Miracle-dz/UniFAR-FTUs huggingface dataset:
Loci identified by genome-wide association studies influence different disease-related phenotypes in chronic obstructive pulmonary disease.

RATIONALE Genome-wide association studies have shown significant associations between variants near hedgehog interacting protein HHIP, FAM13A, and cholinergic nicotinic acetylcholine receptor CHRNA3/5 with increased risk of chronic obstructive pulmonary disease (COPD) in smokers; however, the disease mechanisms behind these associations are not well understood. OBJECTIVES To identify the association between replicated loci and COPD-related phenotypes in well-characterized patient populations. METHODS The relationship between these three loci and COPD-related phenotypes was assessed in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-point (ECLIPSE) cohort. The results were validated in the family-based International COPD Genetics Network (ICGN). MEASUREMENTS AND MAIN RESULTS The CHRNA3/5 locus was significantly associated with pack-years of smoking (P = 0.002 and 3 × 10⁻⁴), emphysema assessed by a radiologist using high-resolution computed tomography (P = 2 × 10⁻⁴ and 4.8 × 10⁻⁵), and airflow obstruction (P = 0.004 and 1.8 × 10⁻⁵) in the ECLIPSE and ICGN populations, respectively. However, variants in the IREB2 gene were only significantly associated with FEV₁. The HHIP locus was not associated with smoking intensity but was associated with FEV₁/FVC (P = 1.9 × 10⁻⁴ and 0.004 in the ECLIPSE and ICGN populations). The HHIP locus was also associated with fat-free body mass (P = 0.007) and with both retrospectively (P = 0.015) and prospectively (P = 0.024) collected COPD exacerbations in the ECLIPSE cohort. Single-nucleotide polymorphisms in the FAM13A locus were associated with lung function. CONCLUSIONS The CHRNA3/5 locus was associated with increased smoking intensity and emphysema in individuals with COPD, whereas the HHIP and FAM13A loci were not associated with smoking intensity. The HHIP locus was associated with the systemic components of COPD and with the frequency of COPD exacerbations. FAM13A locus was associated with lung function.
Components of biological variation in prolyl endopeptidase and dipeptidyl-peptidase IV activity in plasma of healthy subjects.

We investigated the components of biological variation in plasma prolyl endopeptidase (PEP; EC 3.4.21.26) and dipeptidyl-peptidase IV (DPP IV; EC 3.4.14.5) activity in healthy individuals. We took monthly blood samples from 26 healthy volunteers for determination of plasma PEP and DPP IV activity during one calendar year. The estimated CVs for PEP activity were: total (CVt) = 25.0%, interindividual (CVg) = 13.9%, and intraindividual (CVi) = 16.8%. There was a statistically significant (P < 0.0001) seasonal pattern in plasma PEP activity, with significantly higher values in the fall than in the other seasons. The peak-trough difference in the yearly variation in PEP activity, expressed as a percentage of the mean, was as high as 56.8%. The estimated CVs for DPP IV activity were: CVt = 17.1%, CVg = 14.5%, and CVi = 8.2%. DPP IV activity was significantly (P < 0.0001) higher in summer than in the other seasons but the amplitude of the yearly variation was small.
Influence of the Milk and Dairy Beef Quality Assurance Program on dairy farm drug management practices.

OBJECTIVE To test the hypothesis that dairy farms certified in the Milk and Dairy Beef Quality Assurance Program (QAP) were more likely to use prudent drug management practices than farms that were not certified. DESIGN Cross-sectional study. SAMPLE POPULATION 141 Michigan dairy farms of which 74 were not certified in the QAP, 30 were involuntarily certified, and 37 were voluntarily certified. PROCEDURE Dairy producers completed a self-administered questionnaire that focused on herd health management, drug use, record keeping, personnel management, and descriptive characteristics of their farm during 1993. Separate multivariable logistic regression models were developed to determine the association of QAP certification with each of the management practices. RESULTS Results suggested that farms adopted specific management practices irrespective of certification. Many farms used visible identification and non-emergency veterinary services and discussed residue prevention with employees. Involuntary certification was associated with maintenance of good written treatment records and performance of on-farm drug residue testing. Voluntary certification was weakly associated with use of refrigerated drug storage. CONCLUSIONS AND CLINICAL RELEVANCE QAP certification appeared to have been associated with the adoption of only a few prudent drug use practices, although QAP materials and framework were developed to assist veterinarians in the promotion of disease prevention, client communication, and residue prevention practices on farms. Veterinary care would benefit from the development and encouragement of better record keeping on farms.
The implementation of a Deep Recurrent Neural Network Language Model on a Xilinx FPGA

