utilized in synthesis. Herein, hexafluoroisopropanol (HFIP) is shown to be a uniquely simple tool for gold-catalyzed cycloisomerizations, rendering the use of external activators obsolete and leading to highly active catalytic systems with ppm levels of catalyst loading in certain cases. HFIP assumes a dual role as a solvent and an activator, operating via the dynamic activation of the Au-Cl bond through hydrogen bonding, which initiates the catalytic cycle. This special mode of catalysis can enable efficient and scalable cyclization reactions of propargylamides and ynoic acids with simple [AuCl(L)] complexes. A thorough screening of ancillary ligands and counter anions has been performed, establishing this methodology as an alternative to elaborate ligand/catalyst design and to the use of activators. Additionally, this concept is applied in C-C bond-forming cycloisomerization reactions leading to 2H-chromenes and to the design of catalytic systems for sequential or one-pot transformations leading to activated ketoesters, a functionalized N-heterocyclic carbene (NHC) precursor salt, and a compound bearing the bioactive indole core, among others. Importantly, through mechanistic investigations, including a “snapshot” of the species of interest in the solid state, we were able to unambiguously detect the key H-bonding interaction between HFIP and the gold catalyst, shedding light on the intermolecular mode of activation that enables catalysis. In the cases examined herein, HFIP is not only an excellent solvent but also a potent activator and a valuable synthetic handle when incorporated into functional groups of products.
Accreting neutron stars (NSs) represent a unique laboratory for probing the physics of accretion in the presence of strong magnetic fields (B ≳ 108 G). Additionally, the matter inside the NS itself exists in an ultra-dense, cold state that cannot be reproduced in Earth-based laboratories. Hence, observational studies of these objects are a way to probe the most extreme physical regimes. Here we present an overview of the field and discuss the most important outstanding problems related to NS accretion. We show how these open questions regarding accreting NSs in both low-mass and high-mass X-ray binary systems can be addressed with the High-Energy X-ray Probe (HEX-P) via simulated data. In particular, with the broad X-ray passband and improved sensitivity afforded by a low X-ray background, HEX-P will be able to 1) distinguish between competing continuum emission models; 2) provide tighter upper limits on NS radii via reflection modeling techniques that are independent and complementary to other existing methods; 3) constrain magnetic field geometry, plasma parameters, and accretion column emission patterns by characterizing fundamental and harmonic cyclotron lines and exploring their behavior with pulse phase; 4) directly measure the surface magnetic field strength of highly magnetized NSs at the lowest accretion luminosities; as well as 5) detect cyclotron line features in extragalactic sources and probe their dependence on luminosity in the super-Eddington regime in order to distinguish between geometrical evolution and accretion-induced decay of the magnetic field. In these ways HEX-P will provide an essential new tool for exploring the physics of NSs, their magnetic fields, and the physics of extreme accretion.
Introduction: Ultraluminous X-ray sources (ULXs) represent an extreme class of accreting compact objects: from the identification of some of the accretors as neutron stars to the detection of powerful winds travelling at 0.1–0.2 c, the increasing evidence points towards ULXs harbouring stellar-mass compact objects undergoing highly super-Eddington accretion. Measuring their intrinsic properties, such as the accretion rate onto the compact object, the outflow rate, the masses of accretor/companion-hence their progenitors, lifetimes, and future evolution-is challenging due to ULXs being mostly extragalactic and in crowded fields. Yet ULXs represent our best opportunity to understand super-Eddington accretion physics and the paths through binary evolution to eventual double compact object binaries and gravitational-wave sources. Methods: Through a combination of end-to-end and single-source simulations, we investigate the ability of HEX-P to study ULXs in the context of their host galaxies and compare it to XMM-Newton and NuSTAR, the current instruments with the most similar capabilities.Results: HEX-P's higher sensitivity, which is driven by its narrow point-spread function and low background, allows it to detect pulsations and broad spectral features from ULXs better than XMM-Newton and NuSTAR.Discussion: We describe the value of HEX-P in understanding ULXs and their associated key physics, through a combination of broadband sensitivity, timing resolution, and angular resolution, which make the mission ideal for pulsation detection and low-background, broadband spectral studies.
The identification of multiple simultaneous orientations of small molecule inhibitors binding to a protein target is a common challenge. It has recently been reported that the conformational heterogeneity of ligands is widely underreported in the Protein Data Bank, which is likely to impede optimal exploitation to improve affinity of these ligands. Significantly less is even known about multiple binding orientations for fragments (<300 Da), although this information would be essential for subsequent fragment optimisation using growing, linking or merging and rational structure-based design. Here, we use recently reported fragment hits for the SARS-CoV-2 non-structural protein 1 (nsp1) N-terminal domain to propose a general procedure for unambiguously identifying binding orientations of 2-dimensional fragments containing either sulphur or chloro substituents within the wavelength range of most tunable beamlines. By measuring datasets at two energies, using a tunable beamline operating in vacuum and optimised for data collection at very low X-ray energies, we show that the anomalous signal can be used to identify multiple orientations in small fragments containing sulphur and/or chloro substituents or to verify recently reported conformations. Although in this specific case we identified the positions of sulphur and chlorine in fragments bound to their protein target, we are confident that this work can be further expanded to additional atoms or ions which often occur in fragments. Finally, our improvements in the understanding of binding orientations will also serve to improve the rational optimisation of SARS-CoV-2 nsp1 fragment hits.
Ouldali N, Son MBF, McArdle AJ, Vito O, Vaugon E, Belot A, Leblanc C, Murray NL, Patel MM, Levin M. Immunomodulatory therapy for MIS-C. Pediatrics. 2023;152(1):e2022061173.
Noble metal nanostructured substrates enhance photoluminescence emitted from molecules immobilized onto their surface, allowing for the development of highly sensitive immunoassays employing fluorescent labels. In this work, nanostructured silver surfaces were implemented as substrates for the immunochemical detection of two ovarian cancer markers, carbohydrate antigen 125 (CA125) and human epididymis protein 4 (HE4). Biotinylated detection antibodies were used to allow for the detection of immunocomplexes through a reaction with streptavidin conjugated to Rhodamine Red-X. The detection limits achieved were 2.5 U/mL and 0.06 ng/mL for CA125 and HE4, respectively, with linear dynamic ranges, covering the concentration ranges of both healthy and ovarian cancer patients.
HIV/HCV prevention among people who inject drugs (PWID) is of key public health importance. We aimed to assess the impact of COVID-19 and associated response measures on HIV/HCV prevention services and socio-economic status of PWID in high-HIV-risk sites. Sites with recent (2011–2019) HIV outbreaks among PWID in Europe North America and Israel, that had been previously identified, were contacted early May 2020. Out of 17 sites invited to participate, 13 accepted. Semi-structured qualitative site reports were prepared covering data from March to May 2020, analyzed/coded and confirmed with a structured questionnaire, in which all sites explicitly responded to all 103 issues reported in the qualitative reports. Opioid maintenance treatment, needle/syringe programs and antiretroviral treatment /hepatitis C treatment continued, but with important reductions and operational changes. Increases in overdoses, widespread difficulties with food and hygiene needs, disruptions in drug supply, and increased homelessness were reported. Service programs rapidly reformed long established, and politically entrenched, restrictive service delivery policies. Future epidemic control measures should include mitigation of negative side-effects on service provision and socio-economic determinants in PWID.
Despite being relatively rare, Mediterranean tropical-like cyclones, also known as Medicanes, induce significant impacts on coastal Mediterranean areas. Under climate change, it is possible that these effects will increase in frequency and severity. Currently, there is only a broad understanding of the types and mechanisms of these impacts. This work studied Medicane Ianos (September 2020) and its effects on the Ionian Islands, in Greece, by developing a database of distinct impact elements based on field surveys and public records. Through this archive, the study explored the range of Ianos’ impacts to develop a systematic categorization. Results showed different types of effects induced on the natural and the built environment that can be grouped into 3 categories and 39 sub-categories in inland and coastal areas, indicating an extensive diversity of impacts, ranging from flooding and geomorphic effects to damages in various facilities, vehicles and infrastructure. The systematic description of the typology of Medicanes’ effects presented in this study is a contribution to a better understanding of their consequences as means to improve our ability to prepare for, respond to, and recover from them, a necessary stepping stone in improving the overall preparedness of both the general public and relevant authorities.
The influence of neutrosophy on many fields of science and technology, as well as its numerous applications, are evident. Our motivation is to apply neutrosophy for the first time in order to improve methods for solving unconstrained optimization. Particularly, in this research, we propose and investigate an improvement of line search methods for solving unconstrained nonlinear optimization models. The improvement is based on the application of symmetry involved in neutrosophic logic in determining appropriate step size for the class of descent direction methods. Theoretical analysis is performed to show the convergence of proposed iterations under the same conditions as for the related standard iterations. Mutual comparison and analysis of generated numerical results reveal better behavior of the suggested iterations compared with analogous available iterations considering the Dolan and Moré performance profiles and statistical ranking. Statistical comparison also reveals advantages of the neutrosophic improvements of the considered line search optimization methods.
This paper presents the methodology of an applied geophysical and remote sensing research at river deltas for their subsurface and surface structure and its application in the deltaic plain of Pineios River (Thessaly, Greece). The scope is to primarily calculate the thickness of deltaic post alpine deposits, with the contribution of Transient Electromagnetic Method (TEM), but also identify the surficial characteristics (biotic/ abiotic) of the area with the appropriate combination of spectral bands and spectral indices. Regarding the remote sensing approach, some geomorphological features were outlined. This was managed from six false color composites of the area, produced by combining spectral bands and additional five false color composites by combining several spectral indices. •The results of the TEM method along with their statistical analysis provided important information regarding the spatial distribution and thickness of the lithological units along the deltaic plain.•The combination of spectral bands 8, 7, 6 seems to adumbrate the hydrographic network of the area and even detects possible changes in the inflow.•The combination of spectral indices MSAVI2, WV-BI, WV-WI was helpful enough to geomorphological mapping of the deltaic plain.
This paper presents the methodology of an applied geophysical and remote sensing research at river deltas for their subsurface and surface structure and its application in the deltaic plain of Pineios River (Thessaly, Greece). The scope is to primarily calculate the thickness of deltaic post alpine deposits, with the contribution of Transient Electromagnetic Method (TEM), but also identify the surficial characteristics (biotic/ abiotic) of the area with the appropriate combination of spectral bands and spectral indices. Regarding the remote sensing approach, some geomorphological features were outlined. This was managed from six false color composites of the area, produced by combining spectral bands and additional five false color composites by combining several spectral indices. • The results of the TEM method along with their statistical analysis provided important information regarding the spatial distribution and thickness of the lithological units along the deltaic plain • The combination of spectral bands 8, 7, 6 seems to adumbrate the hydrographic network of the area and even detects possible changes in the inflow. • The combination of spectral indices MSAVI2, WV-BI, WV-WI was helpful enough to geomorphological mapping of the deltaic plain.
The dynamics of fluid flows give rise to robust, persistent circulation features that underpin the flow and exert strong control over the advection of water masses, either enhancing it or suppressing it, collectively known as lagrangian coherent structures. Lagrangian approaches and metrics have been shown to be better suited than eulerian ones at locating and delineating such structures and capturing the effect they have on the formation and dispersion of water masses, particularly at the smaller scales. In this paper, we use the framework of lagrangian coherent structures to analyse the ocean velocity fields over a climatological year obtained from a high-resolution eddy-resolving model in order to investigate the lagrangian regimes that affect the motion, separation and mixing of water masses in the Mediterranean Sea. The lagrangian regimes that develop in each sub-basin over the course of the year are characterised and regions of persistent lagrangian activity and coherent structure formation and presence are identified. A quantitative picture of the seasonal variability of the lagrangian coherent structure-induced horizontal mixing and vortex formation is obtained.
The dynamics of fluid flows give rise to robust, persistent circulation features that underpin the flow and exert strong control over the advection of water masses, either enhancing it or suppressing it, collectively known as lagrangian coherent structures. Lagrangian approaches and metrics have been shown to be better suited than eulerian ones at locating and delineating such structures and capturing the effect they have on the formation and dispersion of water masses, particularly at the smaller scales. In this paper, we use the framework of lagrangian coherent structures to analyse the ocean velocity fields over a climatological year obtained from a high-resolution eddy-resolving model in order to investigate the lagrangian regimes that affect the motion, separation and mixing of water masses in the Mediterranean Sea. The lagrangian regimes that develop in each sub-basin over the course of the year are characterised and regions of persistent lagrangian activity and coherent structure formation and presence are identified. A quantitative picture of the seasonal variability of the lagrangian coherent structure-induced horizontal mixing and vortex formation is obtained.
This paper proposes the utilization of large language models as recommendation systems for museum visitors. Since the aforementioned models lack the notion of context, they cannot work with temporal information that is often present in recommendations for cultural environments (e.g., special exhibitions or events). In this respect, the current work aims to enhance the capabilities of large language models through a fine-tuning process that incorporates contextual information and user instructions. The resulting models are expected to be capable of providing personalized recommendations that are aligned with user preferences and desires. More specifically, Generative Pre-trained Transformer 4, a knowledge-based large language model is fine-tuned and turned into a context-aware recommendation system, adapting its suggestions based on user input and specific contextual factors such as location, time of visit, and other relevant parameters. The effectiveness of the proposed approach is evaluated through certain user studies, which ensure an improved user experience and engagement within the museum environment.
We present here the first long Quaternary record of organic-walled dinoflagellate cyst assemblages analysed from sediment cores retrieved during the International Ocean Discovery Program (IODP) Expedition 381 in the Gulf of Corinth. Site M0078A is located in the central part of the Gulf of Corinth (GoC), a semi-isolated marine basin that was repeatedly isolated and reconnected to the Mediterranean Sea during the Quaternary glacial/interglacial cycles. Our results show that dinoflagellate cysts are sorted in two major ecogroups, each group alternating between marine and isolated/brackish conditions. The marine intervals are characterised by high dinocyst diversity whereas the isolated intervals are dominated by taxa thriving in low-salinity conditions such as Spiniferites cruciformis and Pyxidinopsis psilata. In several of these assemblages, S. cruciformis is so prevalent that it forms almost monospecific assemblages. The low salinity dinocyst assemblages are reported for the first time outside the Ponto-Caspian region and they show a close affinity to modern assemblages from the Black Sea, Caspian Sea and Marmara Sea. The alternations between marine and brackish conditions recorded in the Gulf of Corinth reflect changes in surface water salinity (SSS) and temperature (SST), in response to the Quaternary glacial-interglacial cycles. These seem to be in good agreement with regional and global marine isotope and sea-level records. Our findings suggest that the study region sensitively responds to climate forcing at orbital time scales and that local factors most likely drive shifts in dinoflagellate species composition and diversity.
À travers l’étude du système à effet intégrateur de rituels et de cérémonialscélébrant la présidente de l’UFF et de la FDIF Eugénie Cotton, promue en autorité universelle dont les vertus renvoient au modèle marial, le présent travail explore la mise en place dans le monde communiste de la guerre froide du versant féminin du culte du leader. Afin d’en saisir les spécificités par rapport à un phénomène historique dont la riche production historiographique des vingt dernières années consacre naturellement et exclusivement la masculinité, y sont examinés plus particulièrement les circonstances qui lui donnèrent naissance, les temps forts qui scandent son cheminement, les mécanismes de sa diffusion et les glissements genrés opérés dans le processus de son invention." The communist cult of the female leader: Eugénie Cotton (1881-1967), “world mother” "This article considers the rituals and ceremonies celebrating the French pro-communist activist, Eugénie Cotton, president of the Union of French Women (UFW) and of the Women’s International Democratic Federation (WIDF), and the way Cotton was elevated to the rank of universal authority, exemplifying virtues not unrelated to the model of the Virgin Mary. This exploration of the enactment of the female version of the cult of the leader in the communist world during the Cold War contrasts with the masculine focus of the substantial historiographical production of the last twenty years on this topic. The paper examines in particular the circumstances that gave birth to the “Cotton cult”, the key moments in its evolution, the mechanisms of its diffusion and the gender shifts in the process of its invention.
Mots-clés : Eugénie Cotton, culte du leader, UFF, FDIF, pacifisme,guerre froideKeywords: Eugénie Cotton, cult of the leader, UFW, WIDF, pacifism,Cold War
BACKGROUND: Left atrium changes are implicated in atrial fibrillation (AF) substrate and are predictive of AF outcomes. Left atrial appendage (LAA) is an integral component of left atrial structure and could be affected by atrial cardiomyopathy. We aimed to elucidate the association between LAA indices and late arrhythmia recurrence after atrial fibrillation catheter ablation (AFCA).
METHODS: The MEDLINE database, ClinicalTrials.gov, medRxiv and Cochrane Library were searched for studies evaluating LAA and late arrhythmia recurrence in patients undergoing AFCA. Data were pooled by meta-analysis using a random-effects model. The primary endpoint was pre-ablation difference in LAA anatomic or functional indices.
RESULTS: A total of 34 studies were found eligible and five LAA indices were analyzed. LAA ejection fraction and LAA emptying velocity were significantly lower in patients with AF recurrence post-ablation [SMD = - 0.66; 95% CI (- 1.01, - 0.32) and SMD = - 0.56; 95% CI (- 0.73, - 0.40) respectively] as compared to arrhythmia free controls. LAA volume and LAA orifice area were significantly higher in patients with AF recurrence post-ablation (SMD = 0.51; 95% CI 0.35-0.67, and SMD = 0.35; 95% CI 0.20-0.49, respectively) as compared to arrhythmia free controls. LAA morphology was not predictive of AF recurrence post-ablation (chicken wing morphology; OR 1.27; 95% CI 0.79-2.02). Moderate statistical heterogeneity and small case-control studies are the main limitations of our meta-analysis.
CONCLUSIONS: Our findings suggest that LAA ejection fraction, LAA emptying velocity, LAA orifice area and LAA volume differ between patients suffering from arrhythmia recurrence post-ablation and arrhythmia free counterparts, while LAA morphology is not predictive of AF recurrence.
A proper generalization of the extended boundary condition method to calculate the transition matrix, T, for electromagnetic scattering from a homogeneous and isotropic body of arbitrary shape, characterized by a periodically time-varying electric permittivity, is presented. The application of the method on a specific example of a spheroidal dielectric particle confirms that time modulation induces strong inelastic scattering, accompanied by energy transfer between the scatterer and the light field, when the difference of the incident wave frequency to a particle optical resonance matches an integer multiple of the modulation frequency. Moreover, it is shown that, for nonspherical scatterers, these effects can be selectively tuned by external means such as the polarization and the propagation direction of the incident light beam. The method is readily implementable in available dynamic multiple-scattering computer codes, and, because of its versatility and computational efficiency, it can offer new opportunities for studying more complex time-varying photonic structures.
The stability of astrophysical jets in the linear regime is investigated by presenting a methodology to find the growth rates of the various instabilities. We perturb a cylindrical axisymmetric steady jet, linearize the relativistic ideal magnetohydrodynamic (MHD) equations, and analyze the evolution of the eigenmodes of the perturbation by deriving the differential equations that need to be integrated, subject to the appropriate boundary conditions, in order to find the dispersion relation. We also apply the WKBJ approximation and, additionally, give analytical solutions in some subcases corresponding to unperturbed jets with constant bulk velocity along the symmetry axis.
