Publications

Real-time quantitative-PCR has been a priceless tool for gene expression analyses. The reaction, however, needs proper normalization with the use of housekeeping genes (HKGs), whose expression remains stable throughout the experimental conditions. Often, the combination of several genes is required for accurate normalization. Most importantly, there are no universal HKGs which can be used since their expression varies among different organisms, tissues or experimental conditions. In the present study, nine common HKGs (RPL19, tbp, ubx, GAPDH, α-TUB, β-TUB, 14-3-3zeta, RPE and actin3) are evaluated in thirteen different body parts, developmental stages and reproductive and olfactory tissues of two insects of agricultural importance, the medfly and the olive fly. Three software programs based on different algorithms were used (geNorm, NormFinder and BestKeeper) and gave different ranking of HKG stabilities. This confirms once again that the stability of common HKGs should not be taken for granted and demonstrates the caution that is needed in the choice of the appropriate HKGs. Finally, by estimating the average of a standard score of the stability values resulted by the three programs we were able to provide a useful consensus key for the choice of the best HKG combination in various tissues of the two insects.

The V-SVZ adult neurogenic niche is located in the wall of the lateral ventricles and contains neural stem cells, with self-renewing and differentiating ability and postmitotic multiciliated ependymal cells, an important structural and trophic component of the niche. The niche is established at postnatal stages from a subpopulation of radial glial cells, determined during embryogenesis. Radial glial cells constitute a heterogeneous population, which give rise, in addition to niche cellular components, to neurons and glial cells. The mechanisms that direct their fate commitment towards V-SVZ niche cells are largely unknown. In the present review, we discuss recent findings on the signaling networks governing fate commitment decisions of radial glial cells towards multiciliated ependymal cells. We highlight the role of two novel factors: McIdas and GemC1/Lynkeas and the molecular pathways which they activate in order to promote ependymal cell differentiation. Finally, we discuss a possible crosstalk of known signaling pathways, such as Notch, STAT3, and BMPs, for the specification of ependymal versus adult neural stem cells in the V-SVZ niche. GLIA 2017;65:1032-1042.

We aim to construct an exceptionally deep (V ≲ 27) catalog of variable objects in selected Galactic and extragalactic fields visited multiple times by the Hubble Space Telescope (HST). While HST observations of some of these fields were searched for specific types of variables before (most notably, the extragalactic Cepheids), we attempt a systematic study of the population of variable objects of all types at the magnitude range not easily accessible with ground-based telescopes. The variability timescales that can be probed range from hours to years depending on how often a particular field has been visited. For source extraction and cross-matching of sources between visits we rely on the Hubble Source Catalog which includes 107 objects detected with WFPC2, ACS, and WFC3 HST instruments. The lightcurves extracted from the HSC are corrected for systematic effects by applying local zero-point corrections and are screened for bad measurements. For each lightcurve we compute variability indices sensitive to a broad range of variability types. The indices characterize the overall lightcurve scatter and smoothness. Candidate variables are selected as having variability index values significantly higher than expected for objects of similar brightness in the given set of observations. The Hubble Catalog of Variables will be released in 2018.

The Hubble Catalog of Variables (HCV) is a 3 year ESA funded project that aims to develop a set of algorithms to identify variables among the sources included in the Hubble Source Catalog (HSC) and produce the HCV. We will process all HSC sources with more than a predefined number of measurements in a single filter/instrument combination and compute a range of lightcurve features to determine the variability status of each source. At the end of the project, the first release of the Hubble Catalog of Variables will be made available at the Mikulski Archive for Space Telescopes (MAST) and the ESA Science Archives. The variability detection pipeline will be implemented at the Space Telescope Science Institute (STScI) so that updated versions of the HCV may be created following the future releases of the HSC.

Combination antiretroviral treatment (cART) has significantly improved the life expectancy of people living with HIV. The life-long nature of cART increases the risk of side effects, which in some cases may have been caused by specific genetic characteristics. Patients treated with atazanavir (ATV) boosted with ritonavir (rit), which is a protease inhibitor used for the treatment of HIV, present with elevated bilirubin levels, at high proportions. ATV/rit-related hyperbilirubinemia has been previously associated with genetic characteristics in uridine diphosphate glucuronosyltransferase (UGT) enzyme. The prevalence of the UGT1A1*28 variant, which is the most frequent polymorphism in the UGT1A1 superfamily, has been found to range between 9% and ~60% with the highest frequency in Africa. Pharmacokinetics for additional HIV drugs, such as the integrase inhibitors Raltegravir and Elvitegravir, has been also shown to be influenced by UGT1A1 polymorphisms. Pharmacogenetics/pharmacogenomics testing can be useful to identify a patient's susceptibility to drug toxicity and therefore to facilitate selection of the optimal long-term suppressive regimen.

The Small Magellanic Cloud (SMC) hosts a large number of high-mass X-ray binaries, and in particular of Be/X-ray Binaries (BeXRBs; neutron stars orbiting OBe-type stars), offering a unique laboratory to address the effect of metalicity. One key property of their optical companion is Hα in emission, which makes them bright sources when observed through a narrow-band Hα filter. We performed a survey of the SMC Bar and Wing regions using wide-field cameras (WFI@MPG/ESO and MOSAIC@CTIO/Blanco) in order to identify the counterparts of the sources detected in our XMM-Newton survey of the same area. We obtained broad-band R and narrow-band Hα photometry, and identified ~10000 Hα emission sources down to a sensitivity limit of 18.7 mag (equivalent to ~B8 type Main Sequence stars). We find the fraction of OBe/OB stars to be 13% down to this limit, and by investigating this fraction as a function of the brightness of the stars we deduce that Hα excess peaks at the O9-B2 spectral range. Using the most up-to-date numbers of SMC BeXRBs we find their fraction over their parent population to be ~0.002 - 0.025 BeXRBs/OBe, a direct measurement of their formation rate.

Background In the era of widespread rituximab use for Waldenström's macroglobulinaemia, new treatment options for patients with rituximab-refractory disease are an important clinical need. Ibrutinib has induced durable responses in previously treated patients with Waldenström's macroglobulinaemia. We assessed the efficacy and safety of ibrutinib in a population with rituximab-refractory disease. Methods This multicentre, open-label substudy was done at 19 sites in seven countries in adults aged 18 years and older with confirmed Waldenström's macroglobulinaemia, refractory to rituximab and requiring treatment. Disease refractory to the last rituximab-containing therapy was defined as either relapse less than 12 months since last dose of rituximab or failure to achieve at least a minor response. Key exclusion criteria included: CNS involvement, a stroke or intracranial haemorrhage less than 12 months before enrolment, clinically significant cardiovascular disease, hepatitis B or hepatitis C viral infection, and a known bleeding disorder. Patients received oral ibrutinib 420 mg once daily until progression or unacceptable toxicity. The substudy was not prospectively powered for statistical comparisons, and as such, all the analyses are descriptive in nature. This study objectives were the proportion of patients with an overall response, progression-free survival, overall survival, haematological improvement measured by haemoglobin, time to next treatment, and patient-reported outcomes according to the Functional Assessment of Cancer Therapy-Anemia (FACT-An) and the Euro Qol 5 Dimension Questionnaire (EQ-5D-5L). All analyses were per protocol. The study is registered at ClinicalTrials.gov, number NCT02165397, and follow-up is ongoing but enrolment is complete. Findings Between Aug 18, 2014, and Feb 18, 2015, 31 patients were enrolled. Median age was 67 years (IQR 58–74); 13 (42%) of 31 patients had high-risk disease per the International Prognostic Scoring System Waldenström Macroglobulinaemia, median number of previous therapies was four (IQR 2–6), and all were rituximab-refractory. At a median follow-up of 18·1 months (IQR 17·5–18·9), the proportion of patients with an overall response was 28 [90%] of 31 (22 [71%] of patients had a major response), the estimated 18 month progression-free survival rate was 86% (95% CI 66–94), and the estimated 18 month overall survival rate was 97% (95% CI 79–100). Baseline median haemoglobin of 10·3 g/dL (IQR 9·3–11·7) increased to 11·4 g/dL (10·9–12·4) after 4 weeks of ibrutinib treatment and reached 12·7 g/dL (11·8–13·4) at week 49. A clinically meaningful improvement from baseline in FACT-An score, anaemia subscale score, and the EQ-5D-5L were reported at all post-baseline visits. Time to next treatment will be presented at a later date. Common grade 3 or worse adverse events included neutropenia in four patients (13%), hypertension in three patients (10%), and anaemia, thrombocytopenia, and diarrhoea in two patients each (6%). Serious adverse events occurred in ten patients (32%) and were most often infections. Five (16%) patients discontinued ibrutinib: three due to progression and two due to adverse events, while the remaining 26 [84%] of patients are continuing ibrutinib at the time of this report. Interpretation The sustained responses and median progression-free survival time, combined with a manageable toxicity profile observed with single-agent ibrutinib indicate that this chemotherapy-free approach is a potential new treatment choice for patients who had heavily pretreated, rituximab-refractory Waldenström's macroglobulinaemia. Funding Pharmacyclics LLC, an AbbVie Company. © 2017 Elsevier Ltd

Background In the era of widespread rituximab use for Waldenström's macroglobulinaemia, new treatment options for patients with rituximab-refractory disease are an important clinical need. Ibrutinib has induced durable responses in previously treated patients with Waldenström's macroglobulinaemia. We assessed the efficacy and safety of ibrutinib in a population with rituximab-refractory disease. Methods This multicentre, open-label substudy was done at 19 sites in seven countries in adults aged 18 years and older with confirmed Waldenström's macroglobulinaemia, refractory to rituximab and requiring treatment. Disease refractory to the last rituximab-containing therapy was defined as either relapse less than 12 months since last dose of rituximab or failure to achieve at least a minor response. Key exclusion criteria included: CNS involvement, a stroke or intracranial haemorrhage less than 12 months before enrolment, clinically significant cardiovascular disease, hepatitis B or hepatitis C viral infection, and a known bleeding disorder. Patients received oral ibrutinib 420 mg once daily until progression or unacceptable toxicity. The substudy was not prospectively powered for statistical comparisons, and as such, all the analyses are descriptive in nature. This study objectives were the proportion of patients with an overall response, progression-free survival, overall survival, haematological improvement measured by haemoglobin, time to next treatment, and patient-reported outcomes according to the Functional Assessment of Cancer Therapy-Anemia (FACT-An) and the Euro Qol 5 Dimension Questionnaire (EQ-5D-5L). All analyses were per protocol. The study is registered at ClinicalTrials.gov, number NCT02165397, and follow-up is ongoing but enrolment is complete. Findings Between Aug 18, 2014, and Feb 18, 2015, 31 patients were enrolled. Median age was 67 years (IQR 58–74); 13 (42%) of 31 patients had high-risk disease per the International Prognostic Scoring System Waldenström Macroglobulinaemia, median number of previous therapies was four (IQR 2–6), and all were rituximab-refractory. At a median follow-up of 18·1 months (IQR 17·5–18·9), the proportion of patients with an overall response was 28 [90%] of 31 (22 [71%] of patients had a major response), the estimated 18 month progression-free survival rate was 86% (95% CI 66–94), and the estimated 18 month overall survival rate was 97% (95% CI 79–100). Baseline median haemoglobin of 10·3 g/dL (IQR 9·3–11·7) increased to 11·4 g/dL (10·9–12·4) after 4 weeks of ibrutinib treatment and reached 12·7 g/dL (11·8–13·4) at week 49. A clinically meaningful improvement from baseline in FACT-An score, anaemia subscale score, and the EQ-5D-5L were reported at all post-baseline visits. Time to next treatment will be presented at a later date. Common grade 3 or worse adverse events included neutropenia in four patients (13%), hypertension in three patients (10%), and anaemia, thrombocytopenia, and diarrhoea in two patients each (6%). Serious adverse events occurred in ten patients (32%) and were most often infections. Five (16%) patients discontinued ibrutinib: three due to progression and two due to adverse events, while the remaining 26 [84%] of patients are continuing ibrutinib at the time of this report. Interpretation The sustained responses and median progression-free survival time, combined with a manageable toxicity profile observed with single-agent ibrutinib indicate that this chemotherapy-free approach is a potential new treatment choice for patients who had heavily pretreated, rituximab-refractory Waldenström's macroglobulinaemia. Funding Pharmacyclics LLC, an AbbVie Company. © 2017 Elsevier Ltd

The transient IGR J01217-7257 in the Small Magellanic Cloud was found to be in a new outburst during INTEGRAL observations. We triggered an XMM-Newton target of opportunity observation near outburst maximum, which lead to the discovery of X-ray pulsations with a period of 2.165 s. This period is very similar to that detected from XTE J0119-731, suggesting that both sources are identical. The pulse profile obtained from the EPIC-pn instrument is complex and highly energy dependent. Pulse-phase spectroscopy reveals variations in the spectral slope correlated with the changes in flux during the pulse, with the harder X-ray spectrum at pulse maximum and softer during minimum. Analysis of XMM-Newton reflection grating spectra reveals the presence of emission lines that suggest the presence of ionized material around the neutron star. By monitoring the system during its outburst with Swift/XRT we detected a possible transition from the accretor to the propeller stage.

IGF-IR is highly associated with the behaviour of breast cancer cells. In ERalpha-positive breast cancer, IGF-IR is present at high levels. In clinical practice, prolonged treatment with anti-estrogen agents results in resistance to the therapy with activation of alternative signaling pathways. Receptor Tyrosine Kinases, and especially IGF-IR, have crucial roles in these processes. Here, we report a nodal role of IGF-IR in the regulation of ERalpha-positive breast cancer cell aggressiveness and the regulation of expression levels of several extracellular matrix molecules. In particular, activation of IGF-IR, but not EGFR, in MCF-7 breast cancer cells results in the reduction of specific matrix metalloproteinases and their inhibitors. In contrast, IGF-IR inhibition leads to the depletion by endocytosis of syndecan-4. Global important changes in cell adhesion receptors, which include integrins and syndecan-4 triggered by IGF-IR inhibition, regulate adhesion and invasion. Cell function assays that were performed in MCF-7 cells as well as their ERalpha-suppressed counterparts indicate that ER status is a major determinant of IGF-IR regulatory role on cell adhesion and invasion. The strong inhibitory role of IGF-IR on breast cancer cells aggressiveness for which E2-ERalpha signaling pathway seems to be essential, highlights IGF-IR as a major molecular target for novel therapeutic strategies.

The educational activities initiated by the International Medical Informatics Association (IMIA) have had global impacts and influenced national societies and local academic programs in the field of Biomedical and Health Informatics (BMHI). After the successful publication and dissemination of its educational recommendations, IMIA launched an accreditation procedure for educational programs in BMHI. The accreditation procedure was pilot tested by several BMHI academic programs in different countries and continents to obtain a global perspective. This paper presents an overview of IMIA quality assurance and accreditation procedures along with feedback on issues and problems which emerged during the pilot. It appears that IMIA quality assurance and procedures worked quite well in different countries of Europe, the Middle East, South America, and Asia. These first experiences provided adequate information for adapting, modifying, and optimizing the procedures and finally for the planning of future activities. IMIA accreditation framework comprises a single set of standards that apply at various levels to both academic and professional BMHI programs. The pilot phase confirmed the robustness and generalizability of quality assurance standards and associated procedures on which IMIA accreditation is based at an international level.

The updated version of the IMIA educational recommendations has given an adequate guidelines platform for developing educational programs in Biomedical and Health Informatics at all levels of education, vocational training, and distance learning. This chapter will provide a brief introduction of the recommendations pinpointing aspects for developing and assessing educational programs. We will provide a review of the existing feedback we have acquired during the IMIA site visits of accrediting educational programs at a worldwide level and discuss implementations issues. A brief overview of existing academic programs in Europe, North America and in other regions, especially for programs related to Nursing and to Nursing Informatics is provided. Finally, we will draw conclusions as how the IMIA recommendations may be required to be fitted into the specific needs of the Nursing Informatics and the needs of the Nursing professionals when they apply the recommendations to their academic and/or hospital/professional environments.

The randomized phase 3 ENDEAVOR study (N=929) compared carfilzomib and dexamethasone (Kd) with bortezomib and dexamethasone (Vd) in relapsed multiple myeloma (RMM). We performed a subgroup analysis from ENDEAVOR in patients categorized by number of prior lines of therapy or by prior treatment. Median progression-free survival (PFS) for patients with one prior line was 22.2 months for Kd vs 10.1 months for Vd, and median PFS for patients with ≥2 prior lines was 14.9 months for Kd vs 8.4 months for Vd. For patients with prior bortezomib exposure, the median PFS was 15.6 months for Kd vs 8.1 months for Vd, and for patients with prior lenalidomide exposure the median PFS was 12.9 months for Kd vs 7.3 months for Vd. Overall response rates (Kd vs Vd) were 81.9 vs 65.5% (one prior line), 72.0 vs 59.7% (≥2 prior lines), 71.2 vs 60.3% (prior bortezomib) and 70.1 vs 59.3% (prior lenalidomide). The safety profile in the prior lines subgroups was qualitatively similar to that in the broader ENDEAVOR population. In RMM, outcomes are improved when receiving treatment with carfilzomib compared with bortezomib, regardless of the number of prior therapy lines or prior exposure to bortezomib or lenalidomide. © 2017 Macmillan Publishers Limited, part of Springer Nature.

The randomized phase 3 ENDEAVOR study (N=929) compared carfilzomib and dexamethasone (Kd) with bortezomib and dexamethasone (Vd) in relapsed multiple myeloma (RMM). We performed a subgroup analysis from ENDEAVOR in patients categorized by number of prior lines of therapy or by prior treatment. Median progression-free survival (PFS) for patients with one prior line was 22.2 months for Kd vs 10.1 months for Vd, and median PFS for patients with ≥2 prior lines was 14.9 months for Kd vs 8.4 months for Vd. For patients with prior bortezomib exposure, the median PFS was 15.6 months for Kd vs 8.1 months for Vd, and for patients with prior lenalidomide exposure the median PFS was 12.9 months for Kd vs 7.3 months for Vd. Overall response rates (Kd vs Vd) were 81.9 vs 65.5% (one prior line), 72.0 vs 59.7% (≥2 prior lines), 71.2 vs 60.3% (prior bortezomib) and 70.1 vs 59.3% (prior lenalidomide). The safety profile in the prior lines subgroups was qualitatively similar to that in the broader ENDEAVOR population. In RMM, outcomes are improved when receiving treatment with carfilzomib compared with bortezomib, regardless of the number of prior therapy lines or prior exposure to bortezomib or lenalidomide. © 2017 Macmillan Publishers Limited, part of Springer Nature.

Aims: The histidine-rich calcium-binding protein (HRC) Ser96Ala variant has previously been identified as a potential biomarker for ventricular arrhythmias and sudden cardiac death in patients with idiopathic dilated cardiomyopathy. Herein, the role of this variant in cardiac pathophysiology is delineated through a novel mouse model, carrying the human mutation in the homologous mouse position. Methods and results: The mouse HRC serine 81, homologous to human HRC serine 96, was mutated to alanine, using knock-in gene targeting. The HRC-Ser81Ala mice presented increased mortality in the absence of structural or histological abnormalities, indicating that early death may be arrhythmia-related. Indeed, under stress-but not baseline-conditions, the HRC-Ser81Ala mice developed ventricular arrhythmias, whilst at the cardiomyocyte level they exhibited increased occurrence of triggered activity. Cardiac contraction was decreased in vivo, ex vivo, and in vitro. Additionally, Ca2+ transients and SR Ca2+ load were both reduced suggesting that cytosolic Ca2+ overload is not the underlying proarrhythmic mechanism. Interestingly, total SR Ca2+ leak was increased in HRC-Ser81Ala cardiomyocytes, without an increase in Ca2+ spark and wave frequency. However, Ca2+ wave propagation was significantly slower and the duration of the associated Na/Ca exchange current was increased. Moreover, action potential duration was also increased. Notably, Ca2+/Calmodulin kinase II (CaMKII) phosphorylation of the ryanodine receptor was increased, whilst KN-93, an inhibitor of CaMKII, reduced the occurrence of arrhythmias. Conclusions: The homologous mutation Ser81Ala in HRC in mice, corresponding to Ser96Ala in humans, is associated with sudden death and depressed cardiac function. Ventricular arrhythmias are related to abnormal Ca2+ cycling across the SR. The data further support a role for CaMKII with the perspective to treat arrhythmias through CaMKII inhibition.

