Miracle-dz/UniFAR-FTUs huggingface dataset:
Antimycobacterial and Anti-Inflammatory Activities of Substituted Chalcones Focusing on an Anti-Tuberculosis Dual Treatment Approach

Tuberculosis (TB) remains a serious public health problem aggravated by the emergence of M. tuberculosis (Mtb) strains resistant to multiple drugs (MDR). Delay in TB treatment, common in the MDR-TB cases, can lead to deleterious life-threatening inflammation in susceptible hyper-reactive individuals, encouraging the discovery of new anti-Mtb drugs and the use of adjunctive therapy based on anti-inflammatory interventions. In this study, a series of forty synthetic chalcones was evaluated in vitro for their anti-inflammatory and antimycobacterial properties and in silico for pharmacokinetic parameters. Seven compounds strongly inhibited NO and PGE2 production by LPS-stimulated macrophages through the specific inhibition of iNOS and COX-2 expression, respectively, with compounds 4 and 5 standing out in this respect. Four of the seven most active compounds were able to inhibit production of TNF-α and IL-1β. Chalcones that were not toxic to cultured macrophages were tested for antimycobacterial activity. Eight compounds were able to inhibit growth of the M. bovis BCG and Mtb H37Rv strains in bacterial cultures and in infected macrophages. Four of them, including compounds 4 and 5, were active against a hypervirulent clinical Mtb isolate as well. In silico analysis of ADMET properties showed that the evaluated chalcones displayed satisfactory pharmacokinetic parameters. In conclusion, the obtained data demonstrate that at least two of the studied chalcones, compounds 4 and 5, are promising antimycobacterial and anti-inflammatory agents, especially focusing on an anti-tuberculosis dual treatment approach.
Competitive Distribution Estimation: Why is Good-Turing Good

Estimating distributions over large alphabets is a fundamental machine-learning tenet. Yet no method is known to estimate all distributions well. For example, add-constant estimators are nearly min-max optimal but often perform poorly in practice, and practical estimators such as absolute discounting, Jelinek-Mercer, and Good-Turing are not known to be near optimal for essentially any distribution. We describe the first universally near-optimal probability estimators. For every discrete distribution, they are provably nearly the best in the following two competitive ways. First they estimate every distribution nearly as well as the best estimator designed with prior knowledge of the distribution up to a permutation. Second, they estimate every distribution nearly as well as the best estimator designed with prior knowledge of the exact distribution, but as all natural estimators, restricted to assign the same probability to all symbols appearing the same number of times. Specifically, for distributions over k symbols and n samples, we show that for both comparisons, a simple variant of Good-Turing estimator is always within KL divergence of (3 + on(1))/n1/3 from the best estimator, and that a more involved estimator is within On(min(k/n, 1/√n)). Conversely, we show that any estimator must have a KL divergence at least Ωn(min(k/n, 1/n2/3)) over the best estimator for the first comparison, and at least Ωn(min(k/n, 1/√n)) for the second.
Mutation and Selection on the Wobble Nucleotide in tRNA Anticodons in Marine Bivalve Mitochondrial Genomes

Background Animal mitochondrial genomes typically encode one tRNA for each synonymous codon family, so that each tRNA anticodon essentially has to wobble to recognize two or four synonymous codons. Several factors have been hypothesized to determine the nucleotide at the wobble site of a tRNA anticodon in mitochondrial genomes, such as the codon-anticodon adaptation hypothesis, the wobble versatility hypothesis, the translation initiation and elongation conflict hypothesis, and the wobble cost hypothesis. Principal Findings In this study, we analyzed codon usage and tRNA anticodon wobble sites of 29 marine bivalve mitochondrial genomes to evaluate features of the wobble nucleotides in tRNA anticodons. The strand-specific mutation bias favors G and T on the H strand in all the 29 marine bivalve mitochondrial genomes. A bias favoring G and T is also visible in the third codon positions of protein-coding genes and the wobble sites of anticodons, rejecting that codon usage bias drives the wobble sites of tRNA anticodons or tRNA anticodon bias drives the evolution of codon usage. Almost all codon families (98.9%) from marine bivalve mitogenomes support the wobble versatility hypothesis. There are a few interesting exceptions involving tRNATrp with an anticodon CCA fixed in Pectinoida species, tRNASer with a GCU anticodon fixed in Mytiloida mitogenomes, and the uniform anticodon CAU of tRNAMet translating the AUR codon family. Conclusions/Significance These results demonstrate that most of the nucleotides at the wobble sites of tRNA anticodons in marine bivalve mitogenomes are determined by wobble versatility. Other factors such as the translation initiation and elongation conflict, and the cost of wobble translation may contribute to the determination of the wobble nucleotide in tRNA anticodons. The finding presented here provides valuable insights into the previous hypotheses of the wobble nucleotide in tRNA anticodons by adding some new evidence.
Examining Mediators of Structural Assurance Constructs in Business-To-Consumer E-Commerce