Aims: We study the stability properties of relativistic magnetized astrophysical jets in the linear regime. We consider cylindrical cold jet configurations with constant Lorentz factor and constant density profiles across the jet. We are interested in probing the properties of the instabilities and identifying the physical quantities that affect the stability profile of the outflows. Methods: We conducted a linear stability analysis on the unperturbed outflow configurations we are interested in. We focus on the unstable branches, which can disrupt the initial outflow. We proceeded with a parametric study regarding the Lorentz factor, the ratio of the rest mass density of the jet to that of the environment, the magnetization, and the ratio of the poloidal component of the magnetic field to its toroidal counterpart measured on the boundary of the jet. We also consider two choices for the pressure of the environment, either thermal or magnetic, and check if this choice affects the results. Additionally, we applied a WKBJ method at the radius of the jet in order to study the local stability properties. Finally, we adapted the jet configuration in Cartesian geometry and compared the planar flow results with the results of the cylindrical counterpart. Results: While investigating the stability properties of the configurations, we observed the existence of a specific solution branch, which showcases the growth timescale of the instability comparable to the light crossing time of the jet radius. Our analysis focuses on this solution. All of the quantities considered for the parametric study affect the behavior of the mode while the magnetized environments seem to hinder its development compared to the hydrodynamic equivalent. Also, our analysis of the eigenfunctions of the system alongside the WKBJ results show that the mode develops in a very narrow layer near the boundary of the jet, establishing the notion of locality for the specific solution. The results indicate that the mode is a relativistic generalization of the Kelvin-Helmholtz instability. We compare this mode with the corresponding solution in Cartesian geometry and define the prerequisites for the Cartesian Kelvin-Helmholtz to successfully approximate the cylindrical counterpart. Conclusions: We identify the Kelvin-Helmholtz instability for a cold nonrotating relativistic jet carrying a helical magnetic field. Our parametric study reveals the important physical quantities that affect the stability profile of the outflow and their respective value ranges for which the instability is active. The Kelvin-Helmholtz mode and its stability properties are characterized by the locality of the solutions, the value of the angle between the magnetic field and the wavevector, the linear dependence between the mode's growth rate and the wavevector, and finally the stabilization of the mode for flows that are ultrafast magnetosonic. The cylindrical mode can be approximated successfully by the Cartesian Kelvin-Helmholtz instability whenever certain length scales are much larger than the jet radius.
Although the psychoanalytic theories of Heinz Kohut and Otto F. Kernberg have not explicitly focused on loneliness, they have the potential to offer a rich conceptualization of this experience in severe personality pathology. In this study, we attempt to illustrate and discuss the various qualities of loneliness in narcissistic, borderline, and other personality pathology, as implied in these theories. Kohut’s views on selfobjects are presented and the links between selfobjects and loneliness are highlighted. In this theory, loneliness may be regarded as grandiose isolation and object hunger may be viewed as a type of quasi, but not real loneliness. In Kernberg’s theory, emptiness seems to be the essence of loneliness, but it takes on different qualities in several personality disorders. Mature love is proposed as the opposite of loneliness. After identifying some points of convergence between Kohut and Kernberg regarding loneliness, we conclude with the view that real loneliness can be experienced only when genuine intimacy and mature dependence have been established.
We present a detailed compilation and analysis of the X-ray phase space of low- to intermediate-redshift (0 ≤ z ≤ 1) transients that consolidates observed light curves (and theory where necessary) for a large variety of classes of transient/variable phenomena in the 0.3-10 keV energy band. We include gamma-ray burst afterglows, supernovae, supernova shock breakouts and shocks interacting with the environment, tidal disruption events and active galactic nuclei, fast blue optical transients, cataclysmic variables, magnetar flares/outbursts and fast radio bursts, cool stellar flares, X-ray binary outbursts, and ultraluminous X-ray sources. Our overarching goal is to offer a comprehensive resource for the examination of these ephemeral events, extending the X-ray duration-luminosity phase space (DLPS) to show luminosity evolution. We use existing observations (both targeted and serendipitous) to characterize the behavior of various transient/variable populations. Contextualizing transient signals in the larger DLPS serves two primary purposes: to identify areas of interest (i.e., regions in the parameter space where one would expect detections, but in which observations have historically been lacking), and to provide initial qualitative guidance in classifying newly discovered transient signals. We find that while the most luminous (largely extragalactic) and least luminous (largely Galactic) part of the phase space is well populated at t > 0.1 days, intermediate-luminosity phenomena (L X = 1034-1042 erg s-1) represent a gap in the phase space. We thus identify L X = 1034-1042 erg s-1 and t = 10-4 to 0.1 days as a key discovery phase space in transient X-ray astronomy.
Wine quality and typicity are complex concepts that can be hard to define. Wine is a product destined to not only be consumed and appreciated but also marketed, and its distinctiveness, quality and typicity are important characteristics that describe a wine’s sensory profile and, ultimately, add value to the finished product. Even though both quality and typicity are mostly assessed using a sensory evaluation, many studies have examined the feasibility of using chemical analysis methods in order to increase the objectivity of assessments. Today, the use of chemometrics facilitates the handling of big data, and outcomes from various analytical techniques can be integrated to produce more accurate results. This study discusses the existing sensory and analytical approaches, implications and future prospects for an objective measurement of quality and typicity as well as methods for the selection of appropriate data for predictive model development.
Microbial desulfurization has been extensively studied as a promising alternative to the widely applied chemical desulfurization process. Sulfur removal from petroleum and its products becomes essential, as the environmental regulations become increasingly stringent. Rhodococcus qingshengii IGTS8 has gained ground as a naturally occurring model biocatalyst, due to its superior specific activity for desulfurization of dibenzothiophene (DBT). Recalcitrant organic sulfur compounds—DBT included—are preferentially removed by selective carbon-sulfur bond cleavage to avoid a reduction in the calorific value of the fuel. The process, however, still has not reached economically sustainable levels, as certain limitations have been identified. One of those bottlenecks is the repression of catalytic activity caused by ubiquitous sulfur sources such as inorganic sulfate, methionine, or cysteine. Herein, we report an optimized culture medium for wild-type stain IGTS8 that completely alleviates the sulfate-mediated repression of biodesulfurization activity without modification of the natural biocatalyst. Medium C not only promotes growth in the presence of several sulfur sources, including DBT, but also enhances biodesulfurization of resting cells grown in the presence of up to 5 mM sulfate. Based on the above, the present work can be considered as a step towards the development of a more viable commercial biodesulfurization process.
Research shows that, while exposure to English as a lingua franca (ELF) discourse and to discussion of ELF-related interactional strategies – such as rephrasing, paraphrasing and translanguaging – can help raise English language teachers’ and learners’ ELF awareness, this is often not enough nor is the value of such exposure adequately monitored. In this paper, following the principles of ELF awareness (Sifakis, Nicos. 2019. ELF awareness in English language teaching: Processes and practices. Applied Linguistics 40(2). 288–306), I suggest that raising teachers’ and learners’ awareness of and attitudes towards their own experience as users of English inside and outside of the classroom needs to be prioritised, especially in Expanding Circle teaching and learning contexts. Together with this awareness, teachers and learners need to be made fully conscious of their deeper perceptions about key ELF concerns, such as the role of the native speaker in ELF interactions, the nature of intercultural communication, etc. Such awareness can be raised through metalinguistic and metacognitive activities and questions added to existing activities/materials. To this end, I propose a framework and a series of specific step-by-step scenarios and tools for raising teachers’ and learners’ ELF awareness along these lines and present four examples of integrating such metacognitive and metalinguistic activities with those of a specific textbook.
The discovery of therapeutic miRNAs is one of the most exciting challenges for pharmaceutical companies. Since the first miRNA was discovered in 1993, our knowledge of miRNA biology has grown considerably. Many studies have demonstrated that miRNA expression is dysregulated in many diseases, making them appealing tools for novel therapeutic approaches. This review aims to discuss miRNA biogenesis and function, as well as highlight strategies for delivering miRNA agents, presenting viral, non-viral, and exosomic delivery as therapeutic approaches for different cancer types. We also consider the therapeutic role of microRNA-mediated drug repurposing in cancer therapy.
BACKGROUND: Despite significant advancements in multiple myeloma (MM) therapy, the highly heterogenous treatment response hinders reliable prognosis and tailored therapeutics. Herein, we have studied the clinical utility of miRNAs in ameliorating patients' management. METHODS: miRNA-seq was performed in bone marrow CD138+ plasma cells (PCs) of 24 MM and smoldering MM (sMM) patients to analyze miRNAs profile. CD138+ and circulating miR-25 levels were quantified using in house RT-qPCR assays in our screening MM/sMM cohort (CD138+ plasma cells n = 167; subcohort of MM peripheral plasma samples n = 69). Two external datasets (Kryukov et al. cohort n = 149; MMRF CoMMpass study n = 760) served as institutional-independent validation cohorts. Patients' mortality and disease progression were assessed as clinical endpoints. Internal validation was performed by bootstrap analysis. Clinical benefit was estimated by decision curve analysis. RESULTS: miRNA-seq highlighted miR-25 of CD138+ plasma cells to be upregulated in MM vs. sMM, R-ISS II/III vs. R-ISS I, and in progressed compared to progression-free patients. The analysis of our screening cohort highlighted that CD138+ miR-25 levels were correlated with short-term progression (HR = 2.729; p = 0.009) and poor survival (HR = 4.581; p = 0.004) of the patients; which was confirmed by Kryukov et al. cohort (HR = 1.878; p = 0.005) and MMRF CoMMpass study (HR = 1.414; p = 0.039) validation cohorts. Moreover, multivariate miR-25-fitted models contributed to superior risk-stratification and clinical benefit in MM prognostication. Finally, elevated miR-25 circulating levels were correlated with poor survival of MM patients (HR = 5.435; p = 0.021), serving as a potent non-invasive molecular prognostic tool. CONCLUSIONS: Our study identified miR-25 overexpression as a powerful independent predictor of poor treatment outcome and post-treatment progression, aiding towards modern non-invasive disease prognosis and personalized treatment decisions.
BACKGROUND: Mitral valve surgery in octogenarians is a clinical challenge due to the impact of inherent, age-related comorbidities. Within the context of an aging population, the number of mitral surgery candidates over 80 has been gradually increasing. We sought to evaluate our institutional experience with mitral valve surgery in octogenarians to identify factors that may prove useful during the process of clinical decision-making.
METHODS: We retrospectively reviewed our institutional database for all patients over 80 years of age who underwent mitral valve surgery in our department from October 2002 up to February 2021. The primary endpoints of our study were 30-day all-cause mortality and long-term survival after the first postoperative month.
RESULTS: In total, 99 octogenarians underwent mitral valve surgery for various types of mitral pathology. In particular, 70 patients underwent mitral valve replacement with or without concomitant procedures and 29 underwent mitral valve repair with or without concomitant procedures. There was no difference between the two approaches in terms of 30-day mortality and long-term survival. Chronic kidney disease and total operative time were independent predicting factors for 30-day mortality. Etiology of mitral valve pathology and EuroSCORE II was independent predicting factors for long-term survival.
CONCLUSIONS: The type of mitral valve surgery did not affect 30-day and long-term mortality rates in our study. Renal impairment and EuroSCORE II were independent predictors of 30-day mortality and long-term prognosis, respectively. Rheumatic valve disease was also associated with a poorer prognosis.
The main aim of this study is to model the Nature-based solution of Green Roofs (GRs) in order to assess their efficiency as a mitigation strategy for UHI effects and extreme summertime temperatures over Attica in Greece. The area of study is a region that encompasses Athens, the largest Metropolitan area of Greece, and the suburbs. The analysis has been performed with the use of an advanced modeling system that consists of the mesoscale Weather Research and Forecasting model (WRF) and the advanced multilayer urban canopy scheme building energy parameter and building energy model (BEP/BEM). The two modules are fully coupled, forming WRF urban. For a better description of the urban environment and in order to use the full capabilities of the urban canopy scheme, 11 urban classes corresponding to the WUDAPT Local Climate Zones (LCZ) were used instead of the 3 traditional urban classes that the default version uses. Sensitivity tests for a major heatwave that affected the area of study have been performed in order to evaluate the impact of GRs on the UHI structure. Results indicate that the modification of the roof energy budget decreased the maximum temperature during heatwaves and altered the spatio-temporal pattern of the effect.
In the present paper, a manufacturing cell in the presence of faults, coming from the devices of the process, is considered. The modular modeling of the subsystems of the cell is accomplished using of appropriate finite deterministic automata. The desired functionality of the cell as well as appropriate safety specifications are formulated as eleven desired languages. The desired languages are expressed as regular expressions in analytic forms. The languages are realized in the form of appropriate general type supervisor forms. Using these forms, a modular supervisory design scheme is accomplished providing satisfactory performance in the presence of faults as well guaranteeing the safety requirements. The aim of the present supervisor control scheme is to achieve tolerance of basic characteristics of the process coordination to upper-level faults, despite the presence of low-level faults in the devices of the process. The complexity of the supervisor scheme is computed.
For a subpopulation of energetic gamma-ray bursts (GRBs), a moderate baryonic loading may suffice to power ultra-high-energy cosmic rays (UHECRs). Motivated by this, we study the radiative signatures of cosmic-ray protons in the prompt phase of energetic GRBs. Our framework is the internal shock model with multicollision descriptions of the relativistic ejecta (with different emission regions along the jet), plus time-dependent calculations of photon and neutrino spectra. Our GRB prototypes are motivated by Fermi-Large Area Telescope-detected GRBs (including GRB 221009A) for which further, owing to the large energy flux, neutrino nonobservation of single events may pose a strong limit on the baryonic loading. We study the feedback of protons on electromagnetic spectra in synchrotron- and inverse Compton-dominated scenarios to identify the multiwavelength signatures, to constrain the maximally allowed baryonic loading, and to point out the differences between hadronic and inverse Compton signatures. We find that hadronic signatures appear as correlated flux increases in the optical-UV to soft X-ray and GeV-TeV gamma-ray ranges in the synchrotron scenarios, whereas they are difficult to identify in inverse Compton-dominated scenarios. We demonstrate that baryonic loadings around 10, which satisfy the UHECR energetic requirements, do not distort the predicted photon spectra in the Fermi Gamma-Ray Burst Monitor range and are consistent with constraints from neutrino data if the collision radii are large enough (i.e., the time variability is not too short). It therefore seems plausible that under the condition of large dissipation radii a population of energetic GRBs can be the origin of the UHECRs.
We present a multi-messenger model for the prompt emission from GRB 221009A within the internal shock scenario. We consider the time-dependent evolution of the outflow with its impact on the observed light curve from multiple collisions, as well as the self-consistent generation of the electromagnetic spectrum in synchrotron and inverse Compton-dominated scenarios. Our lepto-hadronic model includes UHE protons potentially accelerated in the outflow, and their feedback on spectral energy distribution and on the neutrino emission. We find that we can roughly reproduce the observed light curves with an engine with varying ejection velocity of ultrarelativistic material, which has an intermediate quiescent period of about 200 s and a variability timescale of ~1 s. We consider baryonic loadings of 3 and 30 that are compatible with the hypothesis that the highest-energetic LHAASO photons might come from UHECR interactions with the extragalactic background light, and the paradigm that energetic GRBs may power the UHECR flux. For these values and the high dissipation radii considered, we find consistency with the nonobservation of neutrinos and no significant signatures on the electromagnetic spectrum. Inverse Compton-dominated scenarios from the prompt emission are demonstrated to lead to about an order of magnitude higher fluxes in the HE range; this enhancement is testable via its spectral impact in the Fermi-GBM and LAT ranges.
The blazar PKS 0735+178 is possibly associated with multiple neutrino events observed by the IceCube, Baikal, Baksan, and KM3NeT neutrino telescopes while it was flaring in the γ-ray, X-ray, ultraviolet, and optical bands. We present a detailed study of this peculiar blazar to investigate the temporal and spectral changes in the multiwavelength emission when the neutrino events were observed. The analysis of Swift-XRT snapshots reveal a flux variability of more than a factor 2 in about 5 × 103 s during the observation on 2021 December 17. In the γ-ray band, the source was in its historical highest flux level at the time of the arrival of the neutrinos. The observational comparison between PKS 0735+178 and other neutrino source candidates, such as TXS 0506+056, PKS 1424+240, and GB6 J1542+6129, shows that all these sources share similar spectral energy distributions, very high radio and γ-ray powers, and parsec scale jet properties. Moreover, we present strong supporting evidence for PKS 0735+178 to be, like all the others, a masquerading BL Lac. We perform comprehensive modelling of the multiwavelength emission from PKS 0735+178 within one-zone lepto-hadronic models considering both internal and external photon fields and estimate the expected accompanying neutrino flux. The most optimistic scenario invokes a jet with luminosity close to the Eddington value and the interactions of ~ PeV protons with an external UV photon field. This scenario predicts ~0.067 muon and anti-muon neutrinos over the observed 3-week flare. Our results are consistent with the detection of one very high-energy neutrino like IceCube-211208A.
Nature-based solutions (NbS) can be beneficial to help human communities build resilience to climate change by managing and mitigating related hydro-meteorological hazards (HMHs). Substantial research has been carried out in the past on the detection and assessment of HMHs and their derived risks. Yet, knowledge on the performance and functioning of NbS to address these hazards is severely lacking. The latter is exacerbated by the lack of practical and viable approaches that would help identify and select NbS for specific problems. The EU-funded OPERANDUM project established seven Open-Air Laboratories (OALs) across Europe to co-develop, test, and generate an evidence base from innovative NbS deployed to address HMHs such as flooding, droughts, landslides, erosion, and eutrophication. Herein, we detail the original approaches that each OAL followed in the process of identifying and selecting NbS for specific hazards with the aim of proposing a novel, generic framework for selecting NbS. We found that the process of selecting NBS was overall complex and context-specific in all the OALs, and it comprised 26 steps distributed across three stages: (i) Problem recognition, (ii) NbS identification, and (iii) NbS selection. We also identified over 20 selection criteria which, in most cases, were shared across OALs and were chiefly related to sustainability aspects. All the identified NbS were related to the regulation of the water cycle, and they were mostly chosen according to three main factors: (i) hazard type, (ii) hazard scale, and (iii) OAL size. We noticed that OALs exposed to landslides and erosion selected NbS capable to manage water budgets within the soil compartment at the local or landscape scale, while OALs exposed to floods, droughts, and eutrophication selected approaches to managing water transport and storage at the catchment scale. We successfully portrayed a synthesis of the stages and steps followed in the OALs’ NbS selection process in a framework. The framework, which reflects the experiences of the stakeholders involved, is inclusive and integrated, and it can serve as a basis to inform NbS selection processes whilst facilitating the organisation of diverse stakeholders working towards finding solutions to natural hazards. We animate the future development of the proposed framework by integrating financial viability steps. We also encourage studies looking into the implementation of the proposed framework through quantitative approaches integrating multi-criteria analyses.
Background Multiple HIV outbreaks have been recorded among people who inject drugs (PWID) since 2010. During an intervention for PWID in 2019–2021 in Thessaloniki, Greece, an increasing number of HIV cases was documented. Here, we provide an analysis of this new outbreak. Methods ALEXANDROS was a community-based program and participation included interviewing, rapid HIV/HCV tests, counselling and linkage to care. PWID were recruited through Respondent-Driven Sampling (RDS) in five sampling rounds. Crude and RDS-weighted HIV prevalence estimates were obtained. HIV incidence was estimated from data on 380 initially seronegative PWID with at least two tests. Multivariable Cox proportional hazards model was used to assess risk factors for HIV seroconversion. Results In total, 1,101 PWID were recruited. At first participation, 53.7% were current PWID, 20.1% homeless, 20.3% on opioid substitution treatment and 4.8% had received syringes in the past 12 months. HIV prevalence (95% CI) was 7.0% (5.6–8.7%) and an increasing trend was observed over 2019–2021 (p = 0.002). Two-thirds of the cases (67.5%) were new diagnoses. HIV incidence was 7.0 new infections/100 person-years (95% CI:4.8–10.2). Homelessness in the past 12 months (HR:2.68; 95% CI:1.24–5.81) and receptive syringe sharing (HR:3.86; 95% CI:1.75–8.51) were independently associated with increased risk of seroconversion. By the end of the program, 67.3% of the newly diagnosed cases initiated antiretroviral treatment. Conclusions A new HIV outbreak among PWID was documented in Greece during the COVID-19 pandemic with homelessness and syringe sharing being associated with increased risk of HIV acquisition. Peer-driven programs targeting the population of high-risk underserved PWID can be used to early identify emerging outbreaks and to improve linkage to HIV care.
