Miracle-dz/UniFAR-FTUs huggingface dataset:
Why Molecular Chaperones Buffer Mutational Damage: A Case Study With a Yeast Hsp40/70 System

The malfunctioning of molecular chaperones may result in uncovering genetic variation. The molecular basis of this phenomenon remains largely unknown. Chaperones rescue proteins unfolded by environmental stresses and therefore they might also help to stabilize mutated proteins and thus mask damages. To test this hypothesis, we carried out a genomewide mutagenesis followed by a screen for mutations that were synthetically harmful when the RAC–Ssb1/2 cytosolic chaperones were inactive. Mutants with such a phenotype were found and mapped to single nucleotide substitutions. However, neither the genes identified nor the nature of genetic lesions implied that folding of the mutated proteins was being supported by the chaperones. In a second screen, we identified temperature-sensitive (ts) mutants, a phenotype indicative of structural instability of proteins. We tested these for an association with sensitivity to loss of chaperone activity but found no such correlation as might have been expected if the chaperones assisted the folding of mutant proteins. Thus, molecular chaperones can mask the negative effects of mutations but the mechanism of such buffering need not be direct. A plausible role of chaperones is to stabilize genetic networks, thus making them more tolerant to malfunctioning of their constituents.
Board structure, board committees and corporate performance in Russia

Purpose The purpose of this paper is to investigate the link between board structure and performance of public companies in Russia – an emerging market with unique institutional background and a variability of corporate governance (CG) practices across its companies. Design/methodology/approach Panel data analysis was applied on a sample of 207 Russian companies that frequently traded in the Russian Trading System during the period 2007-2011, in order to test hypotheses on the relationships between board size, board independence, gender diversity, presence of board committees and financial performance, as measured by Tobin’s Q. Findings The results show a positive relationship between Tobin’s Q and the board’s gender diversity. The analysis demonstrates that smaller and bigger boards are associated with a greater Tobin’s Q value. Originality/value The findings provide additional evidence of how board structure is related to its effectiveness and corporate performance in countries with concentrated ownership, highly variable CG practices and a lack of proper implementation of corporate law and governance codes. The paper contributes to the existing empirical evidence on the advantages of small and large-sized boards and on gender diversity, and is the first investigating the relationship between Russian companies’ board committees and market-based performance. The results regarding board independence and committees suggest that these mechanisms are still not widely recognized for their role in CG and company performance in Russia.
Use of the community viral load as a population-based biomarker of HIV burden

Objectives:Recent data suggest that community viral load (CVL) can be used as a population-level biomarker for HIV transmission and its reduction may be associated with a decrease in HIV incidence. Given the magnitude of the HIV epidemic in Washington, District of Columbia, we sought to measure the District of Columbia's CVL. Design:An ecological analysis was conducted. Methods:Mean and total CVL were calculated using the most recent viral load for prevalent HIV/AIDS cases reported to District of Columbia HIV/AIDS surveillance through 2008. Univariate and multivariable analyses were conducted to assess differences in CVL availability, mean CVL, proportion of undetectable viral loads, and 5-year trends in mean CVL and new HIV/AIDS diagnoses. Geospatial analysis was used to map mean CVL and selected indicators of socioeconomic status by geopolitical designation. Results:Among 15 467 HIV/AIDS cases alive from 2004 to 2008, 48.2% had at least one viral load reported. Viral load data completeness increased significantly over the 5 years (P < 0.001). Mean CVL significantly decreased over time (P < 0.0001). At the end of 2008, the mean CVL was 33 847 copies/ml; 57.4% of cases had undetectable viral loads. Overlaps in the geographic distribution of CVL by census tract were observed with the highest means observed in areas with high poverty rates and low high school diploma rates. Conclusion:Mean and total CVL provide markers of access to care and treatment, are indicators of the population's viral burden, and are useful in assessing trends in local HIV/AIDS epidemics. Measurement of CVL is a novel tool for assessing the potential impact of population-level HIV prevention and treatment interventions.
The tdh and serA operons of Escherichia coli: mutational analysis of the regulatory elements of leucine-responsive genes