This study examines the influence of different types of structural assurance on consumer purchasing intentions in business-to-consumer (B2C) electronic commerce. Prior research findings regarding how different types of structural assurance impact consumer purchasing intentions has been limited. Based on the institution-based trust theory, perceived trust theory and the psychological contract theory, this study proposes that perceived vendor guarantee and perceived seals of approval would have positive influence on consumer intentions through psychological contract and perceived trust. Results of this study confirmed the significance of perceived vendor guarantee and perceived seals of approval and the importance of perceived trust in the nomological network.
Patterns and perception of alcohol drinking among the Lahu people, Northern Thailand

Purpose The purpose of this paper is to understand the pattern and perception of alcohol drinking among the Lahu people in northern Thailand. Design/methodology/approach A qualitative method was used to elicit information on the patterns and perceptions of alcohol drinking amongst the Lahu tribespeople. Question guidelines had been developed from literature reviews and approved by three experts in the field of public health and alcohol studies. A total of 21 participants of different ages and sexes from 3 separate Lahu villages were invited to provide information. All interviews were taped and transcribed before analysis. A content analysis was used. Findings Lahu people begin alcohol consumption at an average of 12 years, with males usually beginning before females of the same age. Consuming alcohol is perceived to be a sign of adulthood and is also used as a means of gaining social acceptance from others in the community. Alcohol is consumed throughout the year with young and old, male and females, describing varied reasons for drinking. Income, parental behavior, and peer pressure contributes to the onset of alcohol drinking among young Lahu people. Several factors contributed to the use of alcohol among the Lahu people such as sex, age, occupation and income, peer pressure, taste and price as well as cultural adaptations amongst the farming community that play a significant role in the frequency of alcohol consumption amongst the Lahu community. Originality/value The results should support the development of peer education on the negative impact of alcohol use among the young people, and development of a community agreement on reducing excessive alcohol use in the Lahu community should be implemented.
Disproportionate Experiences in Custody? An Examination of Minority Youths’ Outcomes in Secure Facilities

Abstract While a significant amount of literature has emphasized the identification and explanation of disproportionate minority contact (DMC) in the juvenile justice system, less research has examined racial disparities in postdisposition outcomes. This study seeks to address this gap through its examination of the experiences of youths in custody. Specifically, using a stratified, random subsample of 1514 youths confined in secure confinement facilities between 2010 and 2014 in one Midwestern state, this article explores whether youths’ race impacts in-facility outcomes, such as number of disciplinary infractions, time spent in seclusion, length of stay, and access to educational services, when case-level predictors are accounted for. Findings suggest that race has an inconsistent relationship with the outcomes experienced by youths in custody. However, significant mediating effects of disciplinary infractions on relationships between race and other outcomes appear to have significant implications for non-White youths in custody. Considering these findings, policy recommendations are discussed.
Diabetes in Mice With Selective Impairment of Insulin Action in Glut4-Expressing Tissues