Disruption in neurogenesis and neuronal migration can influence the assembly of cortical circuits, affecting the excitatory-inhibitory balance and resulting in neurodevelopmental and neuropsychiatric disorders. Using ventral cerebral organoids and dorsoventral cerebral assembloids with mutations in the extracellular matrix gene LGALS3BP, we show that extracellular vesicles released into the extracellular environment regulate the molecular differentiation of neurons, resulting in alterations in migratory dynamics. To investigate how extracellular vesicles affect neuronal specification and migration dynamics, we collected extracellular vesicles from ventral cerebral organoids carrying a mutation in LGALS3BP, previously identified in individuals with cortical malformations and neuropsychiatric disorders. These results revealed differences in protein composition and changes in dorsoventral patterning. Proteins associated with cell fate decision, neuronal migration, and extracellular matrix composition were altered in mutant extracellular vesicles. Moreover, we show that treatment with extracellular vesicles changes the transcriptomic profile in neural progenitor cells. Our results indicate that neuronal molecular differentiation can be influenced by extracellular vesicles.
An improved activation function, termed extended sign-bi-power (Esbp), is proposed. An extension of the Li zeroing neural network (ELi-ZNN) based on the Esbp activation is derived to obtain the online solution of the time-varying inversion problem. A detailed theoretical analysis confirms that the new activation function accomplishes fast convergence in calculating the time-varying matrix inversion. At the same time, illustrative numerical experiments substantiate the excellent performance of the proposed activation function over the Li and tunable activation functions. Convergence properties and numerical behaviors of the proposed ELi-ZNN model are examined.
Due to its significance in science and engineering, time-varying linear matrix equation (LME) problems have received a lot of attention from scholars. It is for this reason that the issue of finding the minimum-norm least-squares solution of the time-varying quaternion LME (ML-TQ-LME) is addressed in this study. This is accomplished using the zeroing neural network (ZNN) technique, which has achieved considerable success in tackling time-varying issues. In light of that, two new ZNN models are introduced to solve the ML-TQ-LME problem for time-varying quaternion matrices of arbitrary dimension. Two simulation experiments and two practical acoustic source tracking applications show that the models function superbly.
The Markowitz model, a Nobel Prize winning model for portfolio analysis, paves the theoretical foundation in finance for modern investment. However, it remains a challenging problem in the high frequency trading (HFT) era to find a more time efficient solution for portfolio analysis, especially when considering circumstances with the dynamic fluctuation of stock prices and the desire to pursue contradictory objectives for less risk but more return. In this paper, we establish a recurrent neural network model to address this challenging problem in runtime. Rigorous theoretical analysis on the convergence and the optimality of portfolio optimization are presented. Numerical experiments are conducted based on real data from Dow Jones Industrial Average (DJIA) components and the results reveal that the proposed solution is superior to DJIA index in terms of higher investment returns and lower risks.
Importance sampling, a variant of online sampling, is often used in neural network training to improve the learning process, and, in particular, the convergence speed of the model. We study, here, the performance of a set of batch selection algorithms, namely, online sampling algorithms that process small parts of the dataset at each iteration. Convergence is accelerated through the creation of a bias towards the learning of hard samples. We first consider the baseline algorithm and investigate its performance in terms of convergence speed and generalization efficiency. The latter, however, is limited in case of poor balancing of data sets. To alleviate this shortcoming, we propose two variations of the algorithm that achieve better generalization and also manage to not undermine the convergence speed boost offered by the original algorithm. Various data transformation techniques were tested in conjunction with the proposed scheme to develop an overall training method of the model and to ensure robustness in different training environments. An experimental framework was constructed using three naturally imbalanced datasets and one artificially imbalanced one. The results assess the advantage in convergence of the extended algorithm over the vanilla one, but, mostly, show better generalization performance in imbalanced data environments.
An extension of the photonic layer multiple scattering methodology to dynamic spherical scatterers, which exhibit a periodic time-varying response, is presented. The applicability of the method is demonstrated on specific examples of single- and bi-layers of periodically modulated high-refractive-index spherical particles arranged on a square lattice. The results provide compelling evidence for strong and tunable inelastic scattering effects under the triple resonance condition, fulfilled for optical transitions between neighboring high-Q lattice modes of the appropriate symmetry, which originate from multipolar Mie resonances. A consistent interpretation of the underlying mechanisms is provided and potential applications in the design of nonreciprocal devices are discussed.
Magnetic reconnection is often invoked as a source of high-energy particles, and in relativistic astrophysical systems it is regarded as a prime candidate for powering fast and bright flares. We present a novel analytical model-supported and benchmarked with large-scale three-dimensional kinetic particle-in-cell simulations in electron-positron plasmas-that elucidates the physics governing the generation of power-law energy spectra in relativistic reconnection. Particles with Lorentz factor γ ≳ 3σ (here, σ is the magnetization) gain most of their energy in the inflow region, while meandering between the two sides of the reconnection layer. Their acceleration time is ${t}_{\mathrm{acc}}\sim \gamma \,{\eta }_{\mathrm{rec}}^{-1}{\omega }_{{\rm{c}}}^{-1}\simeq 20\,\gamma \,{\omega }_{{\rm{c}}}^{-1}$ , where η rec ≃ 0.06 is the inflow speed in units of the speed of light and ω c = eB 0/mc is the gyrofrequency in the upstream magnetic field. They leave the region of active energization after t esc, when they get captured by one of the outflowing flux ropes of reconnected plasma. We directly measure t esc in our simulations and find that t esc ~ t acc for σ ≳ few. This leads to a universal (i.e., σ-independent) power-law spectrum ${{dN}}_{\mathrm{free}}/d\gamma \propto {\gamma }^{-1}$ for the particles undergoing active acceleration, and ${dN}/d\gamma \propto {\gamma }^{-2}$ for the overall particle population. Our results help to shed light on the ubiquitous presence of power-law particle and photon spectra in astrophysical nonthermal sources.
DNA sequences of ideal and natural geometries are examined, studying their charge transport properties as mutation detectors. Ideal means textbook geometry. Natural means naturally distorted sequences; geometry taken from available databases. A tight-binding (TB) wire model at the base-pair level is recruited, together with a transfer matrix technique. The relevant TB parameters are obtained using a linear combination of all valence orbitals of all atoms, using geometry, either ideal or natural, as the only input. The investigated DNA sequences contain: (i) point substitution mutations – specifically, the transitions guanine (G) 2 adenine (A) – and (ii) sequences extracted from human chromosomes, modified by expanding the cytosine–adenine–guanine triplet [(CAG)n repeats] to mimic the following diseases: (a) Huntington’s disease, (b) Kennedy’s disease, (c) Spinocerebellar ataxia 6, (d) Spinocerebellar ataxia 7. Quantities such as eigenspectra, density of states, transmission coefficients, and the – more experimentally relevant – current–voltage (I–V) curves are studied, intending to find adequate features to recognize mutations. To this end, the normalised deviation of the I–V curve from the origin (NDIV) is also defined. The features of the NDIV seem to provide a clearer picture, being sensitive to the number of point mutations and allowing to characterise the degree of danger of developing the aforementioned diseases.
Physics-informed neural networks (PINNs) are machine learning models that integrate data-based learning with partial differential equations (PDEs). In this work, for the first time we extend PINNs to model the numerically challenging case of astrophysical shock waves in the presence of a stellar gravitational field. Notably, PINNs suffer from competing losses during gradient descent that can lead to poor performance especially in physical setups involving multiple scales, which is the case for shocks in the gravitationally stratified solar atmosphere. We applied PINNs in three different setups ranging from modeling astrophysical shocks in cases with no or little data to data-intensive cases. Namely, we used PINNs (a) to determine the effective polytropic index controlling the heating mechanism of the space plasma within 1% error, (b) to quantitatively show that data assimilation is seamless in PINNs and small amounts of data can significantly increase the model's accuracy, and (c) to solve the forward time-dependent problem for different temporal horizons. We addressed the poor performance of PINNs through an effective normalization approach by reformulating the fluid dynamics PDE system to absorb the gravity-caused variability. This led to a huge improvement in the overall model performance with the density accuracy improving between 2 and 16 times. Finally, we present a detailed critique on the strengths and drawbacks of PINNs in tackling realistic physical problems in astrophysics and conclude that PINNs can be a powerful complimentary modeling approach to classical fluid dynamics solvers.
To date, mechanistic modeling of oral drug absorption has been achieved via the use of physiologically based pharmacokinetic (PBPK) modeling, and more specifically, physiologically based biopharmaceutics model (PBBM). The concept of finite absorption time (FAT) has been developed recently and the application of the relevant physiologically based finite time pharmacokinetic (PBFTPK) models to experimental data provides explicit evidence that drug absorption terminates at a specific time point. In this manuscript, we explored how PBBM and PBFTPK models compare when applied to the same dataset. A set of six compounds with clinical data from immediate-release formulation were selected. Both models resulted in absorption time estimates within the small intestinal transit time, with PBFTPK models generally providing shorter time estimates. A clear relationship between the absorption rate and the product of permeability and luminal concentration was observed, in concurrence with the fundamental assumptions of PBFTPK models. We propose that future research on the synergy between the two modeling approaches can lead to both improvements in the initial parameterization of PBPK/PBBM models but to also expand mechanistic oral absorption concepts to more traditional pharmacometrics applications.
The study looks at how environmental concerns were gradually elevated inside the CAP's policy-making framework and how they helped towards the “greening” transition of European agriculture. Within the context of multilevel governance, the analysis is based ontheories of policy change, primarily neo-institutionalism and historical institutionalism. Theanalysis reveals that the historical trajectory of the previous era inside the EU and the global setting is being redefined by policy change
For over a century, the identification of high-energy cosmic ray (CR) sources remains an open question. For Galactic CRs with energy up to 1015 eV, supernova remnants (SNRs) have traditionally been thought the main candidate source. However, recent TeV γ-ray observations have questioned the SNR paradigm. Propagating CRs are deflected by the Galactic magnetic field, hence, γ-rays and neutrinos produced via inelastic hadronic interactions are the only means for unveiling the CR sources. In this work, we study the γ-ray and neutrino emission produced by CRs accelerated inside Galactic jets of stellar-mass black holes in X-ray binaries (BHXBs). We calculate the intrinsic neutrino emission of two prototypical BHXBs , Cygnus X-1 and GX 339-4, for which we have high-quality, quasi-simultaneous multiwavelength spectra. Based on these prototypical sources, we discuss the likelihood of the 35 known Galactic BHXBs to be efficient CR accelerators. Moreover, we estimate the potential contribution to the CR spectrum of a viable population of BHXBs that reside in the Galactic plane. When these BHXBs go into outburst, they may accelerate particles up to hundreds of TeV that contribute to the diffuse γ-ray and neutrino spectra while propagating in the Galactic medium. Using HERMES, an open-source code that calculates the hadronic processes along the line of sight, we discuss the contribution of BHXBs to the diffuse γ-ray and neutrino fluxes, and compare these to their intrinsic γ-ray and neutrino emissions. Finally, we discuss the contribution of BHXBs to the observed spectrum of Galactic CRs.
The present study aimed to analyse the associations between spatiotemporal characteristics of the setting and the origin of the ball in terms of the game complexes for junior female volleyball teams. Multinomial logistic regression and multiple correspondence analysis were applied to analyse 3.675 setting actions (Complex I = 1.593, Complex II = 2.082) in the final phase of the Greek Junior Championship. Results showed that the origin of the ball from the left lane of the court eases the setter for an accurate setting during CI while passing from the right lane incommodes the setter during CII. Regarding setting zone, for accurate setting, odds are increased by 3.2 for zone 4 during CI while decreased by 23.8 for zone 3 during CII. The junior setters' distribution of setting is predictable and creates favourable conditions for the opponent to deal with it. The improvement of junior female setters' ability to follow the team's offensive tactic regardless of the ball's origin, to manipulate passes received from the right lane of the court during CII and the acceleration of setting tempo for the wing hitters could be training goals for coaches.
BACKGROUND: Tumor heterogeneity and lack of personalized prognosis leads to bladder cancer (BlCa) patients' lifelong surveillance with invasive interventions, highlighting the need for modern minimally invasive tools for disease management. Herein, we have evaluated the clinical utility of preoperative serum cell-free DNA (cfDNA) in ameliorating patients' risk-stratification and prognosis. METHODS: cfDNA was purified from 190 preoperative BlCa patients and 26 healthy individuals' serum samples and quantified by 2 assays: an in-house quantitative real-time PCR (qPCR) assay using LEP as reference control and a direct fluorometric assay using Qubit HS dsDNA. Capillary electrophoresis was performed in 31 samples for cfDNA fragment profiling. Tumor relapse/progression and metastasis/death were used as clinical endpoints for non-muscle-invasive bladder cancer and muscle-invasive bladder cancer (MIBC), respectively. RESULTS: cfDNA profiling by capillary electrophoresis highlighted that total and fragment-related cfDNA levels were significantly increased in BlCa and associated with advance disease stages. Evaluation of cfDNA levels by both Qubit/qPCR displayed highly consistent results (rs = 0.960; P < 0.001). Higher cfDNA was correlated with MIBC and stronger risk for early metastasis (Qubit:hazard ratio [HR] = 3.016, P = 0.009; qPCR:HR = 2.918, P = 0.004) and poor survival (Qubit:HR = 1.898, P = 0.042; qPCR:HR = 1.888, P = 0.026) of MIBC patients. Multivariate cfDNA-fitted models led to superior risk stratification and net benefit for MIBC prognosis compared to disease established markers. CONCLUSIONS: Elevated preoperative cfDNA levels are strongly associated with higher risk for short-term metastasis and poor outcome of MIBC, supporting modern noninvasive disease prognosis and management.
This paper examines the principles of selection and arrangement of the letters of Basil the Great in the Aldine edition and in one of the major manuscript families, arguing that the ordering of Basil’s letters in them was mainly based on the content of the letters, whether thematical or by addressee. It concludes that the ancient and medieval thematical orderings of the letters are helpful for our understanding of the content of a large collection as that of Basil, compared to the modern reconstructed chronological order presented in the editions.
The origin of extremely fast variability is one of the long-standing questions in the gamma-ray astronomy of blazars. While many models explain the slower, lower energy variability, they cannot easily account for such fast flares reaching hour-to-minute timescales. Magnetic reconnection, a process where magnetic energy is converted to the acceleration of relativistic particles in the reconnection layer, is a candidate solution to this problem. In this work, we employ state-of-the-art particle-in-cell simulations in a statistical comparison with observations of a flaring episode of a well-known blazar, Mrk 421, at a very high energy (VHE, E > 100 GeV). We tested the predictions of our model by generating simulated VHE light curves that we compared quantitatively with methods that we have developed for a precise evaluation of theoretical and observed data. With our analysis, we can constrain the parameter space of the model, such as the magnetic field strength of the unreconnected plasma, viewing angle and the reconnection layer orientation in the blazar jet. Our analysis favours parameter spaces with magnetic field strength 0.1 G, rather large viewing angles (6 − 8°), and misaligned layer angles, offering a strong candidate explanation for the Doppler crisis often observed in the jets of high synchrotron peaking blazars. Full Tables B.1-B.10 are available at the CDS via anonymous ftp to cdsarc.cds.unistra.fr (ftp://130.79.128.5) or via https://cdsarc.cds.unistra.fr/viz-bin/cat/J/A+A/678/A140
During the last decades, the utilization of imaging modalities such as single photon emission computed tomography (SPECT), positron emission tomography (PET), and magnetic resonance imaging (MRI) in every day clinical practice has enabled clinicians to diagnose diseases accurately at early stages. Radiolabeled iron oxide nanoparticles (RIONs) combine their intrinsic magnetic behavior with the extrinsic character of the radionuclide additive, so that they constitute a platform of multifaceted physical properties. Thus, at a practical level, RIONs serve as the physical parent of the so-called dual-modality contrast agents (DMCAs) utilized in SPECT/MRI and PET/MRI applications due to their ability to combine, at real time, the high sensitivity of SPECT or PET together with the high spatial resolution of MRI. This review focuses on the synthesis and in vivo investigation of both biodistribution and imaging efficacy of RIONs as potential SPECT/MRI or PET/MRI DMCAs.
L’adoption d’une approche apaisante similaire, indistinctement et surtout de manière déraisonnable, constitue à la fois une erreur méthodologique et scientifique inhérente, mais aussi un choix diplomatique et national, à fortiori, malheureux qui, je le crains, conduira avec une précision mathématique dans une atteinte, sans précédent et en tout cas irréversible, aux intérêts de notre « commettant » nationalcommun (j’imagine)...Du peuple grec...De l’hellénisme, en général, en Grèce, à Chypre, mais aussi de la diaspora dans son ensemble !!! (qui a récemment acquis le droit de vote, elle est donc désormais légitimée d’avoir son mot à dire dans les affaires publiques!!!
Greece is a country structured by land, several islands and sea. A regional gravity model of such a country demands the involvement of several types of gravity data in order to cover all its territory. In this paper, we present the development of a regional combined gravity model of Greece and its surroundingarea, by integrating terrestrial, marine (shipborne and altimetry-derived gravity data) and satellite data (GOCE and GRACE data). These kinds of data, especially the terrestrial and marine ones, have passed quality and validation control since they were collected from different organizations, which means that they probably have been acquired and processed with different parametersand formulas. Following that, their integration was accomplished with the application of the least-squares collocation (LSC). Therefore, a newly combined regional gravity model of Greece and its surrounding areas has been developed. This gravity model can be valuable for regional geological and geophysical studies of Greece, since it provides homogeneously the distribution of Complete Bouguer anomaly (CBA) all over Greece, with updated gravity data and in good agreement with the initial gravity datasets that have been used.
Based on fresh archival research this article examines the exchange of Romanizing statuary between Italy and Spain during the ventennio fascista. Between 1933 and 1943, Italy and Spain exchanged copies of Roman statues as symbolic gestures, to substantiate their claims to a shared classical heritage of ‘imperial greatness’. Using press reports and documentary film excerpts the article reconstructs public events that took place in Merida, Tarragona, Palma, and Zaragoza and assesses their impact. Behind these exchanges, and public ceremonies staged on their occasion, lay the Fascist concept of romanità: an archaeologically and aesthetically charged discourse placing Late-Republican and Early-Imperial Roman heritage in the epicentre of Fascist identity politics. Through improvised public performances of romanità, classical materialities, monumental as well as spatial, were imbued with Fascist dynamics, as the past turned into the present and projected into the future. Through individual and collective performance these ceremonies embodied a primeval Fascist ideal that appeared at once spectacular and modern.
OBJECTIVES: In the era of precision medicine, the highly aggressive and heterogenous triple-negative breast cancer (TNBC) is still characterized by limited options to support personalized prognosis and guide therapeutic interventions. Thereafter, the aim of the present study has been the thorough evaluation of miR-146a as a novel molecular indicator of TNBC prognosis and treatment outcome, utilizing four independent TNBC cohorts. DESIGN & METHODS: miR-146a levels were clinically evaluated in our screening (n = 122) and three external validation TNBC cohorts (de Rinaldis et al. 2013, n = 114; Jezequel et al. 2015, n = 107; TCGA, n = 180). Analysis of miR-146a and validated gene targets was performed in Jezequel et al. and TCGA validation cohorts. Patients' survival, recurrence and metastasis were determined as clinical endpoints for the survival analysis. Internal validation was performed by bootstrap analysis and clinical net benefit was evaluated by decision curve analysis. RESULTS: Reduction of miR-146a is strongly associated with patients' poor survival and can predict post-treatment disease early-recurrence, independently of tumor size, lymph node status, histological grade and patients' age. The analysis of the external validation cohorts corroborated the unfavorable nature of miR-146a repression regarding patients' survival and, strikingly, unveiled the ability of miR-146a to predict TNBC metastasis. Combined assessment of miR-146a levels and lymph node status resulted in superior risk-stratification of TNBC patients and higher clinical benefit regarding disease prognosis and post-treatment outcome. Ultimately, miR-146a was negatively associated with EGFR and SOX2 expression in TNBC. CONCLUSIONS: miR-146a evaluation could ameliorate personalized prognosis and support precision medicine decisions in TNBC.
