Miracle-dz/UniFAR-FTUs huggingface dataset:
FTO Obesity Variant Circuitry and Adipocyte Browning in Humans.

BACKGROUND Genomewide association studies can be used to identify disease-relevant genomic regions, but interpretation of the data is challenging. The FTO region harbors the strongest genetic association with obesity, yet the mechanistic basis of this association remains elusive. METHODS We examined epigenomic data, allelic activity, motif conservation, regulator expression, and gene coexpression patterns, with the aim of dissecting the regulatory circuitry and mechanistic basis of the association between the FTO region and obesity. We validated our predictions with the use of directed perturbations in samples from patients and from mice and with endogenous CRISPR-Cas9 genome editing in samples from patients. RESULTS Our data indicate that the FTO allele associated with obesity represses mitochondrial thermogenesis in adipocyte precursor cells in a tissue-autonomous manner. The rs1421085 T-to-C single-nucleotide variant disrupts a conserved motif for the ARID5B repressor, which leads to derepression of a potent preadipocyte enhancer and a doubling of IRX3 and IRX5 expression during early adipocyte differentiation. This results in a cell-autonomous developmental shift from energy-dissipating beige (brite) adipocytes to energy-storing white adipocytes, with a reduction in mitochondrial thermogenesis by a factor of 5, as well as an increase in lipid storage. Inhibition of Irx3 in adipose tissue in mice reduced body weight and increased energy dissipation without a change in physical activity or appetite. Knockdown of IRX3 or IRX5 in primary adipocytes from participants with the risk allele restored thermogenesis, increasing it by a factor of 7, and overexpression of these genes had the opposite effect in adipocytes from nonrisk-allele carriers. Repair of the ARID5B motif by CRISPR-Cas9 editing of rs1421085 in primary adipocytes from a patient with the risk allele restored IRX3 and IRX5 repression, activated browning expression programs, and restored thermogenesis, increasing it by a factor of 7. CONCLUSIONS Our results point to a pathway for adipocyte thermogenesis regulation involving ARID5B, rs1421085, IRX3, and IRX5, which, when manipulated, had pronounced pro-obesity and anti-obesity effects. (Funded by the German Research Center for Environmental Health and others.).
Investigating the cross-linguistic potential of VerbNet-style classification

Verb classes which integrate a wide range of linguistic properties (Levin, 1993) have proved useful for natural language processing (NLP) applications. However, the real-world use of these classes has been limited because for most languages, no resources similar to VerbNet (Kipper-Schuler, 2005) are available. We apply a verb clustering approach developed for English to French - a language for which no such experiment has been conducted yet. Our investigation shows that not only the general methodology but also the best performing features are transferable between the languages, making it possible to learn useful VerbNet style classes for French automatically without language-specific tuning.
Maternal age at first birth and offspring criminality: Using the children of twins design to test causal hypotheses

Abstract Teenage childbirth is a risk factor for poor offspring outcomes, particularly offspring antisocial behavior. It is not clear, however, if maternal age at first birth (MAFB) is causally associated with offspring antisocial behavior or if this association is due to selection factors that influence both the likelihood that a young woman gives birth early and that her offspring engage in antisocial behavior. The current study addresses the limitations of previous research by using longitudinal data from Swedish national registries and children of siblings and children of twins comparisons to identify the extent to which the association between MAFB and offspring criminal convictions is consistent with a causal influence and confounded by genetic or environmental factors that make cousins similar. We found offspring born to mothers who began childbearing earlier were more likely to be convicted of a crime than offspring born to mothers who delayed childbearing. The results from comparisons of differentially exposed cousins, especially born to discordant monozygotic twin sisters, provide support for a causal association between MAFB and offspring criminal convictions. The analyses also found little evidence for genetic confounding due to passive gene–environment correlation. Future studies are needed to replicate these findings and to identify environmental risk factors that mediate this causal association.
Effects of different dosages of propylene glycol in dry cows and cows in early lactation