OBJECTIVE Impaired insulin-dependent glucose disposal in muscle and fat is a harbinger of type 2 diabetes, but murine models of selective insulin resistance at these two sites are conspicuous by their failure to cause hyperglycemia. A defining feature of muscle and fat vis-à-vis insulin signaling is that they both express the insulin-sensitive glucose transporter Glut4. We hypothesized that diabetes is the result of impaired insulin signaling in all Glut4-expressing tissues. RESEARCH DESIGN AND METHODS To test the hypothesis, we generated mice lacking insulin receptors at these sites (“GIRKO” mice), including muscle, fat, and a subset of Glut4-positive neurons scattered throughout the central nervous system. RESULTS GIRKO mice develop diabetes with high frequency because of reduced glucose uptake in peripheral organs, excessive hepatic glucose production, and β-cell failure. CONCLUSIONS The conceptual advance of the present findings lies in the identification of a tissue constellation that melds cell-autonomous mechanisms of insulin resistance (in muscle/fat) with cell-nonautonomous mechanisms (in liver and β-cell) to cause overt diabetes. The data are consistent with the identification of Glut4 neurons as a distinct neuroanatomic entity with a likely metabolic role.
The 'Flat Tax(Es)': Principles and Evidence

One of the most striking tax developments in recent years, and one that continues to attract considerable attention, is the adoption by several countries of a form of 'flat tax'. Discussion of these quite radical reforms has been marked, however, more by assertion and rhetoric than by analysis and evidence. This paper reviews experience with the flat tax, seeking to redress the balance. It stresses that the flat taxes that have been adopted differ fundamentally, and that empirical evidence on their effects is very limited. This precludes simple generalization, but several lessons emerge: there is no sign of Laffer-type behavioral responses generating revenue increases from the tax cut elements of these reforms; their impact on compliance is theoretically ambiguous, but there is evidence for Russia that compliance did improve; the distributional effects of the flat taxes are not unambiguously regressive, and in some cases they may have increased progressivity, including through the impact on compliance; adoption of the flat tax has not resolved common challenges in taxing capital income; and it may have strengthened, not weakened, the automatic stabilizers. Looking forward, the question is not so much whether more countries will adopt a flat tax as whether those that have will move away from it.
The clinical development candidate CCT245737 is an orally active CHK1 inhibitor with preclinical activity in RAS mutant NSCLC and Eμ-MYC driven B-cell lymphoma

CCT245737 is the first orally active, clinical development candidate CHK1 inhibitor to be described. The IC50 was 1.4nM against CHK1 enzyme and it exhibited>1,000-fold selectivity against CHK2 and CDK1. CCT245737 potently inhibited cellular CHK1 activity (IC50 30-220nM) and enhanced gemcitabine and SN38 cytotoxicity in multiple human tumor cell lines and human tumor xenograft models. Mouse oral bioavailability was complete (100%) with extensive tumor exposure. Genotoxic-induced CHK1 activity (pS296 CHK1) and cell cycle arrest (pY15 CDK1) were inhibited both in vitro and in human tumor xenografts by CCT245737, causing increased DNA damage and apoptosis. Uniquely, we show CCT245737 enhanced gemcitabine antitumor activity to a greater degree than for higher doses of either agent alone, without increasing toxicity, indicating a true therapeutic advantage for this combination. Furthermore, development of a novel ELISA assay for pS296 CHK1 autophosphorylation, allowed the quantitative measurement of target inhibition in a RAS mutant human tumor xenograft of NSCLC at efficacious doses of CCT245737. Finally, CCT245737 also showed significant single-agent activity against a MYC-driven mouse model of B-cell lymphoma. In conclusion, CCT245737 is a new CHK1 inhibitor clinical development candidate scheduled for a first in man Phase I clinical trial, that will use the novel pS296 CHK1 ELISA to monitor target inhibition.
Brief Review of Techniques Used to Develop Adaptive Evolutionary Algorithms

This paper presents a brief review of techniques used to allow evolutionary algorithms to adapt to optimization problems in dynamic environments, through exploration of the control parameters of genetic algorithms as well as genotypic interpreters. A description of some of the most used evolutionary techniques is included, with major emphasis on genetic algorithms and their relationship with the problem of adaptation to the environment. The article also discusses state used models to tackle these kinds of problems, including self-adaptation and genotypephenotype mapping.
Determining and Measuring Self-Efficacy During the Student Teaching Semester