The tdh promoter of Escherichia coli is induced seven- to eightfold when cells are grown in the presence of exogenous leucine. A scheme was devised to select mutants that exhibited high constitutive expression of the tdh promoter. The mutations in these strains were shown to lie within a previously identified gene (lrp) that encodes Lrp (leucine-responsive regulatory protein). By deletion analysis, the site of action of Lrp was localized to a 25-bp region between coordinates -69 and -44 of the tdh promoter. Disruption of a 12-bp presumptive target sequence found in this region of tdh resulted in constitutively derepressed expression from the tdh promoter. Similar DNA segments (consensus, TTTATTCtNaAT) were also identified in a number of other promoters, including each of the Lrp-regulated promoters whose nucleotide sequence is known. The sequence of the promoter region of serA, an Lrp-regulated gene, was determined. No Lrp consensus target sequence was present upstream of serA, suggesting that Lrp acts indirectly on the serA promoter. A previously described mutation in a leucine-responsive trans-acting factor, LivR (J. J. Anderson, S. C. Quay, and D. L. Oxender, J. Bacteriol. 126:80-90, 1976), resulted in constitutively repressed expression from the tdh promoter and constitutively induced expression from the serA promoter. The possibility that LivR and Lrp are allelic is discussed.
X-ray Absorption Spectroscopy Reveals a Substantial Increase of Sulfur Oxidation in Transthyretin (TTR) upon Fibrillization*

Transthyretin (TTR) amyloid fibrils are the main component of the amyloid deposits occurring in Familial Amyloidotic Polyneuropathy patients. This is 1 of 20 human proteins leading to protein aggregation disorders such as Alzheimer's and Creutzfeldt-Jakob diseases. The structural details concerning the association of the protein molecules are essential for a better understanding of the disease and consequently the design of new strategies for diagnosis and therapeutics. Disulfide bonds are frequently considered essential for the stability of protein aggregates and since in the TTR monomers there is one cysteine residue, it is important to determine unambiguously the redox state of sulfur present in the fibrils. In this work we used x-ray spectroscopy to further characterize TTR amyloid fibrils. The sulfur K-edge absorption spectra for the wild type and some amyloidogenic TTR variants in the soluble and fibrillar forms were analyzed. Whereas in the soluble proteins the thiol group from cysteine (R-SH) and the thioether group from methionine (R-S-CH3) are the most abundant forms, in the TTR fibrils there is a significant oxidation of sulfur to the sulfonate form in the cysteine residue and a partial oxidation of sulfur to sulfoxide in the methionine residues. Further interpretation of the data reveals that there are no disulfide bridges in the fibrillar samples and suggest conformational changes in the TTR molecule, namely in strand A and/or in its vicinity, upon fibril formation.
The influence of race and religion on abstinence from alcohol, cigarettes and marijuana among adolescents.

OBJECTIVE Past research has not fully explained why black youth are less likely than white youth to use alcohol and other substances. One plausible yet underexamined explanation is the "religion hypothesis," which posits that black youth are more likely than white youth to abstain because they are more religious than white youth. The present study tested this hypothesis empirically. METHOD The study examined data from large, nationally representative samples of white and black 10th graders from the Monitoring the Future project. RESULTS Relative to white students, black students are more likely to abstain from alcohol, cigarettes and marijuana and are more highly religious. Consistent with the "religiosity hypothesis," race differences in abstinence are substantially reduced when race differences in religiosity are controlled. Unexpectedly, however, highly religious white youth are more likely than highly religious black youth to abstain from alcohol and marijuana use. CONCLUSIONS Although religion is an important protective factor against alcohol and other substance use for both white and black adolescents, it appears to impact white youth at an individual level, whereas for black youth the influence of religion seems greatest at the group level. Future research should seek to better understand the mechanisms through which religion promotes adolescents' abstinence from the use of drugs and should seek to explain why the magnitude of its effect varies for black and white adolescents.
The effectiveness of the Reach for Health Community Youth Service learning program in reducing early and unprotected sex among urban middle school students.