In this Research Paper we hypothesised that the temporary insulin resistance seen during the transition period in dairy cows may cause significant differences in the efficacy of PG at different sampling periods and that in some cases this effect will be dose dependent. Eighty four sampling sets were generated by studying 7 multiparous Holstein cows repeatedly at 4 sampling periods of 3 d length (dry cows: days 40, 39 and 38 antepartum; close up cows: days 10, 9 and 8 antepartum; fresh cows: days 3, 4 and 5 post-partum; lactating cows: days 38, 39 and 40 post-partum). On each of these days 3 h after morning feeding propylene glycol was drenched in different dosages of 100, 300 or 500 ml once per day (cross over study). The different doses were applied in an alternating order (Latin square). Blood samples were taken before, every 30 min up to 4 h, after 6 and 12 h after PG application. Following parameters have been measured: insulin, non-esterified fatty acids (NEFA), betahydroxybutyrate (BHB), bilirubin, cholesterol, potassium, aspartate aminotransferase (AST) and glutamate dehydrogenase (GLDH). Revised Quantitative Insulin Sensitivity Check Index (RQUICKI) was calculated. It was found that glucose, insulin, NEFA, BHB, bilirubin and potassium concentrations were influenced differently by the three defined dosages of propylene glycol at four different sampling periods. Whereas RQUICKI, cholesterol, AST and GLDH did not differ between the sampling periods and treatments. The major results of the study are that the effect of PG is dose-dependent and that the effect of PG is depending on the time of application according to calving. It can be concluded that in fresh cows higher dosages are necessary to provoke similar effects in comparison to dry, close up and lactating cows. Although the study did not compare to topdressing of PG from the results it is reasonable to believe that bolus application of a specific PG volume is necessary to provoke the effect.
The Methylenetetrahydrofolate Reductase C677T Polymorphism and Risk for Late-Onset Alzheimer's disease: Further Evidence in an Italian Multicenter Study.

BACKGROUND A functional polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene, namely C677T (rs1801133), results in increased Hcy levels and has been associated with risk of late-onset Alzheimer's disease (LOAD). Many investigators reported association between rs1801133 and LOAD risk in Asian populations and in carriers of the apolipoprotein E (APOE) ɛ4 allele, but recent meta-analyses suggest a contribution also in other populations, including Caucasians and/or northern Africans. OBJECTIVE To further address this issue, we performed a relatively large case-control study, including 581 LOAD patients and 468 matched controls of Italian origin. APOE data were available for a subgroup of almost 600 subjects. METHODS Genotyping for rs1801133 was performed with PCR-RFLP techniques. RESULTS In the total population, the MTHFR 677T allele (OR = 1.20; 95% CI = 1.01-1.43) and carriers of the MTHFR 677T allele (CT+TT versus CC: OR = 1.34; 95% CI = 1.03-1.73) resulted in increased LOAD risk. Similarly, in APOEɛ4 carriers, we observed an increased frequency of MTHFR 677CT carriers (CT versus CC: OR = 2.82; 95% CI = 1.25-6.32). Very interestingly, also in non-APOEɛ4 carriers, both MTHFR 677T allele (OR = 1.38; 95% CI = 1.03-1.85) and MTHFR 677TT genotype (OR = 2.08; 95% CI = 1.11-3.90) were associated with LOAD. All these associations survived after corrections for age, gender, and multiple testing. CONCLUSIONS The present results suggest that the MTHFR C677T polymorphism is likely a LOAD risk factor in our cohort, either in APOEɛ4 or in non-APOEɛ4 carriers.
Learning to Work with Trauma Survivors: Lessons from Tbilisi, Georgia

Survivors of armed conflict may experience traumatic stress, psychological symptoms, distress, or other behavioral health issues related to the disaster of war. This article outlines the historical background of the Russian-Georgian war, details the implementation of social work in the developing country of Georgia, and describes the training and application of social work knowledge and values using macro and micro examples of interventions that provide Masters of social work students and social workers with tools to address the needs of refugees affected by disaster. Following the macro- and microexamples, pedagogy and implications for social workers and social work students working with victims of trauma with few available resources are discussed.
Transvaginal sonographic assessment of cervix in prediction of admission to delivery interval in preterm premature rupture of membranes