Purpose I will discuss the prospect of pharmaceutically enhancing human morality and decision making in such a way as to eliminate morally unjustifiable choices and promote desirable ones. Background Our species in the relatively short period since it has emerged has enormously advanced in knowledge, science, and technical progress. When it comes to moral development, the distance it has covered is almost negligible. What if we could medically accelerate our moral development? What if we could once and for all render our species totally immune to certain vices? Methodology I will examine whether pharmaceutically intervening in human morality would compromise the autonomy of moral agents. I will argue that the argument from the autonomy of the moral agent is neither stable nor convincing. Conclusions In the light of Kantian ethics we might consider moral enhancement by pharmaceutical means to be a perfect duty for moral agents.

Mitochondria are the powerhouses of cells and produce cellular energy in the form of ATP. Mitochondrial dysfunction contributes to biological aging and a wide variety of disorders including metabolic diseases, premature aging syndromes, and neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). Maintenance of mitochondrial health depends on mitochondrial biogenesis and the efficient clearance of dysfunctional mitochondria through mitophagy. Experimental methods to accurately detect autophagy/mitophagy, especially in animal models, have been challenging to develop. Recent progress towards the understanding of the molecular mechanisms of mitophagy has enabled the development of novel mitophagy detection techniques. Here, we introduce several versatile techniques to monitor mitophagy in human cells, Caenorhabditis elegans (e.g., Rosella and DCT-1/ LGG-1 strains), and mice (mt-Keima). A combination of these mitophagy detection techniques, including cross-species evaluation, will improve the accuracy of mitophagy measurements and lead to a better understanding of the role of mitophagy in health and disease.

Perturbation of mitochondrial function is a major hallmark of several pathological conditions and ageing, underlining the essential role of fine-tuned mitochondrial activity (Lopez-Otin et al., 2013). Mitochondrial selective autophagy, known as mitophagy, mediates the removal of dysfunctional and/or superfluous organelles, preserving cellular and organismal homeostasis (Palikaras and Tavernarakis, 2014; Pickrell and Youle, 2015; Scheibye-Knudsen et al., 2015). In this protocol, we describe a method for assessing mitophagy in the nematode Caenorhabditis elegans.

INTRODUCTION: Surgical site infections (SSIs) and especially organ/space infection (O/SI) after resection or ablation of liver tumors are associated with increased morbidity and mortality. A secondary blood stream infection (BSI) is considered an O/SI but the exact prevalence is unknown. We aimed to investigate the incidence of O/SI and BSIs in a cohort of consecutive patients after liver resection or ablation, to seek for a possible connection between them and to search for potential risk factors. MATERIALS AND METHODS: We reviewed all patients who underwent hepatic resection or intraoperative liver ablation between January 2012 and December 2016 in our department. We focused on age, gender, Child-Pugh score, preoperative biliary drainage, indication for surgery, type of resection, resection or ablation of tumor, need for bilioenteric reconstruction, additional procedure to hepatectomy, blood transfusion, operative time, postoperative admission to ICU, and antibiotic chemoprophylaxis. All positive cultures from intra-abdominal fluids and blood were recorded. O/SI and BSIs were diagnosed by the criteria set by Centers for Disease Control. All variables were compared between the group with O/SI and the group without infection. BSIs were associated with these infections also. RESULTS: Eighty-one consecutive patients with a mean age of 64 years were enrolled. Fifteen patients presented a positive culture postoperatively: intra-abdominal fluid in eight, blood cultures in six, and both blood and intra-abdominal fluid in one patient. The directly estimated incidence of O/SI amounted to 11.1%. Four blood cultures were secondary to O/SI, and the remaining two secondary to central line catheter. O/SI was diagnosed indirectly, through the BSI in an additional 4.9% of the patients, raising the incidence of SSI to 16%. Among the factors studied, only admission to the ICU was found to be statistically significant as a risk factor for the development of O/SI ( = 0.026). CONCLUSION: O/SI should be actively seeked for after liver surgery including blood cultures. Patients with affected physical status, comorbidities are in greater risk of developing O/SI.

In this paper, we discuss the correlation between isoseismal contour maps and gravity residual anomaly maps and how it might contribute to the characterization of vulnerable areas to earthquake damage, especially in urban areas, where the geophysical data collection is difficult. More specifically, we compare a couple of isoseismal maps that have been produced and published after the catastrophic earthquake of 7th September 1999 (5.9R) in Athens, the metropolis of Greece, with the residual map produced from the processing and data reduction of a gravity survey that has been carried out in the Athens basin recently. The geologic and tectonic regime of the Athens basin is quite complicated and it is still being updated with new elements. Basically it is comprised of four different geotectonic units, one of them considered as the autochthon. During the gravity investigation, 807 gravity stations were collected, based on a grid plan with spacing almost 1km, covering the entire basin and supported by a newly established gravity base network comprised by thirteen bases. Differential DGPS technique was used for the accurate measurement of all the gravity stations and bases coordinates. After the appropriate data reduction and the construction of the Complete Bouguer Anomaly map, we applied FFT filtering in order to remove the regional component and produce the Residual Anomaly Map. The comparison of the Residual Anomaly Map with the isoseismal contours revealed that the areas with the most damage because of the earthquake were located in the areas with the minimum values of the Residual Anomaly Map.

Aims: Organismal aging can be delayed by mutations that either activate stress responses or reduce the nutrient-sensing pathway signaling; thus, by using Drosophila melanogaster as an in vivo experimental screening platform, we searched for compounds that modulate these pathways. Results: We noted that oral administration of the glycogen synthase kinase 3 (Gsk-3) inhibitor 6-bromoindirubin-3′-oxime (6BIO) in Drosophila flies extended healthy life span. 6BIO is not metabolized in fly tissues, modulated bioenergetic pathways, decreased lipid and glucose tissue load, activated antioxidant and proteostatic modules, and enhanced resistance to stressors. Mechanistically, we found that the effects on the stress-responsive pathways were largely dependent on the activity of the transcription factor nuclear factor erythroid 2-related factor (Nrf-2). Genetic inhibition of Gsk-3 largely phenocopied the 6BIO-mediated effects, while high levels of Gsk-3 expression and/or kinase activity suppressed proteostatic modules and reduced flies' longevity; these effects were partially rescued by 6BIO. Also, 6BIO was found to partially reduce the 3-phosphoinositide-dependent protein kinase-1 (Pdpk1) activity, a major effector of the insulin/insulin-like growth factor-1 cell signaling pathways. Innovation: 6BIO exerts the unique property of increasing stress tolerance and in parallel partially suppressing the nutrient-sensing pathway signaling. Conclusion: Our findings suggest that the 6BIO scaffold can be used for the development of novel antiaging compounds. Antioxid. Redox Signal. 27, 1027-1047.

is a Gram negative bacterium that colonizes the stomach of almost half human population. It has evolved to escape immune surveillance, establishes lifelong inflammation, predisposing to genomic instability and DNA damage, notably double strand breaks. The epithelial host cell responds by activation of DNA damage repair (DDR) machinery that seems to be compromised by the infection. It is therefore now accepted that genetic damage is a major mechanism operating in cases of induced carcinogenesis. Here, we review the data on the molecular pathways involved in DNA damage and DDR activation during infection.

Both large-wildlife loss and climatic changes can independently influence the prevalence and distribution of zoonotic disease. Given growing evidence that wildlife loss often has stronger community-level effects in low-productivity areas, we hypothesized that these perturbations would have interactive effects on disease risk. We experimentally tested this hypothesis by measuring tick abundance and the prevalence of tick-borne pathogens ( and spp) within long-term, size-selective, large-herbivore exclosures replicated across a precipitation gradient in East Africa. Total wildlife exclusion increased total tick abundance by 130% (mesic sites) to 225% (dry, low-productivity sites), demonstrating a significant interaction of defaunation and aridity on tick abundance. When differing degrees of exclusion were tested for a subset of months, total tick abundance increased from 170% (only mega-herbivores excluded) to 360% (all large wildlife excluded). Wildlife exclusion differentially affected the abundance of the three dominant tick species, and this effect varied strongly over time, likely due to differences among species in their host associations, seasonality, and other ecological characteristics. Pathogen prevalence did not differ across wildlife exclusion treatments, rainfall levels, or tick species, suggesting that exposure risk will respond to defaunation and climate change in proportion to total tick abundance. These findings demonstrate interacting effects of defaunation and aridity that increase disease risk, and they highlight the need to incorporate ecological context when predicting effects of wildlife loss on zoonotic disease dynamics.

The subject of this work is the investigation of the interaction between groundwater and seismic waves, resulting in liquefaction of the soil, a particularly dangerous phenomenon. Therefore, estimates of liquefaction potential can significantly contribute to the prevention of such effects and consequently to reduction of the seismic risk. The study area is Cephalonia Island, the most earthquake prone region of Europe. A dataset consisting of seismic ambient noise, accelerograms and datasheet from geotechnical boreholes, obtained after the 2014 earthquake crisis, has been analysed using a series of methodologies. Ambient noise analysis provided amplification functions, Vs30 models and synthetic time histories for numerous sites across the 2014 epicentral area. These were used for the seismic site characterization across the western part of the island and the estimation of the liquefaction potential in the coastal areas of Argostoli and Lixouri, where liquefaction phenomena were observed after the occurrence of the two strongest earthquakes in 2014. The results of the analyses are found to be compliant with the overall arrangement of the 2014 secondary earthquake effects, implying for strong site effects and interaction with the groundwater.

Research has shown that frequent, intense, and poorly resolved conflict between parents relates to adolescents’ adjustment problems but the mechanisms that explain such a link have not been fully uncovered. In this prospective study, we relied on the spillover hypothesis and investigated through an integrated multi-informant model whether maternal psychological control would account for the associations between interparental conflict and adolescents’ relational aggression and loneliness. Participants were 527 Turkish adolescents (M age = 14.36 years, SD = 0.33) and 307 mothers (M age = 41.18 years, SD = 4.47). Analyses through structural equation modeling indicated that interparental conflict (as assessed by both the adolescents and their mothers) related positively to maternal psychological control (as assessed again by both of them) which in turn predicted adolescent-reported relational aggression and loneliness, 8 months later. These findings are in line with the spillover hypothesis and show that dysfunctional relationships between parents are related to poor parenting practices and in turn to adolescents’ maladjustment.

Long period pulsars (P> 1000 s) constitute a sub-population ofhigh-mass X-ray binaries. To date, only a few of these rare systems,which occupy the tail of the spin period distribution of X-ray pulsars,have been discovered. Nevertheless, their study offers unique insightsinto evolutionary scenarios of the high-mass X-ray binary population. Wepropose four XMM-Newton observations aiming at improving our understandingof long period pulsars. The proposed observations will be performedto two systems located in the Large Magellanic Cloud with known spinperiods for studying their spin evolution, and two new candidate longperiod pulsars in order to increase the number of known systems.

The research aim of this study is to investigate the perceived innovation of the Big Data Technology in Healthcare. A survey was conducted using a theoretical model based on Rogers' Innovation Diffusion Theory, on Davis' Technology Acceptance Model, and relative research work. The results reveal that the Big Data Technology may be an innovation on the field of Health Informatics as it offers a lot of advantages compared to the traditional ways of data handling and processing, and it is compatible with the current technological status on the healthcare domain. Additionally, the current study presents the positive attitude of the Informatics Experts about the usage of the Big Data innovative technology on Health sector.

BACKGROUND: Age-related macular degeneration (AMD) is a multifactorial degenerative ocular disease that leads to loss of central vision. Functional gene polymorphisms have already been associated with the disease (for example, ARMS2 A69S, rs10490924). AIM: The goal of our study was to verify the correlation of the aforementioned ARMS2 variation with the disease, to examine, for the first time, the role of the CD14 C260T variation (rs2569190), and to investigate the association of two TLR4 polymorphisms (Asp299Gly or rs4986790 and Thr399Ile or rs4986791) in a Greek population with the wet form of AMD. PATIENTS AND METHODS: Genomic DNAs were isolated from blood samples of 103 healthy controls and 120 Greek patients with wet AMD who were age- and sex-matched, and all of whom were clinically evaluated. For the genotyping of all selected polymorphisms, polymerase chain reaction-restriction fragment length polymorphism analysis was performed. RESULTS AND CONCLUSIONS: This study confirmed the association between the ARMS2 variation and AMD, detecting the T risk allele in a significantly higher frequency in the patient group, compared with the control subjects (45% vs 29.13%, P<0.001, odds ratio [OR] 1.99, confidence interval 1.34-2.95). For the CD14 polymorphism, no statistically significant correlation was observed. As for the TLR4 polymorphisms, the percentage of heterozygotes increased from 2.9% to 11.7% in the patient population for Asp299Gly and from 1.9% to 10% for the Thr399Ile polymorphism (ORs 4.40 [P=0.01] and 5.61 [P=0.0088], respectively). Although our ARMS2 and CD14 results provided definite conclusions, the role of innate immunity TLR4 gene awaits further investigation in larger AMD populations with more clinical data collected on past microbial infections

Background Ageing is defined as the time-dependent decline of functional capacity and stress resistance resulting in increased morbidity and mortality. Hypothesis/Purpose Reportedly, these effects can be delayed by mild genetic or pharmacological activation of the main modules of the proteostasis network. Study Design-Methods By employing advanced phytochemical methods we isolated natural products from the fruits of Platanus orientalis and studied (via a bio-guided approach) their effects in Drosophila flies, as well as in normal human fibroblasts. Results We report herein that dietary administration in Drosophila flies of a phenolics-enriched methanol extract from the fruits of Platanus orientalis exerted antioxidant effects; activated proteostatic mechanisms and mildly extended flies' longevity. We then isolated the two major compounds of the extract, namely Platanoside and Tiliroside and found that enrichment of the total extract with these compounds decreased oxidative stress and (in the case of the Tiliroside enriched extract) activated proteostatic mechanisms. Administration of purified Tiliroside in flies activated proteostatic genes, enhanced proteasome and lysosomal-cathepsin activities and decreased tissues' oxidative load; moreover, it delayed the rate of age-related decrease in flies' locomotion activity and increased flies' longevity. Notably, Tiliroside also activated proteasome in normal human fibroblasts and delayed progression of cellular senescence indicating that it may also impact on human cells rate of senescence. Conclusion Our presented findings highlight the potential anti-ageing activity of naturals products derived from the fruits of P. orientalis.

Objectives: we present seismic and geodetic data analysis of the shallow, normal-faulting earthquake sequence offshore Lesvos (Aegean Sea, Greece) that was initiated by the June 12, 2017 M6.3 earthquake.Methods and Results: We use seismological data (relocated events and Moment Tensor solutions from NOA and KOERI catalogues) to identify the ESE-WNW striking seismic fault and to refine its geometry and kinematics using inversion techniques. Despite the large magnitude of the mainshock (M6.3), the surface deformation is not visible with InSAR because of the offshore occurrence of theearthquake. However, cm-size co-seismic horizontal offsets were recorded by the continuous GPS stations (of two private networks) operating at both Lesvos and Chios islands. In Sentinel co-seismic interferograms (C-band) we see no co-seismic displacements within ±0.3-0.5 fringe (±10mm). There are two local InSAR displacement patterns close to Plomari, possibly attributed to slope instabilities, which require further investigation. Lack of signal coherence was detected in the area of village Vrissa, that was heavily damaged by the earthquake.Conclusions: The spatial distribution of relocated events shows the activation of one fault with a total length of about 20 km, at depths 5-15 km. The fault-dip direction is not retrievable from GPS/InSAR but a south-dip is inferred from the aftershocks distribution and sea-bottom geomorphology. The absence of visible InSAR signal is consistent with the slip-model predictions, based on the GPS models.

K-ras oncogene is a key factor in colorectal cancer. Based on published and our data we propose that K-ras could be the oncogene responsible for the inactivation of the tumor-suppressor gene APC, currently considered as the initial step in colorectal tumorigenesis. K-ras fulfills the criteria of the oncogene-induced DNA damage model, as it can provoke well-established causes for inactivating tumor-suppressors, i.e. DNA double-strand breaks (causing allele deletion) and ROS production (responsible for point mutation). The model we propose is a variation of the currently existing model and hypothesizes that, in a subgroup of colorectal carcinomas, K-ras mutation may precede APC inactivation, representing the earliest driving force and, probably, an early biomarker of colorectal carcinogenesis. This observation is clinically useful, since it may modify the preventive colorectal cancer strategy, restricting numerically patients undergoing colonoscopies to those bearing K-ras mutation in their colorectum, either in benign polyps or the normal accompanying mucosa.

PURPOSE: Fetuin-A and adiponectin, major hepatokine and adipokine respectively, have been implicated in systematic inflammation. Our aim was to jointly investigate whether kinetics of circulating fetuin-A, adiponectin and its isoform HMWA predict 28-day mortality in sepsis. MATERIALS AND METHODS: In a prospective study, serum fetuin-A, adiponectin and HMWA were determined in 102 ICU patients fulfilling the diagnostic criteria of SEPSIS-3, at enrollment and one week after, and in 102 healthy controls matched on age and gender. RESULTS: Serum fetuin-A was significantly lower in septic patients than controls (p<0.001). Among septic patients, those with septic shock and nonsurvivors presented lower fetuin-A, but higher adiponectin and HMWA compared to patients with sepsis and survivors respectively, both at baseline and day 7 (p<0.001). Fetuin-A exhibited negative correlations with APACHE II, CRP, procalcitonin, adiponectin and IL-6 but a positive one with albumin. Reduced fetuin-A as well as lower serum kinetics of fetuin-A (HR: 0.55, 95% C.I. 0.34-0.91, p=0.02), adiponectin but not HMWA were independently associated with 28-day mortality adjusting for age, gender, BMI, APACHE II, septic shock and laboratory biomarkers. CONCLUSIONS: Circulating fetuin-A kinetics may be a prognostic biomarker in septic patients. More research is essential to elucidate fetuin-A's ontological role in sepsis pathophysiology.

Behavioral analysis in preclinical neuropsychopharmacology relies on the accurate measurement of animal behavior. Several excellent solutions for computer-assisted behavioral analysis are available for specialized behavioral laboratories wishing to invest significant resources. Herein, we present an open source straightforward software solution aiming at the rapid and easy introduction to an experimental workflow, and at the improvement of training staff members in a better and more reproducible manual scoring of behavioral experiments with the use of visual aids-maps. Currently the program readily supports the Forced Swim Test, Novel Object Recognition test and the Elevated Plus maze test, but with minor modifications can be used for scoring virtually any behavioral test. Additional modules, with predefined templates and scoring parameters, are continuously added. Importantly, the prominent use of visual maps has been shown to improve, in a student-engaging manner, the training and auditing of scoring in behavioral rodent experiments.

Behavioral analysis in preclinical neuropsychopharmacology relies on the accurate measurement of animal behavior. Several excellent solutions for computer-assisted behavioral analysis are available for specialized behavioral laboratories wishing to invest significant resources. Herein, we present an open source straightforward software solution aiming at the rapid and easy introduction to an experimental workflow, and at the improvement of training staff members in a better and more reproducible manual scoring of behavioral experiments with the use of visual aids-maps. Currently the program readily supports the Forced Swim Test, Novel Object Recognition test and the Elevated Plus maze test, but with minor modifications can be used for scoring virtually any behavioral test. Additional modules, with predefined templates and scoring parameters, are continuously added. Importantly, the prominent use of visual maps has been shown to improve, in a student-engaging manner, the training and auditing of scoring in behavioral rodent experiments.