Self-efficacy is the belief that an individual is able to control the outcomes of potentially stressful situations. How teacher candidates feel about their ability to control new challenges can affect their performance in the classroom. Those with a poorer sense of self-efficacy may believe situations are out of their control. A more positive sense of perceived self-efficacy can lead to more positive outcomes. This article reports the results of a teacher self-efficacy scale administered to elementary and secondary teacher candidates at the beginning and end of their student teaching semester. Findings suggest that perceived self-efficacy among student teachers increases throughout the course of the student teaching experience.
Lipset Reconsidered : A Rational Theory of the Stability of Democracy ∗

This paper studies the endogenous emergence of political regimes, in particular democracy or oligarchy, in heterogeneous societies in which institutions do not ensure political commitments. Democracy emerges if the ruling coalition that makes political decisions represents the majority of individuals of the population, while oligarchy emerges when the political decisions are made by a minority of the population. The findings show that for any economic environment there exists a distribution of resources such that democracy is a possible political outcome within a heterogeneous society, whereas the opposite does not hold. The model also delivers results on the stability of democracy. Variations in inequality across several dimensions due to unbalanced technological change, immigration or changes in the demographic structure can reduce the scope for democracy or may even lead to its breakdown.
Real-time passive source localization: a practical linear-correction least-squares approach

A linear-correction least-squares estimation procedure is proposed for the source localization problem under an additive measurement error model. The method, which can be easily implemented in a real-time system with moderate computational complexity, yields an efficient source location estimator without assuming a priori knowledge of noise distribution. Alternative existing estimators, including likelihood-based, spherical intersection, spherical interpolation, and quadratic-correction least-squares estimators, are reviewed and comparisons of their complexity, estimation consistency and efficiency against the Cramer-Rao lower bound are made. Numerical studies demonstrate that the proposed estimator performs better under many practical situations.
Replication study of significant single nucleotide polymorphisms associated with myopia from two genome-wide association studies

Purpose Two previous genome-wide association studies (GWAS) of high myopia in a Japanese population found several single nucleotide polymorphisms (SNPs) associated with the disease. The present study examined whether these markers are associated with myopia in a Chinese population. Methods Individuals with or without complex myopia were recruited from Chinese university students, and probands with early onset high myopia were identified in the Pediatric and Genetic Eye Clinic of the Zhongshan Ophthalmic Center. DNA was prepared from venous leukocytes. Three SNPs, rs577948 and rs11218544 at chromosome position 11q24.1 and rs2839471 at chromosome position 21q22.3, were genotyped. The allele and genotype frequencies of these SNPs were compared between the myopia cases and controls using a χ2 test. Results A total of 2,870 subjects were examined in this study, including 1,255 individuals with complex myopia (−10.00 diopter (D)<spherical refraction≤-4.00 D), 563 with early onset high myopia (spherical refraction≤-6.00 D), and 1,052 healthy controls (−0.50 D≤spherical equivalent≤ +2.00 D). There were no statistically significant differences found for the genotype or allele frequencies of the three SNPs between the myopia cases and controls in the Chinese population under study. Conclusions We did not find evidence for the association of myopia with rs577948, rs11218544, or rs2839471 in the Chinese population studied.
Signal Delay in RC Tree Networks

In MOS integrated circuits, signals may propagate between stages with fanout. The MOS interconnect may be modeled by an RC tree. Exact calculation of signal delay through such networks is difficult. However, upper and lower bounds for delay that are computationally simple are presented here. The results can be used (1) to bound the delay, given the signal threshold; or (2) to bound the signal voltage, given a delay time; or (3) to certify that a circuit is "fast enough", given both the maximum delay and the voltage threshold.
Sources of Lifetime Inequality