Abstract Objective: To assess the usefulness of cervical parameters measured by transvaginal sonography, that is, cervical length and posterior cervical angle, in predicting the admission to delivery interval in women with preterm rupture of membranes. Methods: This prospective study was conducted in a tertiary care centre in South India. Women with preterm premature rupture of membranes at 28–34 weeks, confirmed clinically, not in labour and presenting within 24 hours to hospital were included. We evaluated the relationship between latency interval and transvaginal sonographic parameters (cervical length and posterior cervical angle), parity, age, Amniotic Fluid Index (AFI), total leucocyte count at admission using Cox proportional hazards model. Results: Mean time interval between the membrane rupture and delivery was 96.9 h. Majority of the women (63.8% (n = 51)) delivered within 48 hours. Transvaginal sonographic cervical length was not shown to be associated with latency interval (p = .559), whereas. Posterior cervical angle was shown to be significantly associated with the interval (hazard ratio 1.03, 95%CI: 1.01–1.06; p = .003) Conclusions: Posterior cervical angle assessment using transvaginal sonography is an useful tool in the assessing the latency interval in women with preterm premature rupture of membranes (PPROM). This could help in counselling and planning timely referral to centres with neonatal facilities.
LEARN THE DISTRIBUTION ? S OME T HEORY AND E MPIRICS

Do GANS (Generative Adversarial Nets) actually learn the target distribution? The foundational paper of Goodfellow et al. (2014) suggested they do, if they were given “sufficiently large” deep nets, sample size, and computation time. A recent theoretical analysis in Arora et al. (2017) raised doubts whether the same holds when discriminator has bounded size. It showed that the training objective can approach its optimum value even if the generated distribution has very low support —in other words, the training objective is unable to prevent mode collapse. The current paper makes two contributions. (1) It proposes a novel test for estimating support size using the birthday paradox of discrete probability. Using this evidence is presented that well-known GANs approaches do learn distributions of fairly low support. (2) It theoretically studies encoder-decoder GANs architectures (e.g., BiGAN/ALI), which were proposed to learn more meaningful features via GANs and (consequently) to also solve the mode-collapse issue. Our result shows that such encoder-decoder training objectives also cannot guarantee learning of the full distribution because they cannot prevent serious mode collapse. More seriously, they cannot prevent learning meaningless codes for data, contrary to usual intuition.
Mechanical Behaviour of Polypropylene And Human Hair Fibres And Polypropylene Reinforced Polymeric Composites

Bio fibres have recently become eye-catching to researchers, engineers and scientist as an alternative reinforcement for FRP (fibre reinforced polymer) composite. Due to their low cost, fairly good mechanical properties, high aspect strength . Three to four ton of human hair fibre wasted in India annually . These fibre pose an environmental challenge In order to find commercial application the wasted human hair fibre mixed with polypropylene. Polypropylene based composite are prepared using hair fibre obtained from human hair. Human hair fibres are mixed into polypropylene (PP) at 3,5,10 and 15 % by wt. using two roll mills. The composite are compression moulded at specific time and temperature. Polypropylene and hair fibre polymer reinforced composite have better flexural and impact strength than PP (Polypropylene) and lower the tensile strength of polypropylene and hair fibre polymer reinforced composite than (PP) polypropylene. Keyword : human hair fibre, composite, mechanical properties, polypropylene
Replication of Type 2 Diabetes Candidate Genes Variations in Three Geographically Unrelated Indian Population Groups