BACKGROUND: Despite great improvements in prevention over the last years, much has to be done to reduce new human immunodeficiency virus (HIV) infections. Substantial evidence shows that the six-month period of recent HIV infection contributes disproportionately to HIV transmission. OBJECTIVE: This study aims to investigate knowledge, normative beliefs, and attitudes of people who inject drugs (PWID) regarding recent HIV infection. METHODS: People who inject drugs in Athens, Greece were recruited in the fifth round of a respondent- driven sampling program (ARISTOTLE). The participants were tested for HIV and answered a structured questionnaire, which also included items on knowledge, normative beliefs, and attitudes regarding recent infection to address needs of the social network-based Transmission Reduction Intervention Project. The multivariable analyses included logistic regression models, which produced odds ratios (OR) and 95% confidence intervals (CI). RESULTS: In total, 1,407 people (mean age: 36.3 +/- 7.9 years old; males: 81.9%) took part in the fifth round of ARISTOTLE. Of these, 61.5% knew that HIV-infected people who are not on treatment are more likely to transmit HIV during the first six months of their infection and 58.4% reported that people in their network would react positively towards a recently HIV-infected person. People who inject drugs who were knowledgeable of recent HIV infection were more likely to disagree with statements such as that one should avoid all contact with a person recently infected by HIV (adjusted OR: 1.510, 95% CI: 1.090, 2.091) or more likely to agree with statements such as that an HIV+ person is much less likely to transmit HIV when h/she is on combination antiretroviral treatment (adjusted OR: 2.083, 95% CI: 1.231, 3.523). CONCLUSION: A considerable proportion of PWID in Athens, Greece, were aware of the high HIV transmission risk of recent HIV infection, although improvement is needed for some population segments. People who inject drugs who were knowledgeable of the role of recent HIV infection were more likely to have normative beliefs and attitudes that favor behaviors that could help rather than harm or stigmatize people who have recently been infected with HIV. Interventions that are based on the role of recent HIV infection in HIV transmission could be important to HIV prevention.

Resumen: El presente trabajo se centra en la enseñanza del léxico del español como lengua extranjera. En concreto, se explican las razones por las cuales el tratamiento léxico debe formar parte de la enseñanza de ELE y debe ser programado, organizado y sistemático. Asimismo, se exponen diferentes perspectivas metodológicas de su presentación en el aula. Finalmente, se ofrecen algunas propuestas de tipo didáctico que pueden servir de apoyo y orientación a los docentes implicados en la enseñanza del léxico a aprendientes griegos de español.  

En 1946, des enseignants de l’Institut français d’Athènes, saisis par l’inefficacité de la méthodologie traditionnelle employée en Grèce pour l’enseignement du français, mirent au point, avec l’appui du directeur de l’établissement, une stratégie d’apprentissage « adaptée » aux besoins des débutants : la « méthode orale » inspirée de la méthodologie directe. L’application de la nouvelle méthode nécessita la préparation d’un matériel d’appoint, ainsi que l’organisation de stages pédagogiques et de perfectionnement à l’intention des maîtres de français en herbe et en exercice. Grâce à des stratégies efficaces de diffusion, la « méthode orale » bénéficia en Grèce et en France d’une reconnaissance pédagogique certaine et servit à son tour de source d’inspiration à d’autres institutions culturelles françaises en Europe. Bel exemple à la fois de transfert d’une pratique enseignante et d’ajustement de ses procédés et supports pédagogiques au sein de différentes institutions d’accueil, elle finit par disparaître du paysage éducatif hellénique en 1961. In reaction to the ineffectiveness of the traditional methodology used in Greece for the teaching of the French language, a group of teachers of the French Institute of Athens developed in 1946 a new learning strategy more suitable for the needs of the beginners : the so called “oral method” had been inspired from the direct method. The implementation of the new method required the development/production of materials, as well as the organization of pedagogical courses for aspiring and confirmed teachers of French. Thanks to the use of effective strategies of diffusion, the “oral method” was acknowledged as a valid pedagogical method and became a source of inspiration for other cultural institutions in Europe. It ceased to be used in Greece in 1961.

A coastal and submarine geomorphological investigation took place in the coasts of eastern Attica, aiming to identify palaeoshorelines. Former sea-level positions were deduced from emerged and submerged tidal notches. Eight fossil shorelines were deduced in the study area; two emerged ones at about +24 ± 30 and +40 ± 30 cm, and six submerged ones at about −22 ± 30 (modern), −40 ± 30, −60 ± 30, −80 ± 30, −130 ± 30 and −460 ± 30 cm. It is worth mentioning that a rather different tectonic behavior may be distinguished between the south (AT1-AT5) and the north (AT10-AT28) part of the study area.

In this paper the tectonic behavior of Leukas and Meganisi islands (Ionian Sea) is examined through underwater research carried out in both islands. A possible Late Holocene correlation between coseismic subsidences is attempted and evidenced by submerged tidal notches in both islands. These subsidence events probably occurred after the uplift that affected the northernmost part of Leukas around 4 to 5ka BP. In conclusion, although the whole area was affected by a similar tectonic strain, certain coseismic events were only recorded in one of the two islands and in some cases they affected only part of the study area.

INTRODUCTION: True Left-sided gallbladder (LSG) is a rare anatomical variation with a prevalence of 0.3%. Mainly discovered during the operation, its surgical approach in the laparoscopic setting may be challenging even for an experienced surgeon. PRESENTATION OF CASE: LSG was unexpectedly discovered in a young man during laparoscopic cholecystectomy. There were no pre-operative indications of this sinistroposition. The laparoscopic cholecystectomy was performed with minor surgical modifications and it was uneventful. A meticulous review of recent literature about LSGs was conducted as well. DISCUSSION: LSG is a scarce anatomical aberration that is difficultly identified pre-operatively. Surgeons should be aware of this aberration and of its accompanying anatomical variations in order to perform a safe laparoscopic cholecystectomy. CONCLUSION: Surgeons, by placing the patient to left-side up position, are able to expose the Calot's triangle and possible accompanying anatomical anomalies and thus perform a safe laparoscopic cholecystectomy without difficult surgical modifications.

Legionella pneumophila infects human alveolar macrophages and is responsible for Legionnaire's disease, a severe form of pneumonia. L. pneumophila encodes more than 300 putative effectors, which are translocated into the host cell via the Dot/Icm type IV secretion system. These effectors highjack the host's cellular processes to allow bacterial intracellular growth and replication. Here we adopted a multidisciplinary approach to investigate WipB, a Dot/Icm effector of unknown function. The crystal structure of the N-terminal domain at 1.7 A resolution comprising residues 25 to 344 revealed that WipB harbours a Ser/Thr phosphatase domain related to the eukaryotic phospho-protein phosphatase (PPP) family. The C-terminal domain (residues 365-524) is sufficient to pilot the effector to acidified LAMP1-positive lysosomal compartments, where WipB interacts with the v-ATPase and the associated LAMTOR1 phosphoprotein, key components of the lysosomal nutrient sensing (LYNUS) apparatus that controls the mammalian target of rapamycin (mTORC1) kinase complex at the lysosomal surface. We propose that WipB is a lysosome-targeted phosphatase that modulates cellular nutrient sensing and the control of energy metabolism during Legionella infection.

INTRODUCTION: Leiomyomatosis peritonealis disseminata (LPD) is a peculiar benign clinical disorder characterized by proliferation of peritoneal and subperitoneal nodules. LPD is a difficultly diagnosed benign disease that rarely degenerates into malignancy. PRESENTATION OF CASE: A 40-year-old Caucasian female with vaginal bleeding proceeded to our institution for elective excision of abdominal and pelvic masses which were firstly considered as leiomyosarcomas. The histologic diagnosis of the mass lesions revealed smooth muscle benign cells. This is the first case of LPD reported in Greece. A meticulous review of the literature was conducted as well. DISCUSSION: The differential diagnosis of LPD is difficult due to its clinical resemblance with peritoneal carcinomatosis or metastatic lesions and with benign metastasizing leiomyoma (BML) as well. Etiological factors, pathophysiology and clinical manifestations which lead to a safe diagnosis of LPD are adequately described. CONCLUSION: Surgeons' thorough knowledge concerning this rare clinical condition is fundamental and crucial in order to establish a correct diagnosis and assert the appropriate treatment and the minimization of the probability of malignant transformation of LPD.

Hemorrhoids are a common anal disorder which affects both men and women of all ages. One out of ten patients with hemorrhoidal disease, requires surgical treatment. Unfortunately though, hemorrhoidectomy is closely related to complications that can be present early or late postoperatively. In the present manuscript, the safe surgical technique which emphasizes to the identification of the key anatomical structure of the ligament of Parks (Trietz's muscle) is adequately described. A total of 200 patients with grades III and IV hemorrhoids, underwent Milligan-Morgan or Ferguson's hemorrhoidectomy. The mucosal ligament of Parks was identified to all patients and was used as a key anatomical structure through the excision of the hemorrhoids. Its identification guides surgeons during the operation and reduces the major problem of postoperative complications. Finally, since the mucosal ligament of Parks represents a constantly identifiable landmark, it allows simple and reliable identification of the internal sphincter muscle and minimizes the probability of postoperative complications.

There is little morphological evidence for little v as a verbalizing head in the literature. Greek, however, exhibits systematic verbalizing morphology and provides us with a strong case study for a robust morphophonological manifestation of the verbalizing v head. Evidence comes from the second-conjugation verbs (e.g., aɣap-ó ‘I love’, ster-ó ‘I deprive’), which display certain distinct morphophonological properties: (a) they take a vocalic extension in certain forms (e.g., aɣáp-i-s-a ‘I loved’) and (b) they exhibit post-root stress, unlike other verb forms (e.g., miní-o ‘I sue’, pal-év-o ‘I fight’). Following Spyropoulos et al. (2015), we argue that both characteristics reflect the morphophonological effects of the exponence of a verbalizing head v by means of an empty vocalic element  V. Furthermore, we provide evidence that a set of verbalizers, almost exclusively identified with a number of derivational suffixes (e.g., -ev, -iz, -(i)az, -on, -ar and -en), are also exponents of this verbalizing v head which is distinct from Voice, is not correlated with agentivity, transitivity and inner aspect / Aktionsart, and, more importantly, do not follow the second conjugation pattern. We propose that the abstract vocalic slot and the verbal derivational suffixes compete for the same morphosyntactic position and that they are both exponents of the verbalizing head v. 

The ability for effective, accurate and precise thermoregulation is of paramount importance for ectotherms. Sympatric lizards often partition their niche and select different microhabitats. These microhabitats, however, usually differ in their thermal conditions and lizards have to adapt their thermoregulation behavior accordingly. Here, we evaluated the impact of habitat partitioning on the thermal biology of three syntopic, congeneric lacertids (Podarcis peloponnesiacus, P. tauricus and P. muralis) from central Peloponnese, Greece. We assessed thermoregulation effectiveness (E) using the three standard thermal parameters: body (Tb), operative (Te) and preferred (Tpref) temperatures. We hypothesized that the microhabitats used by each species would differ in thermal quality. We also predicted that all species would effectively thermoregulate, as they inhabit a thermally challenging mountain habitat. As expected, the partition of the habitat had an effect on the thermoregulation of lizards since microhabitats had different thermal qualities. All three species were effective and accurate thermoregulators but one of them achieved smaller E values as a result of the lower Tb in the field. This discrepancy could be attributed to the cooler (but more benign) thermal microhabitats that this species occupies.

The aftermath of the Second World War is characterized by an intense intellectual activity that influences all academic fields: literature, art, philosophy…Greece, a small, devastated country, just emerging out of a long, bitter Civil War, contributes to that intellectual movement with whatever meager means possible. However, this intellectual progress is closely observed and followed by the majority of Greek scholars of the time. The Greek intelligentsia, submerged to a great extent in the French language and culture, is clearly affiliated with France which has, after all, been for centuries the hotbed of ideological currents that have drastically shaped the face of modern culture. Consequently, the lack of original creation on the part of Greece is successfully substituted by a great number of works translated from the French language. Amongst the great writers presented to the Greek readership Simone De Beauvoir holds a prominent position. De Beauvoir has enjoyed special recognition from the very start, not being overshadowed to the least by her equally brilliant partner Jean-Paul Sartre, who was one of the most eminent philosophers of his time. The current study intends, on a first level, to depict the various landmarks of the reception awaiting Simone De Beauvoir’s work in Greece. Moving on, our analysis will focus on her basic philosophic essay: The Second Sex. This work is of special interest since it has been repeatedly translated and published in Greece. It is surprising to observe that even this year a new edition of this particular book has come out. A detailed juxtaposition between the prototype and the various Greek translations will help us to observe any omissions, additions or even alterations. Bearing in mind certain vital criteria—the translators’ personalities, their target groups throughout time and the sociopolitical milieu these translations took place in—we will attempt to shed light to the underlying importance of this phenomenon. This is a research that, based on material drawn from the press, the publishing houses and the national archives, highlights the great influence this great thinker had on Greece’s ideological progress.La période qui suit la fin de la Seconde Guerre mondiale est marquée, dans lemonde occidental, par une intense fermentation intellectuelle qui touche tous les domaines de l’esprit : la littérature, l’art, la philosophie... La Grèce, petit pays qui sort ruiné d’une longue guerre civile de quatre ans, apporte une faible contribution à ce mouvement qu’elle suit, tout de même, avec un vif intérêt. L’intelligentsia grecque, formée pour la plupart dans la langue et la culture françaises, est particulièrement tournée vers la France, foyer, depuis des siècles, de courants idéologiques qui ont façonné la physionomie de la civilisation contemporaine. Aussi, le manque d’une création originale est-il compensé par un foisonnement d’oeuvres traduites du français. Parmi les grands auteurs présentés au public grec, Simone de Beauvoir tient une place éminente. Bien que compagne de Jean-Paul Sartre, l’un des plus célèbres esprits de son époque, cette femme de lettres jouit, de prime abord, d’une reconnaissance tout à fait remarquable. Cette étude fait état de la réception de l’oeuvre de Simone de Beauvoir en Grèce et notamment de l’accueil réservé au Deuxième Sexe entre 1949 – année de la parution de la première traduction de cet ouvrage - et 2009 – année de la publication de sa dernière version grecque. Dans une première partie l’analyse porte sur la diffusion de l’oeuvre de la philosophe et distingue deux temps forts : 1949, fin de la guerre civile sanglante amorcée au lendemain de la Seconde Guerre mondiale et 1974, année de la restauration de la République en Grèce après la chute de la junte. Ces moments de rupture avec le passé coïncident avec la parution d'une nouvelle traduction du Deuxième Sexe ce qui est significatif de sa modernité. La deuxième partie de ce travail est consacrée à l’examen des diverses traductions de cette oeuvre importante de Simone de Beauvoir : celle, fragmentaire, de 1949, presque simultanée à la publication du premier volume en France ; celle de 1958, raccourcie dans un effort de rendre l’oeuvre plus accessible au public grec ; celle de 1979, intégrale mais prenant appui non pas sur le texte français mais sur la traduction américaine ; celle, enfin, de 2009, qui est d’ailleurs la plus fidèle à l’original. Inséparables des questions de réception, ces textes accompagnés de notes et d’avant-propos font surgir des questionnements sur la complexité des transferts culturels. En somme, à l’appui de documents puisés dans la presse, chez les éditeurs, aux Archives Nationales, la recherche révèle l’impact important de la pensée beauvoirienne sur l’évolution des idées dans notre pays. H περίοδος που ακολουθεί το τέλος του Δευτέρου Παγκοσμίου Πολέμου σημαδεύεται, στον δυτικό κόσμο από μια έντονη πνευματική ζύμωση που αγγίζει όλους τους τομείς του πνεύματος: τη λογοτεχνία, την τέχνη, τη φιλοσοφία… Η Ελλάδα, μικρή χώρα, που εξέρχεται ρημαγμένη από ένα μακροχρόνιο εμφύλιο πόλεμο, συνεισφέρει με τα πενιχρά της μέσα σε αυτή την κίνηση την οποία ωστόσο παρακολουθεί με ζωηρό ενδιαφέρον. Η ελληνική ιντελλιγγέντσια, διαποτισμένη σε μεγάλο βαθμό με τη γαλλική γλώσσα και κουλτούρα, είναι στραμμένη προς τη Γαλλία, η οποία από εδώ και αιώνες υπήρξε η εστία ιδεολογικών ρευμάτων που διαμόρφωσαν τη φυσιογνωμία του σύγχρονου πολιτισμού. Επομένως, η έλλειψη πρωτότυπης δημιουργίας αντισταθμίζεται από ένα μεγάλο αριθμό έργων μεταφρασμένων από τα γαλλικά.  Ανάμεσα στους μεγάλους συγγραφείς που παρουσιάζονται στο ελληνικό κοινό, η Σιμόν ντε Μπωβουάρ κατέχει μια εξέχουσα θέση.  Αν και σύντροφος του Ζαν-Πωλ Σαρτρ, ενός από τα επιφανέστερα πνεύματα της εποχής, η γυναίκα αυτή των γραμμάτων απολαμβάνει ευθύς εξαρχής μία ιδιαίτερη αναγνώριση. Η παρούσα μελέτη προτίθεται, σε ένα πρώτο επίπεδο, να σκιαγραφήσει τους διάφορους σταθμούς της πρόσληψης του έργου της Σιμόν ντε Μπωβουάρ στην Ελλάδα. Στη συνέχεια, η ανάλυσή μας θα επικεντρωθεί στο βασικό φιλοσοφικό της δοκίμιο: Το Δεύτερο φύλο. Το έργο αυτό παρουσιάζει εξαιρετικό ενδιαφέρον διότι γνώρισε επανειλημμένες μεταφράσεις και εκδόσεις στην Ελλάδα. Ακόμα και εφέτος κυκλοφόρησε μια νέα μετάφραση. Μία λεπτομερής αντιπαραβολή ανάμεσα στο πρωτότυπο και στις διάφορες ελληνικές μεταφράσεις θα μας οδηγήσει στο να εντοπίσουμε τις παραλείψεις, τις προσθήκες και τις αλλοιώσεις.  Ξεκινώντας από ορισμένα κριτήρια – την προσωπικότητα των μεταφραστών και μεταφραστριών, το εκάστοτε κοινό τους και τις ιστορικές στιγμές όπου πραγματοποιήθηκαν αυτές οι μεταφράσεις – θα προσπαθήσουμε να φωτίσουμε την βαθύτερη σημασία αυτού του φαινομένου. Πρόκειται για μία έρευνα η οποία, στηριζόμενη σε υλικό που έχει αντληθεί από τον τύπο, από τους εκδοτικούς οίκους από τα εθνικά αρχεία, αναδεικνύει την μεγάλη επιρροή της στοχάστριας αυτής στην κίνηση των ιδεών στη χώρα.

