Miracle-dz/UniFAR-FTUs huggingface dataset:
A physical model for tiling array analysis

MOTIVATION Chromatin immunoprecipitation (ChIP) is a powerful experimental approach to identify in vivo binding sites of sequence-specific transcription factors (TFs). These experiments are designed to specifically enrich DNA fragments that are bound to the TF. Tiling arrays have become more and more popular for the identification of these DNA fragments. However, many studies showed that only a fraction of the identified DNA fragments contains bona fide binding sites for the TF, suggesting that indirect binding mechanisms play a very important role. We explored the possibility that the lack of binding sites can also be explained by problems in identifying ChIP-enriched DNA fragments from the measured intensities. RESULTS We derived a physical model that explains some (but not all) variation of the measured probe intensities of Affymetrix tiling arrays. We used the physical model to estimate the probe-specific behavior and corrected for it. Subsequently, we developed a method to identify ChIP-enriched DNA fragments. We termed it physical model for tiling array analysis (PMT). We applied PMT to the data of ChIP-chip experiments interrogating chromosome 21 and 22 of the human genome for binding of the TFs MYC, SP1 and P53. Almost all regions recovered by PMT showed evidence for sequence-specific binding of the TFs.
Characterization of Isoenzyme-Selective Inhibitors of Human Sphingosine Kinases

Sphingosine kinases (SKs) are promising new therapeutic targets for cancer because they regulate the balance between pro-apoptotic ceramides and mitogenic sphingosine-1-phosphate. The functions of the two SK isoenzymes, SK1 and SK2, are not redundant, with genetic ablation of SK2 having more pronounced anticancer effects than removal of SK1. Although several small molecule inhibitors of SKs have been described in the literature, detailed characterization of their molecular and cellular pharmacology, particularly their activities against human SK1 and SK2, have not been completed. Computational modeling of the putative active sites of SK1 and SK2 suggests structural differences that might allow isozyme-selective inhibitors. Therefore, we characterized several SK-inhibitory compounds which revealed differential inhibitory effects on SK1 and SK2 as follows: SKI-II and ABC294735 are SK1/2-dual inhibitors; CB5468139 is a SK1-selective inhibitor; and ABC294640 is a SK2-selective inhibitor. We examined the effects of the SK inhibitors on several biochemical and phenotypic processes in A498 kidney adenocarcinoma cells. The SK2-selective inhibitor ABC294640 demonstrated the most pronounced effects on SK1 and SK2 mRNA expression, decrease of S1P levels, elevation of ceramide levels, cell cycle arrest, and inhibition of proliferation, migration and invasion. ABC294640 also down-regulated the expression or activation of several signaling proteins, including STAT3, AKT, ERK, p21, p53 and FAK. These effects were equivalent or superior to responses to the SK1/2-dual inhibitors. Overall, these results suggest that inhibition of SK2 results in stronger anticancer effects than does inhibition of SK1 or both SK1 and SK2.
Relevance of Germline Mutation Screening in Both Familial and Sporadic Head and Neck Paraganglioma for Early Diagnosis and Clinical Management

Background: Head and neck paraganglioma (PGL) are benign tumors that can cause important direct or surgery induced morbidity. Almost all familial and 11–29% of sporadic PGL are caused by inactivating germline mutations in succinate dehydrogenase (SDH) genes. Our aim was to screen for such mutations and to evaluate clinical parameters as predictors of germline mutation. Methods: Seventy-four PGL patients were analyzed for germline mutations and large deletions in SDH genes, VHL and RET. Results were correlated to clinical characteristics including gender, age, tumor localization and multifocality. The surgical approach was evaluated in terms of tumor origin, sequelae and subsequent evolution. Results: Mutations in SDHB and SDHD were identified in equal proportion in 13/13 (100%) of familial and in 15/61 (25%) of sporadic cases. Familiarity, age ≤50 years and male gender were predictors of any germline mutation, while multifocality and carotid/vagal localization were indicative of SDHD mutation in particular. Conclusions: In contrast to other series, this cohort of Spanish patients showed many SDHB mutations. Sporadic cases with germline mutation are frequent and underline the importance of mutational screening of all PGL patients, allowing the identification of relatives at risk and the early diagnosis of the disease, reducing or avoiding morbidity.
Development of Small Diameter Nanofiber Tissue Engineered Arterial Grafts

