Miracle-dz/UniFAR-FTUs huggingface dataset:
Bisphenol A‐associated alterations in the expression and epigenetic regulation of genes encoding xenobiotic metabolizing enzymes in human fetal liver

Alterations in xenobiotic metabolizing enzyme (XME) expression across the life course, along with genetic, nutritional, and environmental regulation, can influence how organisms respond to toxic insults. In this study, we investigated the hypothesis that in utero exposure to the endocrine active compound, bisphenol A (BPA), influences expression and epigenetic regulation of phase I and II XME genes during development. Using healthy 1st to 2nd trimester human fetal liver specimens quantified for internal BPA levels, we examined XME gene expression using PCR Array (n = 8) and RNA‐sequencing (n = 12) platforms. Of the greater than 160 XME genes assayed, 2 phase I and 12 phase II genes exhibited significantly reduced expression with higher BPA levels, including isoforms from the carboxylesterase, catechol O‐methyltransferase, glutathione S‐transferase, sulfotransferase, and UDP‐glucuronosyltransferase families. When the promoters of these candidate genes were evaluated in silico, putative binding sites for the E‐twenty‐six (ETS) and activator protein1 (AP1) related transcription factor families were identified and unique to 97% of all candidate transcripts. Interestingly, many ETS binding sites contain cytosine‐guanine dinucleotides (CpGs) within their consensus sequences. Thus, quantitative analysis of CpG methylation of three candidate genes was conducted across n = 50 samples. Higher BPA levels were associated with increased site‐specific methylation at COMT (P < 0.005) and increased average methylation at SULT2A1 (P < 0.020) promoters. While toxicological studies have traditionally focused on high‐dose effects and hormonal receptor mediated regulation, our findings suggest the importance of low‐dose effects and nonclassical mechanisms of endocrine disruption during development. Environ. Mol. Mutagen. 55:184–195, 2014. © 2013 Wiley Periodicals, Inc.
Radial keyhole sequences for low field projection reconstruction interventional MRI

Interventional magnetic resonance imaging (IMRI) is a rapidly emerging application for MRI in which diagnostic and therapeutic procedures are performed with MR image guidance. Real‐time or near‐real‐time image acquisition and relative insensitivity to motion are essential for most intraoperative, therapeutic, and diagnostic procedures performed under MR guidance. The purpose of this work was to demonstrate the development and utility of two alternative rapid acquisition strategies during IMRI that are analogous to computed tomography fluoroscopy or keyhole MRI in a radial rather than rectilinear coordinate frame. The two strategies discussed here, interleaved projection reconstruction and continuous projection reconstruction, are compared and the feasibility of their application in experimental interventional applications is studied. J. Magn. Reson. Imaging 2001;13:142–151. © 2001 Wiley‐Liss, Inc.
Validation of SECI Model in Education

The use of Knowledge Management (KM) is increasingly relevant to education as our knowledge of factors influencing the effective managing of information and knowledge resources. It is important that educational organizations understand the application of strategies for managing the knowledge resources and providing appropriate access to this information within the University context. This article examines data collected from students doing the Software Engineering Program at UNSW. This data is used to analyse the industrial SECI model of KM as applied to the educational domain. We are looking at the validity of the empirical evidence. Results indicated that the data provided a valid study of KM in this context.
Effectiveness of a brief cognitive-behavioural therapy intervention in the treatment of schizophrenia.

BACKGROUND Little evidence exists to indicate whether community psychiatric nurses can achieve the results reported by expert cognitive-behavioural therapists in patients with schizophrenia. AIMS To assess the effectiveness and safety of a brief cognitive-behavioural therapy (CBT) intervention in a representative community sample of patients with schizophrenia in secondary care settings. METHOD A pragmatic randomised trial was performed involving 422 patients and carers to compare a brief CBT intervention against treatment as usual. RESULTS Patients who received CBT (n=257) improved in overall symptomatology (P=0.015; number needed to treat [NNT]=13), insight (P<0.001; NNT=10) and depression (P=0.003; NNT=9) compared with the control group (n=165). Insight was clinically significantly improved (risk ratio=1.15, 95% CI 1.01-1.31). There was no increase in suicidal ideation. CONCLUSIONS Community psychiatric nurses can safely and effectively deliver a brief CBT intervention to patients with schizophrenia and their carers.
Murine Gammaherpesvirus 68 Infection of Gamma Interferon-Deficient Mice on a BALB/c Background Results in Acute Lethal Pneumonia That Is Dependent on Specific Viral Genes

ABSTRACT Gamma interferon (IFN-γ) is critical for the control of chronic infection with murine gammaherpesvirus 68 (γHV68). Current data indicate that IFN-γ has a lesser role in the control of acute replication of γHV68. Here, we show that IFN-γ-deficient mice on the BALB/c genetic background poorly control acute viral replication and succumb to early death by acute pneumonia. Notably, this acute, lethal pneumonia was dependent not only on the viral dose, but also on specific viral genes including the viral cyclin gene, previously identified to be important in promoting optimal chronic infection and reactivation from latency.
Probing the safety of medications in the frail elderly: evidence from a randomized clinical trial of sertraline and venlafaxine in depressed nursing home residents.