Is lifetime inequality mainly due to differences across people established early in life or to differences in luck experienced over the working lifetime? We answer this question within a model that features idiosyncratic shocks to human capital , estimated directly from data, as well as heterogeneity in ability to learn, initial human capital, and initial wealth. We find that, as of age 23, differences in initial conditions account for more of the variation in lifetime earnings, lifetime wealth, and lifetime utility than do differences in shocks received over the working lifetime. ( JEL D31, D91, J24, J31) To what degree is lifetime inequality due to differences across people established early in life as opposed to differences in luck experienced over the working lifetime? Among the individual differences established early in life, which ones are the most important? A convincing answer to these questions is of fundamental importance. First, and most simply, an answer serves to contrast the potential importance of the myriad policies directed at modifying or at providing insurance for initial conditions (e.g., public education) against those directed at shocks over the working lifetime (e.g., unemployment insurance). Second, a discussion of lifetime inequality cannot go too far before discussing which specific type of initial condition is the most critical for determining how one fares in life. Third, a useful framework for answering these questions should also be central in the analysis of a wide range of policies considered in macroeconomics, public finance, and labor economics. We view lifetime inequality through the lens of a risky human capital model. Agents differ in terms of three initial conditions: initial human capital, learning ability, and financial wealth. Initial human capital can be viewed as controlling the intercept of an agent's mean earnings profile, whereas learning ability acts to rotate
ADP-Glucose Pyrophosphorylase, a Regulatory Enzyme for Bacterial Glycogen Synthesis

SUMMARY The accumulation of α-1,4-polyglucans is an important strategy to cope with transient starvation conditions in the environment. In bacteria and plants, the synthesis of glycogen and starch occurs by utilizing ADP-glucose as the glucosyl donor for elongation of the α-1,4-glucosidic chain. The main regulatory step takes place at the level of ADP-glucose synthesis, a reaction catalyzed by ADP-Glc pyrophosphorylase (PPase). Most of the ADP-Glc PPases are allosterically regulated by intermediates of the major carbon assimilatory pathway in the organism. Based on specificity for activator and inhibitor, classification of ADP-Glc PPases has been expanded into nine distinctive classes. According to predictions of the secondary structure of the ADP-Glc PPases, they seem to have a folding pattern common to other sugar nucleotide pyrophosphorylases. All the ADP-Glc PPases as well as other sugar nucleotide pyrophosphorylases appear to have evolved from a common ancestor, and later, ADP-Glc PPases developed specific regulatory properties, probably by addition of extra domains. Studies of different domains by construction of chimeric ADP-Glc PPases support this hypothesis. In addition to previous chemical modification experiments, the latest random and site-directed mutagenesis experiments with conserved amino acids revealed residues important for catalysis and regulation.
The Serenity of the Meditating Mind: A Cross-Cultural Psychometric Study on a Two-Factor Higher Order Structure of Mindfulness, Its Effects, and Mechanisms Related to Mental Health among Experienced Meditators

Objective To investigate the psychometric and structural properties of the Five Facets Mindfulness Questionnaire (FFMQ) among meditators, to develop a short form, and to examine associations of mindfulness with mental health and the mechanisms of mindfulness. Methods Two independent samples were used, a German (n = 891) and a Spanish (n = 393) meditator sample, practicing various meditation styles. Structural and psychometric properties of the FFMQ were investigated with multigroup confirmatory factor analysis and exploratory structural equation modeling. Associations with mental health and mechanisms of mindfulness were examined with path analysis. Results The derived short form broadly matched a previous item selection in samples of non-meditators. Self-regulated Attention and Orientation to Experience governed the facets of mindfulness on a higher-order level. Higher-order factors of mindfulness and meditation experience were negatively associated with symptoms of depression and anxiety, and perceived stress. Decentering and nonattachment were the most salient mechanisms of mindfulness. Aspects of emotion regulation, bodily awareness, and nonattachment explained the effects of mindfulness on depression and anxiety. Conclusions A two-component conceptualization for the FFMQ, and for the study of mindfulness as a psychological construct, is recommended for future research. Mechanisms of mindfulness need to be examined in intervention studies.