Recently, FPGA has been increasingly applied to problems such as speech recognition, machine learning, and cloud computation such as the Bing search engine used by Microsoft. This is due to FPGAs great parallel computation capacity as well as low power consumption compared to general purpose processors. However, these applications mainly focus on large scale FPGA clusters which have an extreme processing power for executing massive matrix or convolution operations but are unsuitable for portable or mobile applications. This paper describes research on single-FPGA platform to explore the applications of FPGAs in these fields. In this project, we design a Deep Recurrent Neural Network (DRNN) Language Model (LM) and implement a hardware accelerator with AXI Stream interface on a PYNQ board which is equipped with a XILINX ZYNQ SOC XC7Z020 1CLG400C. The PYNQ has not only abundant programmable logic resources but also a flexible embedded operation system, which makes it suitable to be applied in the natural language processing field. We design the DRNN language model with Python and Theano, train the model on a CPU platform, and deploy the model on a PYNQ board to validate the model with Jupyter notebook. Meanwhile, we design the hardware accelerator with Overlay, which is a kind of hardware library on PYNQ, and verify the acceleration effect on the PYNQ board. Finally, we have found that the DRNN language model can be deployed on the embedded system smoothly and the Overlay accelerator with AXI Stream interface performs at 20 GOPS processing throughput, which constitutes a 70.5X and 2.75X speed up compared to the work in Ref.30 and Ref.31 respectively.
Aortic Wall Thickness and Amniotic Fluid Albuminuria in Growth-Restricted Twin Fetuses

Background and objective: Intrauterine growth restriction (IUGR) may be associated with significantly higher aortic intima–media thickening (aIMT) values. It is unknown if fetal aIMT is associated with glomerulosclerosis and amniotic albuminuria in utero. Design, setting, participants, and measurements: Fetal abdominal aIMT and amniotic albumin/creatinine ratio (ACR) were measured in 126 individual twin fetuses, recruited by the Obstetrics and Gynaecology Clinics of the University of Padua (Italy) Medical Center. The IUGR twin fetuses were classified into two groups: Group A were those fetuses whose estimated fetal weight (EFW) was <10th percentile with pulsatility index >2 SD and Group B were those fetuses whose EFW was <10th percentile and had no velocimetry abnormalities. Results: The median fetal aIMT was significantly different in the three groups (Group A = 0.9 mm; Group B = 0.7 mm; and appropriate for gestational age (AGA) = 0.5 mm; p < . 0001). It was significantly higher in Group A than in the AGA group (p < .0001) and than in the Group B fetuses (p = .003), respectively. In addition, ACR was different in the three groups (Group A = 183,500 mg/g; Group B = 6,4720 mg/g; and AGA = 8,2750 mg/g; p = .0002). It was significantly higher in Group A than in the AGA group (p = .03) and than in Group B (p = .02), respectively. Conclusions: Growth-restricted twin fetuses with velocimetry abnormalities present are associated with aIMT and higher ACR levels in amniotic fluid, which could be possible markers in utero of preclinical atherosclerosis, and early glomerulosclerosis.
Molecular genetics of familial hypercholesterolemia in Spain: Ten novel LDLR mutations and population analysis