The evolution of magnetism for graphene oxide (GO) before and after chemical reduction was investigated by means of static magnetization and electron spin resonance (ESR) spectroscopy. Strong paramagnetism with a saturation magnetization of ∼1.2 emu/g and weak antiferromagnetic interactions were identified in pristine GO. Apart from spin-half defect centers, ESR spectroscopy indicated the excitation of high spin states, consistently with the high spin (S = 2) magnetic moments derived from the magnetization analysis, corroborating the formation of spatially "isolated" magnetic clusters in GO. A marked reduction of GO's magnetization (∼0.17 emu/g) along with an appreciable rise of diamagnetism (-2.4 × 10-6emu/g Oe) was detected after chemical reduction by sodium borohydride, reflecting the drastic removal of paramagnetic defects and the concomitant growth of sp2 domains in reduced graphene oxide (rGO). ESR revealed a large drop of the spin susceptibility for rGO, which, in addition to the main paramagnetic Curie component, showed an appreciable Pauli contribution. The latter together with the g-factor shift and the broadening of the ESR line indicated the coupling of localized spins with conduction electrons. The rGO ESR signal presented a metallic line shape, which could be analyzed in terms of two separate spectral components, a broad one that may be related to defect states strongly coupled with itinerant spins within the sp2 clusters and a narrow one due to edge/vacancy defect spins, indicative of rGO's persistent structural inhomogeneity. © 2017 Author(s).

Mt Taygetos (2407m), located at southern Peloponnese (Greece) suffered a large fire during the summer of 2007. The fire burned approximately 45% of the area covered by the endemic Greek fir (Abies cephalonica) and Black Pine (Pinus nigra) forest ecosystems. The aim of the current study is to examine the potential differences on post-fire vegetation recovery imposed by the lithology as well as the geomorphology of the given area over sites of the same climatic and landscape conditions (elevation, aspect, slope etc.). The main lithologies consist of carbonate, permeable, not easily erodible formations (limestones and marbles) and clastic, impermeable (schists, slate and flysch) erodible ones. A time-series of high spatial resolution satellite images were interpreted, analyzed and compared in order to detect changes in vegetation coverage which could prioritize areas of interest for fieldwork campaigns. The remote sensing datasets were acquired before (Ikonos-2), a few months after (Quickbird-2) and some years after (Worldview-3) the 2007 fire. High resolution Digital Elevation Model was used for the ortho-rectification and co-registration of the remote sensing data, but also for the extraction of the mountainous landscape characteristics. The multi-temporal image dataset was analyzed through GEographic-Object Based Image Analysis (GEOBIA). Objects corresponding to different vegetation types through time were identified through spectral and textural features. The classification results were combined with basic layers such as lithological outcrops, pre-fire vegetation, landscape morphology etc., supplementing a spatial geodatabase used for classifying burnt areas with varying post-fire plant community recovery. We validated the results of the classification during fieldwork and found that at a local scale, where the landscape features are quite similar, the bedrock type proves to be an important factor for vegetation recovery, as it clearly defines the soil generation along with its properties. Plant species recovery seems to be controlled by the local lithology as it was found weaker in plots overlying limestones and marbles, comparing to that observed over schists, even for the same species. In conclusion, post-fire vegetation recovery seems to be a complex process controlled not only from species biology, but also from the geological features.

In this paper, we discuss the development and preliminary evaluation of a new educational tool, intended for noviceand advanced vocal students. The software, written in Max / MSP, aims to assist singing practice by providingusers with a visual substitute to their subjective auditory feedback. Under the guidance of their professional vocalinstructor, students can store in the software spectral representations of accurately produced sounds, creatingpersonalized Reference Sound Banks (RSBs). When students practice on their own, the software can be put intopractice, assisting them to match their current Voice Spectrum Harmonic Content to the stored RSBs one note at atime. Results of a preliminary evaluation showed that, when using this software, students achieve a larger numberof accurately produced sounds in a smaller amount of time.

This chapter describes how novice and experienced mathematics teachers integrate authentic workplace contexts into mathematics teaching. This goal is inspired by the European MaSciL project and introduced to the teachers in the context of a masters programme in mathematics education. Under an Activity Theory perspective, we use the notions of activity system and boundary crossing to study the process of teachers’ professional learning. In particular, we analyse teachers’ boundary crossings between two activity systems: mathematics teaching and workplace. Results indicate that collaborative task design and reflection made teachers combine elements from the workplace into mathematics teaching. Different ways of linking reality and mathematics teaching were identified in the modelling process in which the students were asked to be engaged.

NGC 300 ULX-1 is a newly identified ULX pulsar. The system has shown a extraordinary spin up rate within the last year, when it spun-up from 31 sec to 20 sec. We request 2x10 ks chandra observations separated by 2-4 days in order to accurately measure the spin up rate of the pulsar.

Malgré quarante années d’une recherche féconde autant que chaotique, l’histoire de la participation féminine à la Résistance française vue d’en bas recèle encore ses zones d’ombre. Le présent travail se propose d’en apporter un éclairage particulier sur un aspect spécifique mais non moins important pour appréhender la diversité de la contribution de femmes en guerre : sa composante universitaire. Intimement liée aux notions de devoir et de transgression, d’héroïsme et de modestie, de transmission et de mémoire, la mobilisation des professeures de l’enseignement secondaire contre l’ennemi, abordée ici par le biais des récits chargés de véhiculer son souvenir, est notamment intéressante par les paradoxes qu’elle engendre et la dimension supplémentaire qu’elle comporte : la « résistance de l’esprit ». L’ambition du propos est multiple : montrer, tout d’abord, à travers l’approche genrée d’un cas particulier et la spécificité d’une situation professionnelle, la complexité de l’histoire de l’engagement et du sacrifice féminin en temps de guerre et, par là même, suggérer une clé de lecture complémentaire du phénomène résistant ; ouvrir, ensuite, un questionnement sur les enjeux de mémoire au moyen d’un fonds mémoriel enrichi et diversifié au fil des ans ; dégager, enfin, des figures héroïques toutes auréolées du sacrifice accompli et tenter de saisir la complexité identitaire des professeures patriotes. L’histoire de la mémoire rejoint ainsi dans ce propos celle des représentations.

The absence of an epistemologically founded geopolitical analysis method that has been internationally observed was the motivation for writing the following contribution. The paper is divided into two parts: i) Definitions and Example analysis and ii) Determination of the Lakatosian Structure of the Systemic Geopolitical Analysis.

Somatic embryos of carob tree (Ceratonia siliqua L.) were induced from segments excised from immature seeds when cultured on Murashige and Skoog (M.S.) medium supplemented with a gradient of concentrations of 6-benzylaminopurine (BA). Roots and shoots were also formed in the same media. Besides culture media composition, the developmental stage of the explants showed a strong influence on somatic embryogenesis, with embryos and cotyledons providing high levels of induction; thus, elevated frequencies of development occurred on culture media containing various concentrations of BA. The presence of morphologically normal and abnormal somatic embryos was also observed. Upon transfer into full- and half-strength M.S. medium supplemented with sucrose (3%), plantlets were coming through embryos. Attempts to induce embryogenic callus from immature seeds of carob tree were successful. The resulting outgrowths were very high in embryogenetic potential from green immature seeds of carob tree and expants transferred into M.S. enriched with B.A. developed a large number of somatic embryos.

Proteasome inhibitors, e.g. Bortezomib (BTZ) and Carfilzomib (CFZ), have demonstrated clinical efficacy against haematological cancers. Interestingly, several adverse effects are less common, compared to BTZ, in patients treated with CFZ. As the molecular details of these observations remain not well understood we assayed the pathophysiological effects of CFZ vs. BTZ in the Drosophila experimental model. Mass Spectrometry analyses showed that neither CFZ nor BTZ are hydrolysed in flies' tissues, while at doses inducing similar inhibition of the rate limiting for protein breakdown chymotrypsin-like (CT-L) proteasomal activity, CFZ treatment resulted in less intense increase of oxidative stress or activation of antioxidant and proteostatic modules. Also, despite comparable cardiotoxicity likely due to disrupted mitochondrial function, CFZ did not affect developmental processes, showed minimal neuromuscular defects and reduced to a lesser extent flies' healthspan. Studies in flies, human cancer cell lines and blood cells isolated from Multiple Myeloma patients treated with CFZ or BTZ revealed, that the increased BTZ toxicity likely relates to partial co-inhibition of the caspase-like (C-L) proteasomal activity Supportively, co-treating flies with CFZ and a C-L selective proteasome inhibitor exacerbated CFZ-mediated toxicity. Our findings provide a reasonable explanation for the differential adverse effects of CFZ and BTZ in the clinic.

BACKGROUND: Despite the favourable survival rates of childhood acute lymphoblastic leukaemia (ALL), a significant number of patients present resistance to antileukaemic agents and dismal prognosis. In this study, we analysed miR-125b expression in childhood ALL and evaluated its clinical utility for patients treated with Berlin-Frankfurt-Munster (BFM) protocol. METHODS: The study included 272 bone marrow specimens obtained on diagnosis and on BFM day 33 from 125 patients and 64 healthy children. Following extraction, RNA was polyadenylated and reverse transcribed. miR-125b levels were quantified by quantitative PCR. Cytogenetics, immunohistotype and MRD were analysed according to international guidelines. RESULTS: Downregulated miR-125b levels were detected in childhood ALL patients and correlated with adverse prognosis. Following BFM induction, miR-125b levels were significantly increased, however, elevated day 33/diagnosis miR-125b ratio was associated with unfavourable disease features. Loss of miR-125b during diagnosis and higher day 33/diagnosis ratio were correlated with stronger risk for disease short-term relapse and patients' worse survival. Moreover, multivariate regression models highlighted the independent prognostic value of miR-125b for childhood ALL. Finally, the combination of miR-125b with clinically used disease markers clearly enhanced the prediction of patients' resistance to BFM chemotherapy. CONCLUSIONS: miR-125b significantly improves the prognosis of childhood ALL patients' outcome under BFM treatment.

INTRODUCTION: Colorectal cancer is one of the most common gastrointestinal diseases and the second leading cause of cancer-associated deaths among adults. miR-15a-5p is a post-transcriptional regulator of the proto-oncogene MYB, a transcription factor essential for prolonged cancer cell proliferation and survival. In the current study, we assessed the potential diagnostic and prognostic utility of miR-15a-5p expression in colorectal adenocarcinoma. METHODS: To accomplish this goal, total RNA was extracted from 182 colorectal adenocarcinoma specimens and 86 non-cancerous colorectal mucosae. After polyadenylation by poly(A) polymerase and subsequent reverse transcription with an oligo-dT adapter primer, miR-15a-5p expression was analyzed using an in-house developed reverse transcription quantitative real-time PCR method, based on SYBR Green chemistry. SNORD43 (RNU43) was used as an internal control gene. RESULTS: miR-15a-5p was significantly upregulated in colorectal tumors compared to non-cancerous colorectal mucosae, while ROC analysis suggested its potential use for diagnostic purposes. Moreover, miR-15a-5p overexpression predicts poor disease-free survival (DFS) and overall survival (OS). Multivariate Cox regression analysis confirmed that miR-15a-5p overexpression is a significant unfavorable prognosticator of DFS in colorectal adenocarcinoma, independent of other established prognostic factors plus treatment of patients. Importantly, miR-15a-5p overexpression retains its unfavorable prognostic value in patients with T3 colorectal adenocarcinoma and in those without distant metastasis (M0). More importantly, the cumulative DFS probability of patients with early stage disease was significantly lower for those with colorectal adenocarcinoma overexpressing miR-15a-5p. DISCUSSION: In conclusion, elevated expression of the cancer-associated miR-15a-5p predicts poor DFS and OS of colorectal adenocarcinoma patients. The prognostic value of miR-15a-5p expression regarding DFS is independent of clinicopathological factors currently used for colorectal adenocarcinoma prognosis.

AbstractObjectives MicroRNA-34a (miR-34a) is regulated by \{TP53\} and, in response, downregulates the expression of a gamut of protein-coding genes, including apoptosis regulators, transcription factors, cyclins, and cyclin-dependent kinases. Its upregulation initiates a reprogramming of gene expression and promotes apoptosis. The purpose of this study was the investigation of the potential clinical significance of miR-34a as a molecular prognostic biomarker in colorectal adenocarcinoma using an in-house real-time quantitative \{PCR\} (qPCR) methodology. Design and methods Total \{RNA\} was extracted from 113 primary colorectal adenocarcinoma specimens and 61 paired non-cancerous colorectal tissue samples. After polyadenylation and reverse transcription, miR-34a molecules were determined using qPCR based on \{SYBR\} Green chemistry. Calculations were performed using the comparative \{CT\} method. Finally, extensive biostatistical analysis was performed. Results miR-34a expression does not significantly differ between colorectal adenocarcinoma tissue specimens and adjacent non-cancerous mucosae. However, miR-34a increases progressively as colorectal adenocarcinoma loses its differentiation, being highest in grade İII\} tumors (P = 0.010). Moreover, miR-34a expression is a potential unfavorable prognostic biomarker in colorectal adenocarcinoma, predicting poor disease-free and overall survival (P = 0.002 and P = 0.019, respectively), independently of classical clinicopathological parameters. Most importantly, miR-34a expression stratifies patients without local (N0) and/or distant metastasis (M0) at the time of diagnosis into two groups with substantially different prognosis (P = 0.013 and P = 0.002, respectively). Conclusions High miR-34a levels in colorectal adenocarcinoma predict a rather increased risk for disease recurrence and poor overall survival, particularly in patients at an early \{TNM\} stage. The unfavorable prognostic potential of miR-34a expression is independent of established prognostic features of colorectal adenocarcinoma.

Mitochondria are highly dynamic and semi-autonomous organelles, essential for many fundamental cellular processes, including energy production, metabolite synthesis, ion homeostasis, lipid metabolism and initiation of apoptotic cell death. Proper mitochondrial physiology is a prerequisite for health and survival. Generation of new and removal of damaged or unwanted mitochondria are tightly controlled processes that need to be accurately coordinated for the maintenance of mitochondrial and cellular homeostasis. Mitophagy is a conserved, mitochondria-specific autophagic clearance process. An intricate regulatory network balances mitophagy with mitochondrial biogenesis. Proper coordination of these opposing processes is important for stress resistance and longevity. Age-dependent decline of mitophagy both inhibits removal of dysfunctional or superfluous mitochondria and impairs mitochondrial biogenesis resulting in progressive mitochondrial accretion and consequently, deterioration of cell function. Nodal regulatory factors that contribute to mitochondrial homeostasis have been implicated in the pathogenesis of several age-associated pathologies, such as neurodegenerative and cardiovascular disorders and cancer, among others. Thus, mitophagy is emerging as a potential target for therapeutic interventions against diseases associated with ageing. In this review, we survey the molecular mechanisms that govern and interface mitophagy with mitochondrial biogenesis, focusing on key elements that hold promise for the development of pharmacological approaches towards enhancing healthspan and quality of life in the elderly.

Fractional-order dynamical systems were recently introduced in the field of pharmacokinetics where they proved powerful tools for modeling the absorption, disposition, distribution and excretion of drugs which are liable to anomalous diffusion, deep tissue trapping and other nonlinear phenomena. In this paper we present several ways to simulate such fractional order pharmacokinetic models and we evaluate their accuracy and complexity on a fractional order pharmacokinetic model of Amiodarone, an anti-arrhythmic drug. We then propose an optimal administration scheduling scheme and evaluate it on a population of patients. (C) 2017, IFAC (International Federation of Automatic Control) Hosting by Elsevier Ltd. All rights reserved.

During the last six years, our working group elaborated intense work on seismic risk assessment in several Greek cities, targeting site-specific models and allowing for tailor-made management actions in case of a crisis. In this paper we will present the main framework and the outcome of the applied methodologies on several case studies, indicating pros and cons, and highlighting future perspectives. Our approach includes: (a) Probabilistic and deterministic seismic hazard assessment based on comprehensiveTo this, new data concerning the location, geometry, and the seismic potential of faults, together with free-field ambient noise recordings have been collected through numerous field surveys; (b) Vulnerability assessment of elements at risk informed by newly created observed damage databases and in-situ observations; (c) Development of physical risk models including structural damage, and economic loss for several ground motion excitations scenarios. Future improvements that fall in with, and/or are beyond the current state-of-the-art, include: (a) and vulnerability assessment; (b) Socioeconomic impact analyses towards the mitigation of risk, enhancement of preparedness and resilience of the social and economic fabric, and (c) Applications for near real-time damage assessment by implementation of state-of-the-art opensourcesoftware (e.g. RASOR; OpenQuake

Background: High numbers of human immunodeficiency virus type 1 (HIV-1) infections among people who inject drugs (PWID) have been diagnosed in Athens, Greece, since 2011. We aimed to trace the geographic origin of HIV-1 infection for migrants who inject drugs and to investigate whether transmissions occur more frequently among migrants than among Greek nationals. Methods: Multiple cross-sectional studies were pooled to assemble all persons diagnosed with HIV-1 in Greece between 1 January 2011 and 31 October 2014. Phylogenetic analyses used maximum likelihood estimation. The hypothesis of ethnic compartmentalization was tested by reconstructing ancestral states of characters at the tips using the criterion of parsimony over a set of bootstrap trees. Results: Of 2274 persons, 38.4% were PWID. Phylogenetic analyses showed the existence of 4 major PWID-specific local transmission networks (LTNs): CRF14_BG (437 [58.6%]), CRF35_AD (139 [18.6%]), subtype B (116 [15.6%]), and subtype A (54 [7.2%]). Of 184 non-Greek PWID, 78.3% had been infected within the PWID-LTNs. For 173 (94.3%), the origin of their infection was assumed to be in Greece (postmigration). For PWID infected within LTNs, transmissions for subtype A and CRF14_BG occurred more frequently among migrants than would be expected by chance (phyloethnic study). Conclusions: Our analysis showed that the majority of infections among migrants occurred postmigration. The existence of significant transmission networking among migrants highlights that this population is a priority for HIV prevention. As molecular analysis can estimate the probable country of HIV infection, it can help to inform the design of public health strategies.

Background: High numbers of human immunodeficiency virus type 1 (HIV-1) infections among people who inject drugs (PWID) have been diagnosed in Athens, Greece, since 2011. We aimed to trace the geographic origin of HIV-1 infection for migrants who inject drugs and to investigate whether transmissions occur more frequently among migrants than among Greek nationals. Methods: Multiple cross-sectional studies were pooled to assemble all persons diagnosed with HIV-1 in Greece between 1 January 2011 and 31 October 2014. Phylogenetic analyses used maximum likelihood estimation. The hypothesis of ethnic compartmentalization was tested by reconstructing ancestral states of characters at the tips using the criterion of parsimony over a set of bootstrap trees. Results: Of 2274 persons, 38.4% were PWID. Phylogenetic analyses showed the existence of 4 major PWID-specific local transmission networks (LTNs): CRF14_BG (437 [58.6%]), CRF35_AD (139 [18.6%]), subtype B (116 [15.6%]), and subtype A (54 [7.2%]). Of 184 non-Greek PWID, 78.3% had been infected within the PWID-LTNs. For 173 (94.3%), the origin of their infection was assumed to be in Greece (postmigration). For PWID infected within LTNs, transmissions for subtype A and CRF14_BG occurred more frequently among migrants than would be expected by chance (phyloethnic study). Conclusions: Our analysis showed that the majority of infections among migrants occurred postmigration. The existence of significant transmission networking among migrants highlights that this population is a priority for HIV prevention. As molecular analysis can estimate the probable country of HIV infection, it can help to inform the design of public health strategies.