Accumulation of DNA damage resulting from reactive oxygen species was proposed to cause neurological and degenerative disease in patients, deficient in nucleotide excision repair (NER) or its transcription-coupled subpathway (TC-NER). Here, we assessed the requirement of TC-NER for the repair of specific types of oxidatively generated DNA modifications. We incorporated synthetic 5′,8-cyclo-2′-deoxypurine nucleotides (cyclo-dA, cyclo-dG) and thymine glycol (Tg) into an EGFP reporter gene to measure transcription-blocking potentials of these modifications in human cells. Using null mutants, we further identified the relevant DNA repair components by a host cell reactivation approach. The results indicated that NTHL1-initiated base excision repair is by far the most efficient pathway for Tg. Moreover, Tg was efficiently bypassed during transcription, which effectively rules out TC-NER as an alternative repair mechanism. In a sharp contrast, both cyclopurine lesions robustly blocked transcription and were repaired by NER, wherein the specific TC-NER components CSB/ERCC6 and CSA/ERCC8 were as essential as XPA. Instead, repair of classical NER substrates, cyclobutane pyrimidine dimer and N-(deoxyguanosin-8-yl)-2-acetylaminofluorene, occurred even when TC-NER was disrupted. The strict requirement of TC-NER highlights cyclo-dA and cyclo-dG as candidate damage types, accountable for cytotoxic and degenerative responses in individuals affected by genetic defects in this pathway.
The core components of both traditional and contemporary control systems are the proportional–integral–derivative (PID) control systems, which have established themselves as standards for technical and industrial applications. Therefore, the tuning of the PID controllers is of high importance. Utilizing optimization algorithms to reduce the mean square error of the controller’s output is one approach of tuning PID controllers. In this paper, an appropriately modified metaheuristic optimization algorithm dubbed beetle antennae search (BAS) is employed for robust tuning of PID controllers. The findings of three simulated experiments on stabilizing feedback control systems show that BAS produces comparable or higher performance than three other well-known optimization algorithms while only consuming a tenth of their time.
Mitochondria are cellular organelles that play an essential role in generating the chemical energy needed for the biochemical reactions in cells. Mitochondrial biogenesis, i.e., de novo mitochondria formation, results in enhanced cellular respiration, metabolic processes, and ATP generation, while autophagic clearance of mitochondria (mitophagy) is required to remove damaged or useless mitochondria. The balance between the opposing processes of mitochondrial biogenesis and mitophagy is highly regulated and crucial for the maintenance of the number and function of mitochondria as well as for the cellular homeostasis and adaptations to metabolic demands and extracellular stimuli. In skeletal muscle, mitochondria are essential for maintaining energy homeostasis, and the mitochondrial network exhibits complex behaviors and undergoes dynamic remodeling in response to various conditions and pathologies characterized by changes in muscle cell structure and metabolism, such as exercise, muscle damage, and myopathies. In particular, the involvement of mitochondrial remodeling in mediating skeletal muscle regeneration following damage has received increased attention, as modifications in mitophagy-related signals arise from exercise, while variations in mitochondrial restructuring pathways can lead to partial regeneration and impaired muscle function. Muscle regeneration (through myogenesis) following exercise-induced damage is characterized by a highly regulated, rapid turnover of poor-functioning mitochondria, permitting the synthesis of better-functioning mitochondria to occur. Nevertheless, essential aspects of mitochondrial remodeling during muscle regeneration remain poorly understood and warrant further characterization. In this review, we focus on the critical role of mitophagy for proper muscle cell regeneration following damage, highlighting the molecular mechanisms of the mitophagy-associated mitochondrial dynamics and network reformation.
Panteri E, Bernauer U, Bodin L, Chaudhry Q, Coenraads PJ, Dusinska M, Gaffet E, Rousselle C, Stepnik M, Wijnhoven S, et al.SCCS scientific opinion on HAA299 (nano) - SCCS/1634/21. Regulatory Toxicology and Pharmacology [Internet]. 2023;139. Website
The chemical investigation of the organic extract of the red alga Laurencia majuscula collected from Hurghada reef in the Red Sea resulted in the isolation of five C15 acetogenins, including four tricyclic ones of the maneonene type (1–4) and a 5-membered one (5), 15 sesquiterpenes, including seven lauranes (6–12), one cuparane (13), one seco-laurane (14), one snyderane (15), two chamigranes (16, 17), two rearranged chamigranes (18, 19) and one aristolane (20), as well as a tricyclic diterpene (21) and a chlorinated fatty acid derivative (22). Among them, compounds 1–3, 5, 7, 8, 10, 11 and 14 are new natural products. The structures and the relative configurations of the isolated natural products have been established based on extensive analysis of their NMR and MS data, while the absolute configuration of maneonenes F (1) and G (2) was determined on the basis of single-crystal X-ray diffraction analysis. The anti-inflammatory activity of compounds 1, 2, 4–8, 10, 12–16, 18 and 20–22 was evaluated by measuring suppression of nitric oxide (NO) release in TLR4-activated RAW 264.7 macrophages in culture. All compounds, except 6, exhibited significant anti-inflammatory activity. Among them, metabolites 1, 4 and 18 did not exhibit any cytostatic activity at the tested concentrations. The most prominent anti-inflammatory activity, accompanied by absence of cytostatic activity at the same concentration, was exerted by compounds 5 and 18, with IC50 values of 3.69 μM and 3.55 μΜ, respectively.
In recent years, on the one hand, we have witnessed the rise of blockchain technology, which has led to better transparency, traceability, and therefore, trustworthy exchange of digital assets among different actors. On the other hand, achieving trustworthy content exchange has been one of the primary objectives of the Semantic Web, part of the World Wide Web Consortium. Semantic Web and blockchain technologies are the fundamental building blocks of Web3 (the third version of the Internet), which aims to link data through a decentralized approach. Blockchain provides a decentralized and secure framework for users to safeguard their data and take control over their data and Web3 experiences. However, developing trustworthy decentralized applications (Dapps) is a challenge because many blockchain-based functionalities must be developed from scratch, and combined with data semantics to open new innovative opportunities. In this survey paper, we explore the cross-cutting domain of the Semantic Web and blockchain and identify the critical building blocks required to achieve trust in the Next-Generation Internet. The application domains that could benefit from these technologies are also investigated. We developed a deep analysis of the published literature between 2015 and 2023. We performed our analysis in different digital libraries (e.g., Elsevier, IEEE, ACM), and as a result of our research, we retrieved 137 papers, of which 97 were retrieved as relevant to include in the paper. Furthermore, we studied several aspects (e.g., network type, transactions per second) of existing blockchain platforms. Semantic Web and blockchain technologies can be used to realize a verification and certification process for data quality. Examples of mechanisms to achieve this are the Decentralized Identities of the Semantic Web or the various blockchain consensus protocols that help achieve decentralization and realize democratic principles. Therefore, Semantic Web and blockchain technologies should be combined to achieve trust in the highly decentralized, semantically complex, and dynamic environments needed to build smart applications of the future.
Sitting volleyball (SV) is a dynamic with short actions sport in the paralympic programme. The purpose of the study was to identify the volleyball skills that best discriminate between winning and losing an SV set, for both the genders. The data were collected from all sets played (N = 224) on the 2019 European men and women SV Championship. Cluster analysis established three types of sets according to the final score difference: 2–4 points (balanced), 5–11 points (semi-balanced) and over 11 points (unbalanced). Three-way MANOVAs were conducted to analyse gender, type of set and type of result differences for selected performance indicators. The analyses revealed significant multivariate differences across gender (p <.001), types of set (p =.014) and result (p <.001) and significant interaction effect of result with gender (p =.025) and type of set (p <.001). A follow-up discriminant analysis showed that setting and attacking were the most important skills for all sets. The results showed that in SV the attack is the most important factor, which determines winners and losers, even in balanced sets. In SV, the importance of skills across gender was similar to volleyball, while there were differences in the structure of the game compared to the sequential order of skills in volleyball.
Glutathione and malondialdehyde are two compounds commonly used to evaluate the oxidative stress status of an organism. Although their determination is usually performed in blood serum, saliva is gaining ground as the biological fluid of choice for oxidative stress determination at the point of need. For this purpose, surface-enhanced Raman spectroscopy (SERS), which is a highly sensitive method for the detection of biomolecules, could offer additional advantages regarding the analysis of biological fluids at the point of need. In this work, silicon nanowires decorated with silver nanoparticles made by metal-assisted chemical etching were evaluated as substrates for the SERS determination of glutathione and malondialdehyde in water and saliva. In particular, glutathione was determined by monitoring the reduction in the Raman signal obtained from substrates modified with crystal violet upon incubation with aqueous glutathione solutions. On the other hand, malondialdehyde was detected after a reaction with thiobarbituric acid to produce a derivative with a strong Raman signal. The detection limits achieved after optimization of several assay parameters were 50 and 3.2 nM for aqueous solutions of glutathione and malondialdehyde, respectively. In artificial saliva, however, the detection limits were 2.0 and 0.32 μM for glutathione and malondialdehyde, respectively, which are, nonetheless, adequate for the determination of these two markers in saliva.
Early diagnosis and monitoring are essential for the effective treatment and survival of patients with different types of malignancy. To this end, the accurate and sensitive determination of substances in human biological fluids related to cancer diagnosis and/or prognosis, i.e., cancer biomarkers, is of ultimate importance. Advancements in the field of immunodetection and nanomaterials have enabled the application of new transduction approaches for the sensitive detection of single or multiple cancer biomarkers in biological fluids. Immunosensors based on surface-enhanced Raman spectroscopy (SERS) are examples where the special properties of nanostructured materials and immunoreagents are combined to develop analytical tools that hold promise for point-of-care applications. In this frame, the subject of this review article is to present the advancements made so far regarding the immunochemical determination of cancer biomarkers by SERS. Thus, after a short introduction about the principles of both immunoassays and SERS, an extended presentation of up-to-date works regarding both single and multi-analyte determination of cancer biomarkers is presented. Finally, future perspectives on the field of SERS immunosensors for cancer markers detection are briefly discussed.
Depression and anxiety disorders carry a tremendous worldwide burden and emerge as a significant cause of disability among western societies. Both disorders are known to disproportionally affect women, as they are twice more likely to be diagnosed and moreover, they are also prone to suffer from female-specific mood disorders. Importantly, the prevalence of these affective disorders has notably risen after the COVID pandemic, especially in women. In this chapter, we describe factors that are possibly contributing to the expression of such sex differences in depression and anxiety. For this, we overview the effect of transcriptomic and genetic factors, the immune system, neuroendocrine aspects, and cognition. Furthermore, we also provide evidence of sex differences in antidepressant response and their causes. Finally, we emphasize the importance to consider sex as a biological variable in preclinical and clinical research, which may facilitate the discovery and development of new and more efficacious antidepressant and anxiolytic pharmacotherapies for both women and men.
Accretion disks around compact objects are expected to enter an unstable phase at high luminosity1. One instability may occur when the radiation pressure generated by accretion modifies the disk viscosity, resulting in the cyclic depletion and refilling of the inner disk on short timescales2. Such a scenario, however, has only been quantitatively verified for a single stellar-mass black hole3-5. Although there are hints of these cycles in a few isolated cases6-10, their apparent absence in the variable emission of most bright accreting neutron stars and black holes has been a continuing puzzle11. Here we report the presence of the same multiwavelength instability around an accreting neutron star. Moreover, we show that the variability across the electromagnetic spectrum—from radio to X-ray—of both black holes and neutron stars at high accretion rates can be explained consistently if the accretion disks are unstable, producing relativistic ejections during transitions that deplete or refill the inner disk. Such a new association allows us to identify the main physical components responsible for the fast multiwavelength variability of highly accreting compact objects.
BACKGROUND: Chemotherapy (CT) is central to the treatment of triple negative breast cancer (TNBC), but drug toxicity and resistance place strong restrictions on treatment regimes. Fasting sensitizes cancer cells to a range of chemotherapeutic agents and also ameliorates CT-associated adverse effects. However, the molecular mechanism(s) by which fasting, or short-term starvation (STS), improves the efficacy of CT is poorly characterized. METHODS: The differential responses of breast cancer or near normal cell lines to combined STS and CT were assessed by cellular viability and integrity assays (Hoechst and PI staining, MTT or H(2)DCFDA staining, immunofluorescence), metabolic profiling (Seahorse analysis, metabolomics), gene expression (quantitative real-time PCR) and iRNA-mediated silencing. The clinical significance of the in vitro data was evaluated by bioinformatical integration of transcriptomic data from patient data bases: The Cancer Genome Atlas (TCGA), European Genome-phenome Archive (EGA), Gene Expression Omnibus (GEO) and a TNBC cohort. We further examined the translatability of our findings in vivo by establishing a murine syngeneic orthotopic mammary tumor-bearing model. RESULTS: We provide mechanistic insights into how preconditioning with STS enhances the susceptibility of breast cancer cells to CT. We showed that combined STS and CT enhanced cell death and increased reactive oxygen species (ROS) levels, in association with higher levels of DNA damage and decreased mRNA levels for the NRF2 targets genes NQO1 and TXNRD1 in TNBC cells compared to near normal cells. ROS enhancement was associated with compromised mitochondrial respiration and changes in the metabolic profile, which have a significant clinical prognostic and predictive value. Furthermore, we validate the safety and efficacy of combined periodic hypocaloric diet and CT in a TNBC mouse model. CONCLUSIONS: Our in vitro, in vivo and clinical findings provide a robust rationale for clinical trials on the therapeutic benefit of short-term caloric restriction as an adjuvant to CT in triple breast cancer treatment.
The simultaneous determination of two inflammatory diseases biomarkers, namely procalcitonin (PCT) and interleukin-6 (IL-6), in human serum samples employing a Point-of-Care device based on Multi Area Reflectance Spectroscopy is presented. Dual-analyte detection was achieved using silicon chips with two silicon dioxide areas of different thickness, one functionalized with an antibody specific for PCT and the other with an antibody specific for IL-6. The assay included reaction of immobilized capture antibodies with mixtures of PCT and IL-6 calibrators with the biotinylated detection antibodies, streptavidin and biotinylated-BSA. The reader provided for the automated execution of the assay procedure, as well as for the collection and processing of the reflected light spectrum, the shift of which is correlated to analytes concentration in the sample. The assay was completed in 35 min and the detection limits for PCT and IL-6 were 2.0 and 0.01 ng/mL respectively. The dual-analyte assay was characterized by high reproducibility (the intra- and inter-assay coefficients of variation were less than 10% for both analytes) and accuracy (the percent recovery values ranged from 80 to 113% for both analytes). Moreover, the values determined for the two analytes in human serum samples with the assay developed were in good agreement with the values determined for the same samples by clinical laboratory methods. These results support the potential of the proposed biosensing device application for inflammatory biomarkers determination at the Point-of-Need
Harnessing the potential beneficial effects of kinase signalling through the generation of direct kinase activators remains an underexplored area of drug development(1-5). This also applies to the PI3K signalling pathway, which has been extensively targeted by inhibitors for conditions with PI3K overactivation, such as cancer and immune dysregulation. Here we report the discovery of UCL-TRO-1938 (referred to as 1938 hereon), a small-molecule activator of the PI3Kalpha isoform, a crucial effector of growth factor signalling. 1938 allosterically activates PI3Kalpha through a distinct mechanism by enhancing multiple steps of the PI3Kalpha catalytic cycle and causes both local and global conformational changes in the PI3Kalpha structure. This compound is selective for PI3Kalpha over other PI3K isoforms and multiple protein and lipid kinases. It transiently activates PI3K signalling in all rodent and human cells tested, resulting in cellular responses such as proliferation and neurite outgrowth. In rodent models, acute treatment with 1938 provides cardioprotection from ischaemia-reperfusion injury and, after local administration, enhances nerve regeneration following nerve crush. This study identifies a chemical tool to directly probe the PI3Kalpha signalling pathway and a new approach to modulate PI3K activity, widening the therapeutic potential of targeting these enzymes through short-term activation for tissue protection and regeneration. Our findings illustrate the potential of activating kinases for therapeutic benefit, a currently largely untapped area of drug development.
Many issues arise from the recession of sea cliffs, including threats to coastal communities and infrastructure. The best proxy to study cliff instability processes is the cliff face evolution. Unfortunately, due to its verticality, this proxy is difficult to observe and measure. This study proposed and compared three remote sensing methods based on structure-from-motion (SfM) photogrammetry or stereorestitution: boat-based SfM photogrammetry with smartphones, unmanned aerial system (UAS) or unmanned aerial vehicle (UAV) photogrammetry with centimetric positioning and Pléiades tri-stereo imagery. An inter-comparison showed that the mean distance between the point clouds produced by the different methods was about 2 m. The satellite approach had the advantage of covering greater distances. The SfM photogrammetry approach from a boat allowed for a better reconstruction of the cliff foot (especially in the case of overhangs). However, over long distances, significant geometric distortions affected the method. The UAS with centimetric positioning offered a good compromise, but flight autonomy limited the extent of the monitored area. SfM photogrammetry from a boat can be used as an initial estimate for risk management services following a localized emergency. For long-term monitoring of the coastline and its evolution, satellite photogrammetry is recommended.
This study aimed to investigate the ways subtypes of social withdrawal and dimensions of solitude are related to existential concerns in emerging adulthood. The links between social withdrawal/solitude and existential well-being are a highly neglected research issue. Participants were 774 emerging adults (50.4% males) aged 18?25 (M = 20.07) from Greece. They completed measures on social withdrawal, solitude, authenticity, meaning in life, existential anxiety, and existential loneliness. We used structural equation modeling to analyze the data. Results indicated that shyness, avoidance, and isolation were associated with more existential concerns, whereas unsociability was associated with less existential concerns. The solitude dimensions - enlightenment, freedom, intimacy, and loneliness - were differentially associated with existential concerns, with enlightenment exhibiting the most existential benefits. Findings showed that existential well-being is dependent on emerging adults? quality of withdrawal experiences and ability to make constructive use of solitude.
The goal of the paper is the design of soft sensors for single input single output (SISO) nonlinear processes. This goal is of essential importance for process monitoring, fault detection and fault isolation. The observer‐based technique, being a fruitful direction in soft sensor design, is followed to develop soft sensors for nonlinear processes with known dynamics and unknown physical parameters. A new and general approach, based on the identified I/O linear approximant system descriptions, around prespecified operating points, and a bank of switching linear observers, will be developed. The system property of the I/O reconstructability of the state space linear approximant of a nonlinear model is presented. The design of each observer is based on the I/O measurements and structural characteristics of the nonlinear process. Observer‐oriented target areas are introduced, and the respective dense web principle is formulated. The design is completed by the design of a data‐driven rule‐based system, providing stepwise switching among the observers of the bank. The number of observers of the bank is equal to the number of the linear approximants of the nonlinear process model and is equal to the number of the respective target operating areas. The target operating areas are required to satisfy the dense web principle. The information provided by the soft sensor is the estimation of the non‐measured variables of the process. The information used by the soft sensor is the identified I/O approximants of the process as well as the real time values of the measurement variables. The efficiency of the design scheme is illustrated through symbolic and numerical simulation results for a chemostat. The nonlinear model of the chemostat is initially approximated by a set of ten linear approximants. After, the I/O approximants are identified, the respective observers are designed and the target operating areas are determined, where several cases of the satisfaction of the dense web principle are investigated. The soft sensor is composed in terms of the designed observers. Simulation results illustrate the satisfactory performance of the designed soft sensor.
Problem definition: We consider pricing of services with strategic customers who have heterogeneous delay costs motivated by transportation systems. Customers are strategic decision makers who weigh the reward from the transport service against the waiting cost for the vehicle at a transportation station. Customers arrive at the station according to a Poisson process, and the vehicle visits the station according to a renewal process. We analyze the optimal price and the equilibrium for different levels of information available to customers. Methodology/results: We represent the service system as a stochastic clearing process, heterogeneity in delay cost as a random variable, and heterogeneity in rewards as a positive affine transformation of delay cost. For each information level, we identify the equilibrium behavior of customers and solve the revenue-maximization problem based on this equilibrium. The equilibrium turns out to be unique in each case, and it is of a threshold form in the sense that for each value of the information, it is best to join either for all types of customers, only for those who are sufficiently price sensitive, only for those who are sufficiently delay sensitive, or for none. The optimal fee is also unique in nontrivial cases. This enables us to perform comparisons across different information structures. Managerial implications: The effect of heterogeneity depends highly on model parameters as well as the available information. For a fixed fee, an increase in heterogeneity has a positive overall impact on the customer population, whereas the effect on the revenue can be positive (slow service at a high fee) or negative (fast service at a low fee). Unlike with fixed fee, for the optimal fee, an increase in heterogeneity can have a negative overall effect on customers. Ignoring heterogeneity can lead to a substantial opportunity loss for the system.
