Miracle-dz/UniFAR-FTUs huggingface dataset:
Determining the catalytic role of remote substrate binding interactions in ketosteroid isomerase

A fundamental difference between enzymes and small chemical catalysts is the ability of enzymes to use binding interactions with nonreactive portions of substrates to accelerate chemical reactions. Remote binding interactions can localize substrates to the active site, position substrates relative to enzymatic functional groups and other substrates, trigger conformational changes, induce local destabilization, and modulate an active site environment by solvent exclusion. We investigated the role of remote substrate binding interactions in the reaction catalyzed by the enzyme ketosteroid isomerase (KSI), which catalyzes a double bond migration of steroid substrates through a dienolate intermediate that is stabilized in an oxyanion hole. Comparison of a single-ring and multiple-ring substrate allowed the catalytic contribution of binding interactions with the distal substrate rings to be determined. The value of kcat/KM for a single-ring substrate is reduced 27,000-fold relative to a multiple-ring steroid substrate, suggesting that remote binding interactions with the steroid substrate contribute substantially to the KSI reaction. Nevertheless, the reaction rates for KSI-bound single- and multiple-ring substrates (kcat) are within 2-fold. Further, oxyanion hole mutations have the same effect on reactions of the single- and multiple-ring substrates. These results suggest that remote binding interactions contribute >5 kcal/mol to catalysis by KSI but that local rather than remote interactions dictate the catalytic contributions from KSI's general base and oxyanion hole.
Reinventing Higher Education: the leadership challenge

Abstract This paper argues that external and internal changes affecting higher education require institutions, and the system as a whole to redefine missions, purposes and practice. Achieving significant change of this kind, however, requires leadership at many levels. The paper presents six dimensions of leadership which can contribute to the task of reinventing higher education.
The Induction of Cytochrome P450 3A5 (CYP3A5) in the Human Liver and Intestine Is Mediated by the Xenobiotic Sensors Pregnane X Receptor (PXR) and Constitutively Activated Receptor (CAR)*

Induction of cytochrome P450 3A (CYP3A) by xenobiotics may lead to clinically relevant drug interactions. In contrast with other CYP3A family members, studies on the inducibility of CYP3A5 indicate conflicting results. We report the induction of CYP3A5 mRNA in 13 of 16 hepatocyte preparations exposed to rifampin. Furthermore, induction of CYP3A5 mRNA was observed in intestinal biopsies in three of eight probands following exposure to the antibiotic. The highest absolute levels of CYP3A5 transcripts were found following rifampin treatment in hepatocytes and intestines from carriers of CYP3A5*1 alleles. Elucidation of the mechanism involved in CYP3A5 induction revealed that constitutively activated receptor (CAR) and pregnane X receptor (PXR) transactivated the CYP3A5 promoter (–688 to +49) and that the transactivation was dependent on an everted repeat separated by 6 bp (ER6-dependent). Treatment with the prototypical PXR ligand rifampin led to a 2-fold induction of the CYP3A5 promoter activity. In agreement with these observations, PXR and CAR bound specifically to the ER6 motif. Hepatic expression of PXR correlated with that of CYP3A5 mRNA levels in a bank of liver samples. Taken together, studies here revealed the presence of a functional ER6 motif in the CYP3A5 promoter located –100 bp upstream from the transcription start site, suggesting that CYP3A5 is inducible by mechanisms similar to those involved in CYP3A4 induction. Enhanced expression of CYP3A5 caused by exposure to inducers may phenocopy the effects of the high expression allele CYP3A5*1. In this manner, induction of CYP3A5 may contribute to the overall importance of this P450 in drug metabolism and drug interactions.
Trust Expectations, Information Sharing, Climate of Trust, and Negotiation Effectiveness and Efficiency