BACKGROUND AND AIMS: Despite advances in our knowledge of effective services for people who use drugs over the last decades globally, coverage remains poor in most countries, while quality is often unknown. This paper aims to discuss the historical development of successful epidemiological indicators and to present a framework for extending them with additional indicators of coverage and quality of harm reduction services, for monitoring and evaluation at international, national or subnational levels. The ultimate aim is to improve these services in order to reduce health and social problems among people who use drugs, such as human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection, crime and legal problems, overdose (death) and other morbidity and mortality. METHODS AND RESULTS: The framework was developed collaboratively using consensus methods involving nominal group meetings, review of existing quality standards, repeated email commenting rounds and qualitative analysis of opinions/experiences from a broad range of professionals/experts, including members of civil society and organisations representing people who use drugs. Twelve priority candidate indicators are proposed for opioid agonist therapy (OAT), needle and syringe programmes (NSP) and generic cross-cutting aspects of harm reduction (and potentially other drug) services. Under the specific OAT indicators, priority indicators included 'coverage', 'waiting list time', 'dosage' and 'availability in prisons'. For the specific NSP indicators, the priority indicators included 'coverage', 'number of needles/syringes distributed/collected', 'provision of other drug use paraphernalia' and 'availability in prisons'. Among the generic or cross-cutting indicators the priority indicators were 'infectious diseases counselling and care', 'take away naloxone', 'information on safe use/sex' and 'condoms'. We discuss conditions for the successful development of the suggested indicators and constraints (e.g. funding, ideology). We propose conducting a pilot study to test the feasibility and applicability of the proposed indicators before their scaling up and routine implementation, to evaluate their effectiveness in comparing service coverage and quality across countries. CONCLUSIONS: The establishment of an improved set of validated and internationally agreed upon best practice indicators for monitoring harm reduction service will provide a structural basis for public health and epidemiological studies and support evidence and human rights-based health policies, services and interventions.

BACKGROUND AND AIMS: Despite advances in our knowledge of effective services for people who use drugs over the last decades globally, coverage remains poor in most countries, while quality is often unknown. This paper aims to discuss the historical development of successful epidemiological indicators and to present a framework for extending them with additional indicators of coverage and quality of harm reduction services, for monitoring and evaluation at international, national or subnational levels. The ultimate aim is to improve these services in order to reduce health and social problems among people who use drugs, such as human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection, crime and legal problems, overdose (death) and other morbidity and mortality. METHODS AND RESULTS: The framework was developed collaboratively using consensus methods involving nominal group meetings, review of existing quality standards, repeated email commenting rounds and qualitative analysis of opinions/experiences from a broad range of professionals/experts, including members of civil society and organisations representing people who use drugs. Twelve priority candidate indicators are proposed for opioid agonist therapy (OAT), needle and syringe programmes (NSP) and generic cross-cutting aspects of harm reduction (and potentially other drug) services. Under the specific OAT indicators, priority indicators included 'coverage', 'waiting list time', 'dosage' and 'availability in prisons'. For the specific NSP indicators, the priority indicators included 'coverage', 'number of needles/syringes distributed/collected', 'provision of other drug use paraphernalia' and 'availability in prisons'. Among the generic or cross-cutting indicators the priority indicators were 'infectious diseases counselling and care', 'take away naloxone', 'information on safe use/sex' and 'condoms'. We discuss conditions for the successful development of the suggested indicators and constraints (e.g. funding, ideology). We propose conducting a pilot study to test the feasibility and applicability of the proposed indicators before their scaling up and routine implementation, to evaluate their effectiveness in comparing service coverage and quality across countries. CONCLUSIONS: The establishment of an improved set of validated and internationally agreed upon best practice indicators for monitoring harm reduction service will provide a structural basis for public health and epidemiological studies and support evidence and human rights-based health policies, services and interventions.

Objective: To assess shape covariation of the palate and craniofacial complex (CFC) in children and adolescents. Methods: Pre-treatment lateral cephalometric radiographs and corresponding maxillary casts of 100 children (8-10 years) and 100 adolescents (15-20 years) were digitized. Exclusion criteria were previous orthodontic treatment, craniofacial syndromes, mouth breathing, finger sucking, crossbite, tooth agenesis, and tooth impaction. Palatal shape was described with 239 surface and curve semilandmarks and craniofacial shape with 10 fixed landmarks and 117 curve semilandmarks. Procrustes superimposition and principal component analysis were applied for evaluation of shape variability. Shape covariation between palate and CFC was assessed with partial least squares analysis. Results: The first five principal components explained 77 per cent (palate) and 60 per cent (CFC) of total shape variability. The palate varied mainly in height (adolescent group) and width-length (both groups), whereas the CFC varied mainly in the vertical dimension. Significant covariation was found between the craniofacial and palatal components (RV coefficient: 0.27, children; RV: 0.23, adolescents). Variation of the CFC in the vertical and anteroposterior direction was mainly related to variation in the height-width and the width-length ratio of the palate, respectively. Limitations: The use of lateral cephalometric radiographs eliminated the transverse dimension from the craniofacial shape analysis. The study was cross-sectional, so the observed intergroup differences should be interpreted with caution. Conclusions: Covariation strength and pattern were similar in children and adolescents. The closer a subject was to the high-angle end of the variability spectrum, the higher and narrower was the palate, and conversely.

Objectives: To evaluate the patterns of covariation between palatal and craniofacial morphology in Class II subjects in the early mixed dentition by means of geometric morphometrics. Methods: A cross-sectional sample of 85 Class II subjects (44 females, 41 males; mean age 8.7 years ± 0.8) was collected retrospectively according to the following inclusion criteria: European ancestry (white), Class II skeletal relationship, Class II division 1 dental relationship, early mixed dentition, and prepubertal skeletal maturation. Pre-treatment digital 3D maxillary dental casts and lateral cephalograms were available. Landmarks and semilandmarks were digitized (239 on the palate and 121 on the cephalogram) and geometric morphometric methods (GMM) were applied. Procrustes analysis and principal component analysis (PCA) were performed to reveal the main patterns of palatal shape and craniofacial skeletal shape variation. Two-block partial least squares analysis (PLS) assessed patterns of covariation between palatal morphology and craniofacial morphology. Results: For the morphology of the palate, the first principal component (PC1) described variation in all three dimensions. For the morphology of the craniofacial complex, PC1 showed shape variation mainly in the vertical direction. Palatal shape and craniofacial shape covaried significantly (RV coefficient: 0.199). PLS1 accounted for more than 64 per cent of total covariation and related divergence of the craniofacial complex to palatal height and width. The more a Class II subject tended towards high-angle divergence, the narrower and higher was the palate. Conclusions: Class II high-angle patients tended to have narrower and higher palates, while Class II low-angle patients were related to wider and more shallow palates.

Through the eyes of western women of the 18th and 19th centuries, this paper discusses the Ottoman slavery institution and 'the real position of women in the religious system of Islam' (Garnett 1895: 61).  Focusing on primary sources, first-hand accounts of European women travel writers, authors and journalists in Ottoman territories and principally in Asia Minor (Turkey), this article confirms that all the harem inmates were women of different nations and races: Islamized slaves, liberated slaves and descendants of slaves. Western women, in their intimate contacts with the harem inmates—free and slave—discuss the Ottoman dynasty’s reproductive politics, forced abortion, marriage, divorce, veiling or Muslim women’s attire,  slave rights and social mobility, including requirements for slave liberation. This researcher concludes that the Multiethnic-Multiracial Harem Slavery Institution was the collective segregation, confinement or enslavement of the female gender in one specific space (household/harem), as one collective identity since all the women—slave and free—shared or legally belonged to one man or master: sultan, grand vizier, vizier, pacha, etc. Keywords: slavery, sexual slavery, social mobility, polygyny, eunuchs, children’s harem, seraglio, marriage, divorce, veiling  

Muscle Lim Protein (MLP) is a protein with multiple functional roles in striated muscle physiology and pathophysiology. Herein, we demonstrate that MLP directly binds to slow, fast, and cardiac myosin-binding protein C (MyBP-C) during myogenesis, as shown by yeast two-hybrid and a range of protein-protein interaction assays. The minimal interacting domains involve MLP inter-LIM and MyBP-C [C4]. The interaction is sensitive to cytosolic Ca(2+) concentrations changes and to MyBP-C phosphorylation by PKA or CaMKII. Confocal microscopy of differentiating myoblasts showed MLP and MyBP-C colocalization during myoblast differentiation. Suppression of the complex formation with recombinant MyBP-C [C4] peptide overexpression, inhibited myoblast differentiation by 65%. Suppression of both MLP and MyBP-C expression in myoblasts by siRNA revealed negative synergistic effects on differentiation. The MLP/MyBP-C complex modulates the actin activated myosin II ATPase activity in vitro, which could interfere with sarcomerogenesis and myofilaments assembly during differentiation. Our data demonstrate a critical role of the MLP/MyBP-C complex during early myoblast differentiation. Its absence in muscles with mutations or aberrant expression of MLP or MyBP-C could be directly implicated in the development of cardiac and skeletal myopathies.

Neurodegenerative disease are frequently characterized by microglia activation and/or leukocyte infiltration in the parenchyma of the central nervous system and at the molecular level by increased oxidative modifications of proteins, lipids and nucleic acids. NADPH oxidases (NOX) emerged as a novel promising class of pharmacological targets for the treatment of neurodegeneration due to their role in oxidant generation and presumably in regulating microglia activation. The unique function of NOX is the generation of superoxide anion (O2(*-)) and hydrogen peroxide (H2O2). However in the context of neuroinflammation, they present paradoxical features since O2(*-)/H2O2 generated by NOX and/or secondary reactive oxygen species (ROS) derived from O2(*-)/H2O2 can either lead to neuronal oxidative damage or resolution of inflammation. The role of NOX enzymes has been investigated in many models of neurodegenerative diseases by using either genetic or pharmacological approaches. In the present review we provide a critical assessment of recent findings related to the role of NOX in the CNS as well as how the field has advanced over the last 5 years. In particular, we focus on the data derived from the work of a consortium (Neurinox) funded by the European Commission's Programme 7 (FP7). We discuss the evidence gathered from animal models and human samples linking NOX expression/activity with neuroinflammation in neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) and Creutzfeldt-Jakob disease as well as autoimmune demyelinating diseases like multiple sclerosis (MS) and chronic inflammatory demyelinating polyneuropathy (CIDP). We address the possibility to use measurement of the activity of the NOX2 isoform in blood samples as biomarker of disease severity and treatment efficacy in neurodegenerative disease. Finally we clarify key controversial aspects in the field of NOX, such as NOX cellular expression in the brain, measurement of NOX activity, impact of genetic deletion of NOX in animal models of neurodegeneration and specificity of NOX inhibitors.

© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim The design and synthesis of a glucose-based acridone derivative (GLAC), a potent inhibitor of glycogen phosphorylase (GP) are described. GLAC is the first inhibitor of glycogen phosphorylase, the electronic absorption properties of which are clearly distinguishable from those of the enzyme. This allows probing subtle interactions in the catalytic site. The GLAC absorption spectra, associated with X-ray crystallography and quantum chemistry cal culations, reveal that part of the catalytic site of GP behaves as a highly basic environment in which GLAC exists as a bis-anion. This is explained by water-bridged hydrogen-bonding interactions with specific catalytic site residues.

We investigate from first principles the fieldlike spin-orbit torques (SOTs) in a Ag2Bi-terminated Ag(111) film grown on ferromagnetic Fe(110). We find that a large part of the SOT arises from the spin-orbit interaction (SOI) in the Ag2Bi layer far away from the Fe layers. These results clearly hint at a long-range spin transfer in the direction perpendicular to the film that does not originate in the spin Hall effect. In order to bring evidence of the nonlocal character of the computed SOT, we show that the torque acting on the Fe layers can be engineered by the introduction of Bi vacancies in the Ag2Bi layer. Overall, we find a drastic dependence of the SOT on the disorder type, which we explain by a complex interplay of different contributions to the SOT in the Brillouin zone.

AIM: We reviewed our 20-year experience with non-Whipple operations (pancreas-preserving duodenectomy and transduodenal ampullectomy) for the treatment of benign, premalignant or early-stage malignant duodenal lesions. PATIENTS AND METHODS: Twenty-four patients who underwent non-Whipple operations between January 1996 and December 2015 were identified from an institutional database and retrospectively analyzed. RESULTS: Between 1996 and 2015, 10 patients underwent pancreas-preserving duodenectomy and 14 patients underwent transduodenal ampullectomy. The mean follow-up was 25.8 months (range=6-54 months) and no patient was lost to follow-up. Eighteen patients had preoperative diagnosis of duodenal adenomatosis, three patients had preoperative diagnosis of duodenal adenocarcinoma, one had a bleeding polyp and two had localized inflammation. Average operative time was 145 min (range=127-168 min) for transduodenal ampullectomy and 183 min (range=173-200 min) for pancreas-preserving duodenectomy (p<0.05). The estimated blood loss for transduodenal ampullectomy was 85 vs. 125 ml for pancreas-preserving duodenectomy (p<0.05). Early postoperative complications were noted in 13 cases (54.17%). There were no postoperative (90-day) deaths observed in this series and there were no recurrences during follow-up for the patients operated on with neoplastic lesions. CONCLUSION: For carefully selected patients, transduodenal ampullectomy and pancreas-preserving duodenectomy may be used in place of the Whipple operation for benign and occasionally early-stage malignant (Tis and T1) duodenal and ampullary disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic (DAergic) neurons in the substantia nigra and the gradual depletion of dopamine (DA). Current treatments replenish the DA deficit and improve symptoms but induce dyskinesias over time, and neuroprotective therapies are nonexistent. Here we report that Nuclear receptor-related 1 (Nurr1):Retinoid X receptor α (RXRα) activation has a double therapeutic potential for PD, offering both neuroprotective and symptomatic improvement. We designed BRF110, a unique in vivo active Nurr1:RXRα-selective lead molecule, which prevents DAergic neuron demise and striatal DAergic denervation in vivo against PD-causing toxins in a Nurr1-dependent manner. BRF110 also protects against PD-related genetic mutations in patient induced pluripotent stem cell (iPSC)-derived DAergic neurons and a genetic mouse PD model. Remarkably, besides neuroprotection, BRF110 up-regulates tyrosine hydroxylase (TH), aromatic l-amino acid decarboxylase (AADC), and GTP cyclohydrolase I (GCH1) transcription; increases striatal DA in vivo; and has symptomatic efficacy in two postneurodegeneration PD models, without inducing dyskinesias on chronic daily treatment. The combined neuroprotective and symptomatic effects of BRF110 identify Nurr1:RXRα activation as a potential monotherapeutic approach for PD.

Even though rare, mega-fires raging during very dry and windy conditions, record catastrophic impacts on infrastructure, the environment and human life, as well as extremely high suppression and rehabilitation costs. Apart from the direct consequences, mega-fires induce long-term effects in the geomorphological and hydrological processes, influencing environmental factors that in turn can affect the occurrence of other natural hazards, such as floods and mass movement phenomena. This work focuses on the forest fire of 2007 in Peloponnese, Greece that to date corresponds to the largest fire in the country's record that burnt 1773 km2, causing 78 fatalities and very significant damages in property and infrastructure. Specifically, this work examines the occurrence of flood and mass movement phenomena, before and after this mega-fire and analyses different influencing factors to investigate the degree to which the 2007 fire and/or other parameters have affected their frequency. Observational evidence based on several data sources collected during the period 1989–2016 show that the 2007 fire has contributed to an increase of average flood and mass movement events frequency by approximately 3.3 and 5.6 times respectively. Fire affected areas record a substantial increase in the occurrence of both phenomena, presenting a noticeably stronger increase compared to neighbouring areas that have not been affected. Examination of the monthly occurrence of events showed an increase even in months of the year were rainfall intensity presented decreasing trends. Although no major land use changes has been identified and chlorophyll is shown to recover 2 years after the fire incident, differences on the type of vegetation as tall forest has been substituted with lower vegetation are considered significant drivers for the observed increase in flood and mass movement frequency in the fire affected areas.

This study investigates developmental patterns in the ability of Greek foreign language learners to make offers. Drawing data from role-plays and retrospective verbal reports it attempts to explore the initial offer strategies and the degree of insistence that learners of three different proficiency levels (lower intermediate, intermediate and advanced) employ when performing offers in different social situations. The results suggest that, although there is a great deal of grammatical and pragma-linguistic development in regard to both initial offer strategies and syntactic modification devices, this does not guarantee concomitant levels of socio-pragmatic development (cf. Bardovi-Harlig 1999).

Abstract Spectroscopic methods such as absorption spectroscopy in ultraviolet (UV), visible (Vis), near-infrared (NIR), or mid-infrared (MIR) or their combinations have been used for nondestructive, fast, real-time, off/online monitoring of olive oil quality parameters, and for detection and determination of olive oil adulterants as well as geographic origin. These methods have also been used in the industrial sector to analyze the quality of olive fruit with respect to oil content, moisture, color, and fatty acid content. This chapter considers several applications of UV-Vis-NIR or/and MIR spectroscopy in off/on-line monitoring of olive oil functional compounds and oxidation status in combination with appropriately used spectral preprocessing and data analysis (chemometrics). The UV-Vis-NIR and MIR spectroscopic methods have the advantages of minimal or no sample preparation and the ability of a very simple and rapid simultaneous analysis of several constituents. They constitute one of the most promising and useful on/in-line detection methods for olive oil quality control.

Achievement goal theory is an important framework to understand students' achievement goals, motivation, and engagement in academic situations and to study teachers' instructional practices. There has been a debate about whether optimal motivation involves the pursuit of mastery goals only (i.e., mastery goal perspective) or the combined pursuit of mastery and performance-approach goals (i.e., multiple goal perspective; Barron & Harackiewicz, 2001, 2003). In the present correlational research we tested these two goal perspectives in two Peruvian samples of high school students (Sample 1: N = 1505; Sample 2: N = 551) and further examined whether students in classes, in which teachers were perceived to promote mastery goals only or performance-approach goals, would display the most optimal learning pattern. After controlling for learners' performance-avoidance goal pursuit, results provided only slim evidence for the additive goal perspective, as the effects of students' pursuit of mastery goals were more robust and consistent across both samples and outcomes (i.e., learning strategies and math grades). Along similar lines, at the class level, perceived teacher-promoted mastery goals positively predicted deep-level learning strategies, while class-level perceived teacher-promoted performance-avoidance goals related to lower academic achievement. (C) 2017 Elsevier Inc. All rights reserved.

The purpose is to: 1) foster the national BioMedical Informatics (BMI) foundation aligning with the international medical informatics association (IMIA) in order to remodel the national strategies; 2) structure the BMHI strategic plans in Egypt and Jordan as models for other Arab States; 3) define the requirements for new joint EU-Mediterranean BMHI projects and initiatives; and 4) encourage and support the BMHI centres of excellence in Egypt and Jordan. BIOMed will synergistically apply up-to-date European and International methodologies & standards. The pre-defined challenges were integrating multiple segregated BMHI initiatives and policies; overcoming obstructions- socio, political, economic; recommendation adaptation, assessing the current and proposed solutions; defining the national health systems real demands; identifying different European best practices. Political instability in the Middle East after the Arab Spring in 2011 added further challenges as well as improved the importance of the EU-MENA (EU and Middle East and North Africa) cooperation.

The aim of this study is to spatially assess fire severity and to explore the relationship between the Normalized Vegetation Index (NDVI) derived from WorldView- 2 imagery and the field-based fire severity index “Composite Burn Index” (CBI) on a recent large fire that occurred on the island of Chios, Greece, in 2016. The statistical analysis indicated a relatively strong linear relationship between the NDVI and the CBI (R2 = 0.71). Predictive local thresholds of NDVI values have been determined for accurate thematic classification and mapping of fire severity classes. The overall classification accuracy based on NDVI from WorldView-2 was relatively high (71%), pointing to the potential of using such data for mapping forest fires in the Mediterranean as well as for assessing their severity. The application of the classification thresholds calculated in this study over other forest fire events on similar ecosystem types, could support the rapid assessment of fire severity and hence could enable the decisions needed for proper post-fire management.

This paper examines the dynamic linkages among major exchange rates during the Global Financial Crisis and Eurozone Sovereign Debt Crisis. We extend the previous literature on volatility spillover linkages among the currencies by taking into account the uncovered interest-rate parity hypothesis for 2004–2015. The results indicate that the Canadian Dollar and Great British Pound were affected mainly by the US Dollar across the two crises due to strong financial and economic ties among the three economies, while the Japanese Yen shows evidence of a safe-haven currency. We also provide evidence of varying vulnerability of currencies to both crises, implying increased portfolio diversification benefits, since holding a portfolio with diverse currencies is less subject to systematic risk. These results show that the policy makers need to adopt a stricter form of monetary policy coordination among central banks, since the different vulnerability of currencies across turbulent periods reveals possible non-cooperative monetary policies.