Standard electronic computing based on nanoelectronics and logic gates has upended our lives in a profound way. However, suffering from, both, Moore’s law and Joule’s law, further development of logic devices based solely on elec-tricity has gradually stuck in the mire. All-optical logic devices are believed to be a potential solution for such a problem. This work proposes an all-optical digital logical system (AODLS) based on unidirectional (one-way propagation) modes in the microwave regime. In a Y-shaped module of the AODLS, the basic seven logic gates, including OR, AND, NOT, NOR, NAND, XOR, and XNOR gates, are achieved for continuous broadband operation relying on the existence of unidi-rectional electromagnetic signals. Extremely large extinction and contrast ratios are found in these logic gates. The idea of “negative logic” is used in designing the AODLS. Moreover, the authors further demonstrate that the AODLS can be assembled to multi-input and/or multi-output logical functionalities, which is promising for parallel computation. Besides, numerical simulations perfectly fit with and corroborate the theoretical analyses presented here. The low-loss, broadband, and robust characteristics of this system are outlined and studied in some detail. The AODLS consisting of unidirectional structures may open a new route for all-optical calculation and integrated optical circuits.
All-optical logic gates have been studied intensively owing to their potential to enable broadband, low-loss and high-speed communications. However, poor tunability has remained a key challenge in this field. In this work, we propose a Y-shaped structure composed of Yttrium Iron Garnet (YIG) layers that can serve as tunable all-optical logic gates, including, but not limited to, OR, AND and NOT gates, by applying external magnetic fields to magnetize the YIG layers. Our findings reveal that these logic gates are founded on protected one-way edge modes, where by tuning the wavenumber k of the operating mode to a sufficiently small (or even zero) value, the gates can become nearly immune to nonlocal effects. This not only enhances their reliability but also allows for maintaining extremely high precision in their operations. Furthermore, the operating band itself of the logic gates is also shown to be tunable. We introduce a straightforward and practical method for controlling and switching these gates between "work", "skip", and "stop" modes. These findings have potentially significant implications for the design of high-performance and robust all-optical microwave communication systems.
Extraordinary optical transmission (EOT) is a hallmark of surface plasmons and a precursor to nanoplasmonics and metamaterials. However, to the best of our knowledge, this effect has never been topologically protected in three dimensions, leaving it vulnerable to structural imperfections, nonlocal effects, and backreflections. We report broadband, three-dimensional unidirectional structures that allow for EOT (normalized transmission > 1) through deep-subdiffractional single holes, immune to these deleterious effects. These structures avoid unnecessary propagation losses and achieve maximum transmission through a single hole, limited only by unavoidable dissipative losses. In the limit of vanishing losses, the transmission through a deep-subdiffractional hole can approach unity, significantly surpassing existing devices, and rivaling the performance of negative-index ‘perfect’ lenses. The topological stability of these structures renders them robust against surface roughness, defects, and nonlocality, without the need for elaborate meta-structures or tapering.
In the recent strategic queueing literature, there is a large number of papers that study the join-or-balk dilemma in queueing systems with server’s on-off periods, modeling vacations and failures. These studies consider the customers as discrete units and adopt the assumption that reneging is not permitted. In the present paper, we depart from this framework and study the effect of the reneging option in such systems. We consider the fluid on-off model of the basic queue with vacations/failures and study reneging vs. no-reneging when customers are strategic. We derive the equilibrium customer strategies and the corresponding performance measures of the system, and we use them to study the equilibrium throughput and social welfare. The main finding is that the existence of the reneging option is very beneficial for overloaded systems, i.e., for such systems balking alone is not sufficient to achieve good outcomes. On the contrary, for underloaded systems the reneging option is not particularly valuable.
Context. Using data from eROSITA, the soft X-ray instrument aboard Spectrum-Roentgen-Gamma (SRG), we report the discovery of two new hard transients, eRASSU J050810.4-660653 and eRASSt J044811.1-691318, in the Large Magellanic Cloud. We also report the detection of the Be/X-ray binary RX J0501.6-7034 in a bright state. Aims: We initiated follow-up observations to investigate the nature of the new transients and to search for X-ray pulsations coming from RX J0501.6-7034. Methods: We analysed the X-ray spectra and light curves from our XMM-Newton observations, obtained optical spectra using the South African Large Telescope to look for Balmer emission lines and utilised the archival data from the Optical Gravitational Lensing Experiment (OGLE) for the long-term monitoring of the optical counterparts. Results: We find X-ray pulsations for eRASSU J050810.4-660653, RX J0501.6-7034, and eRASSt J044811.1-691318 of 40.6 s, 17.3 s, and 784 s, respectively. The Hα emission lines with equivalent widths of −10.4 Å (eRASSU J050810.4-660653) and −43.9 Å (eRASSt J044811.1-691318) were measured, characteristic for a circumstellar disc around Be stars. The OGLE I- and V-band light curves of all three systems exhibit strong variability. A regular pattern of deep dips in the light curves of RX J0501.6-7034 suggests an orbital period of ∼451 days. Conclusions: We identify the two new hard eROSITA transients eRASSU J050810.4-660653 and eRASSt J044811.1-691318 and the known Be/X-ray binary RX J0501.6-7034 as Be/X-ray binary pulsars.
A number of observations of astrophysical jets, at different scales, have shown that jets are often non-uniform outflows in their cross-section. Their structure is believed to play an important role in their overall stability. In this work, we combine analytical methods and numerical simulations to investigate the stability of non-uniform jets originating from active galactic nuclei. We adopt a standard 'spine and sheath' model, using a fast, light inner spine and a heavier, slower outer sheath. In the first part of this work, we conduct a linear stability analysis, finding the time-scales for the growth of the instabilities and the corresponding eigenfunctions. We focus on the nature of the physical processes that dominate and drive the destabilization of configurations. In the second part, we examine the evolution of the perturbed jets through relativistic 3D numerical simulations using the PLUTO code. Starting with the eigenfunctions found in the first part as initial conditions, we derive instability growth times and evolution which are in good agreement with the linear analysis.
The potential distribution in a MEMS capacitor with a thin dielectric film on the bottom electrode and under the presence of field emission leakage current is presented for the first time. The paper also demonstrated the build-up of dielectric charging during this process. The investigation is based on obtaining current-voltage characteristics in clockwise and counter clockwise loops and analyzing the transport mechanisms in MIM capacitors. Same procedure is applied to monitor the dielectric charging build-up during field emission in MEMS capacitors. The data of pristine current-voltage characteristics in both MIM and MEMS are used to determine the Voltage drops across the dielectric film and the gap as well as their dependence on the flowing current.
We study the interactions over 22 years between one mathematics teacher and his resources for teaching, especially digital ones, with a dual focus on the teacher’s documentational and identity trajectories and professional development. We combined a theoretical framework on teachers’ work with resources —documentational approach to didactics (DAD)— with a framework based on social practice theory—patterns of participation (PoP). The DAD analysis provided rich descriptions of which digital resources the teacher interacted with and of the transformative evolution of these interactions over time. The PoP analysis offered explanations of how and why the teacher transformed his interactions with the resources through foregrounding affective and contextual factors as significant for the teacher’s formation of identity. We conclude that the combination of the two frameworks provided deeper and complementary insights into the teacher’s long-term professional development with digital resources, and that such networking is needed to develop balanced understandings of teachers’ long-term interactions with digital resources.
We provide a first principles derivation of the supersymmetric Casimir energy of N=1 SCFTs in four dimensions using the supercharge algebra on general conformal supergravity backgrounds that admit Killing spinors. The superconformal Ward identities imply that there exists a continuous family of conserved R-currents on supersymmetric backgrounds, as well as a continuous family of conserved currents for each conformal Killing vector. These continuous families interpolate between the consistent and covariant R-current and energy-momentum tensor. The resulting Casimir energy, therefore, depends on two continuous parameters corresponding to the choice of conserved currents used to define the energy and R-charge. This ambiguity is in addition to any possible scheme dependence due to local terms in the effective action. As an application, we evaluate the general expression for the supersymmetric Casimir energy we obtain on a family of backgrounds with the cylinder topology R×S3R×S3 and admitting two supercharges of opposite R-charge. Our result is a direct consequence of the supersymmetry algebra, yet it resembles more known expressions for the non-supersymmetric Casimir energy on such backgrounds and differs from the supersymmetric Casimir energy obtained from the zero temperature limit of supersymmetric partition functions. We defer a thorough analysis of the relation between these results to future work.
Open laboratories (OpenLabs) in Cultural Heritage institutions are an effective way to provide visibility into the behind-the-scenes processes and promote documentation data collected and produced by domain specialists. However, presenting these processes without proper explanation or communication with specialists may cause issues in terms of visitors’ understanding. To support OpenLabs and disseminate information, digital media and efficient data management can be utilized. The CAnTi (Conservation of Ancient Tiryns) project seeks to design and implement virtual and mixed reality applications that visualize conservation and restoration data, supporting OpenLab operations at the Acropolis of Ancient Tiryns. Semantic Web technologies will be used to model the digital content, facilitating organization and interoperability with external sources in the future. These applications will be part of the OpenLab activities on the site, enhancing visitors’ experiences and understanding of current and past conservation and restoration practices.
BACKGROUND: Gallbladder cancer (GBC) is rare but aggressive. The extent of surgical intervention for different GBC stages is non-uniform, ranging from cholecystectomy alone to extended resections including major hepatectomy, resection of adjacent organs and routine extrahepatic bile duct resection (EBDR). Robust evidence here is lacking, however, and survival benefit poorly defined. This study assesses factors associated with recurrence-free survival (RFS), overall survival (OS) and morbidity and mortality following GBC surgery in high income countries (HIC) and low and middle income countries (LMIC).
METHODS: The multicentre, retrospective Operative Management of Gallbladder Cancer (OMEGA) cohort study included all patients who underwent GBC resection across 133 centres between 1st January 2010 and 31st December 2020. Regression analyses assessed factors associated with OS, RFS and morbidity.
FINDINGS: On multivariable analysis of all 3676 patients, wedge resection and segment IVb/V resection failed to improve RFS (HR 1.04 [0.84-1.29], p = 0.711 and HR 1.18 [0.95-1.46], p = 0.13 respectively) or OS (HR 0.96 [0.79-1.17], p = 0.67 and HR 1.48 [1.16-1.88], p = 0.49 respectively), while major hepatectomy was associated with worse RFS (HR 1.33 [1.02-1.74], p = 0.037) and OS (HR 1.26 [1.03-1.53], p = 0.022). Furthermore, EBDR (OR 2.86 [2.3-3.52], p < 0.0010), resection of additional organs (OR 2.22 [1.62-3.02], p < 0.0010) and major hepatectomy (OR 3.81 [2.55-5.73], p < 0.0010) were all associated with increased morbidity and mortality. Compared to LMIC, patients in HIC were associated with poorer RFS (HR 1.18 [1.02-1.37], p = 0.031) but not OS (HR 1.05 [0.91-1.22], p = 0.48). Adjuvant and neoadjuvant treatments were infrequently used.
INTERPRETATION: In this large, multicentre analysis of GBC surgical outcomes, liver resection was not conclusively associated with improved survival, and extended resections were associated with greater morbidity and mortality without oncological benefit. Aggressive upfront resections do not benefit higher stage GBC, and international collaborations are needed to develop evidence-based neoadjuvant and adjuvant treatment strategies to minimise surgical morbidity and prioritise prognostic benefit.
FUNDING: Cambridge Hepatopancreatobiliary Department Research Fund.
The research field of digital storytelling is cross-disciplinary and extremely wide. In this paper, methods, frameworks, and tools that have been created for authoring and presenting digital narratives, are selected and examined among hundreds of works. The basic criterion for selecting these works has been their ability to create content by computational, emergent methods. By delving into the work of many researchers, the objective is to study current trends in this research field and discuss possible future directions. Most of the relevant tools and methods have been designed with a specific purpose in mind, but their use could be expanded to other areas of interest or could at least be the steppingstone for other ideas. Therefore, the following works show elements of computational and emergent narrative creation and a classification is proposed according to their purpose of existence. Finally, new potential research directions in the field are identified and possible future research steps are discussed.
Using techniques from TRO equivalence of masa bimodules we prove various transference results: We show that when α is a group homomorphism which pushes forward the Haar measure of G to a measure absolutely continuous with respect to the Haar measure on H, then (α×α)−1 preserves sets of compact operator synthesis, and conversely when α is onto. We also prove similar preservation results for operator Ditkin sets and operator M-sets, obtaining preservation results for M-sets as corollaries. Some of these results extend or complement existing results of Ludwig, Shulman, Todorov and Turowska.
Many studies have assessed students’ motivation through surveys, but only a few studies systematically investigated through students’ own words the reasons and aims of their achievement striving. In the present study, we rely on the Goal Complex Perspective (Sommet and Elliot in J Educ Psychol 109(8):1141–1162, 2017. https://doi.org/10.1037/edu0000199; Vansteenkiste et al. in Educ Psychol 49(3):153–174, 2014. https://doi.org/10.1080/00461520.2014.928598) to uncover qualitative differences in achievement motivation. Content analysis of 1303 statements made by 597 Greek secondary students revealed (i) more autonomous motivation than controlled motivation statements, (ii) spontaneously generated statements of mastery-learning and outcome goals but rarely of performance-normative goals, (iii) mastery-learning goals being coupled with both autonomous and controlled motivation, providing ecological support for the conceptualization of mastery goal complexes. Logistic regression analyses verified our classification, as students’ statements were predicted by corresponding types of motivation assessed by close, Likert-type questions. These findings, which align with the Goal Complex Perspective, are discussed in terms of the operational definition of autonomous and controlled motivation and achievement goals.
It is well known that minimum-cost portfolio insurance (MPI) is an essential investment strategy. This article presents a time-varying version of the original static MPI problem, which is thus more realistic. Then, to solve it efficiently, we propose a powerful recurrent neural network called the linear-variational-inequality primal-dual neural network (LVI-PDNN). By doing so, we overcome the drawbacks of the static approach and propose an online solution. In order to improve the performance of the standard LVI-PDNN model, an adaptive fuzzy-power LVI-PDNN (F-LVI-PDNN) model is also introduced and studied. This model combines the fuzzy control technique with LVI-PDNN. Numerical experiments and computer simulations confirm the F-LVI-PDNN model’s superiority over the LVI-PDNN model and show that our approach is a splendid option to accustomed MATLAB procedures.
The computation of the time-varying matrix pseudoinverse has become crucial in recent years for solving time-varying problems in engineering and science domains. This paper investigates the issue of calculating the time-varying pseudoinverse based on full-rank decomposition (FRD) using the zeroing neural network (ZNN) method, which is currently considered to be a cutting edge method for calculating the time-varying matrix pseudoinverse. As a consequence, for the first time in the literature, a new ZNN model called ZNNFRDP is introduced for time-varying pseudoinversion and it is based on FRD. FourFive numerical experiments investigate and confirm that the ZNNFRDP model performs as well as, if not better than, other well-performing ZNN models in the calculation of the time-varying pseudoinverse. Additionally, theoretical analysis and numerical findings have both supported the effectiveness of the proposed model.
The efficient solution of the time-varying quaternion matrix inverse (TVQ-INV) is a challenging but crucial topic due to the significance of quaternions in many disciplines, including physics, engineering, and computer science. The main goal of this research is to employ the higher-order zeroing neural network (HZNN) strategy to address the TVQ-INV problem. HZNN is a family of zeroing neural network models that correlates to the hyperpower family of iterative methods with adjustable convergence order. Particularly, three novel HZNN models are created in order to solve the TVQ-INV both directly in the quaternion domain and indirectly in the complex and real domains. The noise-handling version of these models is also presented, and the performance of these models under various types of noises is theoretically and numerically tested. The effectiveness and practicality of these models are further supported by their use in robotic motion tracking. According to the principal results, each of these six models can solve the TVQ-INV effectively, and the HZNN strategy offers a faster convergence rate than the conventional zeroing neural network strategy.
INTRODUCTION: Despite recent advances in epithelial ovarian cancer (EOC) management, the highly heterogenous histological/molecular tumour background and patients' treatment response obstructs personalised prognosis and therapeutics. Herein, we have studied the role and clinical utility of the novel subclass of tRNA-derived small RNA fragments emerging via 3'-trailer processing of pre-tRNAs (3'U-tRFs) in EOC. METHODS: SK-OV-3 and OVCAR-3 cells were used for in vitro study. Following transfection, cell growth and migration were assessed by CCK8 and wound healing assays, respectively. 3'U-tRFs levels were assessed by reverse transcription quantitative PCR (RT-qPCR), following 3'-end RNA polyadenylation. A screening (OVCAD, n = 100) and institutionally independent validation (TU Munich, n = 103) cohorts were employed for survival analysis using disease progression and patients' death as clinical end-points. Bootstrap analysis was performed for internal validation, and decision curve analysis was used to evaluate clinical benefit on disease prognosis. RESULTS: Following primary clinical assessment, target prediction and gene ontology analyses, the 3'U-tRF(ValCAC) (derived from pre-tRNA(ValCAC)) was highlighted to regulate cell proliferation and adhesion, and to correlate with inferior patients' outcome. 3'U-tRF(ValCAC) transfection of SK-OV-3 and OVCAR-3 cells resulted in significantly increased cell growth and migration, in a dose-dependent manner. Elevated tumour 3'U-tRF(ValCAC) levels were associated with significantly higher risk for early progression and worse survival following first-line platinum-based chemotherapy, independently of patients' clinicopathological data, chemotherapy response, and residual tumour. Interestingly, 3'U-tRF(ValCAC)-fitted multivariate models improved risk stratification and provided superior clinical net benefit in prediction of treatment outcome compared to disease established markers. CONCLUSIONS: 3'U-tRF(ValCAC) promotes tumour cell growth and migration and supports modern risk stratification and prognosis in EOC.
In this work we demonstrate a two-pixel solid-state photoluminescent device able to emit white light covering the entire visible spectrum from 380nm up to 800nm. The device is based on a combination of porous Si, hydrothermally grown ZnO and carbon quantum dots, in a two-pixel formation, with porous Si and ZnO acting independently while the carbon quantum dots are deposited on top of the entire device. All processing is done using standard Si processing techniques. Moreover, the device design allows for tunability of the emitted spectrum simply by choosing the desired combination of the materials. Overall, the demonstrated device is low cost, environmentally safe and biocompatible.
Prostate cancer is one of the most common malignant diseases in men, and it contributes significantly to the increased mortality rate in men worldwide. This study aimed to review the roles of p300 and TMPRSS2 (transmembrane protease, serine 2) in the AR (androgen receptor) pathway as they are closely related to the development and progression of prostate cancer. This paper represents a library-based study conducted by selecting the most suitable, up-to-date scientific published articles from online journals. We focused on articles that use similar techniques, particularly those that use prostate cancer cell lines and immunohistochemical staining to study the molecular impact of p300 and TMPRSS2 in prostate cancer specimens. The TMPRSS2:ERG fusion is considered relevant to prostate cancer, but its association with the development and progression as well as its clinical significance have not been fully elucidated. On the other hand, high p300 levels in prostate cancer biopsies predict larger tumor volumes, extraprostatic extension of disease, and seminal vesicle involvement at prostatectomy, and may be associated with prostate cancer progression after surgery. The inhibition of p300 has been shown to reduce the proliferation of prostate cancer cells with TMPRSS2:ETS (E26 transformation-specific) fusions, and combining p300 inhibitors with other targeted therapies may increase their efficacy. Overall, the interplay between the p300 and TMPRSS2 pathways is an active area of research
Transporters mediate the uptake of solutes, metabolites and drugs across the cell membrane. The eukaryotic FurE nucleobase/H symporter of Aspergillus nidulans has been used as a model protein to address structure-function relationships in the APC transporter superfamily, members of which are characterized by the LeuT-fold and seem to operate by the so-called 'rocking-bundle' mechanism. In this study, we reveal the binding mode, translocation and release pathway of uracil/H by FurE using path collective variable, funnel metadynamics and rational mutational analysis. Our study reveals a stepwise, induced-fit, mechanism of ordered sequential transport of proton and uracil, which in turn suggests that FurE, functions as a multi-step gated pore, rather than employing 'rocking' of compact domains, as often proposed for APC transporters. Finally, our work supports that specific residues of the cytoplasmic N-tail are involved in substrate translocation, in line with their essentiality for FurE function.