BACKGROUND In nursing home residents and other frail elderly patients, old age and potential drug-drug and drug-disease interactions may affect the relative safety and efficacy of medications. The purpose of this study was to examine the efficacy and tolerability of venlafaxine and sertraline for the treatment of depression among nursing home residents. METHOD The study was a 10-week randomized, double-blind, controlled trial of venlafaxine (doses up to 150 mg/day) versus sertraline (doses up to 100 mg/day) among 52 elderly nursing home residents with a DSM-IV depressive disorder and, at most, moderate dementia. The primary measure of outcome was the Hamilton Rating Scale for Depression (HAM-D). Adverse events were monitored and recorded systematically during the trial. RESULTS Twelve subjects were discontinued due to serious adverse events (SAE), 5 were discontinued due to other significant side effects, and 2 withdrew consent. Tolerability estimated by the time to termination was lower for venlafaxine than sertraline for serious adverse events (log rank statistic = 5.28, p =.022), for serious adverse events or side effects (log rank statistic = 8.08, p =.005), or for serious adverse events, side effects, or withdrawal of consent (log rank statistic = 10.04, p =.002). Mean (SD) HAM-D scores at baseline were 20.2 (3.4) for sertraline and 20.3 (3.7) for venlafaxine; intent-to-treat endpoint HAM-D scores were 12.2 (5.1) and 15.7 (6.2) (F = 3.45; p =.069). There were no differences in categorical responses for the intent-to-treat sample or completers. CONCLUSION In this frail elderly population, venlafaxine was less well tolerated and, possibly, less safe than sertraline without evidence for an increase in efficacy. This unexpected finding demonstrates the need for systematic research on the safety of drugs in the frail elderly.
Locomotor performance of closely related Tropidurus species: relationships with physiological parameters and ecological divergence

SUMMARY Tropidurid lizards have colonized a variety of Brazilian open environments without remarkable morphological variation, despite ecological and structural differences among habitats used. This study focuses on two Tropidurus sister-species that, despite systematic proximity and similar morphology, exhibit great ecological divergence and a third ecologically generalist congeneric species providing an outgroup comparison. We quantified jumping capacity and sprint speed of each species on sand and rock to test whether ecological divergence was also accompanied by differences in locomotor performance. Relevant physiological traits possibly associated with locomotor performance – metabolic scopes and fiber type composition, power output and activity of the enzymes citrate synthase, pyruvate kinase and lactate dehydrogenase of the iliofibularis muscle – were also compared among the three Tropidurus species. We found that the two sister-species exhibited remarkable differences in jumping performance, while Tropidurus oreadicus, the more distantly related species, exhibited intermediate values. Tropidurus psamonastes, a species endemic to sand dunes, exhibited high absolute sprint speeds on sand, jumped rarely and possessed a high proportion of glycolytic fibers and low activity of citrate synthase. The sister-species Tropidurus itambere, endemic to rocky outcrops, performed a large number of jumps and achieved lower absolute sprint speed than T. psamonastes. This study provides evidence of rapid divergence of locomotor parameters between sister-species that use different substrates, which is only partially explained by variation in physiological parameters of the iliofibularis muscle.
ARE : Automated Reverse Engineering of Machine Code

Binary code analysis is a challenging problem, but it is essential for many applications such as program analysis, verification, security, and optimization. BAE Systems developed the Automated Reverse Engineering (ARE) system for binary analysis to detect potential flaws in software and find inputs that steer program execution to reach areas of interest such as unexplored instructions, dangerous operations, or desired functionality. At a high level, the system provides a unique combination of static and dynamic analyses, efficient program databases, flexible constraint systems, and advanced software defect detection. This paper describes the major components of the ARE system, explains how they work together, and illustrates the steps of a demonstration.
Effect of high-frequency resistance exercise on adaptive responses in skeletal muscle.