The popularity of recommendation systems has made them a substantial component of many applications and projects. This work proposes a framework for package recommendations that try to meet users' preferences as much as possible through the satisfaction of several criteria. This is achieved by modeling the relation between the items and the categories these items belong to aiming to recommend to each user the top-k packages which cover their preferred categories and the restriction of a maximum package cost. Our contribution includes an optimal and a greedy solution. The novelty of the optimal solution is that it combines the collaborative filtering predictions with a graph based model to produce recommendations. The problem is expressed through a minimum cost flow network and is solved by integer linear programming. The greedy solution performs with a low computational complexity and provides recommendations which are close to the optimal solution. We have evaluated and compared our framework with a baseline method by using two popular recommendation datasets and we have obtained promising results on a set of widely accepted evaluation metrics.

Although there is rich evidence for human occupation of Paros’ coastline, there is a lack of data regarding the evolution of the island’s coastal palaeoenvironments. Paros Island is part of the Cyclades Islands complex, in the central Aegean Sea. It is the third largest island of the Cyclades. The Island is of great geoarchaeological significance, with the earliest evidence of occupation dating back around the 5th millennium BC, while the nearby island of Saliagos has yielded a Neolithic settlement. The studied site, Livadia, is located in the northwestern part of Paros Island, near the modern capital, Paroikia.For the purposes of this work, a multiproxy analysis was undertaken, which included sedimentological and biostratigraphic analyses of Late Holocene coastal deposits from lagoonal environment, aiming to reconstruct the evolution of coastal landscapes in Paroikia Bay (Paros Island, Greece). In order provide insights into the coastal evolution and the RSL changes of this sector of the Aegean, the dated samples of this study were compared with already published archaeological data, geomorphological sea level indicators and with the RSL curve derived from the glacio-hydro-isostatic model for the region.

Abstract Species occurring in sympatry have to effectively segregate their niche in order to co-exist. In the case of ectotherms in particular, the very important parameter of thermal biology has to be taken into account. Here we investigated the thermoregulatory effectiveness (E) of two endemic Greek lizards (Hellenolacerta graeca and Podarcis peloponnesiacus) that live syntopically on a rocky cliff in the Peloponnese. We presumed that the two species would select different microhabitats, to avoid interspecific competition, and follow a similar thermoregulation pattern as they experience the same conditions. We also expected that E values for both species would differ depending on the season. Overall, we found that the two species had similar E values for each season but differentiated partial thermoregulatory attributes. Though they both occurred in the same types of microhabitat, H. graeca selected higher sites (average 99cm above ground) than P. peloponnesiacus (average 44cm). Also, the latter achieved higher preferred temperatures during summer and winter. Finally, the effectiveness of thermoregulation for both species varied interseasonally and received its highest values during summer, in response to the lowest thermal quality that was observed then. Similar studies stress the importance of thermal shifts for ectotherm co-existence.

Selective serotonin reuptake inhibitor medications (SSRIs) are the first lines of treatment for maternal affective disorders, and are prescribed to up to 10% of pregnant women. Concern has been raised about how perinatal exposure to these medications affect offspring neurobehavioral outcomes, particularly those related to social interactions, as recent research has reported conflicting results related to autism spectrum disorder (ASD) risk in children prenatally exposed to SSRIs. Therefore, the aim of this work was to investigate the effects of perinatal exposure to the SSRI fluoxetine on social play behaviors and the hypothalamic pituitary adrenal system, using a model of pre-gestational maternal stress. We also investigated synaptic proteins in the CA2, CA3, and dentate gyrus of the hippocampus, as well as number of immature neurons in the granule cell layer, as both measures of plasticity in the hippocampus have been linked to social behaviors. In pre-adolescent male and female Sprague-Dawley rat offspring, main findings show that perinatal fluoxetine prevents the negative effect of maternal stress on sibling play behavior. However, perinatal fluoxetine increased social aggressive play with a novel conspecific in both sexes and decreased time grooming a novel conspecific in males only. Perinatal fluoxetine also increased serum corticosteroid binding globulin levels, 5-HT levels in the hippocampus, and pre-synaptic density assessed via synaptophysin in the dentate gyrus. Social interaction was significantly correlated with changes in plasticity in the CA2 region of the hippocampus. Pre-gestational maternal stress exposure resulted in significantly decreased rates of hippocampal neurogenesis and synaptophysin density in the dentate gyrus of pre-adolescent males, but not females. Together, these results further characterize the role of perinatal SSRIs, maternal stress prior to conception, and sex/gender on developing social behaviors and related plasticity in the hippocampus of pre-adolescent offspring.

Selective serotonin reuptake inhibitor medications (SSRIs) are the first lines of treatment for maternal affective disorders, and are prescribed to up to 10% of pregnant women. Concern has been raised about how perinatal exposure to these medications affect offspring neurobehavioral outcomes, particularly those related to social interactions, as recent research has reported conflicting results related to autism spectrum disorder (ASD) risk in children prenatally exposed to SSRIs. Therefore, the aim of this work was to investigate the effects of perinatal exposure to the SSRI fluoxetine on social play behaviors and the hypothalamic pituitary adrenal system, using a model of pre-gestational maternal stress. We also investigated synaptic proteins in the CA2, CA3, and dentate gyrus of the hippocampus, as well as number of immature neurons in the granule cell layer, as both measures of plasticity in the hippocampus have been linked to social behaviors. In pre-adolescent male and female Sprague-Dawley rat offspring, main findings show that perinatal fluoxetine prevents the negative effect of maternal stress on sibling play behavior. However, perinatal fluoxetine increased social aggressive play with a novel conspecific in both sexes and decreased time grooming a novel conspecific in males only. Perinatal fluoxetine also increased serum corticosteroid binding globulin levels, 5-HT levels in the hippocampus, and pre-synaptic density assessed via synaptophysin in the dentate gyrus. Social interaction was significantly correlated with changes in plasticity in the CA2 region of the hippocampus. Pre-gestational maternal stress exposure resulted in significantly decreased rates of hippocampal neurogenesis and synaptophysin density in the dentate gyrus of pre-adolescent males, but not females. Together, these results further characterize the role of perinatal SSRIs, maternal stress prior to conception, and sex/gender on developing social behaviors and related plasticity in the hippocampus of pre-adolescent offspring.

Salmeterol (SAL) is a long-acting beta 2-adrenergic agonist, which is widely used in the therapy of asthma. The aim of this study was to investigate the pharmacokinetics (PK) of inhaled salmeterol in asthma patients using two different dry powder inhalers. This analysis was based on data from 45 subjects who participated in a two-sequence, four-period crossover bioequivalence (BE) study after single administration of the test (T) and reference (R) products. In order to mimic more closely the real treatment conditions, activated charcoal was not co-administered. Plasma concentration-time (C-t) data were initially analysed using classic non-compartmental PK approaches, while the main objective of the study was to apply population PK modeling. The relative fraction of the dose absorbed via the lungs (R-L) was set as a parameter in the structural model. The plasma C-t profiles of salmeterol showed a biphasic time course indicating a parallel pulmonary and gastrointestinal (GI) absorption. A two-compartment disposition model with first order absorption from the GI and very rapid absorption from lungs (like an i.v. bolus) was found to describe successfully the C-t profiles of salmeterol. The estimated R-L value was 13% suggesting a high gut deposition of inhaled salmeterol. Women were found to exert less capability to eliminate salmeterol than men, while body weight (in allometric form) was found to be an important covariate on the peripheral volume of distribution.

Precise Ca cycling through the sarcoplasmic reticulum (SR), a Ca storage organelle, is critical for proper cardiac muscle function. This cycling initially involves SR release of Ca via the ryanodine receptor, which is regulated by its interacting proteins junctin and triadin. The sarco/endoplasmic reticulum Ca ATPase (SERCA) pump then refills SR Ca stores. Histidine-rich Ca-binding protein (HRC) resides in the lumen of the SR, where it contributes to the regulation of Ca cycling by protecting stressed or failing hearts. The common Ser96Ala human genetic variant of HRC strongly correlates with life-threatening ventricular arrhythmias in patients with idiopathic dilated cardiomyopathy. However, the underlying molecular pathways of this disease remain undefined. Here, we demonstrate that family with sequence similarity 20C (Fam20C), a recently characterized protein kinase in the secretory pathway, phosphorylates HRC on Ser96. HRC Ser96 phosphorylation was confirmed in cells and human hearts. Furthermore, a Ser96Asp HRC variant, which mimics constitutive phosphorylation of Ser96, diminished delayed aftercontractions in HRC null cardiac myocytes. This HRC phosphomimetic variant was also able to rescue the aftercontractions elicited by the Ser96Ala variant, demonstrating that phosphorylation of Ser96 is critical for the cardioprotective function of HRC. Phosphorylation of HRC on Ser96 regulated the interactions of HRC with both triadin and SERCA2a, suggesting a unique mechanism for regulation of SR Ca homeostasis. This demonstration of the role of Fam20C-dependent phosphorylation in heart disease will open new avenues for potential therapeutic approaches against arrhythmias.

The interaction of visible and near-infrared light with spin waves in appropriately designed dual nanocavities, for both photons and magnons, is investigated by means of rigorous calculations, correct to arbitrary order in the magneto-optical coupling parameter. It is shown that the concurrent localization of the interacting photon and magnon fields in the same region of space for a long period of time enhances their mutual interaction, provided that specific selection rules are fulfilled. Our results provide evidence for the occurrence of strong effects, beyond the linear response approximation, which lead to enhanced modulation of light by spin waves through multimagnon absorption and emission processes by a photon.

Type IIn supernovae (SNe), a rare subclass of core collapse SNe, explode in dense circumstellar media that have been modified by the SNe progenitors at their last evolutionary stages. The interaction of the freely expanding SN ejecta with the circumstellar medium gives rise to a shock wave propagating in the dense SN environment, which may accelerate protons to multi-PeV energies. Inelastic proton-proton collisions between the shock-accelerated protons and those of the circumstellar medium lead to multimessenger signatures. Here, we evaluate the possible neutrino signal of Type IIn SNe and compare with IceCube observations. We employ a Monte Carlo method for the calculation of the diffuse neutrino emission from the SN IIn class to account for the spread in their properties. The cumulative neutrino emission is found to be ∼10 per cent of the observed IceCube neutrino flux above 60 TeV. Type IIn SNe would be the dominant component of the diffuse astrophysical flux, only if 4 per cent of all core collapse SNe were of this type and 20-30 per cent of the shock energy was channeled to accelerated protons. Lower values of the acceleration efficiency are accessible by the observation of a single Type IIn SN as a neutrino point source with IceCube using up-going muon neutrinos. Such an identification is possible in the first year following the SN shock breakout for sources within 20 Mpc.

A ferrocene containing o-aminoanilide, N1-(2-aminophenyl)-N8-ferrocenyloctanediamide (2b, Pojamide) displayed nanomolar potency vs HDAC3. In comparison to RGFP966, a potent and selective HDAC3 inhibitor, Pojamide displayed superior activity in HCT116 colorectal cancer cell invasion assays; however, TCH106 and romidepsin, potent HDAC1 inhibitors, outperformed Pojamide in cellular proliferation and colony formation assays. Together, these data suggest that HDAC1,3 inhibition is desirable to achieve maximum anticancer benefits. Additionally, we explored Pojamide-induced redox pharmacology. Indeed, treating HCT116 cells with Pojamide, SNP (sodium nitroprusside), and glutathione (GSH) led to greatly enhanced cytotoxicity and DNA damage, attributed to activation to an Fe(III) species.

We report optical photometric and polarimetric observations of the blazar OJ 287 gathered during 2016/17. The high level of activity, noticed after the General Relativity Centenary flare, is argued to be part of the follow-up flares that exhibited high levels of polarization and originated in the primary black hole jet. We propose that the follow-up flares were induced as a result of accretion disk perturbations, travelling from the site of impact towards the primary SMBH. The timings inferred from our observations allowed us to estimate the propagation speed of these perturbations. Additionally, we make predictions for the future brightness of OJ 287.

Climate evolution of the Mediterranean region during the Holocene exhibits strong spatial and temporal variability, which is notoriously difficult for models to reproduce. We propose here a new proxy-based climate synthesis synthesis and its comparison – at a regional (∼ 100 km) level – with a regional climate model to examine (i) opposing northern and southern precipitation regimes and (ii) an east-to-west precipitation dipole during the Holocene across the Mediterranean basin. Using precipitation estimates inferred from marine and terrestrial pollen archives, we focus on the early to mid-Holocene (8000 to 6000 cal yr BP) and the late Holocene (4000 to 2000 cal yr BP), to test these hypotheses on a Mediterranean-wide scale. Special attention was given to the reconstruction of season-specific climate information, notably summer and winter precipitation. The reconstructed climatic trends corroborate the north–south partition of precipitation regimes during the Holocene. During the early Holocene, relatively wet conditions occurred in the south–central and eastern Mediterranean regions, while drier conditions prevailed from 45° N northwards. These patterns then reverse during the late Holocene. With regard to the existence of a west–east precipitation dipole during the Holocene, our results show that the strength of this dipole is strongly linked to the reconstructed seasonal parameter; early-Holocene summers show a clear east–west division, with summer precipitation having been highest in Greece and the eastern Mediterranean and lowest over Italy and the western Mediterranean. Summer precipitation in the east remained above modern values, even during the late-Holocene interval. In contrast, winter precipitation signals are less spatially coherent during the early Holocene but low precipitation is evidenced during the late Holocene. A general drying trend occurred from the early to late Holocene, particularly in the central and eastern Mediterranean.For the same time intervals, pollen-inferred precipitation estimates were compared with model outputs, based on a regional-scale downscaling (HadRM3) of a set of global climate-model simulations (HadAM3). The high-resolution detail achieved through the downscaling is intended to enable a better comparison between site-based paleo-reconstructions and gridded model data in the complex terrain of the Mediterranean; the model outputs and pollen-inferred precipitation estimates show some overall correspondence, though modeled changes are small and at the absolute margins of statistical significance. There are suggestions that the eastern Mediterranean experienced wetter summer conditions than present during the early and late Holocene; the drying trend in winter from the early to the late Holocene also appears to be simulated. The use of this high-resolution regional climate model highlights how the inherently patchy nature of climate signals and paleo-records in the Mediterranean basin may lead to local signals that are much stronger than the large-scale pattern would suggest. Nevertheless, the east-to-west division in summer precipitation seems more marked in the pollen reconstruction than in the model outputs. The footprint of the anomalies (like today, or dry winters and wet summers) has some similarities to modern analogue atmospheric circulation patterns associated with a strong westerly circulation in winter (positive Arctic Oscillation–North Atlantic Oscillation (AO–NAO)) and a weak westerly circulation in summer associated with anticyclonic blocking; however, there also remain important differences between the paleo-simulations and these analogues. The regional climate model, consistent with other global models, does not suggest an extension of the African summer monsoon into the Mediterranean. Therefore, the extent to which summer monsoonal precipitation may have existed in the southern and eastern Mediterranean during the mid-Holocene remains an outstanding question.

Women suffer from depression and anxiety disorders more often than men, and as a result they receive antidepressants to a greater extent. Sex differences in antidepressant response in humans have been modestly studied, and results have been controversial. At the same time, preclinical studies on animal models of depression and antidepressant response have provided insights with regard to sex differences that could be useful for the design and interpretation of future clinical trials. This Mini-Review discusses such sex-differentiated findings with regard to the presentation of depression, endophenotypes, and antidepressant response. In particular, men and women differ in symptomatology of depression, and animal models of depression have revealed sex differences in behavioral indices. However, although in experimental studies behavioral indices and models are adjusted to identify sex differences properly, this is not the case in the use of depression rating scales in clinical studies. Accordingly, preclinical studies highlight the importance of sex differences at the baseline behavioral response and the underlying mechanisms that often converge after antidepressant treatment. This is also a neglected issue in human studies. Finally, preclinical research suggests that, in the quest for potential biomarkers for depression, sex should be an important factor to consider. Careful consideration of sex differences in preclinical research could facilitate and ameliorate the design and quality of clinical studies for disease biomarkers and novel fast-acting antidepressants that are so essential for both men and women suffering from depression. © 2016 Wiley Periodicals, Inc.

Women suffer from depression and anxiety disorders more often than men, and as a result they receive antidepressants to a greater extent. Sex differences in antidepressant response in humans have been modestly studied, and results have been controversial. At the same time, preclinical studies on animal models of depression and antidepressant response have provided insights with regard to sex differences that could be useful for the design and interpretation of future clinical trials. This Mini-Review discusses such sex-differentiated findings with regard to the presentation of depression, endophenotypes, and antidepressant response. In particular, men and women differ in symptomatology of depression, and animal models of depression have revealed sex differences in behavioral indices. However, although in experimental studies behavioral indices and models are adjusted to identify sex differences properly, this is not the case in the use of depression rating scales in clinical studies. Accordingly, preclinical studies highlight the importance of sex differences at the baseline behavioral response and the underlying mechanisms that often converge after antidepressant treatment. This is also a neglected issue in human studies. Finally, preclinical research suggests that, in the quest for potential biomarkers for depression, sex should be an important factor to consider. Careful consideration of sex differences in preclinical research could facilitate and ameliorate the design and quality of clinical studies for disease biomarkers and novel fast-acting antidepressants that are so essential for both men and women suffering from depression. © 2016 Wiley Periodicals, Inc.

Metamaterials provide functionalities that are not present in naturally occurring materials, including negative refraction, super-lenses or hyper-lens, cloaking, and ultraslow and stopped light [1-5]. Usually, both the electric permittivity and the magnetic permeability need to be controlled to realize metamaterials. © 2017 IEEE.

HIV remains an important public health issue worldwide. However, new prevention approaches have recently been developed and are very promising. Antiretroviral treatment as prevention, or as a prophylaxis after exposure to HIV, has been shown to reduce the likelihood of HIV acquisition. Over the last years, animal studies and randomized clinical trials in humans showed that antiretrovirals can also be efficacious and safe if used once daily, or intermittently, as prophylaxis before an individual is exposed to HIV (Pre-exposure Prophylaxis - PrEP). Fears about development of resistant strains have not been justified insofar given the accumulated evidence from research studies. Demonstration projects are ongoing and first results indicate that interests in the uptake of PrEP are high and adherence is satisfactory. Models suggest that PrEP could be a cost-effective or cost-saving approach under certain provisions including delivery to people at high risk of HIV infection, using less expensive medications, delivery in high HIV prevalence settings, short-term use for periods of higher risk, and evaluation in a longer-term period. The current review summarizes evidence on efficacy, safety and effectiveness of PrEP, and discusses future challenges and perspectives.

In this paper we discuss the preliminary results of the Transient Electromagnetic Method (TEM) that was applied in the area of Karla Lake, located in the East Thessaly basin. A grid of 71 TEM soundings was planned and executed in order to investigate the subsurface lithological and hydrogeological conditions of the area. The geological regime of the area is comprised of the alpine basement (marbles, gneisses and schists), ophiolites, transgression formations and finally a package of post-alpine deposits with respectful thickness. Resistivity maps for certain depths of investigation along with a pseudo-3D representation were produced, based on the processed TEM data. The vertical distribution of the resistivity values revealed important information about the lithological succession of the area and the hydrogeological status of the post-alpine sediments covering the basin. Moreover, the limits of the former Karla Lake were delineated and the alpine bedrock was also adumbrated under the thick Tertiary and Quaternary deposits. Finally, taking into account older piezometric maps of 2009 and our geophysical results, we managed to indicate the decline of the groundwater level since then, in the central part of the study area and the broader area of Kileler settlement.