Extreme weather events can trigger various hydrogeomorphic phenomena and processes including slope failures. These shallow instabilities are difficult to monitor and measure due to the spatial and temporal scales in which they occur. New technologies such as unmanned aerial systems (UAS), photogrammetry and the structure-from-motion (SfM) technique have recently demonstrated capabilities useful in performing accurate terrain observations that have the potential to provide insights into these geomorphic processes. This study explores the use of UAS-aided photogrammetry and change detection, using specialized techniques such as the digital elevation model (DEM) of differences (DoD) and cloud-to-cloud distance (C2C) to monitor and quantify geomorphic changes before and after an extreme medicane event in Myrtos, a highly visited touristic site on Cephalonia Island, Greece. The application demonstrates that the combination of UAS with photogrammetry allows accurate delineation of instabilities, volumetric estimates of morphometric changes, insights into erosion and deposition processes and the delineation of higher-risk areas in a rapid, safe and practical way. Overall, the study illustrates that the combination of tools facilitates continuous monitoring and provides key insights into geomorphic processes that are otherwise difficult to observe. Through this deeper understanding, this approach can be a stepping stone to risk management of this type of highly-visited sites, which in turn is a key ingredient to sustainable development in high-risk areas.
BACKGROUND: There is a lack of evidence regarding the effectiveness of virtual simulators as a means to acquire hands-on exposure to endoscopic retrograde cholangiopancreatography (ERCP). The present study aimed to assess the outcome and construct validity of virtual ERCP when training on the GI II Mentor simulator.
METHODS: A group of seven experienced endoscopists were compared with 31 novices. After a short introduction, they were requested to carry out three virtual ERCP procedures: diagnosing and removing a common bile duct (CBD) stone; diagnosing and taking brush cytology from a hilar stenosis; and, finally, diagnosing and treating a cystic leakage with a BD stent. For each task, the total time required to complete the task, time required to correctly view the papilla, total time of irradiation, time to deep cannulation, time to define diagnosis, time to complete sphincterotomy, and time to complete the respective intervention were measured. Cannulation of the BD, correct diagnosis, sphincterotomy, and time to complete intervention were assessed by an assessor blinded to the status of the endoscopist who performed the virtual ERCP.
RESULTS: The time required to visualize the papilla and to cannulate deeply when removing the BD stone was significantly shorter for the experts (both < 0.05). The time to visualize the papilla, cannulate deeply, reach a diagnosis, complete sphincterotomy, and complete the intervention was significantly shorter for the experts when managing cystic leakage (all < 0.05). In diagnosing and taking brush cytology from a hilar stenosis, there was only a trend toward the experts needing less time for the deep cannulation of the BD ( = 0.077).
CONCLUSION: The performance differed between experts and novices, especially in the management of cystic leakage. This corroborates the construct validity of the GI II Mentor simulator.
Although the scientific community, particularly academic publishing, claims to be gender-neutral and based on meritocracy, it mirrors other parts of modern society, wherein residual gender imbalances and implicit and explicit gender biases are reproduced. In this report, we address gender imbalances (in particular, the overrepresentation of men) in the editorial workforce of academic journals as barriers to women's promotion and career progression in addiction science. We also consider potential gender-related elements and biases in the peer-review and editorial decision-making processes, which may result in women's lower publication rates, thereby creating another gender-related barrier to women's promotion, career progression and academic recognition. Establishing a more balanced gender representation in addiction publishing will require the adoption of the SAGER guidelines and the development of Gender Equality Plans for addiction specialty journals. Finally, although our focus concerns gender, the organisational mechanisms identified here also affect other types of heterogeneity and intersectional thinking.
BACKGROUND: For years, physical activity (PA) has been considered a mixed blessing in terms of the risk of incident atrial fibrillation (AF). Previous analyses have had equivocal results regarding the cut-off of PA level beyond which AF risk increases, if such a limit really does exist. Data regarding females in particular have been scarce.
METHODS: We performed a dose-response meta-analysis to investigate the relationship between weekly PA and the risk for AF in females. Major electronic databases were searched for studies assessing the association between leisure time PA and the risk for incident AF in females from the general population. The linearity of the dose-response curve was assessed using the restricted cubic spline model.
RESULTS: A total of 15 studies, which involved 1,821,422 females, were included in the final analysis. AF incidence was 3.7%. Dose-response analysis revealed an inverse nonlinear relationship between weekly PA and the risk for incident AF (p for linearity <0.0001). No significant heterogeneity was documented (I = 37%). Cautious interpretation is needed for PA exceeding 50 metabolic equivalents of task- hours per week (METs- h/w), due to limited available data for these high levels of PA.
CONCLUSION: According to this analysis, physicians can safely advise females to perform up to 50METs- h/w of moderate or vigorous PA, to reduce the risk for future AF. Interestingly, significant benefit can be attained even at low levels of regular weekly PA.
Centaurus A is one of the closest radio galaxies to Earth. Its proximity allowed us to extensively study its active galactic nucleus but the core emission mechanism remains elusive because of local strong dust and gas obscuration. The capability of polarimetry to shave-off contaminating emission has been exploited without success in the near-infrared by previous studies but the very recent measurement of the 2-8 keV polarization by the Imaging X-ray Polarimetry Explorer (IXPE) brought the question back to the fore. To determine what is the prevalent photon generation mechanism to the multiwavelength emission from the core of Centaurus A, we retrieved from the archives the panchromatic polarization measurements of the central compact component. We built the total and polarized flux spectral energy distributions of the core and demonstrated that synchrotron self-Compton models nicely fit the polarized flux from the radio to the X-ray band. The linear polarization of the synchrotron continuum is perpendicular to the jet radio axis from the optical to the radio band, and parallel to it at higher energies. The observed smooth rotation of the polarization angle in the ultraviolet band is attributed to synchrotron emission from regions that are getting closer to the particle acceleration site, where the orientation of the jet's magnetic fields become perpendicular to the jet axis. This phenomenon support the shock acceleration mechanism for particle acceleration in Centaurus A, in line with IXPE observations of several high-synchrotron peak blazars.
This paper presents a dynamic model based on neutrosophic numbers and a neutrosophic logic engine. The introduced neutrosophic logic/fuzzy adaptive Zeroing Neural Network dynamic is termed NSFZNN and represents an improvement over the traditional Zeroing Neural Network (ZNN) design. The model aims to calculate the matrix pseudo-inverse and the minimum-norm least-squares solutions of time-varying linear systems. The improvement of the proposed model emerges from the advantages of neutrosophic logic over fuzzy and intuitionistic fuzzy logic in solving complex problems associated with predictions, vagueness, uncertainty, and imprecision. We use neutrosphication, de-fuzzification, and de-neutrosophication instead of fuzzification and de-fuzzification exploited so far. The basic idea is based on the known advantages of neutrosophic systems compared to fuzzy systems. Simulation examples and engineering applications on localization problems and electrical networks are presented to test the efficiency and accuracy of the proposed dynamical system.
Within Deep Space and at a distance greater than 1 AU and less than 3.5 AU are twoasteroid belts that are quite important for finding new natural resources. These arethe Near-Earth Asteroids Area and the Main Asteroid Belt. Except these celestialbodies, the Moon is also an important place for mining. It is estimated that withinthe next decades these will be an important source of rare earth mining, but alsoother materials such as nickel and helium-3. The access, usage, and the necessaryactions for their systematic exploitation mark the expansion of the Living Space ofstates beyond the surface of the Earth.Therefore, in the coming decades will begin a new race that will result in theexpansion of mining rights and consequently the possession of celestial bodies landsby states. Also, it will cause the emergence of new forms of cooperation involvingone or more states and companies undertaking the implementation of the trade arm.
Περίληψη: Η φτώχεια και ο κοινωνικός αποκλεισμούς έχουν απασχολήσει αρκετές δεκαε- τίες την επιστημονική κοινότητα, η οποία έχει δώσει ιδιαίτερη έμφαση στη διερεύνηση των παραγόντων και συνθηκών που οδηγούν ορισμένες πληθυσμιακές ομάδες στο κοινωνικό περιθώριο. Η ευαλωτότητα συχνά ορίζεται ως ο βαθμός στον οποίο ένας πληθυσμός, ένα άτομο ή ένας οργανισμός αδυνατεί να έχει προσδοκίες, να αντιμετωπίσει, να αντισταθεί και να ανακάμψει από τις επιπτώσεις μιας καταστροφής. Ωστόσο, η ευαλωτότητα δεν είναι μόνο αποτέλεσμα καταστροφών. Αφορά κυρίως τις κοινωνικοοικονομικές συνθήκες που δημιουργούν το υπόβαθρο για την ανάπτυξη της φτώχειας και της αποστέρησης. Η παρούσα εργασία, εστιάζει στη διερεύνηση του φαινομένου, σύμφωνα με τα νέα δεδομένα και τους σύγχρονους ευρωπαϊκούς δείκτες που αναδεικνύουν τους κινδύνους της φτώχειας και του κοινωνικού αποκλεισμού για σημαντική μερίδα του πληθυσμού. Επιπλέον, διερευνά το ρόλο της Δια βίου μάθησης και της Συμβουλευτικής στην ενδυνάμωση των ατόμων και των ομάδων που βιώνουν τη φτώχεια και τον αποκλεισμό που γεννούν οι δομικές ανισότητες.
Από τη δεκαετία του 1970, όταν εμφανίστηκε για πρώτη φορά στην Αμερική ο όρος σεξουαλική παρενόχληση η προσοχή των ακαδημαϊκών και του κοινού στο συγκεκριμένο φαινόμενο έχει αυξομειωθεί ανά περιόδους βάσει ορισμέ- νων ιστορικών και κοινωνικοπολιτικών γεγονότων. Στη διεθνή βιβλιογραφία το φαινόμενο διακρίνεται σε τρεις μορφές, παρενόχληση βάση φύλου, η οποία σύμφωνα με τις έρευνες αποτελεί το συχνότερο είδος, ανεπιθύμητη σεξουα- λική προσοχή και σεξουαλικός εξαναγκασμός. Ο ιδιαίτερος χαρακτήρας του φαινομένου της σεξουαλικής παρενόχλησης συνοψίζεται στον σχολιασμό της φεμινίστριας νομικού Catharine MacKinnon σύμφωνα με την οποία, ελλείψει όρου ικανού να την περιγράψει, η σεξουαλική παρενόχληση μέχρι το 1979 κυ- ριολεκτικά δεν αρθρωνόταν από τις γυναίκες, γεγονός που καθιστούσε αδύ- νατη τη σύνταξη ενός γενικού, κοινού και κοινωνικού ορισμού (McLaughlin et al., 2017).
The Arkalochori village in central Crete was hit by a large earthquake (Mw = 6.0) on 27 September 2021, causing casualties, injuries, and severe damage to the infrastructure. Due to the absence of apparent surface rupture and the initial focal mechanism solution of the seismic event, we initiated complementary, multi-disciplinary research by combining seismological and remote sensing data processing, followed by extensive field validation. Detailed geological mapping, fault surface measuring accompanied with tectonic analysis, fault photorealistic model creation by unmanned aerial system data processing, post-seismic surface deformation analysis by DInSAR image interpretation coupled with accurately relocated epicenters recorded by locally established seismographs have been carried out. The combination of the results obtained from these techniques led to the determination of the contemporary tectonic stress regime that caused the earthquake in central Crete, which was found compatible with extensional processes parallel to the Hellenic arc.
The Arkalochori village in central Crete was hit by a large earthquake (Mw = 6.0) on 27 September 2021, causing casualties, injuries, and severe damage to the infrastructure. Due to the absence of apparent surface rupture and the initial focal mechanism solution of the seismic event, we initiated complementary, multi-disciplinary research by combining seismological and remote sensing data processing, followed by extensive field validation. Detailed geological mapping, fault surface measuring accompanied with tectonic analysis, fault photorealistic model creation by unmanned aerial system data processing, post-seismic surface deformation analysis by DInSAR image interpretation coupled with accurately relocated epicenters recorded by locally established seismographs have been carried out. The combination of the results obtained from these techniques led to the determination of the contemporary tectonic stress regime that caused the earthquake in central Crete, which was found compatible with extensional processes parallel to the Hellenic arc.
This paper investigates accounts justifying the closures of businesses found on public signs in Athens and London during the COVID-19 pandemic. The data for the study was drawn from a corpus of COVID-19-related public signage collected in the two cities during the first lockdown. The accounts used on these signs are analysed as acts of identity and, specifically, as discursive means deployed by the authors of the signs to project themselves and their businesses favourably. It is shown that the accounts used at the micro-level of discourse align to various degrees with the dominant discourses surrounding the pandemic at the macro-level and with the values these discourses draw upon. It is also shown that the accounts are used to reframe the public’s understanding of the closures and to construct identities congruent with the interests of the business owners, ensuring post-pandemic continuity.
The main goal of the present paper is to discuss how and under what circumstances, active labor market policies and adult education could assist staff to cope with stress and enhance skills and abilities to achieve employment. The high numbers of unemployed in Greece together with the long-term ineffective austerity measures and policies imposed in the country and the reduction of the social welfare state, created many multiple and complex issues that deteriorated after the pandemic. The present paper suggests that specific active labor market policies must be employed together with lifelong learning policies and programmes to ensure future developments. Greece, more than any other modern European country, was faced for several years with extreme austerity measures that affected the social, economic, and personal level. The working population and especially young people had to cope with prolonged unemployment, limited options for reentering the job market and the associated stress that follows exposure to adverse experiences. The phenomena of brain drain and brain waste, are well documented in Greek research and literature. Covid-19 pandemic was another stroke in an already unbalance economy. Lifelong learning programmes, that are meant to assist not only the working but also the general population to increase social and other skills, as a way of ensuring access to the labour market, are addressed to only a small portion of the population and usually to those who need them the least. The current paper presents the challenges that Active labor market and Lifelong policies in Greece must face in the process of coping with prolonged unemployment, brain drain and brain waste.
Some authors have suggested that, contrary to what is usually thought, ‘actually’ and similar expressions (‘in fact’, ‘in reality’, etc.) cannot effect a return to the actual world when used in a context generated by a different modal operator, and so are quite unlike the actuality operator of modal logic. I argue that they can induce such a return. The argument involves comparing them with other devices that can play a similar role, such as scope and mood, and examining the effect of ‘actually’ and the like in a range of different sentences.
A reduced removal of dysfunctional mitochondria is common to aging and age-related neurodegenerative pathologies such as Alzheimer's disease (AD). Strategies for treating such impaired mitophagy would benefit from the identification of mitophagy modulators. Here we report the combined use of unsupervised machine learning (involving vector representations of molecular structures, pharmacophore fingerprinting and conformer fingerprinting) and a cross-species approach for the screening and experimental validation of new mitophagy-inducing compounds. From a library of naturally occurring compounds, the workflow allowed us to identify 18 small molecules, and among them two potent mitophagy inducers (Kaempferol and Rhapontigenin). In nematode and rodent models of AD, we show that both mitophagy inducers increased the survival and functionality of glutamatergic and cholinergic neurons, abrogated amyloid-beta and tau pathologies, and improved the animals' memory. Our findings suggest the existence of a conserved mechanism of memory loss across the AD models, this mechanism being mediated by defective mitophagy. The computational-experimental screening and validation workflow might help uncover potent mitophagy modulators that stimulate neuronal health and brain homeostasis.
We comprehensively review several general methods and analytical tools used for causality evaluation of photonic materials. Our objective is to call to mind and then formulate, on a mathematically rigorous basis, a set of theorems which can answer the question whether a considered material model is causal or not. For this purpose, a set of various distributional theorems presented in literature is collected as the distributional version of the Titchmarsh theorem, allowing for evaluation of causality in complicated electromagnetic systems. Furthermore, we correct the existing material models with the use of distribution theory in order to obtain their causal formulations. In addition to the well-known Kramers–Krönig (K–K) relations, we overview four further methods which can be used to assess causality of given dispersion relations, when calculations of integrals involved in the K–K relations are challenging or even impossible. Depending on the given problem, optimal approaches allowing us to prove either the causality or lack thereof are pointed out. These methodologies should be useful for scientists and engineers analyzing causality problems in electrodynamics and optics, particularly with regard to photonic materials, when the involved mathematical distributions have to be invoked.
Accumulating data has shown a contribution of the renin-angiotensin system in COVID-19 pathogenesis. The role of angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism as a risk factor in developing COVID-19 disease comes from epidemiological data and is controversially discussed. We conducted a retrospective case-control study and assessed the impact of ACE I/D genotype in COVID-19 disease prevalence and severity. In 81 COVID-19 patients explicitly characterized and 316 controls, recruited during the first wave of COVID-19 pandemic, ACE I/D genotype, and ACE activity were determined. A generalized linear model was used and Poisson regression analysis estimated the risk ratios (RRs) of alleles and genotypes for disease severity. DD patients had almost 2.0-fold increased risk (RR: 1.886, confidence limit [CL] 95%: 1.266-2.810, p = 0.0018) of developing a more severe disease when contrasted to ID and II individuals, as did D allele carriers compared to I carriers (RR: 1.372; CL 95%: 1.051-1.791; p = 0.0201). ACE activity (expressed as arbitrary units, AU/L) was lower in patients (3.62 +/- 0.26) than in controls (4.65 +/- 0.13) (p < 0.0001), and this reduction was observed mainly among DD patients compared to DD controls (3.97 +/- 0.29 vs. 5.38 +/- 0.21; p = 0.0014). Our results demonstrate that ACE DD genotype may predispose to COVID-19 increased disease severity via a mechanism associated, at least in part, with the significant fall in their ACE activity. Our findings suggest a more complex pattern of synergy between this polymorphism and ACE activity in COVID-19 patients compared to healthy individuals and set the grounds for large-scale studies assessing ACE genotype-based optimized therapies with ACE inhibitors and angiotensin receptor blockers
BACKGROUND: the apolipoprotein e4 allele (APOE4) constitutes an established genetic risk factor for Alzheimer's Disease Dementia (ADD). We aimed to explore the frequency of the APOE isoforms in the Greek population of Southern Greece. METHODS: peripheral blood from 175 Greek AD patients, 113 with mild cognitive impairment (MCI), and 75 healthy individuals. DNA isolation was performed with a High Pure PCR Template Kit (Roche), followed by amplification with a real-time qPCR kit (TIB MolBiol) in Roche's Light Cycler PCR platform. RESULTS: APOE4 allele frequency was 20.57% in the ADD group, 17.69% in the MCI group, and 6.67% in the control group. APOE3/3 homozygosity was the most common genotype, while the frequency of APOE4/4 homozygosity was higher in the AD group (8.60%). APOE4 carrier status was associated with higher odds for ADD and MCI (OR: 4.49, 95% CI: [1.90-10.61] and OR: 3.82, 95% CI: [1.59-9.17], respectively). CONCLUSION: this study examines the APOE isoforms and is the first to report a higher APOE frequency in MCI compared with healthy controls in southern Greece. Importantly, we report the occurrence of the APOE4 allele, related to ADD, as amongst the lowest globally reported, even within the nation, thus enhancing the theory of ethnicity and latitude contribution
Clinicians trust medical laboratories to provide reliable results on which they rely for clinical decisions. Laboratories fulfil their responsibility for accurate and consistent results by utilizing an arsenal of approaches, ranging from validation and verification experiments to daily quality control procedures. All these procedures verify, on different moments, that the results of a certain examination procedure have analytical performance characteristics (APC) that meet analytical performance specifications (APS) set for a particular intended use. The APC can in part be determined by estimating the measurement uncertainty component under conditions of within-laboratory precision (u(Rw)), which comprises all components influencing the measurement uncertainty of random sources. To maintain the adequacy of their measurement procedures, laboratories need to distinguish aspects that are manageable vs. those that are not. One of the aspects that may influence u(Rw) is the momentary significant bias caused by shifts in reagent and/or calibrator lots, which, when accepted or unnoticed, become a factor of the APC. In this paper, we postulate a model for allocating a part of allowable u(Rw) to between-reagent lot variation, based on the need for long-term consistency of the measurement variability for that specific measurand. The allocation manages the ratio between short-term and long-term variation and indicates laboratories when to reject or correct certain variations due to reagent lots
A strong, shallow earthquake occurred near Heraklion (Crete, Greece) on 27 September 2021. The earthquake produced significant ground deformation in the vicinity of Arkalochori village but without any evidence for surface ruptures of primary origin. We used geodetic (InSAR and GNSS) data to map motions of the Earth’s surface that occurred during and shortly after the earthquake. A 14 cm subsidence of the GNSS station ARKL and a maximum of 19 cm distance from the SAR satellite were recorded. The measured surface displacements were used to constrain the rupture geometry and slip distribution at depth. Our best-fitting inversion model suggests that the rupture occurred on a 13 km-long planar normal fault striking N195° E dipping 55° to the northwest, with major slip occurring to the east and updip of the hypocentre. The fault tip is located 1.2 km beneath the surface. The maximum coseismic slip occurred in the uppermost crust, in the depth interval of 4–6 km. A decrease in the fault offsets toward the Earth’s surface is likely caused by an increased frictional resistance of the shallow layers to rapid coseismic slip. Satellite observations made in the first month after the earthquake detected no post-seismic deformation (i.e., below one fringe or 2.8 cm). The seismic fault may be identified with the Avli (Lagouta) segment of the NNE-SSW striking, west-dipping, 23 km-long neotectonic Kastelli Fault Zone (KFZ). Part of the rupture occurred along the Kastelli segment, indicating a fault segment linkage and a history of overlapping ruptures along KFZ. Based on geological data and footwall topography we estimate an average slip rate between 0.17–0.26 mm/yr for the KFZ. The Arkalochori earthquake is a paradigm example for the on-going extension of Heraklion basin (central Crete) in the WNW-ESE direction, which is almost orthogonal to the E-W Messara graben and other active faults along the south coast of Crete.