Mutations underlying FH in Spain are largely unknown because only a few and limited surveys have been carried out on Spanish FH patients up to now. To gain information on this issue, we have analysed a group of 113 unrelated Spanish FH patients from an eastern area of Spain (Valencian Community). We have screened the LDLR gene by Southern blot and PCR‐SSCP analysis to detect large rearrangements and small mutations, respectively. In addition, we have screened the Apo B gene for mutations known to cause FDB by PCR‐SSCP analysis. We have identified a total of 47 different mutations in the LDLR gene (5 large rearrangements, and 42 small mutations, which were characterized by DNA sequencing), 19 of which have not been described in other populations (Valencia‐1 to ‐4, 112insA, P160R, 790DelATGA, 920insTCAG, G642E, and the ten novel mutations E246A, 884delT, I289T, S305F, Q328X, Y354C, I603del, 2312‐3C>A, V779M, and N804K). Three of these mutations (15%) were present in more than 1 proband, being mutation 112insA the most prevalent (frequency ∼ 8%) in our sample. The Apo B gene R3500Q mutation was found in only one patient and no underlying defect was found in about 27% of patients. Our data support the notion that Spaniards represent a heterogeneous population with its own spectrum of LDLR gene mutations and that, in our population, FDB has a lower frequency or a milder expression than in central Europe countries. © Wiley‐Liss, Inc.
Subcellular Distribution of Urokinase and Urokinase Receptor in Human Neutrophils Determined by Immunoelectron Microscopy

A high-affinity receptor for urokinase-type plasminogen activator (uPAR) has been identified on the plasmamembrane of a number of different cell types, and has been shown to be important for plasminogen activation, cell adhesion, and possibly signal transduction. uPAR and uPA cosediment with secretory vesicles and specific granules by subcellular fractionation and translocate to the plasma membrane upon activation of neutrophils. Here the subcellular distribution of uPAR and uPA is studied by electron microscopy of neutrophils using immunogold double labeling for uPAR and uPA and a set of markers for well-defined subtypes of granules: matrix metalloproteinase type-9 (MMP-9) for gelatinase granules, lactoferrin (LF) for specific granules, and myeloperoxidase (MPO) and neutrophil elastase (NE) for primary granules. With this technique uPAR colocalizes with uPA in 71% of labeled granules. In granules containing uPAR the degree of coexpression with MMP-9, MPO and NE was 19, 66, and 74%, respectively. In granules labeled for uPA the corresponding overlap with MMP-9, MPO and NE was 24, 64, and 51%, respectively. Low levels of co-localization were found for uPAR and LF (7%) and for uPA and lactoferrin (5%). The results indicate that uPAR and uPA arepresent in gelatinase granules and primary granules, but rarely in specific granules. The demonstration of uPAR and uPA in primary granules is of particular interest, and may indicate that uPAR and uPA participate in the activation of latent hepatocyte growth factor of neutrophils.
Optimal use of multi‐informant data on co‐occurrence of internalizing and externalizing problems: the TRAILS study

Strong between‐informant discrepancies are found in ratings of (pre)adolescent problems and in co‐occurrence rates between different domains of psychopathology. These discrepancies can be caused by differences in the context of measurement and the perspective of informants. The aim of this study was to develop a “Multi‐Informant Co‐occurrence” model (MIC), which takes into account these differences in context and perspective. In a population‐based cohort of (pre)adolescents (n = 2230) from a longitudinal study in the north of the Netherlands, internalizing (INT) and externalizing (EXT) problems were rated by the (pre)adolescents themselves, their teachers, and their parents. As hypothesized Principal Component Analysis revealed four independent main components: Between‐domain convergence was captured by a severity component (S), while between‐domain discrepancy was captured by a direction component (D). Between‐informant discrepancies were captured by a perspective (P) and a context (C) component. The use of this MIC‐model will increase reliability and validity of measures of psychopathology and the four components each provide useful specific information. Copyright © 2008 John Wiley & Sons, Ltd.
Los derivados en el concurso: la racionalidad del régimen especial y las peculiaridades españolas

Este trabajo investiga las implicaciones del regimen concursal especial dispensado a los derivados en el funcionamiento de los mercados financieros y en el procedimiento concursal. Y lo hace desde dos opticas. La primera se pregunta sobre la idoneidad del regimen especial para corregir las ineficiencias de los mercados financieros �particularmente el riesgo sistemico� y llama la atencion respecto de los costes sociales que a su vez origina. La otra reflexion tiene que ver con la repercusion que ha tenido en Espana la comercializacion de los swaps de tipo de interes en el desenlace de los concursos de pequenas empresas no financieras. Se ha modificado la normativa originaria �que era acorde con la del resto de los paises de nuestro entorno� para "subsidiar" la colocacion de IRS en el sector minorista a costa de los otros acreedores concursales. El resultado es un regimen singular, sin parangon en ningun otro ordenamiento.
The retinal targets of centrifugal neurons and the retinal neurons projecting to the accessory optic system