© 2017 North American Society for Pediatric and Adolescent Gynecology Study Objective To study the presentation and causes of premature ovarian insufficiency (POI) in adolescents. Design Retrospective notes review. Setting Tertiary referral outpatient clinic for pediatric and adolescent gynecology. Participants Adolescents with POI. Interventions Standard POI evaluation. Main Outcome Measures Age and clinical symptoms at presentation, causative factors for POI, if identified. Results We identified 22 girls with POI, with a mean age of 15.6 years. Eight of them presented with delayed puberty, 3 with primary amenorrhea, and the remainder presented with either irregular bleeding (n = 9) or secondary amenorrhea (n = 2). For those who presented with delayed puberty, only 3 were found to have a sex chromosome abnormality. A clear cause for the POI was identified in 3 further cases. Conclusion Although POI in adolescents traditionally is associated with primary amenorrhea and delayed puberty, a proportion of girls will present with irregular bleeding that might be mistaken for expected menstrual disturbances of puberty, thus delaying the diagnosis. We identified a clear cause for POI in 6 cases. Although there were no familial cases of POI, it remains a possibility that genetic reasons might be involved in the pathogenesis.

BACKGROUND: The prevalence of HIV-1 drug resistance among treatment-naïve patients ranges between 8.3% and 15% in Europe and North America. Previous studies showed that subtypes A and B were the most prevalent in the Greek HIV-1 epidemic. Our aim was to estimate the prevalence of resistance among drug naïve patients in Greece and to investigate the levels of transmission networking among those carrying resistant strains. METHODS: HIV-1 sequences were determined from 3428 drug naïve HIV-1 patients, in Greece sampled during 01/01/2003-30/6/2015. Transmission clusters were estimated by means of phylogenetic analysis including as references sequences from patients failing antiretroviral treatment in Greece and sequences sampled globally. RESULTS: The proportion of sequences with SDRMs was 5.98% (n=205). The most prevalent SDRMs were found for NNRTIs (3.76%), followed by N(t)RTIs (2.28%) and PIs (1.02%). The resistance prevalence was 22.2% based on all mutations associated with resistance estimated using the HIVdb resistance interpretation algorithm. Resistance to NNRTIs was the most common (16.9%) followed by PIs (4.9%) and N(t)RTIs (2.8%). The most frequently observed NNRTI resistant mutations were E138A (7.7%), E138Q (4.0%), K103N (2.3%) and V179D (1.3%). The majority of subtype A sequences (89.7%; 245 out of 273) with the dominant NNRTI resistance mutations (E138A, K103N, E138Q, V179D) were found to belong to monophyletic clusters suggesting regional dispersal. For subtype B, 68.1% (139 out of 204) of resistant strains (E138A, K103N, E138Q V179D) belonged to clusters. For N(t)RTI-resistance, evidence for regional dispersal was found for 27.3% and 21.6% of subtype A and B sequences, respectively. CONCLUSIONS: The TDR rate based on the prevalence of SDRM is lower than the average rate in Europe. However, the prevalence of NNRTI resistance estimated using the HIVdb approach, is high in Greece and it is mostly due to onward transmissions among drug-naïve patients.

We consider a transportation station, where customers arrive according to a Poisson process, observe the delay information and the fee imposed by the administrator and decide whether to use the facility or not. A transportation facility visits the station according to a renewal process and serves all present customers at each visit. We assume that every customer maximizes her individual expected utility and the administrator is a profit maximizer. We model this situation as a two‐stage game among the customers and the administrator, where customer strategies depend on the level of delay information provided by the administrator. We consider three cases distinguished by the level of delay information: observable (the exact waiting time is announced), unobservable (no information is provided) and partially observable (the number of waiting customers is announced). In each case, we explore how the customer reward for service, the unit waiting cost, and the intervisit time distribution parameters affect the customer behavior and the fee imposed by the administrator. We then compare the three cases and show that the customers almost always prefer to know their exact waiting times whereas the administrator prefers to provide either no information or the exact waiting time depending on system parameters.

Background: Successful application of programmed death 1 (PD1) checkpoint inhibitors in the clinic may ultimately benefit from appropriate patient selection based upon predictive biomarkers. Molecular characterization of circulating tumor cells (CTC) is crucial for the investigation of molecular-targeted therapies while predictive biomarkers for response to PD1 checkpoint inhibitors are lacking. We sought to assess whether overexpression of PD-L1 in CTCs could be detected at baseline and at different timepoints during treatment in a prospective cohort of head and neck squamous cell carcinoma (HNSCC) patients and used to predict clinical outcome after treatment with curative intent. Patients and methods: We developed a highly sensitive, specific and robust RT-qPCR assay for PD-L1 mRNA expression in EpCAM(+) CTCs. In a prospective cohort of 113 locally advanced HNSCC patients treated with curative intent we evaluated PD-L1 expression in the EpCAM(+) CTC fraction at baseline, after 2 cycles of induction chemotherapy (week 6) and at the end of concurrent chemoradiotherapy (week 15). Results: PD-L1 overexpression was found in 24/94 (25.5%) patients at baseline, 8/34 (23.5%) after induction chemotherapy and 12/54 (22.2%) patients at the end of treatment. Patients with CTCs overexpressing PD-L1 at end of treatment had shorter progression-free survival (P = 0.001) and overall survival (P < 0.001). Multivariate analysis revealed that PD-L1 overexpression at end of treatment was independent prognostic factor for progression-free survival and overall survival. The absence of PD-L1 overexpression at the end of treatment was strongly associated with complete response with an odds ratio = 16.00 (95% CI = 2.76-92.72, P = 0.002). Conclusions: We demonstrate that detection of CTCs overexpressing PD-L1 is feasible and may provide important prognostic information in HNSCC. Our results suggest that adjuvant PD1 inhibitors deserve evaluation in HNSCC patients in whom PD-L1(+) CTCs are detected at the end of curative treatment.

We present a detailed study of the properties of the molecular gas in the fast outflow driven by the active galactic nucleus (AGN) in the nearby radio-loud Seyfert galaxy IC 5063. By using ALMA observations of a number of tracers of the molecular gas (12CO(1-0), 12CO(2-1), 12CO(3-2), 13CO(2-1) and HCO+(4-3)), we map the differences in excitation, density and temperature of the gas as function of position and kinematics. The results show that in the immediate vicinity of the radio jet, a fast outflow, with velocities up to 800 km s-1, is occurring of which the gas has high excitation with excitation temperatures in the range 30-55 K, demonstrating the direct impact of the jet on the ISM. The relative brightness of the 12CO lines, as well as that of 13CO(2-1) vs. 12CO(2-1), show that the outflow is optically thin. We estimate the mass of the molecular outflow to be at least 1.2 × 106 M☉ and likely to be a factor between two and three larger than this value. This is similar to that of the outflow of atomic gas, but much larger than that of the ionised outflow, showing that the outflow in IC 5063 is dominated by cold gas. The total mass outflow rate we estimated to be 12 M☉ yr-1. The mass of the outflow is much smaller than the total gas mass of the ISM of IC 5063. Therefore, although the influence of the AGN and its radio jet is very significant in the inner regions of IC 5063, globally speaking the impact will be very modest. We used RADEX non-LTE modelling to explore the physical conditions of the molecular gas in the outflow. Models with the outflowing gas being quite clumpy give the most consistent results and our preferred solutions have kinetic temperatures in the range 20-100 K and densities between 105 and 106 cm-3. The resulting pressures are 106-107.5 K cm-3, about two orders of magnitude higher than in the outer quiescent disk. The highest densities and temperatures are found in the regions with the fastest outflow. The results strongly suggest that the outflow in IC 5063 is driven by the radio plasma jet expanding into a clumpy gaseous medium and creating a cocoon of (shocked) gas which is pushed away from the jet axis resulting in a lateral outflow, very similar to what is predicted by numerical simulations.

We present a detailed study of the properties of the molecular gas in the fast outflow driven by the active galactic nucleus (AGN) in the nearby radio-loud Seyfert galaxy IC 5063. By using ALMA observations of a number of tracers of the molecular gas (12CO(1-0), 12CO(2-1), 12CO(3-2), 13CO(2-1) and HCO+(4-3)), we map the differences in excitation, density and temperature of the gas as function of position and kinematics. The results show that in the immediate vicinity of the radio jet, a fast outflow, with velocities up to 800 km s-1, is occurring of which the gas has high excitation with excitation temperatures in the range 30-55 K, demonstrating the direct impact of the jet on the ISM. The relative brightness of the 12CO lines, as well as that of 13CO(2-1) vs. 12CO(2-1), show that the outflow is optically thin. We estimate the mass of the molecular outflow to be at least 1.2 × 106 M⊙ and likely to be a factor between two and three larger than this value. This is similar to that of the outflow of atomic gas, but much larger than that of the ionised outflow, showing that the outflow in IC 5063 is dominated by cold gas. The total mass outflow rate we estimated to be 12 M⊙ yr-1. The mass of the outflow is much smaller than the total gas mass of the ISM of IC 5063. Therefore, although the influence of the AGN and its radio jet is very significant in the inner regions of IC 5063, globally speaking the impact will be very modest. We used RADEX non-LTE modelling to explore the physical conditions of the molecular gas in the outflow. Models with the outflowing gas being quite clumpy give the most consistent results and our preferred solutions have kinetic temperatures in the range 20-100 K and densities between 105 and 106 cm-3. The resulting pressures are 106-107.5 K cm-3, about two orders of magnitude higher than in the outer quiescent disk. The highest densities and temperatures are found in the regions with the fastest outflow. The results strongly suggest that the outflow in IC 5063 is driven by the radio plasma jet expanding into a clumpy gaseous medium and creating a cocoon of (shocked) gas which is pushed away from the jet axis resulting in a lateral outflow, very similar to what is predicted by numerical simulations.

Alzheimer's and Parkinson's diseases are the most prevalent neurodegenerative diseases that generate important health-related direct and indirect socio-economic costs. They are characterized by severe neuronal losses in several disease-specific brain regions associated with deposits of aggregated proteins. In Alzheimer's disease, beta-amyloid peptide-containing plaques and intraneuronal neurofibrillary tangles composed of hyperphosphorylated microtubule-associated protein tau are the two main neuropathological lesions, while Parkinson's disease is defined by the presence of Lewy Bodies that are intraneuronal proteinaceous cytoplasmic inclusions. alpha-Synuclein has been identified as a major protein component of Lewy Bodies and heavily implicated in the pathogenesis of Parkinson's disease. In the past few years, evidence has emerged to explain how these aggregate-prone proteins can undergo spontaneous self-aggregation, propagate from cell to cell, and mediate neurotoxicity. Current research now indicates that oligomeric forms are probably the toxic species. This article discusses recent progress in the understanding of the pathogenesis of these diseases, with a focus on the underlying mechanisms of protein aggregation, and emphasizes the pathophysiological molecular mechanisms leading to cellular toxicity. Finally, we present the putative direct link between beta-amyloid peptide and tau in causing toxicity in Alzheimer's disease as well as alpha-synuclein in Parkinson's disease, along with some of the most promising therapeutic strategies currently in development for those incurable neurodegenerative disorders.

The ubiquitin-proteasome system (UPS) is the main cellular proteolytic system responsible for the degradation of normal and abnormal (e.g. oxidised) proteins. Under catabolic conditions characterised by chronic inflammation, the UPS is activated resulting in proteolysis, muscle wasting and impaired muscle function. Milk proteins provide sulphur-containing amino acid and have been proposed to affect muscle inflammation. However, the response of the UPS to aseptic inflammation and protein supplementation is largely unknown. The aim of this study was to investigate how milk protein supplementation affects UPS activity and skeletal muscle function under conditions of aseptic injury induced by intense, eccentric exercise. In a double-blind, cross-over, repeated measures design, eleven men received either placebo (PLA) or milk protein concentrate (PRO, 4×20 g on exercise day and 20 g/d for the following 8 days), following an acute bout of eccentric exercise (twenty sets of fifteen eccentric contractions at 30°/s) on an isokinetic dynamometer. In each trial, muscle biopsies were obtained from the vastus lateralis muscle at baseline, as well as at 2 and 8 d post exercise, whereas blood samples were collected before exercise and at 6 h, 1 d, 2 d and 8 d post exercise. Muscle strength and soreness were assessed before exercise, 6 h post exercise and then daily for 8 consecutive days. PRO preserved chymotrypsin-like activity and attenuated the decrease of strength, facilitating its recovery. PRO also prevented the increase of NF-κB phosphorylation and HSP70 expression throughout recovery. We conclude that milk PRO supplementation following exercise-induced muscle trauma preserves proteasome activity and attenuates strength decline during the pro-inflammatory phase.

This study presents detrital zircon U-Pb analyses of 23 samples of the Cycladic Blueschist Unit (CBU) from Kea, Kythnos, and Serifos islands, as well as the Lavrion Peninsula of SE Attica. The maximum depositional ages (MDA) and age distributions of detrital zircon U-Pb dates are used to correlate metasediments between the islands considered herein and infer their provenance. Two distinct detrital zircon U-Pb age distributions are found in CBU metasediments: “Proterozoic,” comprised of >40% Neoproterozoic zircons with Triassic-Early Jurassic maximum depositional ages and “Paleozoic,” containing >30% Paleozoic zircons and yielding Late Jurassic-Cretaceous MDAs. Proterozoic affinity metasediments are rift margin deposits derived from the northern Gondwanan margin. Paleozoic metasediments are flysch sediments most probably sourced from the Internal Hellenides. This metamorphosed flysch forms a distinct marker horizon found in a similar structural position in Lavrion, Kythnos, and Serifos. Based on lithologic correlation, sediment provenance, and MDA estimates, the CBU of Kythnos is correlative to the Lavrion Schists of Attica. On the islands of Serifos and Kythnos and within the Lavrion Schists only young-on-old relationships exist between rocks based on MDA estimates.

PURPOSE: Obstructive sleep apnea (OSA) represents a breathing disorder during sleep with significant health consequences. Few studies have examined the prevalence of OSA in psoriatic patients and whether OSA may be associated with psoriasis risk. We aimed to explore: (1) the inverse relationship, that is whether psoriasis might represent an independent predictor of OSA and its severity considering important predisposing factors and (2) the psoriatic phenotype related to severe OSA. METHODS: In a large hospital-based case-control study, we examined a total of 253 patients with OSA and a control group of 104 subjects without OSA, who underwent full nocturnal polysomnography and dermatologic examination. RESULTS: The prevalence of psoriasis was significantly greater in OSA patients than in controls (p = 0.03). Psoriasis was associated with OSA risk (p = 0.04) but not severity of OSA, sleepiness severity or sleep efficiency, independently from age, gender, anthropometric features, and significant comorbidities. The phenotype of a psoriatic patient suffering from severe OSA is not different from that of a patient with severe OSA and is not associated with psoriasis severity indexes. OSA psoriatic patients were not compliant with CPAP treatment in comparison with OSA patients without psoriasis. CONCLUSION: Psoriasis may represent an independent risk factor for OSA above and beyond significant comorbidities, anthropometric and metabolic parameters. Physicians should be aware of the bi-directional association of psoriasis and OSA. Managing psoriasis may be a potential target for preventing OSA as well as the potential cardiovascular mortality related to OSA and psoriasis.

Η πολιτική οικολογία ασχολείται με ένα μεγάλο εύρος θεμάτων, όπως μεταξύ άλλων, τη θεωρητική και φιλοσοφική ανάλυση της σχέσης κοινωνίας-φύσης, την άνιση πρόσβαση στους φυσικούς πόρους, την υφαρπαγή των κοινών αγαθών, τις πολιτικές διαχείρισης του περιβάλλοντος, τις ποικίλες "διακινδυνεύσεις", τους γεωπολιτικούς ανταγωνισμούς για την εκμετάλλευση πόρων και τα κοινωνικά κινήματα τα οποία αντιστέκονται στα ή/και διεκδικούν τα παραπάνω. Η σημαντική διαφορά με την κυρίαρχη οικολογική σκέψη είναι η πολιτικοποίηση των προβλημάτων, η αναζήτηση κερδισμένων και χαμένων κοινωνικών ομάδων και περιοχών και η επιμονή στα ερωτήματα "γιατί, πώς και πού".Ο τόμος περιλαμβάνει ορισμένες από τις εισηγήσεις που έγιναν στο ομότιτλο σεμινάριο που οργάνωσε το Τμήμα Γεωγραφίας του Χαροκόπειου Πανεπιστημίου στην Αθήνα την περίοδο 2013-2014, ως τμήμα των δράσεων του ευρωπαϊκού προγράμματος ENTITLE.

We carried out a pilot campaign of radio and optical band intra-day variability (IDV) observations of five blazars (3C66A, S5 0716+714, OJ287, B0925+504 and BL Lacertae) on 2015 December 18-21 by using the radio telescope in Effelsberg (Germany) and several optical telescopes in Asia, Europe and America. After calibration, the light curves from both 5 GHz radio band and the optical R band were obtained, although the data were not smoothly sampled over the sampling period of about four days. We tentatively analyse the amplitudes and time-scales of the variabilities, and any possible periodicity. The blazars vary significantly in the radio (except 3C66A and BL Lacertae with only marginal variations) and optical bands on intra- and inter-day time-scales, and the source B0925+504 exhibits a strong quasi-periodic radio variability. No significant correlation between the radio- and optical-band variability appears in the five sources, which we attribute to the radio IDV being dominated by interstellar scintillation whereas the optical variability comes from the source itself. However, the radio- and optical-band variations appear to be weakly correlated in some sources and should be investigated based on well-sampled data from future observations.

Radiatively inefficient accretion flow models have been shown to accurately account for the spectrum and luminosity observed from Sgr A* in the X-ray regime down to mm wavelengths. However, observations at a few GHz cannot be explained by thermal electrons alone but require the presence of an additional non-thermal particle population. Here, we propose a model for the origin of such a population in the accretion flow via means of a pulsar orbiting the supermassive black hole in our Galaxy. Interactions between the relativistic pulsar wind with the disc lead to the formation of a bow shock in the wind. During the pulsar's transit through the accretion disc, relativistic pairs, accelerated at the shock front, are injected into the disc. The radio-emitting particles are long lived and remain within the disc long after the pulsar's transit. Periodic pulsar transits through the disc result in regular injection episodes of non-thermal particles. We show that for a pulsar with spin-down luminosity Lsd ∼ 3 × 1035 erg s-1 and a wind Lorentz factor of γw ∼ 104 a quasi-steady synchrotron emission is established with luminosities in the 1-10 GHz range comparable to the observed one.

This randomized, phase III, open-label, multicenter study compared carfilzomib monotherapy against low-dose corticosteroids and optional cyclophosphamide in relapsed and refractory multiple myeloma (RRMM). Relapsed and refractory multiple myeloma patients were randomized (1:1) to receive carfilzomib (10-min intravenous infusion; 20 mg/m 2 on days 1 and 2 of cycle 1; 27 mg/m 2 thereafter) or a control regimen of low-dose corticosteroids (84 mg of dexamethasone or equivalent corticosteroid) with optional cyclophosphamide (1400 mg) for 28-day cycles. The primary endpoint was overall survival (OS). Three-hundred and fifteen patients were randomized to carfilzomib (n=157) or control (n=158). Both groups had a median of five prior regimens. In the control group, 95% of patients received cyclophosphamide. Median OS was 10.2 (95% confidence interval (CI) 8.4-14.4) vs 10.0 months (95% CI 7.7-12.0) with carfilzomib vs control (hazard ratio=0.975; 95% CI 0.760-1.249; P=0.4172). Progression-free survival was similar between groups; overall response rate was higher with carfilzomib (19.1 vs 11.4%). The most common grade ≥3 adverse events were anemia (25.5 vs 30.7%), thrombocytopenia (24.2 vs 22.2%) and neutropenia (7.6 vs 12.4%) with carfilzomib vs control. Median OS for single-agent carfilzomib was similar to that for an active doublet control regimen in heavily pretreated RRMM patients. © 2017 Macmillan Publishers Limited, part of Springer Nature.

