Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of cigarette‐smoking on sperm DNA methylation and its effect on sperm parameters

DNA methylation is an epigenetic modification of the genome. The purpose of this study was to determine the influence of cigarette‐smoking on sperm DNA methylation from a genomewide survey of sperm samples and to ascertain its effect on sperm parameters. Twenty‐eight sperm DNA samples (from 14 fertile smokers as a case study and 14 proven fertile nonsmokers as controls) were subjected to Infinium 450K BeadChip arrays to identify the changes in the DNA methylation level between the two groups. Then, deep bisulphite sequencing was used to validate five CpGs on 78 samples. The results from the Infinium 450K found that only 11 CpGs showed a significant difference in DNA methylation between the case and the control groups. Five CpGs of the eleven (cg00648582, cg0932376, cg19169023, cg23841288 and cg27391564) underwent deep bisulphite sequencing where cg00648582, related to the PGAM5 gene, and the cg23841288 CpGs, related to the PTPRN2 gene amplicons, showed a significant increase in their DNA methylation level in more than one CpG in the case group. In contrast, a significant decrease was found at cg19169023 and at its various neighbouring CpGs in the TYRO3 gene‐related amplicons. Furthermore, this study demonstrated a significant correlation between the variation in sperm DNA methylation level and standard sperm parameters in the case group.
Prevalence of dental caries and dental fluorosis among 12 and 15 years old school children in relation to fluoride concentration in drinking water in an endemic fluoride belt of Andhra Pradesh.

BACKGROUND The published literature on the prevalence and severity of dental caries and dental fluorosis among school going children in Nalgonda district - An Endemic Fluoride belt was lacking . OBJECTIVES To assess the prevalence and severity of dental fluorosis and dental caries among 12 and 15 years old children in relation to fluoride concentration in drinking water . SETTINGS AND DESIGN It was a cross-sectional study, done in Nalgonda district of Andhra Pradesh, India (endemic fluoride belt) . MATERIALS AND METHODS 5 of the 59 mandals in the district of Nalgonda were selected by simple random sampling. Then, 3 schools from each of these selected mandals were chosen at random. All the eligible 6 th and 9 th standard children were considered for final analysis. The demographic and other relevant information was collected by 3 trained and calibrated dentists, using a structured questionnaire. Dental caries were recorded using dentition status and treatment needs and fluorosis were recorded by Dean's fluorosis index. The statistical analysis was done using SPSS version 16. RESULTS The prevalence of dental caries among children was 56.3% with the highest in below optimal fluoride area (71.3%) and lowest in optimal fluoride area (24.3%). The prevalence of dental fluorosis was 71.5%. The prevalence was 39.7% in below optimal fluoride area and 100% in high and very fluoride areas. The prevalence and severity of fluorosis increased with increasing fluoride concentration. The caries experience was more among boys than girls. CONCLUSION There was a negative correlation between dental caries and fluoride concentration for the entire study population. However, in high fluoride areas, there was a positive correlation between fluoride concentration and dental caries. Water defluoridation on an urgent basis is a priority here than water fluoridation, because the prevalence and severity of dental flurorosis is very high.
Clinical Pharmacokinetics of XP13512, a Novel Transported Prodrug of Gabapentin

Gabapentin absorption occurs in only a limited region of the small intestine and saturates at doses used clinically, resulting in dose‐dependent pharmacokinetics, high interpatient variability, and potentially ineffective drug exposure. XP13512/GSK1838262 is a novel transported prodrug of gabapentin that is absorbed throughout the entire length of the intestine by high‐capacity nutrient transporters. In 4 studies of healthy volunteers (136 subjects total), the pharmacokinetics of XP13512 immediate‐ and extended‐release formulations were compared with those of oral gabapentin. XP13512 immediate‐release (up to 2800 mg single dose and 2100 mg twice daily) was well absorbed (>68%, based on urinary recovery of gabapentin), converted rapidly to gabapentin, and provided dose‐proportional exposure, whereas absorption of oral gabapentin declined with increasing doses to <27% at 1200 mg. Compared with 600 mg gabapentin, an equimolar XP13512 extended‐release dose provided extended gabapentin exposure (time to maximum concentration, 8.4 vs 2.7 hours) and superior bioavailability (74.5% vs 36.6%). XP13512 may therefore provide more predictable gabapentin exposure and decreased dosing frequency.
Temporal change in genetic structure and effective population size in steelhead trout (Oncorhynchus mykiss)