Type 2 diabetes (T2D) is a syndrome of multiple metabolic disorders and is genetically heterogeneous. India comprises one of the largest global populations with highest number of reported type 2 diabetes cases. However, limited information about T2D associated loci is available for Indian populations. It is, therefore, pertinent to evaluate the previously associated candidates as well as identify novel genetic variations in Indian populations to understand the extent of genetic heterogeneity. We chose to do a cost effective high-throughput mass-array genotyping and studied the candidate gene variations associated with T2D in literature. In this case-control candidate genes association study, 91 SNPs from 55 candidate genes have been analyzed in three geographically independent population groups from India. We report the genetic variants in five candidate genes: TCF7L2, HHEX, ENPP1, IDE and FTO, are significantly associated (after Bonferroni correction, p<5.5E−04) with T2D susceptibility in combined population. Interestingly, SNP rs7903146 of the TCF7L2 gene passed the genome wide significance threshold (combined P value = 2.05E−08) in the studied populations. We also observed the association of rs7903146 with blood glucose (fasting and postprandial) levels, supporting the role of TCF7L2 gene in blood glucose homeostasis. Further, we noted that the moderate risk provided by the independently associated loci in combined population with Odds Ratio (OR)<1.38 increased to OR = 2.44, (95%CI = 1.67–3.59) when the risk providing genotypes of TCF7L2, HHEX, ENPP1 and FTO genes were combined, suggesting the importance of gene-gene interactions evaluation in complex disorders like T2D.
Trimodal system for in vivo skin cancer screening with combined optical coherence tomography‐Raman and colocalized optoacoustic measurements

A new multimodal system for rapid, noninvasive in vivo skin cancer screening is presented, combining optical coherence tomography (OCT) and optoacoustic (OA) modalities to provide precise tumor depth determination with a Raman spectroscopic modality capable of detecting the lesion type and, thus, providing diagnostic capability. Both OA and Raman setups use wide field skin illumination to ensure the compliance with maximum permissible exposure (MPE) requirements. The Raman signal is collected via the OCT scanning lens to maximize the signal‐to‐noise ratio of the measured signal while keeping radiation levels below MPE limits. OCT is used to optically determine the tumor thickness and for volumetric imaging whereas OA utilizes acoustic signals generated by optical absorption contrast for thickness determination at potentially higher penetration depths compared to OCT. Preliminary results of first clinical trials using our setup are presented. The measured lesion depth is in good agreement with histology results, while Raman measurements show distinctive differences between normal skin and melanocytic lesions, and, moreover, between different skin areas. In future, we will validate the setup presented for reliable detection of pathophysiological parameters, morphology and thickness of suspicious skin lesions.
Performance Evaluation of Layered and Cross Layered based MANETs

The versatile Ad hoc Networks provides communication among wireless nodes which occurs in the wireless medium. Energy effective routing in MANET [5] is a demanding goal which should be taken under consideration. Moreover, energy effective routing is considered to be the most important design criteria for MANETs because mobile nodes will be powered by batteries with limited capacity. The architecture of ad hoc network protocol, generally based on a conventional ‘‘layered approach’’, has been found ineffective to deal with, energy efficient routing and breakage of links in MANET [5]. This paper proposes a Cross Layer based MANET framework to minimize the energy consumption [3] and maximize the network lifetime with comparison to conventional layered architecture. Further the different performance metrics evaluation such as PDR, energy and number of collisions based on simulated scenarios is performed for Layered and Cross Layered based MANET. Furthermore, enhancing the cross-layer communication [1, 18] among different layers, such as network layer, MAC layer and physical layer. The proposed Cross-Layer based AODV (CLAODV) would help to minimize energy consumption and to find an effectual route between the source and the destination, achieving the maximum network
What Is the Evidence That the Tissue Doppler Index E/e′ Reflects Left Ventricular Filling Pressure Changes After Exercise or Pharmacological Intervention for Evaluating Diastolic Function? A Systematic Review

