Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of environmental chemicals with estrogenic activity using a combination of in vitro assays.

Environmental chemicals that function as estrogens have been suggested to be associated with an increase in disease and dysfunctions in animals and humans. To characterize chemicals that may act as estrogens in humans, we have compared three in vitro assays which measure aspects of human estrogen receptor (hER)-mediated estrogenicity. Chemicals were first tested for estrogen-associated transcriptional activity in the yeast estrogen screen (YES). This was created by expressing hER and two estrogen response elements linked to the lacZ gene in yeast. Second, chemicals that were tested in YES were then assayed for direct interaction with hER in a competition binding assay. Third, chemicals were tested in the estrogen-responsive MCF-7 human breast cancer cell line transiently transfected with a plasmid containing two estrogen response elements linked to the luciferase gene. Together, these assays have identified two metabolites of DDT, o,p'-DDD and p,p'-DDD, that have estrogenic activity. Interestingly, previous studies had reported that the DDD metabolites were nonestrogenic in whole animal models. Alachlor, the most frequently used herbicide in the United States, cis-nonachlor, and trans-nonachlor displayed weak estrogenic activity in the combined assays. The antifungal agent benomyl had no estrogenic activity. We propose that a combination of in vitro assays can be used in conjunction with whole animal models for a more complete characterization of chemicals with estrogenic activity. ImagesFigure 1.Figure 2. AFigure 2. BFigure 3.Figure 4.Figure 5.
ISLG 2015 Fourth Workshop on Intelligent Support for Learning in Groups

This paper introduces learner model negotiation not only as a means to increase the accuracy of the learner model and promote metacognitive activities as in past examples, but also as a way to help learners correct peer assessment entries in their learner model, that they consider inaccurate. While open learner models are not new, and negotiated learner models have been developed before, in today’s learning contexts of potentially big data from many sources including other learners, some kind of approach to managing the data as well as helping learners to understand and accept it, or correct it, is needed.
Neural Changes Associated with Nonspeech Auditory Category Learning Parallel Those of Speech Category Acquisition

Native language experience plays a critical role in shaping speech categorization, but the exact mechanisms by which it does so are not well understood. Investigating category learning of nonspeech sounds with which listeners have no prior experience allows their experience to be systematically controlled in a way that is impossible to achieve by studying natural speech acquisition, and it provides a means of probing the boundaries and constraints that general auditory perception and cognition bring to the task of speech category learning. In this study, we used a multimodal, video-game-based implicit learning paradigm to train participants to categorize acoustically complex, nonlinguistic sounds. Mismatch negativity (MMN) responses to the nonspeech stimuli were collected before and after training, and changes in MMN resulting from the nonspeech category learning closely resemble patterns of change typically observed during speech category learning. This suggests that the often-observed “specialized” neural responses to speech sounds may result, at least in part, from the expertise we develop with speech categories through experience rather than from properties unique to speech (e.g., linguistic or vocal tract gestural information). Furthermore, particular characteristics of the training paradigm may inform our understanding of mechanisms that support natural speech acquisition.
Job-related stress and sickness absence among belgian nurses: a prospective study.

PURPOSE The purpose of this study was to investigate the influence of job stress on sickness absence of nurses and determine the predictive power of the Demand-Control-Support (DCS) model, the Effort-Reward Imbalance-Overcommitment (ERI-OC) model, and a combination of both. DESIGN A survey was conducted to measure job stress in a sample of 527 Belgian nurses, followed by prospective data collection of sickness absence (long-term, short-term, and multiple episodes). FINDINGS Perceptions of job strain and ERI increased the odds for long-term (adjusted odds ratio [OR] = 2.26; 99% confidence interval [CI; 1.27-4.04]) and multiple episodes of sickness absence (adjusted OR = 1.64; 95% CI [1.01-2.65]). Iso-strain and ERI-OC increased the odds for long-term (OR = 1.75; 95% CI [0.98-3.11]), multiple episode (adjusted OR = 1.93; 95% CI [1.14-3.26]), and short-term (adjusted OR = 1.69; 95% CI [1.03-2.76]) sickness absence. CONCLUSIONS The combined model of DCS and ERI-OC predicts the odds for long-term and short-term sickness absence and multiple episodes. CLINICAL RELEVANCE This study has implications for human resources management in nursing organizations. Nursing administrators are advised to monitor and balance nurses' job demands and efforts. They should recognize the importance of social support, job control, job rewards, and overcommitment in order to reduce the job stress of nurses.
Silica-gold nanoparticles for atheroprotective management of plaques: results of the NANOM-FIM trial.