There is a wealth of published molecular population genetic studies, however, most do not include historic samples and thus implicitly assume temporal genetic stability. We tested for changes in genetic diversity and structure in three populations of steelhead trout (Oncorhynchus mykiss) from a northern British Columbia watershed using seven microsatellite loci over 40 years. We found little change in genetic diversity (mean allele numbers and observed and expected heterozygosity), despite large variation in the estimated numbers of steelhead returning to the watershed over the same time period. However, the temporal stability in genetic diversity is not reflected in population structure, which appears to be high among populations, yet significantly variable over time. The neighbour‐joining tree showed that, overall, two of the populations (Zymoetz and Kispiox) clustered separately from the third (Babine); a finding which was not consistent with their geographical separation. The clustering pattern was also not temporally consistent. We used the temporal method to estimate the effective number of breeders (Nb) for the three populations; our values (Nb = 17–102) were low for the large and presumed vigorous populations of steelhead trout sampled. The low Nb values were also not consistent with the generally high genetic diversity estimates, suggesting the possibility of intermittent gene flow among the three populations. The use of temporal analyses in population genetic samples should be a priority; first, to verify observed patterns in contemporary data, and second, to build a dataset of temporal analyses to allow generalizations to be made concerning temporal genetic stability and effective population size in natural populations.
Essays on Inequality, Economic Activity and Globalization: Theory and Evidence

Essays on Inequality, Economic Activity and Globalization: Theory and Evidence Jorge Humberto Rojas Vallejos Chair of the Supervisory Committee: Ford and Louisa Van Voorhis Professor of Economics Stephen J. Turnovsky Economics The recent increase in trade liberalization has had substantial distributional consequences, although the direction of this relationship and the mechanism driving it has been open to debate. This thesis analyzes the impact of tariff reductions on the dynamics of wealth and income inequality in a growing economy in which agents accumulate assets such as physical capital and internationally traded bonds. This study comprises a combination of theoretical and empirical analyses, supplemented with numerical simulations. These findings suggest that in the long run a tariff reduction will be expansionary and generally associated with a permanent increase in income inequality, the magnitudes of which depend upon the speed at which the tariff reduction is implemented. For plausible parameterization of the models our numerical simulations seem to be generally consistent with empirical evidence. In addition, this thesis presents a formal model on how committees make decisions, an essential element on any trade agreement. Last, I empirically explore the relationship between income inequality and carbon emissions to highlight the relevance and multiple implications of economic inequality in today’s society.
High‐performance work systems and employee engagement: empirical evidence from China

Employee engagement and commitment has been a very important issue in human resource managers’ agenda. The present study adds to the literature by examining the impact of high-performance work systems (HPWS) on employee attitudes and on employee engagement in China in response to the increasing interest in the universalistic effects of HPWS in the globalized world market. With the data from 782 employees working in China's manufacturing and service sectors, this study shows that HPWS are positively related to employees’ positive mood and job satisfaction, and that job satisfaction and positive mood lead to high employee engagement. Moreover, employee's positive mood and job satisfaction also mediate the relationship between HPWS and employee engagement. The result helps explore one mechanism via which HPWS affect employee behaviors and provides empirical evidence for the applicability of HPWS in an international context.
Three-dimensional fold of the human AQP1 water channel determined at 4 A resolution by electron crystallography of two-dimensional crystals embedded in ice.

Here, we present a three-dimensional (3D) density map of deglycosylated, human erythrocyte aquaporin 1 (AQP1) determined at 4 A resolution in plane and approximately 7 A resolution perpendicular to the bilayer. The map was calculated by analyzing images and electron diffraction patterns recorded from tilted (up to 60 degrees ), ice-embedded, frozen-hydrated 2D crystals of AQP1 in lipid bilayer membranes. This map significantly extends the findings related to the folding of the AQP1 polypeptide chain determined by us at a lower, 7 A by approximately 20 A, resolution. The solvent-accessible volume within a monomer has a vestibular architecture, with a narrow, approximately 6.5 A diameter constriction near the center of the bilayer, where the location of the water-selective channel is postulated to exist. The clearly resolved densities for the transmembrane helices display the protrusions expected for bulky side-chains. The density in the interior of the helix barrel (putative NPA box region) is better resolved compared to our previous map, suggesting clearer linkage to some of the helices, and it may harbor short stretches of alpha-helix. At the bilayer extremities, densities for some of the inter-helix hydrophilic loops are visible. Consistent with these observed inter-helix connections, possible models for the threading of the AQP1 polypeptide chain are presented. A preferred model is deduced that agrees with the putative locations of a group of aromatic residues in the amino acid sequence and in the 3D density map.
Generation and Bioenergetic Profiles of Cybrids with East Asian mtDNA Haplogroups