Background Noninvasive echocardiographic tissue Doppler assessment (E/e′) in response to exercise or pharmacological intervention has been proposed as a useful parameter to assess left ventricular (LV) filling pressure (LVFP) and LV diastolic dysfunction. However, the evidence for it is not well summarized. Methods and Results Clinical studies that evaluated invasive LVFP changes in response to exercise/other interventions and echocardiographic E/e′ were identified from PubMed, Scopus, Embase, and Cochrane Library databases. We grouped and evaluated studies that included patients with preserved LV ejection fraction (LVEF), patients with mixed/reduced LVEF, and patients with specific cardiac conditions. Overall, we found 28 studies with 9 studies for preserved LVEF, which was our primary interest. Studies had differing methodologies with limited data sets, which precluded quantitative meta‐analysis. We therefore descriptively summarized our findings. Only 2 small studies (N=12 and 10) directly or indirectly support use of E/e′ for assessing LVFP changes in preserved LVEF. In 7 other studies (cumulative N=429) of preserved LVEF, E/e′ was not useful for assessing LVFP changes. For mixed/reduced LVEF groups or specific cardiac conditions, results similar to preserved LVEF were found. Conclusions We find that there is insufficient evidence that E/e′ can reliably assess LVFP changes in response to exercise or other interventions. We suggest that well‐designed prospective studies should be conducted for further evaluation.
An Algorithmic Framework to Control Bias in Bandit-based Personalization

Personalization is pervasive in the online space as it leads to higher efficiency and revenue by allowing the most relevant content to be served to each user. However, recent studies suggest that personalization methods can propagate societal or systemic biases and polarize opinions; this has led to calls for regulatory mechanisms and algorithms to combat bias and inequality. Algorithmically, bandit optimization has enjoyed great success in learning user preferences and personalizing content or feeds accordingly. We propose an algorithmic framework that allows for the possibility to control bias or discrimination in such bandit-based personalization. Our model allows for the specification of general fairness constraints on the sensitive types of the content that can be displayed to a user. The challenge, however, is to come up with a scalable and low regret algorithm for the constrained optimization problem that arises. Our main technical contribution is a provably fast and low-regret algorithm for the fairness-constrained bandit optimization problem. Our proofs crucially leverage the special structure of our problem. Experiments on synthetic and real-world data sets show that our algorithmic framework can control bias with only a minor loss to revenue.
CEO Deal-Making Activities and Compensation

Using transactions generally overlooked in the compensation literature—joint ventures, strategic alliances, seasoned equity offerings (SEOs), and spin-offs—we find that, beyond compensation for increases in firm size or complexity, chief executive officers (CEOs) are rewarded for their deal-making activities. Boards pay CEOs for the core motivation of the deal, as well as for deal volume. We find that compensating for volume instead of core value creation occurs under weak board monitoring and that in deal-making firms, neither CEO turnover nor pay-for-performance responds to underperformance. We introduce an input monitoring explanation for these results: boards compensate for deal volume because of their inability to perfectly monitor outputs.
Cyclosporine A, 2.5 mg/kg, Does Not Reduce Myocardial Infarct Size in a Porcine Model of Ischemia and Reperfusion

Background: In recent years, cyclosporine A (CsA) has emerged as a promising therapy to limit myocardial ischemic–reperfusion injury, presumably by inhibiting the opening of the mitochondrial permeability transition pore. Results from different large animal models are conflicting, however, with failure to prove beneficial effects of 10 mg/kg CsA administered at reperfusion. Recently, a small clinical study using a bolus of 2.5 mg/kg CsA showed promising but not unequivocal results. The aim of the present study was to estimate the magnitude of a possible infarct reduction with the use of the latter regimen in a closed-chest porcine model for ischemia and reperfusion. Materials and Methods: Pigs underwent catheterization with balloon occlusion of the left descending coronary artery for 40 minutes, followed by reperfusion for 4 hours. They were randomized to receive an intravenous bolus 7 minutes before reperfusion of either 2.5 mg/kg CsA (n = 12) or saline (control, n = 11). Hearts were stained to quantify area at risk and infarct size. Results: Throughout the experiment, there were no differences between the groups in baseline characteristics or hemodynamic variables. CsA treatment did not reduce infarct size as a proportion of area at risk compared with control (51% ± 6% and 54% ± 6%, respectively, P = .75). Conclusion: In a closed-chest porcine model for myocardial ischemia and reperfusion injury, 2.5 mg/kg CsA administered before reperfusion did not reduce infarct size.