PURPOSE Regulation of skeletal muscle mass is highly dependent on contractile loading. The purpose of this study was to examine changes in growth factor and inflammatory pathways following high-frequency resistance training. METHODS Using a novel design in which male Sprague-Dawley rats undertook a "stacked" resistance training protocol designed to generate a summation of transient exercise-induced signaling responses (four bouts of three sets x 10 repetitions of squat exercise, separated by 3 h of recovery), we determined the effects of high training frequency on signaling pathways and transcriptional activity regulating muscle mass. RESULTS The stacked training regimen resulted in acute suppression of insulin-like growth factor 1 mRNA abundance (P < 0.05) and Akt phosphorylation (P < 0.05), an effect that persisted 48 h after the final training bout. Conversely, stacked training elicited a coordinated increase in the expression of tumor necrosis factor alpha, inhibitor kappa B kinase alpha/beta activity (P < 0.05), and p38 mitogen-activated protein kinase phosphorylation (P < 0.05) at 3 h after each training bout. In addition, the stacked series of resistance exercise bouts induced an increase in p70 S6 kinase phosphorylation 3 h after bouts x3 and x4, independent of the phosphorylation state of Akt. CONCLUSIONS Our results indicate that high resistance training frequency extends the transient activation of inflammatory signaling cascades, concomitant with persistent suppression of key mediators of anabolic responses. We provide novel insights into the effects of the timing of exercise-induced overload and recovery on signal transduction pathways and transcriptional activity regulating skeletal muscle mass in vivo.
R104H may suppress transthyretin amyloidogenesis by thermodynamic stabilization, but not by the kinetic mechanism characterizing T119 interallelic trans-suppression

The tetrameric protein transthyretin (TTR) forms amyloid fibrils upon dissociation and subsequent monomer misfolding, enabling misassembly. Remarkably, the aggregation of one of over 100 destabilized TTR variants leads to familial amyloid disease. It is known that trans-suppression mediated by the incorporation of T119M subunits into tetramers otherwise composed of the most common familial variant V30M, ameliorates disease by substantially slowing the rate of tetramer dissociation, a mechanism referred to as kinetic stabilization of the native state. R104H TTR has been reported to be non-pathogenic, and recently, this variant has been invoked as a trans-suppressor of amyloid fibril formation. Here, we demonstrate that the trans-suppression mechanism of R104H does not involve kinetic stabilization of the tetrameric structure, instead its modest trans-suppression most likely results from the thermodynamic stabilization of the tetrameric TTR structure. Thermodynamic stabilization increases the fraction of tetramer at the expense of the misfolding competent monomer decreasing the ability of TTR to aggregate into amyloid fibrils. As a consequence of this stabilization mechanism, R104H may be capable of protecting patients with modestly destabilizing mutations against amyloidosis by slightly lowering the overall population of monomeric protein that can misfold and form amyloid.
Imputing continuous data under some non‐Gaussian distributions

There has been a growing interest regarding generalized classes of distributions in statistical theory and practice because of their flexibility in model formation. Multiple imputation under such distributions that span a broader area in the symmetry–kurtosis plane appears to have the potential of better capturing real incomplete data trends. In this article, we impute continuous univariate data that exhibit varying characteristics under two well‐known distributions, assess the extent to which this procedure works properly, make comparisons with normal imputation models in terms of commonly accepted bias and precision measures, and discuss possible generalizations to the multivariate case and to larger families of distributions.
Determinants of the species selectivity of oxazolidinone antibiotics targeting the large ribosomal subunit

Abstract Oxazolidinone antibiotics bind to the highly conserved peptidyl transferase center in the ribosome. For developing selective antibiotics, a profound understanding of the selectivity determinants is required. We have performed for the first time technically challenging molecular dynamics simulations in combination with molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) free energy calculations of the oxazolidinones linezolid and radezolid bound to the large ribosomal subunits of the eubacterium Deinococcus radiodurans and the archaeon Haloarcula marismortui. A remarkably good agreement of the computed relative binding free energy with selectivity data available from experiment for linezolid is found. On an atomic level, the analyses reveal an intricate interplay of structural, energetic, and dynamic determinants of the species selectivity of oxazolidinone antibiotics: A structural decomposition of free energy components identifies influences that originate from first and second shell nucleotides of the binding sites and lead to (opposing) contributions from interaction energies, solvation, and entropic factors. These findings add another layer of complexity to the current knowledge on structure-activity relationships of oxazolidinones binding to the ribosome and suggest that selectivity analyses solely based on structural information and qualitative arguments on interactions may not reach far enough. The computational analyses presented here should be of sufficient accuracy to fill this gap.
Detection of Movement Disorders Using Multi SVM By

Gait analysis is very significant for early diagnosis of gait diseases and treatment assessment. Gait analysis is used to assess, plan and to treat the individuals with conditions affecting their ability to walk. In recent years, doctors gain more clarity and exact disease assessment by means of machine learning technologies and this has gained much application of gait analysis. The patients suffering from movement disorders such as Parkinson’s disease (PD), Huntington’s disease (HD), and Amyotrophic Lateral Sclerosis (ALS) can best be diagnosed by gait analysis. For these reasons, analysis of the above said diseases are taken into consideration. In this paper we propose an effective method for detection of movement disorders using multi SVM technique.
Development of an optimised culture medium for keratocytes in monolayer.