The surgical repair of heart and vascular disease often requires implanting synthetic grafts. While synthetic grafts have been successfully used for medium-to-large sized arteries, applications for small diameter arteries (<6 mm) is limited due to high rates of occlusion by thrombosis. Our objective was to develop a tissue engineered vascular graft (TEVG) for small diameter arteries. TEVGs composed of polylactic acid nanofibers with inner luminal diameter between 0.5 and 0.6 mm were surgically implanted as infra-renal aortic interposition conduits in 25 female C17SCID/bg mice. Twelve mice were given sham operations. Survival of mice with TEVG grafts was 91.6% at 12 months post-implantation (sham group: 83.3%). No instances of graft stenosis or aneurysmal dilatation were observed over 12 months post-implantation, assessed by Doppler ultrasound and microCT. Histologic analysis of explanted TEVG grafts showed presence of CD31-positive endothelial monolayer and F4/80-positive macrophages after 4, 8, and 12 months in vivo. Cells positive for α-smooth muscle actin were observed within TEVG, demonstrating presence of smooth muscle cells (SMCs). Neo-extracellular matrix consisting mostly of collagen types I and III were observed at 12 months post-implantation. PCR analysis supports histological observations. TEVG group showed significant increases in expressions of SMC marker, collagen-I and III, matrix metalloproteinases-2 and 9, and itgam (a macrophage marker), when compared to sham group. Overall, patency rates were excellent at 12 months after implantation, as structural integrity of these TEVG. Tissue analysis also demonstrated vessel remodeling by autologous cell.
Prenatal Exposure to Sodium Arsenite Alters Placental Glucose 1, 3, and 4 Transporters in Balb/c Mice

Inorganic arsenic (iAs) exposure induces a decrease in glucose type 4 transporter (GLUT4) expression on the adipocyte membrane, which may be related to premature births and low birth weight infants in women exposed to iAs at reproductive age. The aim of this study was to analyze the effect of sodium arsenite (NaAsO2) exposure on GLUT1, GLUT3, and GLUT4 protein expression and on placental morphology. Female Balb/c mice (n = 15) were exposed to 0, 12, and 20 ppm of NaAsO2 in drinking water from 8th to 18th day of gestation. Morphological changes and GLUT1, GLUT3, and GLUT4 expression were evaluated in placentas by immunohistochemical and image analysis and correlated with iAs and arsenical species concentration, which were quantified by atomic absorption spectroscopy. NaAsO2 exposure induced a significant decrease in fetal and placental weight (P < 0.01) and increases in infarctions and vascular congestion. Whereas GLUT1 expression was unchanged in placentas from exposed group, GLUT3 expression was found increased. In contrast, GLUT4 expression was significantly lower (P < 0.05) in placentas from females exposed to 12 ppm. The decrease in placental GLUT4 expression might affect the provision of adequate fetal nutrition and explain the low fetal weight observed in the exposed groups.
A Social Conscience in the Global Marketplace? Labour Dimensions of Codes of Conduct, Social Labelling and Investor Initiatives

This article analyzes the increasing phenomena of voluntary private sector initiatives in social responsibility and assesses the public impact of the privatized pursuit of social justice. It concludes that the social concerns at the root of the phenomenon under review are a welcome development, yet a number of limitations appear inherent in the very nature of the initiatives. A lack of transparency and of participation by the supposed beneficiaries is attributable to their unilateral origin. Selectivity in the nature of the labour issues addressed as well as an absence of uniformity in the definition of principles underlying best practices result in a disparity between the goals of many initiatives and the universal principles underlying fundamental labour standards. Further limitations in measuring the impact of labour-related goals result from a lack of standardization of labour criteria and methods of implementation, as well as the variability of the external and internal environments of the enterprises concerned. Such limitations have been exposed in a review of more than 200 codes, social labels, investment-fund screening programmes and shareholder initiatives focusing on labour practices.
Psychopathy, the Big Five and empathy as predictors of violence in a forensic sample of substance abusers