OBJECTIVES This study evaluated the effectiveness of a community youth service (CYS) program in reducing sexual risk behaviors among African American and Latino urban young adolescents. METHODS A total of 1061 students at 2 urban middle schools were surveyed at baseline and 6-month follow-up. Students at one school were randomly assigned by classroom to receive either the Reach for Health CYS program or the Reach for Health classroom curriculum only. Students at the other school served as controls. RESULTS At follow-up. CYS participants reported significantly less recent sexual activity (P < .05) and scored lower on a sexual activity index than those in the control condition (P < .03). The greatest effect was among eighth graders, who received the most intensive service program (P < .03). The benefit of the curriculum-only intervention appeared greatest among students in special education classes. CONCLUSIONS Well-organized CYS that couples community involvement with classroom health instruction can have a positive impact on the sexual behaviors of young adolescents at risk for HIV, sexually transmitted diseases, and unintended pregnancy. This study also suggests the importance of including students in special education classes in health education programs.
3-D Absorptive Frequency Selective Reflector for Antenna Radar Cross Section Reduction

A methodology for designing a frequency selective reflector with two-sided absorption bands is proposed. This method is based on utilizing multimode resonators inside a 3-D unit cell to obtain an absorption-reflection-absorption response. Detailed analysis of this 3-D absorptive frequency selective reflector (AFSR) is provided with the aid of an equivalent circuit model to reveal the operating principle. To show the benefit of the new structure in antenna’s radar cross section reduction (RCSR), a dual-polarized 3-D-AFSR integrated with monopole and dipole antennas are simulated, fabricated, and then measured. Compared with their counterparts with normal ground plane, AFSR-backed antennas have shown a remarkable out-of-band RCSR. The −10 dB RCSR has fractional bandwidths of at least 64.7% and 41% with center frequencies of 3.4 and 8.3 GHz, respectively. The radiation characteristics of AFSR-backed antennas are nearly maintained. The realized gains are enhanced by 0.9 and 2.3 dB for monopole and dipole antennas mounted on a 3-D-AFSR, respectively.
Global Analysis of Protein Expression of Inner Ear Hair Cells

The mammalian inner ear (IE) subserves auditory and vestibular sensations via highly specialized cells and proteins. Sensory receptor hair cells (HCs) are necessary for transducing mechanical inputs and stimulating sensory neurons by using a host of known and as yet unknown protein machinery. To understand the protein composition of these unique postmitotic cells, in which irreversible protein degradation or damage can lead to impaired hearing and balance, we analyzed IE samples by tandem mass spectrometry to generate an unbiased, shotgun-proteomics view of protein identities and abundances. By using Pou4f3/eGFP-transgenic mice in which HCs express GFP driven by Pou4f3, we FACS purified a population of HCs to analyze and compare the HC proteome with other IE subproteomes from sensory epithelia and whole IE. We show that the mammalian HC proteome comprises hundreds of uniquely or highly expressed proteins. Our global proteomic analysis of purified HCs extends the existing HC transcriptome, revealing previously undetected gene products and isoform-specific protein expression. Comparison of our proteomic data with mouse and human databases of genetic auditory/vestibular impairments confirms the critical role of the HC proteome for normal IE function, providing a cell-specific pool of candidates for novel, important HC genes. Several proteins identified exclusively in HCs by proteomics and verified by immunohistochemistry map to human genetic deafness loci, potentially representing new deafness genes. SIGNIFICANCE STATEMENT Hearing and balance rely on specialized sensory hair cells (HCs) in the inner ear (IE) to convey information about sound, acceleration, and orientation to the brain. Genetically and environmentally induced perturbations to HC proteins can result in deafness and severe imbalance. We used transgenic mice with GFP-expressing HCs, coupled with FACS sorting and tandem mass spectrometry, to define the most complete HC and IE proteome to date. We show that hundreds of proteins are uniquely identified or enriched in HCs, extending previous gene expression analyses to reveal novel HC proteins and isoforms. Importantly, deafness-linked proteins were significantly enriched in HCs, suggesting that this in-depth proteomic analysis of IE sensory cells may hold potential for deafness gene discovery.
Endoscopic thermal ablation therapies for hepatocellular carcinoma: a multi-center study.