Trust expectations, information quantity shared, the climate of trust, and negotiated outcomes were investigated. Initial trust expectation was manipulated, and participants provided data about the quantity of information shared, the climate of trust, and the outcomes of the negotiations. The 324 participants were practicing managers who conducted a negotiating role play with win-win potential. Information sharing followed from initial trust expectations, and information sharing did not fully mediate the relationship between expectations and climate of trust. Negotiating effectiveness was associated with the quantity of information shared but not with trust. Procedural inefficiency (time to discover the solution) decreased as information quantity increased, but procedural inefficiency was not related to trust. One measure of outcome inefficiency (complexity of the agreement) decreased as trust increased, but another measure of outcome inefficiency (monetary cost of the agreement) was not related to trust. Unexpectedly, buyers’ monetary cost increased as information increased, suggesting that sellers might profit from information exchange and, indirectly, from trust. Contributions and limitations of the study are discussed in addition to implications of trust in negotiations by practicing managers.
Evidence for holistic processing of facial age

A composite face, produced by pairing the top and bottom halves from two different faces, produces a strong percept of a “new” face: It is difficult to identify either half in isolation. Three experiments examined whether a similar “composite face effect” (CFE) occurs with age judgements. Composites contained halves from faces of different ages. Participants tried to judge the age of the top half, ignoring the bottom. Experiment 1 found that age estimates for the composites’ top halves were biased towards the bottom halves’ chronological ages. Inverting the stimuli attenuated this effect but did not eliminate it entirely. The CFE for age perception is not based on skin texture information, since it persists when texture is eliminated by blurring or random noise (Experiments 2 and 3). Methodological differences preclude too detailed a comparison with other CFEs, but possibly the CFEs for age, recognition, and expression perception are all based on a common initial “holistic” encoding phase in face processing.
A seamless, client-centric programming model for type safe web applications

We propose a new programming model for web applications which is (1) seamless; one program and one language is used to produce code for both client and server, (2) client-centric; the programmer takes the viewpoint of the client that runs code on the server rather than the other way around, (3) functional and type-safe, and (4) portable; everything is implemented as a Haskell library that implicitly takes care of all networking code. Our aim is to improve the painful and error-prone experience of today's standard development methods, in which clients and servers are coded in different languages and communicate with each other using ad-hoc protocols. We present the design of our library called Haste.App, an example web application that uses it, and discuss the implementation and the compiler technology on which it depends.
Satellite surveillance of the Gulf and beyond: An overview of the LSU Earth Scan Laboratory's ocean observing capabilities

The Earth Scan Laboratory (ESL), a facility in the Coastal Studies Institute (CSI) of the Department of Oceanography and Coastal Sciences (DOCS) at LSU was founded in 1988, and was one of the first universities in the United States to have a real-time satellite capture capability. The ESL's unique location, north of the central Gulf of Mexico, provides a radio horizon for polar orbiting satellites that extends north, into the Hudson Bay, south beyond Panama, and east/west to cover both seaboards of the United States. Over the past two decades, the ESL has built a reputation for providing access to a variety of sensor systems on board a large array of satellites. With it ability to capture several of the National Océanographie and Atmospheric Administration (NOAA) environmental satellites, including the eastern GOES (Geostationary Operational Environmental Satellite) satellite, the ESL is able to observe local ocean phenomena, such as the Gulf of Mexico Loop Current (LC) as well as the El Niño/La Niña oscillations of the eastern Pacific ocean. The ESL provides a large archive of imagery on its web site (http://www.esl.lsu.edu), and focuses on access to real-time data. An overview of the ESL capabilities and activities is given, with attention to ocean observation, and its role in research, education, commerce, and emergency response.
Protective ventilation to reduce inflammatory injury from one lung ventilation in a piglet model

Objectives: To test the hypothesis that protective ventilation strategy (PVS) as defined by the use of low stretch ventilation (tidal volume of 5 ml·kg−1 and employing 5 cm of positive end expiratory pressure (PEEP) during one lung ventilation (OLV) in piglets would result in reduced injury compared to a control group of piglets who received the conventional ventilation (tidal volume of 10 ml·kg−1 and no PEEP).
Drug Effect Expectancies and Addictive Behavior Change