Abstract It is widely recognized that substance abuse increases the general risk of delinquency and violent offenses in particular. Substance-related disorders are the primary cause of offenders being sentenced to mandatory treatment in forensic psychiatry. However, instead of a mono-causal link between addiction and violence, additional risk factors must be assumed. The current study examined the relations between psychopathy, empathy and general personality traits and their role in statistically predicting violent crimes of substance-abusing offenders. The sample consisted of 164 male and female forensic inpatients with substance-related disorders. They were administered the German versions of the Psychopathic Personality Inventory (PPI-R), the NEO Personality Inventory (NEO-PI-R) and the Interpersonal Reactivity Index (SPF). The psychopathy factor Impulsive Antisociality (IA) emerged as a positive statistical predictor of violent offenses, while Fearless Dominance (FD) served as a negative predictor. The Big Five factors and empathy domains failed to statistically predict violence, despite showing significant correlations with the psychopathy factors. Hence, substance-abusing violent offenders display a distinct pattern of personality characteristics with IA being associated with high Neuroticism, low Agreeableness and low Conscientiousness, as well as high Personal Distress and low Perspective Taking. IA therefore reflects a maladaptive trait that is overrepresented in forensic settings.
Efficacy beliefs as a moderator of the impact of work-related stressors: a multilevel study.

This study built on previous exploratory research (S. M. Jex & D. M. Gudanowski, 1992) that examined both self-efficacy and collective efficacy as moderators of stressor-strain relations. Based on survey data collected from 2,273 U.S. Army soldiers representing 36 companies, it was found that both self- and collective efficacy moderated the relationship between stressors and strains. Multilevel random coefficient model results revealed that respondents with strong self-efficacy reacted less negatively in terms of psychological and physical strain to long work hours and work overload than did those reporting low levels of efficacy. In addition, respondents with high levels of self-efficacy responded more positively in terms of job satisfaction to tasks with high significance than did those with low efficacy. The results also revealed that group-level collective efficacy moderated the relationship between work overload and job satisfaction and between task significance and organizational commitment. Limitations of the study and implications of these findings are discussed.
Body Mass Index and Risk of Rheumatoid Arthritis

AbstractAlthough many epidemiological studies have investigated the association between body mass index (BMI) and risk of rheumatoid (RA), the results have been inconsistent. Therefore, we performed a dose-response meta-analysis to quantify the dose-response association between BMI and RA risk.We systematically searched PubMed, Embase, and Web of Science databases and reference lists of articles for relevant studies published before August 2014 using terms related to BMI and RA. Fixed or random-effects models were used to estimate the pooled relative risk (RR) with 95% confidence interval (CI). Several subgroup analyses, sensitivity analyses, and publication bias tests were performed to explore potential study heterogeneity and biasThirteen studies involving 400,609 participants and 13,562 RA cases were included. The RR of RA was 1.21 (95% CI: 1.02–1.44) for obesity, 1.05 (95% CI: 0.97–1.13) for overweight. The risk of RA increased by 13% (RR: 1.13; 95% CI: 1.01–1.26) for every 5 kg/m2 increase in BMI. The subgroup analyses showed a positive association between BMI and RA risk only in women with an RR of 1.26 (95% CI: 1.12–1.40) for obesity and 1.12(95% CI: 1.07–1.18) for every 5 kg/m2 increase in BMI. Also, an increased risk of RA was found in sero-negative subgroup with an RR of 1.47 (95% CI: 1.11–1.96) for obesity and 1.21 (95% CI: 1.06–1.39) for every 5 kg/m2 increase in BMI.There is evidence that obesity is a risk factor for developing of RA. Furthermore, the positive association between BMI and RA risk may be stronger among women than men.
Thermal conductance through molecular wires