AIM The differing efficacies of radiofrequency ablation and microwave coagulation for hepatocellular carcinoma (HCC) are unknown. Therefore, we performed a multi-center study to assess the factors contributing to survival and local recurrences of HCC among patients with solitary tumors who underwent endoscopic thermal ablation as their primary treatment. METHODS From six institutions, 391 patients with solitary HCC who were first treated by endoscopic thermal ablation were enrolled in this study and assessed retrospectively. We investigated age, gender, location of tumor, longest diameter of tumor, method of anesthesia, type of endoscope, method of thermal ablation, Child-Pugh classification, the Japan Integrated Staging score and the Cancer of the Liver Italian Program score. Statistical analyses were performed using univariate analysis with log-rank test and multivariate analysis with the Cox proportional hazards model. RESULTS On univariate analysis, advanced Child-Pugh score, advanced Italian Program score and local recurrences were significant predictors of poor survival. Young age (</=70), large tumor (>30 mm) and the use of the thoracoscopic approach were significant predictors for the development of local recurrence. On multivariate analysis, local anesthesia and advanced Child-Pugh score were independent predictors of poor survival. Young age, large tumor, local anesthesia and the use of the thoracoscopic approach were independent predictors for the development of local recurrence. The method of thermal ablation did not influence survival or local recurrence. CONCLUSIONS Differences in the effect on survival and local recurrence between microwave and radiofrequency were not observed in this retrospective, multi-center study of endoscopic thermal ablation for HCC.
Productivity Growth from an International Trade Perspective

This paper presents a framework to assess the relative importance of three key sources of productivity growth that international trade research focuses on: (1) inter-industry specialization; (2) intra-industry reallocation of resources across heterogeneous firms; and (3) technological progress. We illustrate how to apply the framework by deciphering the productivity dynamics of the Swiss manufacturing industry. We find that intra-industry reallocations are the most important source of growth in aggregate total factor productivity, spurred by the productivity growth of large, incumbent firms and the entry of new firms. Inter-industry specialization and general technological progress, nevertheless, remain important supplementary sources of productivity growth.
Is gold a hedge and safe haven for stock market?

ABSTRACT The paper aims to examine the hedge and safe haven properties of gold relative to Dow Jones stock industry indices using quantile-GARCH approach. Splitting the sample period into two sub-periods, our results show that the hedge and safe haven properties of gold have a changing nature. In a whole period (1980–2017), gold is not a hedge for Oil&Gas, Basic materials and Utilities; gold is a safe haven for almost all sectors except Technology. While in sub-period I (1980–1995) gold is not a hedge for Oil&Gas but a strong safe haven for all sectors. In sub-period II (1996–2017) gold is not a hedge for Oil&Gas, Basic materials and Utilities, also not a safe haven for Oil&Gas, Basic materials, Utilities, Telecom and Technology.
Outcome of very low birth weight infants: multiple gestation versus singletons.