BACKGROUND Atheroregression becomes an attractive target for cardiovascular treatment. Some clinical trials have demonstrated that intensive therapy with rosuvastatin or recombinant ApoA-I Milano can partially reduce the total atheroma volume (TAV) up to 6.38 mm(3) or 14.1 mm(3) respectively. Our previous bench studies of selected nanotechnologies documented TAV reduction up to an unprecedented 79.4 mm(3). METHODS The completed observational three arms (n = 180) first-in-man trial (the NANOM FIM trial) assessed (NCT01270139) the safety and feasibility of two delivery techniques for nanoparticles (NP), and plasmonic photothermal therapy (PPTT). Patients were assigned to receive either (1) nano-intervention with delivery of silica-gold NP in a bioengineered on-artery patch (n = 60), or (2) nano-intervention with delivery of silica-gold iron-bearing NP with targeted micro-bubbles and stem cells using a magnetic navigation system (n = 60) versus (3) stent implantation (n = 60). The primary outcome was TAV at 12 months. RESULTS The mean TAV reduction at 12 months in the Nano group was 60.3 mm(3) (SD 39.5; min 41.9 mm(3), max 94.2 mm(3); p < 0.05) up to mean 37.8% (95% CI: 31.1%, 51.7%; p < 0.05) plaque burden. The analysis of the event free survival of the ongoing clinical follow-up shows the significantly lower risk of cardiovascular death in the Nano group when compared with others (91.7% vs. 81.7% and 80% respectively; p < 0.05) with no cases of the target lesion-related complications. CONCLUSIONS PPTT using silica-gold NP associated with significant regression of coronary atherosclerosis.
Subclinical male hypogonadism.

INTRODUCTION The concept of subclinical or compensated male hypogonadism (SHG), characterized by increased gonadotropins and normal testosterone levels is emerging. However, its real clinical significance is still conflicting. The aim of the present study is to summarize and discuss the available evidence related to the possible definition of SHG and the possible advantages of testosterone replacement therapy (TRT). EVIDENCE ACQUISITION A comprehensive systematic Medline, Embase and Cochrane search was performed. Publications from January 1, 1969 up to February 29th, 2020 were included. The search was restricted to English-language articles and studies of human participants. EVIDENCE SYNTHESIS Two main clinical forms of SHG can be described. The first identifies young patients who have a positive medical history for testis damage occurring before puberty onset. The second form can occur as a consequence of an age-dependent decline of T. Whereas the former can be the consequence of several congenital or acquired diseases, also possible causes of primary hypogonadism, the real significance of the latter is still debatable. Available evidence indicates that age-related SHG is quite a common phenomenon, occurring in 9.4% of aging men from the general population. Cross-sectional and longitudinal data have documented that it is associated with poor health and can be a sign of forthcoming increased cardiovascular mortality and morbidity. CONCLUSIONS Although available evidence suggests that in aging populations SHG can be considered a particular condition associated with an increased CV risk, it is still unknown if treatment with T can improve any outcomes in these subjects. Hence, further interventional studies are advisable in order to better understand the characteristics of SHG and the possible advantages of an early TRT.
Radiographic measurement of canine tibial angles in the sagittal plane.