This randomized, phase III, open-label, multicenter study compared carfilzomib monotherapy against low-dose corticosteroids and optional cyclophosphamide in relapsed and refractory multiple myeloma (RRMM). Relapsed and refractory multiple myeloma patients were randomized (1:1) to receive carfilzomib (10-min intravenous infusion; 20 mg/m 2 on days 1 and 2 of cycle 1; 27 mg/m 2 thereafter) or a control regimen of low-dose corticosteroids (84 mg of dexamethasone or equivalent corticosteroid) with optional cyclophosphamide (1400 mg) for 28-day cycles. The primary endpoint was overall survival (OS). Three-hundred and fifteen patients were randomized to carfilzomib (n=157) or control (n=158). Both groups had a median of five prior regimens. In the control group, 95% of patients received cyclophosphamide. Median OS was 10.2 (95% confidence interval (CI) 8.4-14.4) vs 10.0 months (95% CI 7.7-12.0) with carfilzomib vs control (hazard ratio=0.975; 95% CI 0.760-1.249; P=0.4172). Progression-free survival was similar between groups; overall response rate was higher with carfilzomib (19.1 vs 11.4%). The most common grade ≥3 adverse events were anemia (25.5 vs 30.7%), thrombocytopenia (24.2 vs 22.2%) and neutropenia (7.6 vs 12.4%) with carfilzomib vs control. Median OS for single-agent carfilzomib was similar to that for an active doublet control regimen in heavily pretreated RRMM patients. © 2017 Macmillan Publishers Limited, part of Springer Nature.

Background.: A "seek-test-treat" intervention (ARISTOTLE) was implemented in response to an outbreak of human immunodeficiency virus (HIV) infection among persons who inject drugs (PWID) in Athens. We assess trends in HIV incidence, prevalence, risk behaviors and access to prevention/treatment. Methods.: Methods included behavioral data collection, provision of injection equipment, HIV testing, linkage to opioid substitution treatment (OST) programs and HIV care during 5 rounds of respondent-driven sampling (2012-2013). HIV incidence was estimated from observed seroconversions. Results.: Estimated coverage of the target population was 88% (71%-100%; 7113 questionnaires/blood samples from 3320 PWID). The prevalence of HIV infection was 16.5%. The incidence per 100 person-years decreased from 7.8 (95% confidence interval, 4.6-13.1) (2012) to 1.7 (0.55-5.31) (2013; P for trend = .001). Risk factors for seroconversion were frequency of injection, homelessness, and history of imprisonment. Injection at least once daily declined from 45.2% to 18.8% (P < .001) and from 36.8% to 26.0% (P = .007) for sharing syringes, and the proportion of undiagnosed HIV infection declined from 84.3% to 15.0% (P < .001). Current OST increased from 12.2% to 27.7% (P < .001), and 48.4% of unlinked seropositive participants were linked to HIV care through 2013. Repeat participants reported higher rates of adequate syringe coverage, linkage to HIV care and OST. Conclusions.: Multiple evidence-based interventions delivered through rapid recruitment in a large proportion of the population of PWID are likely to have helped mitigate this HIV outbreak.

Background: A "seek-test-treat" intervention (ARISTOTLE) was implemented in response to an outbreak of human immunodeficiency virus (HIV) infection among persons who inject drugs (PWID) in Athens. We assess trends in HIV incidence, prevalence, risk behaviors and access to prevention/treatment. Methods: Methods included behavioral data collection, provision of injection equipment, HIV testing, linkage to opioid substitution treatment (OST) programs and HIV care during 5 rounds of respondent-driven sampling (2012-2013). HIV incidence was estimated from observed seroconversions. Results: Estimated coverage of the target population was 88% (71%-100%; 7113 questionnaires/blood samples from 3320 PWID). The prevalence of HIV infection was 16.5%. The incidence per 100 person-years decreased from 7.8 (95% confidence interval, 4.6-13.1) (2012) to 1.7 (0.55-5.31) (2013; P for trend = .001). Risk factors for seroconversion were frequency of injection, homelessness, and history of imprisonment. Injection at least once daily declined from 45.2% to 18.8% (P < .001) and from 36.8% to 26.0% (P = .007) for sharing syringes, and the proportion of undiagnosed HIV infection declined from 84.3% to 15.0% (P < .001). Current OST increased from 12.2% to 27.7% (P < .001), and 48.4% of unlinked seropositive participants were linked to HIV care through 2013. Repeat participants reported higher rates of adequate syringe coverage, linkage to HIV care and OST. Conclusions: Multiple evidence-based interventions delivered through rapid recruitment in a large proportion of the population of PWID are likely to have helped mitigate this HIV outbreak.

The foundation of NATO on April 4th, 1949 marked in the most exquisite manner the disintegration of the alliance of the US, Great Britain and USSR which lasted during WWII. At the same time it coincided with the introduction of a new post-war system of power equilibrium, with the Cold War as its main characteristic. This total geopolitical confrontation of the two superpowers and their respective satellites extended around the globe, begun in the ruins of post-war Europe, where the long-standing geopolitical ambitions of both sides manifested themselves, reinforced through the reproduction of established myths and stereotypes, as well as national interests. This power equilibrium was based on the framework of values and principles put forth by the UN Charter in 1945 as the bedrock of the postwar international system. The guiding principles of the UN Charter prescribe the delegitimization of the use of violence in international relations as an accepted way of solving international disputes (Articles 2.3 and 2.4), respect of the domestic jurisdiction of any state (Article 2.7), and the right of self-defense, even in its version of collective self defense, as defined in Article 51 (and thereafter in the corresponding Article 5 of the NATO Charter and the corresponding provisions of the Warsaw Pact). The new post-war world order was built amidst an atmosphere of insecurity, fear, distrust and even hate, emanating from both sides. As a consequence Germany was divided between two states, while the whole of Europe was divided between two blocs. The so-called West and the USSR came to a confrontation through the blockade of Berlin by the Soviets (1948-1949). It was during that period that ΝΑΤΟ was created.

HCV global sequences have been classified into 7 genotypes, several subtypes and a number of unassigned sequences. Our aim was to perform an in depth investigation of the taxonomic relationships of the unclassified CYHCV025 strain by means of phylogenetic analysis. Phylogenetic tree reconstructions were performed using ML methods on full-length genomic and partial HCV alignments. Phylogenetic analysis of full-length sequences revealed that CYHCV025 clustered close to the root node of genotype 1, showing distant genetic relationships to all previously classified subtypes and unclassified sequences. Single section analysis using the SSE showed that the distances between the query and all subtypes were much higher than distances within and between subtypes of genotype 1 (p<0.05). Recombination analysis revealed no evidence for intersubtype or genetic mixing between the query and the references from different genotype 1 subtypes. Different analyses revealed that CYHCV025 is the most genetically divergent within genotype 1, showing no high- or low-level clustering with any of the previous subtypes or unclassified sequences. Identification of a single lineage within a genotype without any late branching can be explained by "genetic isolation" until the late stage of HCV epidemic spread.

Integrase strand transfer inhibitors (INSTIs) belong to a novel class of antiretroviral agents that have emerged as the new first-line treatments. Three such compounds are currently available, raltegravir, elvitegravir, dolutegravir and two more under development, bictegravir and cabotegravir. These compounds share the same mode of action but exhibit different pharmacokinetic/ pharmacodynamic properties, and drug-drug interactions. A series of studies in the past decade have established their efficacy compared to previous regimens, both in treatment- naïve and experienced patients. INSTIs have demonstrated a favorable safety profile with fewer adverse events and low rates of virological failure. Emergence of resistance to these agents, however, is a worrying concern, particularly for elvitegravir and raltegravir that display a lower genetic barrier than dolutegravir. On-going trials aim at establishing INSTIs as part of dual-drug HIV treatments or even monotherapy. New long-acting, injectable formulations are under investigation for treatment or prevention.

This study investigates fluid-driven seismicity in the Western Greece area. The region is characterized by the subduction of the Nubia (Africa) plate beneath the Aegean (Eurasia) plate (convergence rate of 40 mm/yr.) and is offset by the right-lateral active Cephalonia transform fault. The Ionian sedimentary basin is composed of thick Jurassic-Eocene carbonate and clastic sedimentary sequences underlain by Triassic evaporites that are thought to intrude through cataclastic zones generating diapiric structures. Due to the active tectonic and the abundance of fluids seeping in this region (with emphasis onshoreWestern Peloponnese) seismicity is often expressed as seismic swarms.To better constrain and investigate the evolution of (possible) fluid-driven seismic sequences we deployed from September 2016 to April 2017 a seismic network spanning 200 km from North to South and about 150 km from east to west. The network is composed of 14 temporary installations, while 9 permanent seismological stations are also considered in our analyses. We present results of accurate earthquake locations using a 1D velocity model developed using VELEST, highlighting regions where seismic activity is focused, and fault plane solutions derived from moment tensor inversion and first motion polarities. During the deployment we recorded several regional earthquakes (i.e. larger than M4.0) that allowed us to verify the effects of incoming seismic energy in this region.

BACKGROUND: Medical informatics, or biomedical and health informatics (BMHI), has become an established scientific discipline. In all such disciplines there is a certain inertia to persist in focusing on well-established research areas and to hold on to well-known research methodologies rather than adopting new ones, which may be more appropriate. OBJECTIVES: To search for answers to the following questions: What are research fields in informatics, which are not being currently adequately addressed, and which methodological approaches might be insufficiently used? Do we know about reasons? What could be consequences of change for research and for education? METHODS: Outstanding informatics scientists were invited to three panel sessions on this topic in leading international conferences (MIE 2015, Medinfo 2015, HEC 2016) in order to get their answers to these questions. RESULTS: A variety of themes emerged in the set of answers provided by the panellists. Some panellists took the theoretical foundations of the field for granted, while several questioned whether the field was actually grounded in a strong theoretical foundation. Panellists proposed a range of suggestions for new or improved approaches, methodologies, and techniques to enhance the BMHI research agenda. CONCLUSIONS: The field of BMHI is on the one hand maturing as an academic community and intellectual endeavour. On the other hand vendor-supplied solutions may be too readily and uncritically accepted in health care practice. There is a high chance that BMHI will continue to flourish as an important discipline; its innovative interventions might then reach the original objectives of advancing science and improving health care outcomes.

Whether there is a change of hepatocellular carcinoma (HCC) incidence in chronic hepatitis B patients under long-term therapy with potent nucleos(t)ide analogues is currently unclear. We therefore assessed the HCC incidence beyond year 5 of entecavir/tenofovir (ETV/TDF) therapy and tried to determine possible factors associated with late HCC occurrence. This European, 10-center, cohort study included 1,951 adult Caucasian chronic hepatitis B patients without HCC at baseline who received ETV/TDF for >/=1 year. Of them, 1,205 (62%) patients without HCC within the first 5 years of therapy have been followed for 5-10 (median, 6.8) years. HCCs have been diagnosed in 101/1,951 (5.2%) patients within the first 5 years and 17/1,205 (1.4%) patients within 5-10 years. The yearly HCC incidence rate was 1.22% within and 0.73% after the first 5 years (P = 0.050). The yearly HCC incidence rate did not differ within and after the first 5 years in patients without cirrhosis (0.49% versus 0.47%, P = 0.931), but it significantly declined in patients with cirrhosis (3.22% versus 1.57%, P = 0.039). All HCCs beyond year 5 developed in patients older than 50 years at ETV/TDF onset. Older age, lower platelets at baseline and year 5, and liver stiffness >/=12 kPa at year 5 were independently associated with more frequent HCC development beyond year 5 in multivariable analysis. No patient with low Platelets, Age, Gender-Hepatitis B score at baseline or year 5 developed HCC. CONCLUSION: The HCC risk decreases beyond year 5 of ETV/TDF therapy in Caucasian chronic hepatitis B patients, particularly in those with compensated cirrhosis; older age (especially >/=50 years), lower platelets, and liver stiffness >/=12 kPa at year 5 represent the main risk factors for late HCC development. (Hepatology 2017;66:1444-1453).

Osteoarthritis is a slowly progressive disease which includes the intervention of several cytokines, macrophage metalleinoproteinases reaction, leading to the degradation of the local cartilage but also having an impact on the serum acute phase proteins (APPs). Subsequently, biomarkers seem to be essential to estimate its progression and the need for any surgical intervention such as total arthroplasty, but also can be used as therapeutic agents. Recently, among APPs, fetuin A drew attention regarding its possible anti-inflammatory role in animal models but also as a therapeutic agent in the inflammatory joint disease in clinical trials. In contrast with other APPs such as C-reactive protein, fetuin A appears to be lower in the serum of patients with degenerative joint disease in comparison with the healthy ones, and also acts as an antagonist of the anti-proliferative potential of transforming growth factor-β (TGF-β) cytokines. Because of its lower serum levels in arthritis, an unregulated binding of TGF-β and bone morphogenetic proteins takes place leading to further arthritic lesions. The purpose of the present review is to assess the current evidence regarding the multipotent role of the alpha-2-HS-glycoprotein or as also known Fetuin-a in animal models but also as a biomarker of the degenerative joint arthritis in clinical trials.

Glycosaminoglycans are integral part of the dynamic extracellular matrix (ECM) network that control crucial biochemical and biomechanical signals required for tissue morphogenesis, differentiation, homeostasis and cancer development. Breast cancer cells communicate with stromal ones to modulate ECM mainly through release of soluble effectors during cancer progression. The intracellular cross-talk between cell surface receptors and estrogen receptors is important for the regulation of breast cancer cell properties and production of ECM molecules. In turn, reorganized ECM-cell surface interface modulates signaling cascades, which regulate almost all aspects of breast cell behavior. Heparan sulfate chains present on cell surface and matrix proteoglycans are involved in regulation of breast cancer functions since they are capable of binding numerous matrix molecules, growth factors and inflammatory mediators thus modulating their signaling. In addition to its anticoagulant activity, there is accumulating evidence highlighting various anticancer activities of heparin and nano-heparin derivatives in numerous types of cancer. Importantly, heparin derivatives significantly reduce breast cancer cell proliferation and metastasis in vitro and in vivo models as well as regulates the expression profile of major ECM macromolecules, providing strong evidence for therapeutic targeting. Nano-formulations of the glycosaminoglycan heparin are possibly novel tools for targeting tumor microenvironment. In this review, the role of heparan sulfate/heparin and its nano-formulations in breast cancer biology are presented and discussed in terms of future pharmacological targeting.

AbstractWe employ Real-Time Time-Dependent Density Functional Theory to study hole oscillations within a B-DNA monomer (one base pair) or dimer (two base pairs). Placing the hole initially at any of the bases which make up a base pair, results in THz oscillations, albeit of negligible amplitude. Placing the hole initially at any of the base pairs which make up a dimer is more interesting: For dimers made of identical monomers, we predict oscillations with frequencies in the range f≈ 20–40 THz, with a maximum transfer percentage close to 1. For dimers made of different monomers, f≈ 80–400 THz, but with very small or small maximum transfer percentage. We compare our results with those obtained recently via our Tight-Binding approaches and find that they are in good agreement.

X-ray surveys are believed to be the most efficient way to detect AGN. Recently though, optical variability studies are claimed to probe even fainter AGN. We are presenting results from an HST study aimed to identify Active Galactic Nuclei (AGN) through optical variability selection in the CDFS.. This work is part of the 'Hubble Catalogue of Variables'project of ESA that aims to identify variable sources in the Hubble Source Catalogue.' In particular, we used Hubble Space Telescope (HST) z-band images taken over 5 epochs and performed aperture photometry to derive the lightcurves of the sources. Two statistical methods (standard deviation & interquartile range) resulting in a final sample of 175 variable AGN candidates, having removed the artifacts by visual inspection and known stars and supernovae. The fact that the majority of the sources are extended and variable indicates AGN activity. We compare the efficiency of the method by comparing with the 7Ms Chandra detections. Our work shows that the optical variability probes AGN at comparable redshifts but at deeper optical magnitudes. Our candidate AGN (non detected in X-rays) have luminosities of L_x<6×10^{40} erg/sec at z∼0.7 suggesting that these are associated with low luminosity Seyferts and LINERS.

The site response during a strong earthquake event may be proven crucial for earthquake hazard assessment and risk mitigation. Two moderate magnitude earthquakes that occurred in early 2014 in Cephalonia produced the largest ground motion values ever recorded in Greece, highly exceeding the provisions of the effective seismic code implying for local effects. This motivated the investigation of site response in the epicentral area presented herein.

Haumea—one of the four known trans-Neptunian dwarf planets—is a very elongated and rapidly rotating body. In contrast to other dwarf planets, its size, shape, albedo and density are not well constrained. The Centaur Chariklo was the first body other than a giant planet known to have a ring system, and the Centaur Chiron was later found to possess something similar to Chariklo’s rings. Here we report observations from multiple Earth-based observatories of Haumea passing in front of a distant star (a multi-chord stellar occultation). Secondary events observed around the main body of Haumea are consistent with the presence of a ring with an opacity of 0.5, width of 70 kilometres and radius of about 2,287 kilometres. The ring is coplanar with both Haumea’s equator and the orbit of its satellite Hi’iaka. The radius of the ring places it close to the 3:1 mean-motion resonance with Haumea’s spin period—that is, Haumea rotates three times on its axis in the time that a ring particle completes one revolution. The occultation by the main body provides an instantaneous elliptical projected shape with axes of about 1,704 kilometres and 1,138 kilometres. Combined with rotational light curves, the occultation constrains the three-dimensional orientation of Haumea and its triaxial shape, which is inconsistent with a homogeneous body in hydrostatic equilibrium. Haumea’s largest axis is at least 2,322 kilometres, larger than previously thought, implying an upper limit for its density of 1,885 kilograms per cubic metre and a geometric albedo of 0.51, both smaller than previous estimates. In addition, this estimate of the density of Haumea is closer to that of Pluto than are previous estimates, in line with expectations. No global nitrogen- or methane-dominated atmosphere was detected.

Photonic band gap engineered TiO2 inverse opals were fabricated using self- assembled polystyrene films as sacrificial templates with controlled optical properties, aimed at the identification of the slow-photon effect on dye sensitized TiO2 photocatalysis. The materials’ photocatalytic efficiency was evaluated using Raman spectroscopy, on methylene blue photodegradation following both UVA and monochromatic visible light illumination. Contrary to UVA, where no photonic effect could be traced, laser irradiation within the slow-photon energy range of the TiO2 inverse opals, resulted in a marked increase of the dye photosensitized degradation rate, outperforming not only compact nanocrystalline films but also the benchmark mesoporous Aeroxide® P25 TiO2 films. This effect provides direct evidence for the presence of slow photons that amplify the interaction of visible light with the adsorbed dye molecules on the periodically structured TiO2 film.

Photonic band gap engineered TiO2 inverse opals were fabricated using self-assembled polystyrene films as sacrificial templates with controlled optical properties, aimed at the identification of the slow-photon effect on dye sensitized TiO2 photocatalysis. The materials’ photocatalytic efficiency was evaluated using Raman spectroscopy, on methylene blue photodegradation following both UVA and monochromatic visible light illumination. Contrary to UVA, where no photonic effect could be traced, laser irradiation within the slow-photon energy range of the TiO2 inverse opals, resulted in a marked increase of the dye photosensitized degradation rate, outperforming not only compact nanocrystalline films but also the benchmark mesoporous Aeroxide® P25 TiO2 films. This effect provides direct evidence for the presence of slow photons that amplify the interaction of visible light with the adsorbed dye molecules on the periodically structured TiO2 film. © 2017 Elsevier B.V.