The wildfires of summer 2021 in Greece were among the most severe forest fire events that have occurred in the country over the past decade. The conflagration period lasted for 20 days (i.e., from 27 July to 16 August 2021) and resulted in the devastation of an area of more than 3600 Km2. Forest fire events of similar severity also struck other Mediterranean countries during this period. Apart from their direct impacts, forest fires also render an area more susceptible to runoff erosion by massively removing its vegetation, among other factors. It is clear that immediately after a forest fire, most areas are much more susceptible to erosion. In this paper, we evaluate the erosion hazard of Attica, Northern Euboea, and the Peloponnese that were devastated by forest fires during the summer of 2021 in Greece, in comparison with their geological and geomorphological structures, as well as land cover and management. Given that a very significant part of these areas were burnt during the major conflagrations of this summer, erosion risk, as well as flood risk, are expected to be very high, especially for the coming autumn and winter. For the evaluation of erosion risk, the burnt areas were mapped, and the final erosion-risk maps were constructed through GIS software. The final maps suggest that most of the burnt areas are highly susceptible to future surface runoff erosion events. View Full-Text
Transgenic Caenorhabditis elegans that expresses the full-length wild-type human alpha-synuclein in dopaminergic neurons provides a well-established Parkinson's disease (PD) nematode model. Here, we present a detailed protocol to monitor and dissect the molecular underpinnings of age-associated neurodegeneration using this PD nematode model. This protocol includes preparation of nematode growth media and bacterial food sources, as well as procedures for nematode growth, synchronization, and treatment. We then describe procedures to assess dopaminergic neuronal death in vivo using fluorescence imaging. For complete details on the use and execution of this protocol, please refer to SenGupta et al. (2021).
Geological heritage or geoheritage refers to the total of geosites, i.e., areas of high geological interest in a given area. Geosites have a high potential of attracting geotourists, thus contributing to the development of the local economy. Assessing sites of geological interest can contribute to their promotion, as well as their preservation and protection. Greece’s geotectonic position in the convergent zone between the African and Eurasian plates has contributed to the existence of a considerable wealth of geosites, with the particularly active geotectonic region of the Ionian Sea characterized as a geoheritage hotspot. The purpose of this study is the selection of several such sites from the islands of Lefkas, Meganisi, Kefalonia and Ithaki and their assessment regarding their scientific, environmental, cultural, economic and aesthetic value. The most representative sites for the individual disciplines of geology (e.g., geomorphology, tectonics, stratigraphy and palaeontology) have been chosen, mapped and assessed, while indicative georoutes are proposed, which could aid the island’s geotouristic promotion to geologist and non-geologist future visitors.
Vitamin D receptor (VDR) gene single nucleotide polymorphisms (SNPs) have been investigated over the past years with the aim of identifying any association with the development of Alzheimer's disease (AD). However, information regarding the potential association of VDR SNP haplotypes with AD is limited. The aim of the present study was to provide additional knowledge on the effects of VDR haplotypes on the development of late-onset AD in a cohort of Southeastern European Caucasians (SECs). The study sample included 78 patients with late-onset AD and 103 healthy subjects as the control group. VDR SNPs that were analyzed were TaqI (rs731236), BsmI (rs1544410) and FokI (rs2228570). The CAC (TaqI, BsmI and FokI) haplotype was found to be associated with a 53% lower risk of developing the disease (OR, 0.47; 95% CI, 0.23-0.96; P=0.04) and the TAC (TaqI, BsmI and FokI) haplotype was associated with an ~6-fold greater risk of developing AD (OR, 6.19; 95% CI, 1.91-20.13; P=0.0028). Female subjects carrying the TAC haplotype had a ~9-fold greater risk of developing AD in comparison to female control subjects (OR, 9.27; 95% CI, 1.86-46.28; P<0.05). The TaqI and BsmI polymorphisms were in high linkage disequilibrium (D'=0.9717, r=0.8467) and produced a haplotype with a statistically significant different frequency between the control and AD group. The TA (TaqI and BsmI) haplotype was associated with an ~8-fold greater risk of developing AD (OR, 8.27; 95% CI, 2.70-25.28; P<0.05). Female TA carriers had an ~14-fold greater risk of developing the disease in comparison to female control subjects (OR, 13.93; 95% CI, 2.95-65.87; P<0.05). On the whole, the present study demonstrates that in the SEC population, TAC and TA are risk haplotypes for AD, while the CAC haplotype may act protectively. SEC women carrying the TAC or TA haplotype are at a greater risk of developing AD, thus suggesting that women are markedly affected by the poor utilization of vitamin D induced by the VDR haplotype
The role of vitamin D in Alzheimer's Disease (AD) has been studied over the past years. The results from numerous studies have indicated that the molecular pathways involved in the development of AD are closely related to the molecular pathways of the mechanisms of action of vitamin D. However, only a limited number of studies have described the key role of vitamin D receptor (VDR) in the regulation of the functions of vitamin D and the potential effect of single nucleotide polymorphisms (SNPs) of the VDR gene. Thus, the aim of the present study was to investigate the VDR TaqI polymorphism in relation to AD in a Southeastern European Caucasian (SEC) cohort. Further, the present study aimed to compare the results obtained with those of other AD populations. For this purpose, blood samples from 90 confirmed patients with AD [median age, 74 years; median mini-mental state examination (MMSE) score of 21; median frontal assessment battery (FAB) score of 10] and 103 healthy controls (median age, 57 years) were analyzed to determine the genotypes of TaqI (rs731236) using quantitative PCR. The frequencies (%) of the TaqI TT, TC and CC genotypes in the controls/patients were 34/48.9, 47.6/41.1 and 18.4/10.0, respectively. Statistically significant differences were observed for the TaqI C allele [odds ratio (OR). 0.54; 95% confidence interval (CI), 0.30-0.96; P=0.035], the TaqI TT genotype (OR, 1.86; 95% CI, 1.04-3.32; P=0.035) and the TaqI CC genotype (OR, 0.119; 95% CI, 0.014-0.995; P=0.032,) in relation to the MMSE score <21 in the patient's group. The TaqI TT allele was found to increase the risk of developing AD by 1.86-fold in the SEC population, while the TaqI C allele may act protectively, with a 46% lower risk of developing the disease. Patients with the TaqI CC genotype were found to have an 88% less likelihood of developing severe cognitive impairment based on the MMSE score. On the whole, the present study did not confirm the results of previous studies on the VDR TaqI C allele in patients with AD
Buffle et al are to be congratulated for shedding more light on the electrophysiologic links regarding atrial fibrillation recurrence post radiofrequency catheter ablation. The different approaches of left atrium volume and left atrium diameter assessment employed in this study, is a limitation that should not go unnoticed, since angiographically calculated left atrium volume overestimates volume as compared to 3D echo measurements. Further, the timing of change has been reported to have prognostic significance; namely left atrium diameter reduction within the 3 month blanking period has been reported to independently predict prolonged arrhythmia free survival. Hence, we firmly believe that future studies should examine any potential correlations between left atrium diameter and recurrence mechanisms.
On the eastern part of the Greek island of Crete, in the semi-arid area of Lasithi, lies the old monastery of Toplou. The monastery hosts the unique icon Megas ei Kyrie (“Great are you, O Lord”), written on wood by Ioannis Kornaros in 1770.1 The name of the icon is not that of a person but of a doxological praise; this in itself is indicative of a very unusual theme. The central motif is the baptism of Christ, which is celebrated in the East on the feast of Theophany (January 6). Upon closer inspection, the central motif is placed between heaven (the Trinity and the angels) and earth (Mary with the Christ Child, Adam and Eve), whereas the descent of Christ into the underworld is depicted at the bottom of the icon. Fifty-seven episodes from the Old and the New Testaments surround the central motif on the right and on the left, all connected by running waters. The total of sixtyone motifs are enumerated by the artist and glossed by headings, which faithfully reproduce the verses of the Theophany Poem, attributed to the Patriarch Sophrony of Jerusalem. The poem contains the prayer Megas ei Kyrie (“Great are you, O Lord”), which is the central liturgical event of the
Beachrocks are a window to the past environmental, geological, sedimentological and morphological conditions that were dominant in the coastal zone during their formation. Furthermore, beachrocks have the ability to reduce coastal erosion impact on sandy beaches. This study focuses on the beachrock formation mechanism through the comparison of cement characteristics, mineral chemistry and sedimentology of beachrock occurrences from two different geological and geographical localities: Diolkos, Corinth, Greece and Sumuide, Okinawa, Japan. In addition, in order to investigate a potential soft engineering method to protect coasts from erosion, artificial beachrock samples were created in vitro using sand samples and ureolytic bacteria from both areas under accelerating conditions. For Okinawa artificial beachrock experiments, the bacteria Pararhodobacter sp. was used, and for Diolkos, it was the bacteria Micrococcus yunnainensis sp. For the natural beachrocks, a multi-analytical approach was accomplished with the use of microscopic investigation, a scanning electron microscope, energy-dispersive X-ray spectroscopy, X-ray diffraction and X-ray fluorescence. Correlations were made between natural and artificial beachrocks. Results have shown that Diolkos beachrock was formed in the upper part of the intertidal zone, consisting of detrital material originating from the local bedrock, while Sumuide beachrock formed in the low intertidal–upper subtidal zone, consisting of coral sand and foraminifera fragments. For the artificial beachrocks, three samples were created using the microbial-induced carbonate precipitation (MICP) method, one from Diolkos (Corinth, Greece) and two from Sumuide (Okinawa, Japan). Diolkos artificial beachrock was better consolidated in comparison to Sumuide. Our investigation has shown that bacterial density was the key factor for the creation of the artificial beachrocks, while the samples’ granulometry played a secondary role in the process. The laboratory artificial beachrocks show encouraging results for a new soft engineering method to encounter beach erosion while keeping an ecofriendly character by saving energy, material resources and gas emissions. Artificial beachrocks can share the same properties of a natural beachrock and can contribute positively to marine biodiversity as a natural rocky habitat.
Using the example of the Raymond Duncan family this article will explore the human body as an object of self-determination, a means of overcoming social boundaries, a field of racist shooting and phobic enforcement, a reference point of public outrage and the complex between sociality and corporality, but also as a tool of political vigilance and social intervention. Does a body dressed in a tunic resist the western way of life? Or is it a stereotypical outpouring of people unable to modernize? Is the body instrumentalized as a means of narrating exoticism? The bodies of the Duncan family members are an occasion for discussion in the public sphere, even today.
This study examined the connection between two prominent deficits in schizophrenia: the deficit in parasympathetic regulation and the deficit in cognitive inhibitory control, within the framework of the Neurovisceral Integration Model (NIM).Thirty healthy controls and 30 patients with schizophrenia performed the internationally standardized antisaccade protocol while their electrocardiographic data were recorded. The interaction between the group, the cognitive inhibitory control as measured with error rate (ER) in the antisaccade task and parasympathetic activity as measured with the High Frequency power component of Heart Rate Variability (HF-HRV) was tested.Findings confirmed that decreased HF-HRV was specifically related to increased ER in patients with schizophrenia. In contrast, patient deficits in other oculomotor function measures such as reaction time and reaction time variability related to volitional movement control and cognitive stability respectively were not linked to the deficit in parasympathetic regulation.Our study validates the theory behind NIM proposing that cognitive inhibition has common physiological substrate with parasympathetic regulation. Future research could test this brain-heart link in other mental disorders especially those with a prominent deficit in inhibitory cognitive function.
Αn isotype heterojunction n+-ZnO/n-Si photodetector is developed, demonstrating wavelength-selective or broadband operation, depending on the applied bias voltage. Additionally, at self-powered (zero bias) operation, it distinguishes between UV, visible, and near IR (NIR) photons by polarity control of the photocurrent. The photodetector is developed by atomic layer deposition (ALD) of ZnO on n-Si, followed by electric contact deposition and annealing. Photoluminescence measurements reveal high optical quality and improved crystallinity of annealed ZnO on silicon. Photocurrent measurements as a function of illumination wavelength and bias voltage show small negative values in the UV–visible spectral range at zero and positive bias voltage and high positive values in the NIR spectral range. For these measurements, we consider the electric contact to ZnO as the anode and the electric contact to silicon as the cathode. At negative bias voltage, the device shows broadband operation with high photocurrent values across the UV–vis-NIR.
Objective: A fine-tuned balance of glucocorticoid receptor (GR) activation is essential for organ formation, with disturbances influencing many health outcomes. In utero, glucocorticoids have been linked to brain-related negative outcomes, with unclear underlying mechanisms, especially regarding cell-type-specific effects. An in vitro model of fetal human brain development, induced human pluripotent stem cell (hiPSC)-derived cerebral organoids, was used to test whether cerebral organoids are suitable for studying the impact of prenatal glucocorticoid exposure on the developing brain.
Methods: The GR was activated with the synthetic glucocorticoid dexamethasone, and the effects were mapped using single-cell transcriptomics across development.
Results: The GR was expressed in all cell types, with increasing expression levels through development. Not only did its activation elicit translocation to the nucleus and the expected effects on known GR-regulated pathways, but also neurons and progenitor cells showed targeted regulation of differentiation- and maturation-related transcripts. Uniquely in neurons, differentially expressed transcripts were significantly enriched for genes associated with behavior-related phenotypes and disorders. This human neuronal glucocorticoid response profile was validated across organoids from three independent hiPSC lines reprogrammed from different source tissues from both male and female donors.
Conclusions: These findings suggest that excessive glucocorticoid exposure could interfere with neuronal maturation in utero, leading to increased disease susceptibility through neurodevelopmental processes at the interface of genetic susceptibility and environmental exposure. Cerebral organoids are a valuable translational resource for exploring the effects of glucocorticoids on early human brain development.
Keywords: Biology; Brain; Child/Adolescent Psychiatry; Development; Glucocorticoid Receptor; Neurodevelopmental Disorders; Pre/Peri/Postnatal Issues; Stress; Translational Research.
PLCgamma enzymes are autoinhibited in resting cells and form key components of intracellular signaling that are also linked to disease development. Insights into physiological and aberrant activation of PLCgamma require understanding of an active, membrane-bound form, which can hydrolyze inositol-lipid substrates. Here, we demonstrate that PLCgamma1 cannot bind membranes unless the autoinhibition is disrupted. Through extensive molecular dynamics simulations and experimental evidence, we characterize membrane binding by the catalytic core domains and reveal previously unknown sites of lipid interaction. The identified sites act in synergy, overlap with autoinhibitory interfaces, and are shown to be critical for the phospholipase activity in cells. This work provides direct evidence that PLCgamma1 is inhibited through obstruction of its membrane-binding surfaces by the regulatory region and that activation must shift PLCgamma1 to a conformation competent for membrane binding. Knowledge of the critical sites of membrane interaction extends the mechanistic framework for activation, dysregulation, and therapeutic intervention.
BACKGROUND: The global burden of hypertension is constantly increasing with adverse cardiovascular and ocular sequelae. The association between elevated blood pressure and choroidal thickness (CT), as assessed via optical coherence tomography (OCT), is poorly understood.
OBJECTIVES AND DESIGN: Studies including hypertensive adults and normotensive controls undergoing OCT were evaluated for inclusion in this meta-analysis. The primary endpoint was CT difference between hypertensive and normotensive adults.
DATA SOURCES AND METHODS: We conducted a systematic review and after searching 1011 results from MEDLINE, ClinicalTrials.gov, medRxiv and Cochrane Library, six studies were deemed eligible and were pooled according to a random-effect model.
RESULTS: A statistically significant reduction in choroidal thickness was found in hypertensive adults ( = 454) as compared with normotensive controls ( = 365) [mean difference: -0.77; 95% confidence intervals: (-1.20, -0.34); = 0.0004]. The main limitations of this meta-analysis are the relatively small population included and the high statistical heterogeneity ( = 87%) among the various studies. Of note, after excluding one study the heterogeneity was markedly reduced.
CONCLUSION: Choroidal thickness is reduced among hypertensive subjects compared with normotensive controls. This finding mandates further examination in the context of long-term clinical outcomes.
Undisputedly, the 61st round of Greek-Turkish exploratory talks has not comeas something totally unexpected. Several signs at the level either of Greece’s internal policy-making processes or the one of international alliances have indicated that Ankara sought persistently for a lifeline and finally, this was given by Athens. The current paper describes analytically the evolutions before the “Greek-Turkish dialogue”, makes an extensive analysis of the content of recent agreements of EEZ delineation and proceeds into policy proposals with regard to how Greek geostrategy has to be formed while it stands critical against current strategic decisions. For this reason and on the eve of the “dialogue”, relevant questions are posed: Under what conditions will it take place? With what correlations of power at operational level? How far does Turkey intend to go in order to shape these correlations to its benefit and to what extent does Greece intend to continue to back down, given that making concessions all the time gives rise to new demands? Citing maps and law texts, this paper gives emphasis on the pathogenies of Greek foreign policy and how these are reflected onto current policies.
The broad high-energy spectral component in blazars is usually attributed to various inverse Compton scattering processes in the relativistic jet, but has not been clearly identified in most cases due to degeneracies in physical models. AP Librae, a low-synchrotron-peaking BL Lac object (LBL) detected in 2015 by H.E.S.S. at very high energies (VHE; >0.5 TeV), has an extremely broad high-energy spectrum, covering ~9 decades in energy. Standard synchrotron self-Compton models generally fail to reproduce the VHE emission, which has led to the suggestion that it might arise not from the blazar core, but on kiloparsec scales from inverse Compton (IC) scattering of cosmic microwave background (CMB) photons by a still-relativistic jet (IC/CMB). IC/CMB models for the TeV emission of AP Librae in prior works have implied a high level of infrared emission from the kiloparsec-scale jet. With newly obtained Hubble Space Telescope (HST) imaging, we obtain a deep upper limit on the kiloparsec-scale jet emission at 1.6 μm, well below the expected level. High-resolution Atacama Large Millimeter/submillimeter Array imaging in bands 3-9 reveals a residual dust-disk signature after core subtraction, with a clearly thermal spectrum, and an extent (~500 pc) that matches with a nonjet residual emission seen after point-spread function subtraction in our 1.6 μm HST imaging. We find that the unusually broad GeV and VHE emission in AP Librae can be reproduced through the combined IC scattering of photons from the CMB and the dust disk, respectively, by electrons in both the blazar core and subkiloparsec jet.