OBJECTIVE To describe a method for radiographic measurement of the mechanical joint angles of the tibia in the sagittal plane and report reference ranges for a population of dogs with cranial cruciate ligament disease, and specifically for Labrador Retrievers. STUDY DESIGN Retrospective evaluation of radiographs. ANIMALS Canine tibia (n=150) of dogs evaluated for cranial cruciate ligament disease; 104 tibiae were from Labrador Retrievers, 46 tibiae were from other medium- to large-breed dogs. METHODS Medial-lateral radiographs were used to establish anatomic landmarks and measure the mechanical cranial distal tibial angle (mCrDTA) and mechanical caudal proximal tibial angle (mCaPTA). RESULTS For all tibiae mean mCrDTA was 81.6 degrees and mCaPTA, 63.6 degrees . For Labrador Retriever tibiae mean mCrDTA was 81.7 degrees and mCaPTA, 63.8 degrees . For non-Labradors, means mCrDTA was 81.5 degrees and mCaPTA, 63 degrees . Labrador Retrievers were significantly younger than non-Labradors in our study population. No significant differences were noted between Labrador Retrievers and non-Labradors for mCrDTA or mCaPTA and correlations between mCrDTA and mCaPTA were neither strong nor significant. CONCLUSION A method was established for radiographic measurement of mechanical joint angles of the canine tibia in the sagittal plane. Reference ranges are reported for a population of Labrador Retrievers and a population of non-Labradors with cranial cruciate ligament disease. CLINICAL RELEVANCE Measurement method and reference ranges provided for mechanical tibial angles may be used to aid in diagnosis, surgical planning, and postoperative critique for hindlimb angular deformities.
Indian Ocean warming modulates Pacific climate change

It has been widely believed that the tropical Pacific trade winds weakened in the last century and would further decrease under a warmer climate in the 21st century. Recent high-quality observations, however, suggest that the tropical Pacific winds have actually strengthened in the past two decades. Precise causes of the recent Pacific climate shift are uncertain. Here we explore how the enhanced tropical Indian Ocean warming in recent decades favors stronger trade winds in the western Pacific via the atmosphere and hence is likely to have contributed to the La Niña-like state (with enhanced east–west Walker circulation) through the Pacific ocean–atmosphere interactions. Further analysis, based on 163 climate model simulations with centennial historical and projected external radiative forcing, suggests that the Indian Ocean warming relative to the Pacific’s could play an important role in modulating the Pacific climate changes in the 20th and 21st centuries.
Tracing quiz set to identify novices' programming misconceptions

Novice programmers' understanding of conditional and loop constructs are often incomplete. They seem to understand a single conditional or single loop, but fail to understand the combination of them. We propose a method for finding misconceptions underlying this failure. We first developed a tracing quiz set to locate the exact points at which students will fail. Second, we identified some misconceptions from experiments on five courses. Third, to use and validate these misconceptions, we developed an interactive test system which showed the correct answers to the students and requested them to describe their explanations. The experiments showed that some misconceptions affected the overall performance of the students.
Separation of an instantaneous mixture of Gaussian autoregressive sources by the exact maximum likelihood approach

This paper deals with the problem of blind separation of an instantaneous mixture of Gaussian autoregressive sources, without additive noise, by the exact maximum likelihood approach. The maximization of the likelihood function is divided, using relaxation, into two suboptimization problems, solved by relaxation methods as well. The first one consists of the estimation of the separating matrix when the autoregressive structure of the sources is fixed. The second one aims at estimating this structure when the separating matrix is fixed. We show that the first problem is equivalent to the determinant maximization of the separating matrix under nonlinear constraints. We prove the existence and the consistency of the maximum likelihood estimator. We also give the expression of Fisher's information matrix. Then, we study, by computer simulations, the performance of our estimator and show the improvement of its achievements w.r. t. both quasimaximum likelihood and second-order blind identification (SOBI) estimators.
Truth or Punishment: Secrecy and Punishing the Self