We consider phononic heat transport through molecular chains connecting two thermal reservoirs. For relatively short molecules at normal temperatures we find, using classical stochastic simulations, that heat conduction is dominated by the harmonic part of the molecular force-field. We develop a general theory for the heat conduction through harmonic chains in three-dimensions. Our approach uses the standard formalism that leads to the generalized ~quantum! Langevin equation for a system coupled to a harmonic heat bath, however the driving and relaxation terms are considered separately in a way that leads directly to the steady-state response and the heat current under nonequilibrium driving. A Landauer-type expression for the heat conduction is obtained, in agreement with other recent studies. We used this general formalism to study the heat conduction properties of alkane. We find that for relatively short ~1‐30 carbon molecules! the length and temperature dependence of the molecular heat conduction results from the balance of three factors: ~i! The molecular frequency spectrum in relation to the frequency cutoff of the thermal reservoirs, ~ii! the degree of localization of the molecular normal modes and ~iii! the molecule‐heat reservoirs coupling. The fact that molecular modes at different frequency regimes have different localization properties gives rise to intricate dependence of the heat conduction on molecular length at different temperature. For example, the heat conduction increases with molecular length for short molecular chains at low temperatures. Isotopically substituted disordered chains are also studied and their behavior can be traced to the above factors together with the increased mode localization in disordered chain and the increase in the density of low frequency modes associated with heavier mass substitution. Finally, we compare the heat conduction obtained from this microscopic calculation to that estimated by considering the molecule as a cylinder characterized by a macroscopic heat conduction typical to organic solids. We find that this classical model overestimates the heat conduction of single alkane molecules by about an order of magnitude at room temperature. Implications of the present study to the problem of heating in electrically conducting molecular junctions are pointed out. © 2003 American Institute of Physics. @DOI: 10.1063/1.1603211#
Exploring the effects of polls on public opinion: How and when media reports of policy preferences can become self-fulfilling prophesies

Recent work has suggested that media reporting about the public’s policy preferences may be self-reinforcing, contributing to greater policy conformity. This article presents additional evidence in support of this theory and adds new detail about the conditionality of these effects. Results from two experiments are described in which respondents are presented with excerpted news stories containing varying polling information about six separate issues. Findings indicate that (a) exposure to such poll results can elicit differences in support for the issue by as much as 10–15 percentage points; (b) the magnitude of these effects varies systematically and inversely in relation to overall attitudinal intensity levels for each issue; and (c) the opinions of specific subgroups referenced in polls matter, producing larger or smaller effects depending on how salient the group is to receivers of the information. Taken together, these results underscore why news reporting about public attitudes deserves greater attention as an important factor in the policy process.
Predictors of adverse events in surgical admissions in Australia.

OBJECTIVE The purpose of this study was to determine risk factors of adverse events in five surgical procedures. DESIGN Retrospective record review was used to determine adverse events and risk factors of 1,177 surgical admissions. Procedures included in this study were transurethral resection of prostate, hysterectomy, hip and knee arthroplasty, cholecystectomy and herniorrhaphy. Risk factors included comorbidity, lifestyle factors and medications. Stepwise multiple logistic regression was used to determine predictors of adverse events. SETTING Two teaching hospitals in regional New South Wales, Australia. PARTICIPANTS 1,177 surgical admissions for five high volume procedures. MAIN OUTCOME MEASURES Identified predictors of adverse events in surgical admissions. RESULTS The adverse event rate was 23.1% for all procedures (range 17.5-33.7% for the five procedures). Two factors were strongly predictive of an adverse event in all surgical admissions: age >70 years [odds ratio (OR) 1.9, 95% confidence intervals (CI) 1.3-2.6] and duration of operation (P = 0.005). Other predictive factors were: contaminated surgical site (OR 2.1, 95% CI 1.2-3.7) and anaemia (OR 1.8, 95% CI 1.1-2.8). Predictive factors of individual procedures included: urine retention (transurethral resection of the prostate); extended duration of operation and asthma (hysterectomy); acute admissions and extended duration of operation (cholecystectomy); and warfarin type drugs, ethanol abuse, failed prostheses, GI ulcer/inflammation, rheumatoid arthritis, and ischaemic heart disease (hip and knee joint arthroplasty). CONCLUSIONS The results of this study suggest that five factors should be routinely monitored for patients undergoing these procedures: age >70 years, type of procedure, duration of operation >2 h, contaminated surgical site and anaemia.
Promoting Preschoolers’ Emotional Competence Through Prosocial TV and Mobile App Use