While expectancies are considered an important factor in the etiology of addiction, less is known about expectancies for drugs other than alcohol, and there has been little effort to systematically incorporate expectancies into programs designed to change addictive behavior. This report reviews the expectancy construct and the role of expectancies in the development of substance abuse. Cognitive and behavioral strategies for changing substance use expectancies and the means by which expectancies may facilitate changes in addictive behaviors are described. Examples of strategies to incorporate expectancy-based change efforts into clinical intervention for addictive behavior are presented.
Red Clover Aryl Hydrocarbon Receptor (AhR) and Estrogen Receptor (ER) Agonists Enhance Genotoxic Estrogen Metabolism

Many women consider botanical dietary supplements (BDSs) as safe alternatives to hormone therapy for menopausal symptoms. However, the effect of BDSs on breast cancer risk is largely unknown. In the estrogen chemical carcinogenesis pathway, P450 1B1 metabolizes estrogens to 4-hydroxylated catechols, which are oxidized to genotoxic quinones that initiate and promote breast cancer. In contrast, P450 1A1 catalyzed 2-hydroxylation represents a detoxification pathway. The current study evaluated the effects of red clover, a popular BDS used for women’s health, and its isoflavones, biochanin A (BA), formononetin (FN), genistein (GN), and daidzein (DZ), on estrogen metabolism. The methoxy estrogen metabolites (2-MeOE1, 4-MeOE1) were measured by LC-MS/MS, and CYP1A1 and CYP1B1 gene expression was analyzed by qPCR. Nonmalignant ER-negative breast epithelial cells (MCF-10A) and ER-positive breast cancer cells (MCF-7) were derived from normal breast epithelial tissue and ER+ breast cancer tissue. Red clover extract (RCE, 10 μg/mL) and isoflavones had no effect on estrogen metabolism in MCF-10A cells. However, in MCF-7 cells, RCE treatments downregulated CYP1A1 expression and enhanced genotoxic metabolism (4-MeOE1/CYP1B1 > 2-MeOE1/CYP1A1). Experiments with the isoflavones showed that the AhR agonists (BA, FN) preferentially induced CYP1B1 expression as well as 4-MeOE1. In contrast, the ER agonists (GN, DZ) downregulated CYP1A1 expression likely through an epigenetic mechanism. Finally, the ER antagonist ICI 182,780 potentiated isoflavone-induced XRE-luciferase reporter activity and reversed GN and DZ induced downregulation of CYP1A1 expression. Overall, these studies show that red clover and its isoflavones have differential effects on estrogen metabolism in “normal” vs breast cancer cells. In breast cancer cells, the AhR agonists stimulate genotoxic metabolism, and the ER agonists downregulate the detoxification pathway. These data may suggest that especially breast cancer patients should avoid red clover and isoflavone based BDSs when making choices for menopausal symptom relief.
Assumptions associated with mental health literacy training – Insights from initiatives in rural Australia

Abstract The impact of depression on the Australian community is well established. A number of approaches have been proposed to address this problem, including targeted programs to promote mental health literacy. This paper explores four assumptions associated with community mental health literacy programs: that individuals would increase their mental health knowledge; increase their confidence to help others experiencing mental ill health; report reduced stigmatising attitudes towards mental illness; and help others experiencing mental ill health. Findings from a rural Victorian community mental health literacy program focused on sports team coaches and other club leaders is reported in the context of these assumptions. Pre–post questionnaire data and focus group data were collected from participants in the mental health literacy program. Participants reported increased knowledge of key mental health conditions, increased confidence to help others experiencing mental ill health and less stigmatizing attitudes toward mental ill health. Limited evidence was noted to support the assumption that, following training, individuals will help others experiencing mental ill health. Difficulties in determining if transfer of benefit to others has occurred following mental health literacy training are discussed, along with a number of mechanisms that, if included in training, may extend the benefit of that mental health literacy training to others.
They shouldn't let them out for us to see': Empathy and affect intensity as determinants of responses to representations of the facially disfigured in charity advertising