Abstract In birds, neurons of the isthmo-optic nucleus (ION), as well as “ectopic” neurons, send axons to the retina, where they synapse on cells in the inner nuclear layer (INL). Previous work has shown that centrifugal axons can be divided into two anatomically distinct types depending on their mode of termination: either “convergent” or “divergent” (Ramon y Cajal, 1889; Maturana & Frenk, 1965). We show that cytochrome-oxidase histochemistry specifically labels “convergent” centrifugal axons and target neurons which appear to be amacrine cells, as well as three “types” of ganglion cells: two types found in the INL (displaced ganglion cells) and one in the ganglion cell layer. Labeled target amacrine cells have distinct darkly labeled “nests” of boutons enveloping the somas, are associated with labeled centrifugal fibers, and are confined to central retina. Lesions of the isthmo-optic tract abolish the cytochrome-oxidase labeling in the centrifugal axons and in the target amacrine cells but not in the ganglion cells. Cytochrome-oxidase-labeled ganglion cells in the INL are large; one type is oval and similar to the classical displaced ganglion cells of Dogiel, which have been reported to receive centrifugal input; the other type is rounder. Rhodamine beads injected into the accessory optic system results in retrograde label in both types of cells, showing that two distinct types of displaced ganglion cells project to the accessory optic system in chickens. The ganglion cells in the ganglion cell layer that label for cytochrome oxidase also project to the accessory optic system. These have proximal dendrites that ramify in the outer inner plexiform layer. Neither the target amacrine cells nor either of the displaced ganglion cells are immunoreactive for the inhibitory transmitter gamma aminobutyric acid. At least some of the target amacrine cells may, however, be cholinoceptive: we found that the antibody to the alpha-7 subunit of the nicotinic ACh receptor labels a population of cells in the INL that are similar in location, size, and the presence of labeled bouton-like structures to those we find labeled with cytochrome oxidase. This antibody also labels neurons in the ION proper but not ectopic cells. In conclusion, it appears that cytochrome oxidase may be a marker for “convergent” centrifugal axons and at least one of their target cells in the INL.
Long-term trends and characteristics of visibility in two megacities in southwest China: Chengdu and Chongqing

Visibility is a good indicator of air quality because it reflects the combined influences of atmospheric pollutants and synoptic processes. Trends in visibility and relationships with various factors in Chengdu and Chongqing, two megacities in southwest China, were analyzed using daily data from National Climatic Data Center and the Air Pollution Index (API) of the Ministry of Environmental Protection of China. Average annual visibility during the period of 1973–2010 was 8.1 ± 3.9 in Chengdu and 6.2 ± 4.3 km in Chongqing. PM10 dominates the reported primary pollutants in both cities, although concentrations have decreased from a high of 127.9 and 150 µg m3 before 2005 to 100.4 and 93.5 µg m−3 in Chengdu and Chongqing, respectively. Low average visibility and extremely high levels of PM10 were observed in winter, whereas relative humidity had irregular and weak seasonal variations. Visibility in both cities has deteriorated in comparison to the 1960s and 1970s, mostly due to the elevation of optical depth caused by anthropogenic pollution. Correlations and principal component analysis (PCA) were undertaken to determine the key factors affecting visibility. Visibility was only moderately correlated with PM10. In Chengdu, visibility displayed weak correlations with various factors, whereas visibility in Chongqing was most strongly related to relative humidity due to the atmospheric particulates in the region containing more hygroscopic components. PCA results further confirmed that high relative humidity and low wind speed increased the occurrence of low visibility events under high PM10 concentrations. Temperature and pressure, as indicators of weather systems, also played important roles in affecting visibility. Mathematical models of visibility prediction indicated that wind speed had the largest coefficients among all meteorological factors, and reductions in PM10 concentration only led to minor improvements in visibility. Implications: Long-term data indicates that visibility in Chengdu and Chongqing has been lower than 10 km since the 1970s, and the poor visibility primarily results from anthropogenic pollution. Although PM10 concentrations have decreased consistently to around 100 μg m−3, trends of visibility have shown no improvement but much fluctuation. Correlation and principal component analysis demonstrate that low visibility in Chengdu is influenced by high relative humidity, while in Chongqing the degrading visibility is related with high relative humidity and pressure and low wind speed under a stable weather system. The results are important to understand the widespread haze event in the two megacities of southwest China. Supplemental Materials: Supplemental materials are available for this paper. Go to the publisher's online edition of the Journal of the Air & Waste Management Association.
Novel insulin analogues and its mitogenic potential