UNLABELLED Our objective was to formulate a medium for monolayer culture optimising both keratocyte growth and preservation of the keratocyte phenotype. METHODS An experimental matrix selected 14 media to test, using 7 components. Selection criteria were growth rates over 5 passages and expression of the CD34 marker. RESULTS Acetylcholine, insulin and vitamin C had no effect on growth and differentiation. The DMEM + Ham F12 1 : 1 based medium was selected for its initial effect on growth. At concentrations of 5 ng/ml, b-FGF improved the percentage of CD34+ cells without reducing growth rates. New-born calf serum (NCS) had a greater effect on growth than foetal calf serum (FCS). We showed three major interactions: between b-FGF and IGF-1, FCS and IGF-1 and NCS and b-FGF. CONCLUSION We selected the following medium, which provides optimal growth and preservation of the CD34+ phenotype: DMEM/HAM-F12 + 10% NCS + 5 ng/ml b-FGF + antibiotics.
Studies in forced compliance: commitment and magnitude of inducement to comply as determinants of opinion change.

Abstract : Subjects were enticed to record a strongly counterattitudinal statement about an important issue under three levels of commitment (anonymous audio recording, identified video recording with subsequent explanation or identified video recording with no opportunity to recant). 1/2 of the subjects were paid $. 50 to make the recording; the other 1/2 were paid $2.50 for the counterattitudinal task. In the two higher commitment conditions (identified video recording), subjects given low financial inducement showed significantly more attitude change than those given the large reward. In the low commitment (anonymous audio recording) condition, large amounts of money produced more attitude change. (Author)
Cuscore Statistics to Monitor a Non‐stationary System

We investigate the monitoring of a process subject to minimum mean‐squared error feedback control using cumulative score (Cuscore) charts. Specifically, we design Cuscore statistics to discover spike, step, bump, and ramp signals hidden in non‐stationary disturbance for feedback‐controlled processes. We develop the adjustment and monitoring policies for combinations of process dynamics, disturbance, and signal that are practical in industry. We also address issues of detection probabilities and distributions using simulation. A manufacturing case study is used to illustrate the utility of the Cuscore approach. Copyright © 2006 John Wiley & Sons, Ltd.
Relative efficacy of chelating agents on excretion and tissue distribution of manganese in mice

The effect of repeated parenteral administration of a number of structurally diverse chelating agents on the excretion and tissue distribution of manganese was assessed in mice following 4 weeks of manganese exposure. Males Swiss mice received s.c. injections of manganese(II) chloride tetrahydrate (8.9 mg Mn kg−1 body wt.) for 4 weeks (5 days per week). After the end of this exposure period, cyclohexanediaminetetraacetic acid (CDTA), ethyleneglycol‐bis‐(β‐aminoethylether)‐NN'‐tetraacetic acid (EGTA), N‐(2‐hydroxyethyl)ethylenediamine triacetic acid (HEDTA), isonicotinyl hydrazine (INH), L‐dopa, sodium 4,5‐dihydroxy‐1,3‐benzenedisulphonate (Tiron), p‐aminosalicylic acid (PAS) or 0.9% saline (control group) were given i.p. for five consecutive days. The doses of the chelators were approximately equal to one‐eighth of their respective LD50 values. Urine and faeces were daily collected for 5 days. Twenty‐four hours after the final chelator injection, mice were killed and manganese concentrations were determined in various tissues. Although CDTA, EGTA and HEDTA significantly enhanced the elimination of manganese into urine, none of the chelators increased faecal excretion. Tissue concentrations of manganese were significantly reduced only by CDTA. According to these results, among the compounds tested only CDTA would mobilize effectively manganese in manganese‐loaded mice.
A trust-region derivative-free algorithm for constrained optimization

We propose a trust-region algorithm for constrained optimization problems in which the derivatives of the objective function are not available. In each iteration, the objective function is approximated by a model obtained by quadratic interpolation, which is then minimized within the intersection of the feasible set with the trust region. Since the constraints are handled in the trust-region subproblems, all the iterates are feasible even if some interpolation points are not. The rules for constructing and updating the quadratic model and the interpolation set use ideas from the BOBYQA software, a largely used algorithm for box-constrained problems. The subproblems are solved by ALGENCAN, a competitive implementation of an Augmented Lagrangian approach for general-constrained problems. Some numerical results for the Hock–Schittkowski collection are presented, followed by a performance comparison between our proposal and three derivative-free algorithms found in the literature.