Test subjects were exposed to made-up advertisements for a hypothetical facial disfigurement charity. Certain groups saw an advertisement featuring a disfigured young person on his own; others a similar representation but with the addition of either a physically attractive or unattractive female announcer. Responses to a written appeal accompanying the visual imagery were measured and analysed according to test subjects' levels of emotionality and predisposition to experience empathy. The experiment was repeated using control groups who were given comparable advertisements that did not include any sight of a disfigured person — only an attractive or unattractive female announcer. It emerged that advertisements containing both a disfigured individual and a physically attractive announcer evoked the most favourable responses.
The safety of macrolides during lactation.

BACKGROUND Infantile exposure to macrolides has been associated with hypertrophic pyloric stenosis causing projectile vomiting, dehydration, electrolyte abnormalities, and in rare cases death possibly via macrolide interaction with gastric motilin receptors. Large population-based cohorts have suggested that exposure to macrolides via breastmilk may be associated with pyloric stenosis. METHODS In this prospective, controlled observational study designed to assess the safety of macrolides during lactation, we followed infants whose mothers contacted our Drug Consultation Center at the Assaf Harofeh Medical Center (Zerrifin, Israel) inquiring about safety of macrolides during lactation and compared them to a cohort of infants exposed to amoxicillin during breastfeeding. RESULTS Fifty-five infants exposed to macrolide antibiotics were compared to a control cohort of 36 infants exposed to amoxicillin via lactation. The infants in the macrolide group were all exposed to erythromycin and the newer macrolides: azithromycin, clarithromycin, and roxithromycin. The rate of adverse reactions the infant experienced while being exposed to both antibiotics was comparable. Seven (12.7%) infants in the macrolide group experienced adverse reactions versus three infants (8.3%) in the amoxicillin group (odds ratio = 1.6, 95% confidence interval, 0.38-6.65, p = 0.73). The adverse reactions in the infants exposed to macrolides were rash, diarrhea, loss of appetite, and somnolence, whereas the infants exposed to amoxicillin experienced rashes and somnolence. Factors such as gestational age, age and weight at exposure, maternal age, or type of macrolide were not associated with the infant's adverse reaction in multivariate regression analysis. CONCLUSIONS Rates and types of minor adverse reactions in breastfed infants exposed to a macrolide or amoxicillin in breastmilk were comparable. Macrolide exposure during breastfeeding was not associated with pyloric stenosis, although larger prospective studies are required to confirm our observation.
Workplace assessment in New Zealand: stated intentions and realisations

Abstract Workplace assessment (WPA) of New Zealand’s National Qualifications Framework (NQF) competencies has become a significant alternative pathway for vocational adult education. This article reports on a research project which compares stated intentions for workplace assessment with evidence of its practical realization. The perceptions of the workplace assessors and candidates are analysed in a case study of qualitative interviews of ambulance service officers. Assessment guidelines are reviewed and then compared to a discussion of selected findings. Three areas of the research project are discussed in this article. The first covers how workplace assessments meet technical prescriptions for evidence-gathering and discusses findings on the validity, directness and sufficiency of evidence. Secondly, the development of a holistic Interplay model offers a counter to ‘checklist’ assessment methods. Lastly the article discusses the nature of the assessor/candidate relationship and develops Positive and Negative Closeness Models. Recommendations are made for workplace assessor training.
Fluctuations in Learners’ Willingness to Communicate During Communicative Task Performance: Conditions and Tendencies