BACKGROUND: Burn injury (BI) is one of the most serious causes of morbidity and mortality in the pediatric population. BI triggers an initial stage of hyperinflammation, followed by hypersecretion of both pro- and anti-inflammatory cytokines. IL- 18 is a vital pro-inflammatory cytokine, the effect of which has been investigated not only in animal models but also in adult patients. No study has yet examined the association of serum IL- 18 levels and the clinical significance in the course of pediatric BI. METHODS: We conducted a prospective study including all children with burn injuries who were hospitalized from December 2015 to December 2018 in a tertiary Children's Hospital. RESULTS: A total of 55 children with BI were included. In the present study, we found a strong positive correlation between total body surface area (TBSA) and the levels of IL-18 at admission and on the third day postburn, respectively. The WBC count, the number of lymphocytes and the CRP levels at admission revealed a strong, positive correlation with IL-18 levels. The correlation between IL-18 levels at admission and the length of stay (LOS) was moderate. CONCLUSIONS: This study has shown that the levels of IL-18 collected at admission correlate positively with the extent of TBSA and inflammatory indices in pediatric patients. Moreover, IL-18 levels at admission may not be the most accurate prognostic factor regarding the LOS. However, further research is needed in order to establish more accurate predictive factors for the outcome of BIs in pediatric patients
Inflammation plays a prominent role in the development of atherosclerosis and other cardiovascular diseases, and anti-inflammatory agents may improve cardiovascular outcomes. For years, colchicine has been used as a safe and well-tolerated agent in diseases such as gout and familial Mediterranean fever. The widely available therapeutic has several anti-inflammatory effects, however, that have proven effective in a broad spectrum of cardiovascular diseases as well. It is considered standard-of-care therapy for pericarditis, and several clinical trials have evaluated its role in postoperative and postablation atrial fibrillation, postpericardiotomy syndrome, coronary artery disease, percutaneous coronary interventions, and cerebrovascular disease. We aim to summarize colchicine's pharmacodynamics and the mechanism behind its anti-inflammatory effect, outline thus far accumulated evidence on treatment with colchicine in cardiovascular disease, and present ongoing randomized clinical trials. We also emphasize real-world clinical implications that should be considered on the basis of the merits and limitations of completed trials. Altogether, colchicine's simplicity, low cost, and effectiveness may provide an important addition to other standard cardiovascular therapies. Ongoing studies will address complementary questions pertaining to the use of low-dose colchicine for the treatment of cardiovascular disease.
The infinite time of oral drug absorption was conceived from the first day of the birth of pharmacokinetics when H. Dost introduced the term pharmacokinetics in his book published in 1953. He adopted the function developed by H. Bateman back in 1908 for the decay of the nuclei isotopes to describe oral drug absorption as a first-order process. We unveiled this false hypothesis relying on common wisdom i.e. drugs are absorbed in finite time. This false assumption had dramatic effects on the evolution of oral pharmacokinetics but most importantly on the bioavailability and bioequivalence concepts and metrics. This work focuses on the finite absorption time (FAT) concept, the relevant Physiologically Based Finite Time (PBFTPK) models developed and their applications in oral pharmacokinetics, bioavailability and bioequivalence. The crux of the matter is that drug absorption from the gastrointestinal tract takes place under sink conditions because of the high blood flow rate in the vena cava. The termination of oral, pulmonary and intranasal drug absorption at a specific time point, calls for regulatory changes in bioavailability and bioequivalence studies in terms of the study design and metrics used for the bioequivalence assessment.
In this study, the geoeducational value of five geosites, located in the aspiring geopark of the volcanic island of Nisyros, SE Aegean Sea, was assessed by means of two methods: the G-P method of Brilha (2016) and the M-GAM method. The first method takes into account 12 criteria belonging to the educational potential. The M-GAM method, on the other hand, takes into account the opinions of visitors who, as non-experts, express a different point of view that is rarely calculated or evaluated in different geosite assessment methods. For the better and more objective comparison of the two methods of evaluation of the educational potential of the study areas, the results were converted to a percentage scale (%). The first G-P method clearly highlights the high geological value of the studied geosites, which have a relatively high score and can be used for geotourism and geoeducation. The second method, on the other hand, yields a moderate score in areas with objectively high geological value. This is clearly evident, as this method considers the opinions of visitors who lack the necessary cognitive geological background, thereby underestimating the significance and potential of certain geological features due to lack of formal training.
We study the giant outbursts of SMC X-3 and RX J0209.6-7427 (hereafter RX J0209) to compare their super-Eddington accretion regime with that of Swift J0243.6+6124 (hereafter Swift J0243). The high double-peak profile of SMC X-3 is found to be 0.25 phase offset from that below 2.3 × 1038 erg s-1, which is similar to Swift J0243 (happened around 0.9 × 1038 erg s-1). The profile of RX J0209 shows a similar 0.25 phase offset between high double-peak and low double-peak around 1.25 × 1038 erg s-1. The 0.25 phase offset corresponds to a 90° angle change of the emission beam and strongly supports for a transition from a fan beam to a pencil beam. Their critical luminosities imply a surface magnetic field ~4 × 1013 and 2 × 1013 G for SMC X-3 and RX J0209, respectively, based on the recently measured cyclotron line of Swift J0243. The spin-up rate and luminosity of SMC X-3 follows a relation of $\dot{\nu }\propto L^{0.94\pm 0.03}$, while that of RX J0209 follows $\dot{\nu }\propto L^{1.00\pm 0.03}$, which are similar to Swift J0243 and consistent with the prediction of a radiation-pressure-dominated disc. These results indicate that accretion columns are indeed formed above Eddington luminosity, and the population of ultraluminous X-ray pulsars likely corresponds to X-ray pulsars of highest magnetic field.
The caper (Capparis spinosa L.) is a winter deciduous, perennial plant that grows and completes its life cycle entirely during the dry season in the Mediterranean region. Mature caper fruits and their pericarp, collected from the wild shrubs of the Capparis spinosa grown in the inland and coastal sites of Greece during summer, have been studied in order to improve and complete our knowledge of the successful establishment of the C. spinosa in Mediterranean ecosystems. Caper fruits possess substantial nutritional, medicinal and ecological properties that vary according to the developmental stage, agroclimatic and geographical parameters; however, the fruit pericarp and pedicel, unlike the other aboveground plant parts of the caper, have not hitherto been studied. The higher sugar and starch content in the pericarps and fruit pedicels harvested from wild caper plants grown in coastal habitats was investigated in comparison with those from inland habitats, while the higher proline and nitrogen content in pericarps and fruit pedicels harvested from wild caper plants grown in inland habitats was investigated in comparison with those from coastal habitats. The PCA, based on the considered functional traits underlying the constitutional aspects, reveals groupings of fruit pericarp specimens of the C. spinosa collected from coastal and inland habitats that are grounds for adaptive variation.
The maintenance of a healthy mitochondrial network and the ability to adjust organelle population in response to internal or external stimuli are essential for the function and the survival of eukaryotic cells. Over the last two decades several studies have demonstrated the paramount importance of mitophagy, a selective form of autophagy that removes damaged and/or superfluous organelles, in organismal physiology. Post-mitotic neuronal cells are particularly vulnerable to mitochondrial damage, and mitophagy impairment has emerged as a causative factor in multiple neurodegenerative pathologies, including Alzheimer's disease and Parkinson's disease among others. Although mitochondrial turnover is a multifaceted process, neurons have to tackle additional complications, arising from their pronounced bioenergetic demands and their unique architecture and cellular polarisation that render the degradation of distal organelles challenging. Mounting evidence indicates that despite the functional conservation of mitophagy pathways, the unique features of neuronal physiology have led to the adaptation of compartmentalised solutions, which serve to ensure seamless mitochondrial removal in every part of the cell. In this review, we summarise the current knowledge concerning the molecular mechanisms that mediate mitophagy compartmentalisation and discuss their implications in various human pathologies.
INTRODUCTION: This study evaluated complete blood count-derived inflammation indices in patients with retinal vein occlusion (RVO). METHODS: Participants in this case-control study were 54 patients with RVO and 54 age- and sex-matched control subjects. All participants underwent a thorough ophthalmic examination, as well as blood sample testing for complete blood count. Comparison of all parameters derived from complete blood count as well as calculation of specific indices was performed between patients with RVO and controls. RESULTS: Patients with RVO presented significantly higher white blood cell count (p = 0.033), neutrophil count (p = 0.003), neutrophil-to-lymphocyte ratio (NLR, p = 0.002), red cell distribution width (RDW, p = 0.009), mean platelet volume (MPV, p = 0.023), and systemic immune-inflammatory index (SII, p = 0.007) compared to controls. Receiver operator characteristic curve (ROC) analysis showed that NLR was superior to other inflammatory indices, having the greatest area under the curve. The optimal cutoff value for NLR to predict RVO was 2.29 with 46.2% sensitivity and 77.8% specificity. CONCLUSION: Patients with RVO presented increased NLR, RDW, MPV, and SII, providing evidence that inflammation plays an important role in the pathogenesis of RVO. Complete blood cell count-derived indices can be easily calculated and may serve as an easy, simple, and cost-effective tool to evaluate the degree of systemic inflammation in patients with RVO, so as to potentially guide treatment
Complex time-dependent Lyapunov equation (CTDLE), as an important means of stability analysis of control systems, has been extensively employed in mathematics and engineering application fields. Recursive neural networks (RNNs) have been reported as an effective method for solving CTDLE. In the previous work, zeroing neural networks (ZNNs) have been established to find the accurate solution of time-dependent Lyapunov equation (TDLE) in the noise-free conditions. However, noises are inevitable in the actual implementation process. In order to suppress the interference of various noises in practical applications, in this paper, a complex noise-resistant ZNN (CNRZNN) model is proposed and employed for the CTDLE solution. Additionally, the convergence and robustness of the CNRZNN model are analyzed and proved theoretically. For verification and comparison, three experiments and the existing noise-tolerant ZNN (NTZNN) model are introduced to investigate the effectiveness, convergence and robustness of the CNRZNN model. Compared with the NTZNN model, the CNRZNN model has more generality and stronger robustness. Specifically, the NTZNN model is a special form of the CNRZNN model, and the residual error of CNRZNN can converge rapidly and stably to order 10−5 when solving CTDLE under complex linear noises, which is much lower than order 10−1 of the NTZNN model. Analogously, under complex quadratic noises, the residual error of the CNRZNN model can converge to 2∥A∥F/ζ3 quickly and stably, while the residual error of the NTZNN model is divergent.
The game analysis is known as a useful tool for understanding the level of technical-tactical performance of volleyball. As one of the main characteristics of volleyball is defined as the intense relationship between its skills and concluded performance, the present study aimed to perform a comprehensive analysis of the serve reception zone, set zone and attack quality of the top-level volleyball players. The analysis process included reviewing the videos of the games by an experienced scout man who was an expert analyst and specialist in the knowledge of volleyball skills. Initially, during each game video checking, data were collected, and irrelevant/invalid outputs were deleted. Data were exported to the Data Volley special volleyball analysis software. Bivariate associations were assessed for pairs of variables with Pearson’s chi-squared tests. Statistical significance was set at p<0.05. Moreover, the effect size was calculated in terms of Crammer’s V, with values of <0.1, 0.1-0.3 and > 0.5 for small, medium, and large effects respectively. The results showed that there were significant relationships between reception zone with setting zone, setting zone with attack quality as well as reception zone with attack quality. Coaches may consider the relationship between critical skills of volleyball to promote their team performance.
This paper investigates the problem of computing the time-varying {2,3}- and {2,4}-inverses through the zeroing neural network (ZNN) method, which is presently regarded as a state-of-the-art method for computing the time-varying matrix Moore–Penrose inverse. As a result, two new ZNN models, dubbed ZNN23I and ZNN24I, for the computation of the time-varying {2,3}- and {2,4}-inverses, respectively, are introduced, and the effectiveness of these models is evaluated. Numerical experiments investigate and confirm the efficiency of the proposed ZNN models for computing the time-varying {2,3}- and {2,4}-inverses.
In this paper we use learning trajectories to study 11th grade students’ conceptualization of function as a covariational relationship between two quantities while they engaged in modeling tasks to support their experimentation and conceptualizations. Pairs of students used digital tools that offer integrated representations of functions while working on an instructional sequence of modeling tasks in their mathematics classrooms. The analysis shows students’ progressive conceptualization of functional relationships starting from quantitative and covariational relationships using learning trajectories. The findings indicate the potential of upper secondary students to conceptualize function as a covariational relationship involving the rate of change, as well as the role of the available tools and the role of models and their connections in students’ conceptualizations.
Psychiatric disorders that are characterized by impairments in sustained attention, including attention deficit hyperactivity disorder (ADHD), post-traumatic stress disorder (PTSD), and major depression are also sensitive to exacerbation by stress. Sustained attention relies on cholinergic and non-cholinergic projections from the nucleus basalis of Meynert (NBM) in the basal forebrain to the medial prefrontal cortex (mPFC). We have previously shown that central administration of the stress neuropeptide corticotropin releasing factor (CRF) impairs performance on the sustained attention task (SAT) in adult male and female rats. The present study investigated whether this effect was mediated by CRF's action in the NBM. Rats were administered CRF in the NBM and subsequent SAT performance was measured. A high dose of CRF (100 ng) significantly impaired performance on non-signaled events across sex. Because performance on non-signaled events is believed to depend on non-cholinergic (i.e., GABA and glutamate) signaling, high performance liquid chromatography was used to quantify amino acid levels in the NBM and mPFC. We found females have higher levels of glutamate, glutamine, GABA glycine, and alanine in the NBM than males. Importantly, CRF in the NBM led to a local decrease of taurine and several amino acids involved in glutamate synthesis in males and females, changes which may mediate the CRF-induced SAT performance deficit. Together these studies suggest that CRF regulation of amino acids in the NMB contributes to stress-induced attention deficits.
In mitochondria, complex IV (CIV) can be found as a monomer, a dimer or in association with other respiratory complexes. The atomic structure of the yeast S. cerevisiae CIV in a supercomplex (SC) with complex III (CIII) pointed to a region of significant conformational changes compared to the homologous mammalian CIV structures. These changes involved the matrix side domain of Cox5A at the CIII-CIV interface, and it was suggested that it could be required for SC formation. To investigate this, we solved the structure of the isolated monomeric CIV from S. cerevisiae stabilised in amphipol A8-35 at 3.9 A using cryo-electron microscopy. Only a minor change in flexibility was seen in this Cox5A region, ruling out large CIV conformational shift for interaction with CIII and confirming the different fold of the yeast Cox5A subunit compared to mammalian homologues. Other differences in structure were the absence of two canonical subunits, Cox12 and Cox13, as well as Cox26, which is unique to the yeast CIV. Their absence is most likely due to the protein purification protocol used to isolate CIV from the III-IV SC.
Summary Global warming affects the aquatic ecosystems, accelerating pathogenic microorganisms' and toxic microalgae's growth and spread in marine habitats, and in bivalve molluscs. New parasite invasions are directly linked to oceanic warming. Consumption of pathogen-infected molluscs impacts human health at different rates, depending, inter alia, on the bacteria taxa. It is therefore necessary to monitor microbiological and chemical contamination of food. Many global cases of poisoning from bivalve consumption can be traced back to Mediterranean regions. This article aims to examine the marine bivalve's infestation rate within the scope of climate change, as well as to evaluate the risk posed by climate change to bivalve welfare and public health. Biological and climatic data literature review was performed from international scientific sources, Greek authorities and State organizations. Focusing on Greek aquaculture and bivalve fisheries, high-risk index pathogenic parasites and microalgae were observed during summer months, particularly in Thermaikos Gulf. Considering the climate models that predict further temperature increases, it seems that marine organisms will be subjected in the long term to higher temperatures. Due to the positive linkage between temperature and microbial load, the marine areas most affected by this phenomenon are characterized as ‘high risk’ for consumer health.
Recent synthesis of cyclo[18]carbon has spurred increasing interest in carbon rings. We focus on a comparative inspection of ground and excited states{,} as well as of hole transfer properties of cumulenic and polyynic cyclo[18]carbon via Density Functional Theory (DFT){,} time-dependent DFT (TD-DFT) and real-time time-dependent DFT (RT-TDDFT). Zero-point vibrations are also accounted for{,} using a Monte Carlo sampling technique and a less exact{,} yet mode-resolved{,} quadratic approximation. The inclusion of zero-point vibrations leads to a red-shift on the HOMO–LUMO gap and the first singlet and triplet excitation energies of both conformations{,} correcting the values of the ‘static’ configurations by 9% to 24%. Next{,} we oxidize the molecule{,} creating a hole at one carbon atom. Hole transfer along polyynic cyclo[18]carbon is decreased in magnitude compared to its cumulenic counterpart and lacks the symmetric features the latter displays. Contributions by each mode to energy changes and hole transfer between diametrically opposed atoms vary{,} with specific bond-stretching modes being dominant.
Mistry AK, Albers HM, Arıcı T, Banerjee A, Benzoni G, Cederwall B, Gerl J, Górska M, Hall O, Hubbard N, et al.The DESPEC setup for GSI and FAIR. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. 2022;1033:166662.
The paper presents the background, design, implementation and impact of the Continuous Professional Development (CPD) programme of the EU-funded ENRICH Project, which ran from 2018 to 2021. The programme, which has been freely available online since January 2022 (http://enrichproject.eu), aims at implementing the principles and processes of ELF awareness in empowering English language teachers to integrate the role of English as a Lingua Franca in their multilingual classrooms. We begin by justifying the development of the ENRICH Project with reference to the policies of the European Union supporting multilingualism and go on to discuss the principles of ELF awareness that informed the ENRICH CPD programme. We also present the priorities, target groups, key objectives and innovative practices of the ENRICH CPD programme. The paper is rounded up with a sample of participants’ responses to certain CPD activities and with an appreciation of the impact of the programme on participant teachers and their learners.
The paper presents four premises and two principles guiding the ENRICH Project, an EU-funded (Erasmus+) project that ran from 2018 to 2021 and developed an innovative online continuous professional development programme aimed at educating teachers of English as a foreign language in raising their own and their learners’ ELF awareness. I further discuss my own observations from the extensive training programme with regard to implications of ELF aware teacher education and pedagogy and present the essential ingredients of what I call the “ELF state of mind”.
Purpose
The development of health literacy skills is of paramount importance especially for students, as it is associated with their wellbeing and academic success. Assessing students' health literacy is necessary for its advancement. This study comes to fill the need for a valid multidimensional health literacy assessment instrument for secondary school students.
Design/methodology/approach
Initially, the authors defined the conceptual framework within which the items of this instrument were generated. Its final form was obtained through three pilot studies. A test-retest followed and, finally, a nationwide survey was conducted on Greek seventh-, ninth- and tenth-grade students (N = 2,800).
Findings
A 37-item instrument, the Health Literacy Assessment for Secondary School Students (HeLiASeSS), was developed which includes the following nine dimensions/skills of health literacy: “access to”, “understand” and “evaluate” (health information), “functional communication”, “interactive communication” and “critical communication”, “relying on health information”, “self-efficacy regarding health matters” and “intention for active citizenship regarding health matters”. HeLiASeSS proved to have good stability (ICC = 0.943) and high internal consistency reliability (a = 0.903).
Originality/value
HeLiASeSS offers the possibility of a reliable and valid assessment of secondary school students' health literacy skills providing a multidimensional evaluation of this construct and is expected to be useful in interventions aiming at promoting this type of literacy.