Human mitochondrial DNA (mtDNA) variants and haplogroups may contribute to susceptibility to various diseases and pathological conditions, but the underlying mechanisms are not well understood. To address this issue, we established a cytoplasmic hybrid (cybrid) system to investigate the role of mtDNA haplogroups in human disease; specifically, we examined the effects of East Asian mtDNA genetic backgrounds on oxidative phosphorylation (OxPhos). We found that mtDNA single nucleotide polymorphisms such as m.489T>C, m.10398A>G, m.10400C>T, m.C16223T, and m.T16362C affected mitochondrial function at the level of mtDNA, mtRNA, or the OxPhos complex. Macrohaplogroup M exhibited higher respiratory activity than haplogroup N owing to its higher mtDNA content, mtRNA transcript levels, and complex III abundance. Additionally, haplogroup M had higher reactive oxygen species levels and NAD+/NADH ratios than haplogroup N, suggesting difference in mitonuclear interactions. Notably, subhaplogroups G2, B4, and F1 appeared to contribute significantly to the differences between haplogroups M and N. Thus, our cybrid-based system can provide insight into the mechanistic basis for the role of mtDNA haplogroups in human diseases and the effect of mtDNA variants on mitochondrial OxPhos function. In addition, studies of mitonuclear interaction using this system can reveal predisposition to certain diseases conferred by variations in mtDNA.
Rural EMR adoption rates overtake those in urban areas

OBJECTIVE To assess rural-urban differences in electronic medical record (EMR) adoption among office-based physician practices in the United States. METHODS Survey data on over 270 000 office-based physician sites (representing over 1 280 000 physicians) in the United States from 2012 was used to assess differences in EMR adoption rates among practices in rural and urban areas. Logistic regression tests for differences in the determinants of EMR adoption by geography, and a nonlinear decomposition is used to quantify how much of the rural-urban gap is due to differences in measureable characteristics (such as type of practice or affiliation with a health system). RESULTS Overall EMR adoption rates were significantly higher for practices in rural areas (56%) vs those in urban areas (49%) in 2012 (P < 0.001). Twenty-nine states had statistically significantly different adoption rates between rural and urban areas, with only two states demonstrating higher rates in urban areas. EMR adoption continues to be higher for primary care practices when compared to specialists (51% vs 49%, P < 0.001), and state-level rural-urban differences in adoption are more pronounced for specialists. The decomposition technique finds that only 14% of the rural-urban gap can be explained by differences in measurable characteristics between practices. CONCLUSIONS At the national level, rates of EMR adoption are higher for rural practices than for their urban counterparts, reversing earlier trends. This suggests that outreach efforts, namely the Regional Extension Centers created by the Office of the National Coordinator, have been particularly effective in increasing EMR adoption in rural areas.
Regulation of secretory leukocyte proteinase inhibitor (SLPI) production by human bronchial epithelial cells: increase of cell-associated SLPI by neutrophil elastase.

BACKGROUND To protect against the extracellular activity of serine proteinases, the lung is equipped with serine proteinase inhibitors including secretory leukocyte proteinase inhibitor (SLPI) and elafin. Both SLPI and elafin are locally produced by airway epithelial cells, but the mechanisms that regulate the expression of these proteinase inhibitors are relatively unknown. Previous studies using airway epithelial cell lines indicated that neutrophil elastase (NE) increases SLPI mRNA transcripts while decreasing SLPI protein release. Similar results were observed for elafin. The aim of the present study was to investigate the effect of NE on SLPI and elafin synthesis in cultures of human primary bronchial epithelial cells (PBEC). METHODS Subcultures of human PBEC were incubated with NE, followed by preparation of cell-free supernatants and cellular lysates and determination of SLPI and elafin protein levels by enzyme-linked immunoadsorbent assay. The effect of NE on SLPI mRNA transcripts was determined by Northern blot analysis. RESULTS The results showed that NE increased SLPI mRNA expression while decreasing SLPI protein release. This NE-induced decrease was associated with an increase in cell-associated SLPI, providing an explanation for the apparent paradox of increased SLPI mRNA transcripts and decreased SLPI protein levels present in supernatants. In addition, NE had a stimulatory effect on the release of elafin by airway epithelial cells, whereas no increase in cell-associated elafin was observed. CONCLUSIONS The results from the present study indicate that NE may play a role in the regulation of the antiproteinase screen in the lung and the formation of a protective surface at the epithelial site.
Survival and cure of acute myeloid leukaemia in England, 1971‐2006: a population–based study