Abstract: Insulin analogues were developed to modify the structure of the human insulin molecule in order to more accurately approximate the endogenous secretion of insulin. With the help of recombinant technology and site‐directed mutagenesis, the insulin molecule can be modified to either delay or shorten absorption time, providing better insulin treatment options and facilitating the achievement of glycaemic goals. Changing the structure of the insulin molecule, however, may significantly alter both its metabolic and mitogenic activity. Multiple factors such as residence time on the receptor, dissociation rate, rate of receptor internalization and the degree of phosphorylation of signalling proteins can affect the mitogenic potencies of insulin analogues.
Bioenergetics of Archaea: ATP Synthesis under Harsh Environmental Conditions

Archaea are a heterogenous group of microorganisms that often thrive under harsh environmental conditions such as high temperatures, extreme pHs and high salinity. As other living cells, they use chemiosmotic mechanisms along with substrate level phosphorylation to conserve energy in form of ATP. Because some archaea are rooted close to the origin in the tree of life, these unusual mechanisms are considered to have developed very early in the history of life and, therefore, may represent first energy-conserving mechanisms. A key component in cellular bioenergetics is the ATP synthase. The enzyme from archaea represents a new class of ATPases, the A1A₀ ATP synthases. They are composed of two domains that function as a pair of rotary motors connected by a central and peripheral stalk(s). The structure of the chemically-driven motor (A1) was solved by small-angle X-ray scattering in solution, and the structure of the first A1A₀ ATP synthases was obtained recently by single particle analyses. These studies revealed novel structural features such as a second peripheral stalk and a collar-like structure. In addition, the membrane-embedded electrically-driven motor (A₀) is very different in archaea with sometimes novel, exceptional subunit composition and coupling stoichiometries that may reflect the differences in energy-conserving mechanisms as well as adaptation to temperatures at or above 100°C.
Differences in characteristics and outcomes between community- and hospital-acquired acute kidney injury: A systematic review and meta-analysis .

INTRODUCTION No comprehensive review has examined the difference between community-acquired (CA) and hospital-acquired (HA) acute kidney injury (AKI) in terms of patient characteristics, in-hospital mortality, and hospital stay length. MATERIALS AND METHODS We conducted a systematic review and meta-analysis of observational studies, using MEDLINE, EMBASE, Web of Science, Google Scholar, and the Cochrane Library from their inceptions to April 10, 2016. Observational studies that (1) were published in peer-reviewed journals; (2) compared CA-AKI with HA-AKI, irrespective of the AKI definition during the same period; and (3) investigated in-hospital mortality and length of hospital stay were studied. Differences in the patients' baseline characteristics were analyzed, and a meta-analysis was conducted to compare the in-hospital mortality and length of hospital stay. RESULTS Eight eligible observational studies with 17,939 patients were included. The systematic review showed that patients with CA-AKI had a significantly higher rate of AKI stage 3 compared with those with HA-AKI. The meta-analysis revealed that patients with CA-AKI showed significantly lower in-hospital mortality (odds ratio (OR) = 2.79; Z = 8.22; 95% confidence interval (CI), 2.18 - 3.56; p < 0.001) and shorter length of hospital stay (OR = 2.55; Z = 5.81; 95% CI, 1.86 - 3.50; p < 0.001). Subanalyses of studies conducted in developing and developed countries showed that patients with CA-AKI had lower in-hospital mortality and shorter length of hospital stay. Jackknife sensitivity analyses confirmed the replicability of these findings (p < 0.001). CONCLUSIONS The results indicate that significant differences exist in clinical phenotypes between CA- and HA-AKI, even when standardized diagnosis criteria are used.