We live in a world that values justice; when a crime is committed, just punishment is expected to follow. Keeping one’s misdeed secret therefore appears to be a strategic way to avoid (just) consequences. Yet, people may engage in self-punishment to right their own wrongs to balance their personal sense of justice. Thus, those who seek an escape from justice by keeping secrets may in fact end up serving that same justice on themselves (through self-punishment). Six studies demonstrate that thinking about secret (vs. confessed) misdeeds leads to increased self-punishment (increased denial of pleasure and seeking of pain). These effects were mediated by the feeling one deserved to be punished, moderated by the significance of the secret, and were observed for both self-reported and behavioral measures of self-punishment.
Reliable Non-Zero Skew Clock Trees Using Wire Width Optimization

Recognizing that routing constraints and process variations make non-zero skew inevitable, this paper describes a novel methodology for constructing reliable low-skew clock trees. The algorithm efficiently calculates clock-tree delay sensitivities to achieve a target delay and a target skew. Moreover, the sensitivities also show that wires should be widened as opposed to lengthened to reduce skew since the former improves reliability while the latter reduces it. This paper introduces the concept of designing reliable clock nets with process-insensitive skew.
MIMO Sliding Mode Controller for Gait Exoskeleton Driven by Pneumatic Muscles

In the past decade, pneumatic muscle (PM) actuated rehabilitation robotic devices have been widely researched, mainly due to the actuators’ intrinsic compliance and high power to weight ratio. However, the PMs are highly nonlinear and subject to hysteresis behavior. Hence, robust trajectory and compliance control are important to realize different training strategies and modes for improving the effectiveness of the rehabilitation robots. This paper presents a multi-input–multioutput sliding mode controller, which is developed to simultaneously control the angular trajectory and compliance of the knee joint mechanism of a gait rehabilitation exoskeleton. Experimental results indicate good multivariable tracking performance of this controller, which provides a good foundation for the further development of assist-as-needed training strategies in gait rehabilitation.
Theoretical and numerical analysis for the quasi-continuum approximation of a material particle model

In many applications materials are modeled by a large number of particles (or atoms) where any one of particles interacts with all others. Near or nearest neighbor interaction is expected to be a good simplification of the full interaction in the engineering community. In this paper we shall analyze the approximate error between the solution of the simplified problem and that of the full-interaction problem so as to answer the question mathematically for a one-dimensional model. A few numerical methods have been designed in the engineering literature for the simplified model. Recently much attention has been paid to a finite-element-like quasicontinuum (QC) method which utilizes a mixed atomistic/continuum approximation model. No numerical analysis has been done yet. In the paper we shall estimate the error of the QC method for this one-dimensional model. Possible ill-posedness of the method and its modification are discussed as well.
Cardiovascular Morbidity and Mortality After Treatment for Ductal Carcinoma In Situ of the Breast

Recent concerns about potential overdiagnosis and overtreatment of ductal carcinoma in situ of the breast (DCIS) render evaluation of late effects of treatment, such as cardiovascular disease (CVD), of great importance. We studied cardiovascular morbidity and mortality in a large population-based cohort of DCIS patients. Data on all incident DCIS case patients in the Netherlands between 1989 and 2004 who were diagnosed before the age of 75 years were obtained (n = 10 468). CVD data was acquired through linkage with population-based registries. Standardized mortality ratios were calculated by comparing mortality in our cohort with that in the Dutch female population, taking into account person-years of observation. Within-cohort comparisons were based on multivariable competing-risk regression. cohort was comprised of 10 444 DCIS patients. admission/surgical intervention/death. The first hospitalization of each specific CVD was used in the analyses. Follow-up on second neoplasia, vital cardiovascular and hospital admissions The was approved by and Statistics Netherlands.
Compaction and segregation of sister chromatids via active loop extrusion