ABSTRACT This study explored the relationship between preschoolers’ exposure to Daniel Tiger’s Neighborhood television programming and its accompanying mobile app and preschoolers’ emotion knowledge and use of emotion regulation strategies. An experiment involving 121 parent-child dyads from 3 US metro areas found that children who played with the Daniel Tiger’s Neighborhood app, and those who both played with the app and watched episodes of the program, employed the emotion regulation strategies taught by Daniel Tiger’s Neighborhood media more frequently 1 month later than children in a control condition. Preschoolers (3- and 4-year-olds) also exhibited higher levels of emotion knowledge 1 month after playing with the app. In addition, watching Daniel Tiger’s Neighborhood TV episodes in the home led to increases in parents’ provision of active mediation. Implications for families, educators, and producers of educational media content are discussed.
Pharmacodynamics of Trovafloxacin, Ofloxacin, and Ciprofloxacin against Streptococcus pneumoniae in an In Vitro Pharmacokinetic Model

ABSTRACT An in vitro pharmacokinetic model was used to simulate the pharmacokinetics of trovafloxacin, ofloxacin, and ciprofloxacin in human serum and to compare their pharmacodynamics against eightStreptococcus pneumoniae strains. The MICs of ofloxacin and ciprofloxacin ranged from 1 to 2 μg/ml. Trovafloxacin was 8- to 32-fold more potent, with MICs of 0.06 to 0.12 μg/ml. Logarithmic-phase cultures were exposed to peak concentrations of trovafloxacin, ofloxacin, or ciprofloxacin achieved in human serum after 200-, 400-, and 750-mg oral doses, respectively. Trovafloxacin was dosed at 0 and 24 h, and ofloxacin and ciprofloxacin were dosed at 0, 12, and 24 h. Human elimination pharmacokinetics were simulated, and viable bacterial counts were measured at 0, 2, 4, 6, 8, 12, 24, and 36 h. Trovafloxacin was rapidly and significantly bactericidal against all eight strains evaluated, with viable bacterial counts decreasing at least 5 logs to undetectable levels. Times to 99.9% killing were only 1 to 3 h. Although the rate of killing with ofloxacin was substantially slower than that with trovafloxacin, ofloxacin was also able to eradicate all eight strains from the model, despite a simulated area under the inhibitory curve/MIC ratio (AUC/MIC) of only 49. In contrast, ciprofloxacin eradicated only five strains (AUC/MIC = 44) from the model. Against the other three strains (AUC/MIC = 22), the antibacterial activity of ciprofloxacin was substantially diminished. These data corroborate clinical data and suggest that trovafloxacin has a pharmacodynamic advantage over ciprofloxacin and ofloxacin against S. pneumoniae in relation to its enhanced antipneumococcal activity.
The Relationship between Iranian English High School Teachers’ Reflective Practices, Their Self-Regulation and Teaching Experience

The study examined the relationship between English teachers’ reflective practices and their self-regulation. It also explored the relationships between self-regulation and teachers’ teaching experiences. To achieve the goal of the study, 103 English teachers from different senior and junior high schools were selected through convenience sampling based on availability and based on their consent to participate in the study. They were asked to complete two questionnaires: the English Language Teaching Reflection Inventory (ELTRI) and the Teacher SelfRegulation Scale (TSRS). The relationship between teachers’ reflective practices and their self-regulation was examined by running Spearman correlation coefficient formula. Additionally, the power of reflection and the teachers’ experiences in predicting English teachers’ self-regulation was investigated by running a multiple regression analysis. The findings revealed a positive relationship between the teachers’ reflective practices and their self-regulation. Nevertheless, there were no significant relationships between teachers’ selfregulation and their experiences. Reflective practice was also found to be a strong predictor of self-regulation. In light of the results gained, a list of reflective practice techniques for improving English teachers’ teaching quality and selfregulation in teacher education were suggested. The results of this study have implications for English language teachers, researchers and teacher trainers in Iran and abroad.