The 5‐year relative survival of adults diagnosed with acute myeloid leukaemia (AML) was less than 10% during the 1970s and 1980s in England. This population‐based study estimated the 5‐year relative survival and ‘cure’ for 48 380 adult patients diagnosed with AML in England during 1971–2006. Relative survival and cure mixture models were used to produce estimates of 5‐year relative survival and the percentage ‘cured’. ‘Cure’ was defined as the proportion of a group of survivors for whom there is no excess mortality compared with the general population. The 5‐year relative survival and the percentage ‘cured’ increased for patients aged under 70 years at diagnosis during 1971–2006, but advancing age was associated with poorer outcome. During the study period a dramatic increase in 5‐year relative survival occurred in those aged 15–24 years, from 7% to 53%. The percentage ‘cured’ was less than 10% for all ages in 1975, but increased to 45% for those aged 15–24 years in 2000. Cure could not be estimated for patients over 70 years, because survival was consistently low (<5%). The long‐term outcome of patients with AML has improved substantially, particularly in younger patients. The potential exists for further increasing levels of ‘cure’.
Empirical methods for assessing meaningful neuropsychological change following epilepsy surgery

Abstract Traditional methods for assessing the neurocognitive effects of epilepsy surgery are confounded by practice effects, test-retest reliability issues, and regression to the mean. This study employs 2 methods for assessing individual change that allow direct comparison of changes across both individuals and test measures. Fifty-one medically intractable epilepsy patients completed a comprehensive neuropsychological battery twice, approximately 8 months apart, prior to any invasive monitoring or surgical intervention. First, a Reliable Change (RC) index score was computed for each test score to take into account the reliability of that measure, and a cutoff score was empirically derived to establish the limits of statistically reliable change. These indices were subsequently adjusted for expected practice effects. The second approach used a regression technique to establish “change norms” along a common metric that models both expected practice effects and regression to the mean. The RC index scores provide the clinician with a statistical means of determining whether a patient's retest performance is “significantly” changed from baseline. The regression norms for change allow the clinician to evaluate the magnitude of a given patient's change on 1 or more variables along a common metric that takes into account the reliability and stability of each test measure. Case data illustrate how these methods provide an empirically grounded means for evaluating neurocognitive outcomes following medical interventions such as epilepsy surgery. (JINS, 1996, 2, 556–564.)
Fluorescence correlation studies of lipid domains in model membranes (Review)

Advances in optical microscopy techniques and single-molecule detection have paved the way to exploring new approaches for investigating membrane dynamics and organization, thereby revealing details on the processing of signals, complex association/dissociation, chemical reactions and transport at and around the membrane. These events rely on a tight regulation of lipid-protein and protein-protein interactions in space and time. Fluorescence Correlation Spectroscopy (FCS) provides exquisite sensitivity in measuring local concentrations, association/dissociation constants, chemical rate constants and, in general, in probing the chemical environment of the species of interest and its interactions with potential partners. Here, we review some applications of FCS to lipid and protein organization in biomimetic membranes with lateral heterogeneities, which share some physico-chemical properties with cellular rafts. What we learn from investigations of lipid-lipid and lipid-protein interactions in simple model membranes can be regarded as an essential basic lecture for studies in more complex cellular membranes.
Reference services in liberal arts libraries

This study addresses a gap in the literature regarding reference services at liberal arts institutions. The author conducted a literature review to examine the existing body of research on reference services and distributed a survey to the 80 member libraries of the Oberlin Group in February 2015. The study found that a wide range of reference practices are in place at liberal arts libraries and focused especially on the use of a designated reference desk, which is widespread. However, there is a correlation between higher librarian satisfaction with reference services and the absence of a desk. Comments from respondents are included in the discussion and reflected common themes associated with decisions around reference services. Some limitations of the study include its small sample size and conflicting responses from librarians at the same institution. Nevertheless, this article provides a starting point for further research into liberal arts reference. It could provide other libraries with a tool for reevaluating their own reference models, and the factors relating to librarian satisfaction, the themes running through the comments, or the trends discussed in the literature review may be relevant for determining the most effective reference model at any institution.
A review of the harmonic and unbalance effects in electrical distribution networks due to EV charging

For wide use of electric vehicles (EVs), there are different aspects of the electric power system to consider for making it ready for the increased load by battery charging. The topics include power production, peak load management, distribution transmission capacity but also distribution network power quality and many more. This paper presents an overview on the likely power quality impacts in the distribution networks associated with EV charging. Based on a literature review, focus is especially put on harmonics and load unbalance in the network. Most relevant papers observing these topics are presented summarizing their contribution. The power quality aspects in distribution networks discussed here are not often presented within analysis of permissible EV penetration levels. Harmonics or voltage unbalance and effects associated with these could introduce additional limits to the EV charging capacity for the distribution networks. Therefore the analysis on the EV charging influence on these power quality topics requires also high-priority discussions before drawing conclusions on the distribution networks capabilities.