The mechanism by which chromatids and chromosomes are segregated during mitosis and meiosis is a major puzzle of biology and biophysics. Using polymer simulations of chromosome dynamics, we show that a single mechanism of loop extrusion by condensins can robustly compact, segregate and disentangle chromosomes, arriving at individualized chromatids with morphology observed in vivo. Our model resolves the paradox of topological simplification concomitant with chromosome “condensation”, and explains how enzymes a few nanometers in size are able to control chromosome geometry and topology at micron length scales. We suggest that loop extrusion is a universal mechanism of genome folding that mediates functional interactions during interphase and compacts chromosomes during mitosis.
Maternal Melatonin Therapy Rescues Prenatal Dexamethasone and Postnatal High-Fat Diet Induced Programmed Hypertension in Male Rat Offspring

Prenatal dexamethasone (DEX) exposure and high-fat (HF) intake are linked to hypertension. We examined whether maternal melatonin therapy prevents programmed hypertension synergistically induced by prenatal DEX plus postnatal HF in adult offspring. We also examined whether DEX and melatonin causes renal programming using next-generation RNA sequencing (NGS) technology. Pregnant Sprague-Dawley rats received intraperitoneal dexamethasone (0.1 mg/kg) or vehicle from gestational day 16 to 22. In the melatonin-treatment groups (M), rats received 0.01% melatonin in drinking water during their entire pregnancy and lactation. Male offspring were assigned to five groups: control, DEX, HF, DEX+HF, and DEX+HF+M. Male offspring in the HF group were fed a HF diet from weaning to 4 months of age. Prenatal DEX and postnatal HF diet synergistically induced programmed hypertension in adult offspring, which melatonin prevented. Maternal melatonin treatment modified over 3000 renal transcripts in the developing offspring kidney. Our NGS data indicate that PPAR signaling and fatty acid metabolism are two significantly regulated pathways. In addition, maternal melatonin therapy elicits longstanding alterations on renal programming, including regulation of the melatonin signaling pathway and upregulation of Agtr1b and Mas1 expression in the renin-angiotensin system (RAS), to protect male offspring against programmed hypertension. Postnatal HF aggravates prenatal DEX induced programmed hypertension in adult offspring, which melatonin prevented. The protective effects of melatonin on programmed hypertension is associated with regulation of the RAS and melatonin receptors. The long-term effects of maternal melatonin therapy on renal transcriptome require further clarification.
Optimization of liquid-state fermentation conditions for the glyphosate degradation enzyme production of strain Aspergillus oryzae by ultraviolet mutagenesis

ABSTRACT This study aimed to obtain strains with high glyphosate-degrading ability and improve the ability of glyphosate degradation enzyme by the optimization of fermentation conditions. Spore from Aspergillus oryzae A-F02 was subjected to ultraviolet mutagenesis. Single-factor experiment and response surface methodology were used to optimize glyphosate degradation enzyme production from mutant strain by liquid-state fermentation. Four mutant strains were obtained and named as FUJX 001, FUJX 002, FUJX 003, and FUJX 004, in which FUJX 001 gave the highest total enzyme activity. Starch concentration at 0.56%, GP concentration at 1,370 mg/l, initial pH at 6.8, and temperature at 30°C were the optimum conditions for the improved glyphosate degradation endoenzyme production of A. oryzae FUJX 001. Under these conditions, the experimental endoenzyme activity was 784.15 U/100 ml fermentation liquor. The result (784.15 U/100 ml fermentation liquor) was approximately 14-fold higher than that of the original strain. The result highlights the potential of glyphosate degradation enzyme to degrade glyphosate.
Investments in Education and Welfare in a Two-Sector, Random Matching Economy

We consider a random matching model where heterogeneous agents choose optimally to invest time and real resources in education. Generically, there is a steady state equilibrium where some agents, but not all of them, invest. Regular steady state equilibria are constrained inefficient in a strong sense. The Hosios (1990) condition is neither necessary nor sufficient for constrained efficiency. We also provide restrictions on the fundamentals sufficient to guarantee that equilibria are characterized by overeducation (or undereducation), present some results on their comparative statics properties, and discuss the nature of welfare improving policies.