Abstract A person’s willingness to communicate (WTC), believed to stem from a combination of proximal and distal variables comprising psychological, linguistic, educational and communicative dimensions of language, appears to be a significant predictor of success in language learning. The ability to communicate is both a means and end of language education, since, on the one hand, being able to express the intended meanings in the target language is generally perceived as the main purpose of any language course and, on the other, linguistic development proceeds in the course of language use. However, MacIntyre (2007, p. 564) observes that some learners, despite extensive study, may never become successful L2 speakers. The inability or unwillingness to sustain contacts with more competent language users may influence the way learners are evaluated in various social contexts. Establishing social networks as a result of frequent communication with target language users is believed to foster linguistic development. WTC, initially considered a stable personality trait and then a result of context-dependent influences, has recently been viewed as a dynamic phenomenon changing its intensity within one communicative event (MacIntyre and Legatto, 2011; MacIntyre et al., 2011). The study whose results are reported here attempts to tap into factors that shape one’s willingness to speak during a communicative task. The measures employed to collect the data - selfratings and surveys - allow looking at the issue from a number of perspectives.
Consensus Problems with Distributed Delays, with Application to Traffic Flow Models

This paper focuses on consensus problems for a class of linear systems with distributed delay that are encountered in modeling traffic flow dynamics. In the application problems the distributed delay, whose kernel is a $\gamma$-distribution with a gap, represents the human drivers' behavior in the average. The aim of the paper is to give a characterization of the regions in the corresponding delay parameter space, where a consensus is reached for all initial conditions. The structure and properties of the system are fully exploited, which leads to explicit and computationally tractable expressions. As a by-product a stability theory for distributed delay systems with a $\gamma$-distribution kernel is developed. Also explicit expressions for the consensus function(al) of time-delay systems with constant and distributed delays that solve a consensus problem are provided. Several illustrative examples complete the presentation.
Physical and Psychological Factors in Sense of Community

Sense of community is often mentioned as an asset of new urbanism. The purpose of the study was to explore this claim by comparing Kentlands, a prototypic new urbanist community, with a traditional suburban development near it. Four domains of sense of community were examined, each in terms of 17 distinct aspects of the physical environment, through surveys as well as interviews with residents. The findings suggest thatKentlands residents perceive substantially greater sense of community; they express stronger attachment to their community and sense of identity with it. Natural features and open spaces play a particularly important role in sense of community and Kentlands provides a rich variety of these, fostering pedestrianism and increasing the likelihood of social interactions. The overall layout of the community and traditional architectural style, as well as many other physical features, play vital functions in achieving sense of community
Perceptions of Classroom Environment, Achievement Goals, and Achievement Outcomes.

Two studies examined the relationship between undergraduates' perceptions of their classroom environment, their adoption of achievement goals for the course, and their graded performance and intrinsic motivation. Results revealed a distinct antecedent profile for each goal in the trichotomous framework: Mastery goals were linked to the presence of lecture engagement and the absence of an evaluation focus and harsh evaluation, performance-approach goals were linked to the presence of evaluation focus, and performance-avoidance goals were linked to the presence of evaluation focus and harsh evaluation. When the perceived classroom environment and achievement goal variables were tested together as predictors of graded performance and intrinsic motivation, the results clearly demonstrated that the influence of the perceived classroom environment on these outcomes measures was indirect; the perceived classroom environment influenced achievement goal adoption, and achievement goal adoption, in turn, directly influenced graded performance and intrinsic motivation.
The Rationality of Risky Decisions A Changing Message

Over the years research in risky decision making has diagnosed variable degrees of irrationality in people's judgements and choices. In the 1960s an optimistic view dominated of a widely rational decision maker. The work of Tversky and Kahneman at the beginning of the 1970s led to a pessimistic view of basically flawed decision processes that frequently end up in `cognitive illusions'. In the 1980s a movement gained strength that pointed to the adaptiveness of seemingly irrational decisions. Recent work demonstrates that seemingly irrational choices may be due to different task construal between experimenters and participants. The respective evaluative change in what the rationality issue is generally taken to show is overdue, however. The negative message of fundamentally flawed human decision making has to be replaced by a more positive picture that acknowledges that some reactions to task and context are advantages rather than disadvantages of human decision making. Recent work on systems of thinking s.