OBJECTIVE Multiple gestation infants are overrepresented in intensive care nurseries, and have been reported to have greater morbidity than singletons. A cohort of very low birth weight infants was examined to determine outcome of premature infants based on gestation type (multiple or single) and hypothesized that at this low birth weight, the outcome of the groups would be similar. METHOD The sample was composed of all infants with birth weights < or = 1250 g born in a 10-year period (September 1977 through September 1987). Ninety-two percent (n = 364) of the infants discharged were seen at 1 year of age, and 73% (n = 249) were observed to school age. Morbidity was assessed by neurodevelopmental examinations and standard developmental tests. RESULTS At 1 year of age and at school age, there were no differences in neurologic or neurosensory outcome between multiple gestation and single gestation infants. Logistic regression analyses were performed on the school age data, using cognitive outcome as the dependent variable and gestation type, birth weight, gestational age, intracranial hemorrhage, chronic lung disease, and a social risk factor as predictor variables. Gestation type was not associated with cognitive outcome at school age. Social risk factors and chronic lung disease showed an association with cognitive outcome at school age. CONCLUSIONS Multiple gestation was not related to increased morbidity in this very low birth weight group. The developmental outcome of all infants with birth weights < or = 1250 g in this study was related to medical and social risk factors. These findings were consistent for a large group of infants over a 10-year period.
The natural history of the use of healthcare information by women with breast cancer: a conceptual model

The overall goal of our research agenda is to contribute to improved quality of healthcare by identifying factors that foster or inhibit the use of healthcare information by patients to make informed healthcare decisions. We propose to study the natural history of the use of healthcare information by women with breast cancer to support decisions about health care. To do so in this paper we propose a conceptual model developed based on an extensive literature review and critique that describes patients' health information use over the disease course. It will guide our further investigation of the complex relationships among patients' personal circumstances, the progress of their medical treatment, and their satisfaction and empowerment as informed decision-makers. The model will help policy makers and health professionals identify the best means to provide patients with useful information, and help all stakeholders in health care acquire information needed to improve healthcare quality.
Impact of ambulatory, family-focused teamwork intervention on glycemic control in youth with type 1 diabetes.

OBJECTIVE To evaluate an ambulatory, family-focused intervention aimed at optimizing STUDY DESIGN Study design We randomly assigned 105 children and adolescents, 8 to 17 years of age, with T1DM for < or =6 years, to a family-focused teamwork (TW) intervention or to standard multidisciplinary diabetes care (SC). Patients in both study groups were seen at 3- to 4-month intervals and were followed prospectively for 1 year. Measures of family involvement in diabetes tasks, DFC, and quality of life were performed at baseline and after 1 year. Hemoglobin A1c was measured at each visit. RESULTS Patients (n = 100) completed follow-up, (50 in TW and 50 in SC). At entry, A1c was 8.4% +/- 1.3% in TW and 8.3% +/- 1.0% in SC. After 1 year, A1c was 8.2% +/- 1.1% in TW compared with 8.7% +/- 1.5% in SC (P <.05). Both groups had similar frequencies of blood glucose monitoring (BGM) and insulin dosing. Families exposed to the TW intervention maintained or increased family involvement significantly more than families exposed to SC (P =.05). In multivariate analysis, the TW intervention and the daily frequency of BGM significantly predicted A1c (R (2) = 0.17, P =. 05). Despite increased family involvement, the TW group reported no increase in DFC or decrease in quality of life. CONCLUSIONS The ambulatory TW intervention prevented the expected deterioration in glycemic control seen with SC in youths with T1DM of < or =6 years' duration. Successful family involvement may assist in the preservation of health and the prevention of long-term diabetes complications for youth with diabetes.
Nature and causes of trends in male diabetes prevalence, undiagnosed diabetes, and the socioeconomic status health gradient

This paper investigates levels in diabetes prevalence patterns across key socioeconomic status indicators and how they changed over time. The investigation spans both the conventional concept of diagnosed diabetes and a more comprehensive measure that includes those whose diabetes is undiagnosed. By doing so, I separate the distinct impact of covariates on trends over time in disease onset and the probability of disease diagnosis. The principal force leading to higher diabetes prevalence over time is excessive weight and obesity, which was only partially offset by improvements in the education of the population over time. Undiagnosed diabetes remains an important health problem, but much less so than 25 years ago. Although race and ethnic differentials in undiagnosed diabetes were eliminated over the last 25 years, the disparities became larger across other measures of disadvantage, such as education.