Miracle-dz/UniFAR-FTUs huggingface dataset:
Classification of missense substitutions in the BRCA genes: A database dedicated to Ex‐UVs

Unclassified sequence variants (UVs) arising from clinical mutation screening of cancer susceptibility genes present a frustrating issue to clinical genetics services and the patients that they serve. We created an open‐access database holding missense substitutions from the breast and ovarian cancer susceptibility genes BRCA1 and BRCA2. The main inclusion criterion is that each variant should have been assessed in a published work that used the Bayesian integrated evaluation of unclassified BRCA gene variants. Transfer of data on these substitutions from the original publications to our database afforded an opportunity to analyze the missense substitutions under a single model and to remove inconsistencies that arose during the evolution of the integrated evaluation over the last decade. This analysis also afforded the opportunity to reclassify these missense substitutions according to the recently published IARC 5‐Class system. From an initial set of 248 missense substitutions, 31 were set aside due to nonnegligible probability to interfere with splicing. Of the remaining substitutions, 28 fell into one of the two pathogenic classes (IARC Class 4 or 5), 174 fell into one of the two nonpathogenic classes (IARC Class 1 or 2), and 15 remain in IARC Class 3, “Uncertain. ” The database is available at http://brca.iarc. fr/LOVD. Hum Mutat 33:22–28, 2012. © 2011 Wiley Periodicals, Inc.
Oxidative Stress induced lipid accumulation via SREBP 1 c activation in HepG 2 cells

SREBP1c (sterol regulatory element binding protein 1c) is a metabolic-syndrome–associated transcription factor that controls fatty acid biosynthesis under glucose/insulin stimulation. Oxidative stress increases lipid accumulation, which promotes the generation of reactive oxygen species (ROS). However, we know little about the role of oxidative stress in fatty acid biosynthesis. To clarify the action of oxidative stress in lipid accumulation via SREBP1c, we examined SREBP1c activity in H2O2-treated mammalian cells. We introduced a luciferase reporter plasmid carrying the SREBP1c binding site into HepG2 or COS7 cells. With increasing H2O2 dose, SREBP1c transcriptional activity increased in HepG2 cells but declined in COS7 cells. RT-PCR analysis revealed that mRNA expression of SREBP1c gene or of SREBP1c-regulated genes rose H2O2-dose-dependently in HepG2 cells but dropped in COS7 cells. Lipid accumulation and levels of the nuclear form of SREBP1c increased in H2O2-stimulated HepG2 cells. ROS may stimulate lipid accumulation in HepG2 cells via SREBP1c activation.
Simulation Analysis of Tightening Torque and Temperature Characteristics of Distribution Network Fasteners

To investigate the impact of tightening torque on tension clamps and conductor temperature variation in overhead power lines, a simplified structural finite element model of the NLL-4 tension clamp was created using COMSOL Multiphysics. Electromagnetic-thermal coupling finite element simulations of the tension clamp were conducted under power frequency AC currents ranging from 600A to 800A, with adjustments to the tightening torque. Ultimately, a three-dimensional temperature field distribution of the tension clamp and conductor was obtained. The simulation results reveal that, under a 600A power frequency AC current, the tightening torque steadily decreases, leading to an overall increase in the temperature of both the tension clamp and conductor. When the tightening torque remains constant, applying different power frequency AC currents in the range of 600A to 800A results in an overall temperature rise in the tension clamp with increasing current. Furthermore, regardless of changes in current and tightening torque, the temperature of the compressed segment of the conductor consistently exceeds that of the uncompressed portion.
The relationship between bone mineral density and blood pressure in the Korean elderly population: the Korea National Health and Nutrition Examination Survey, 2008–2011

Abstract It is not clear whether the inverse relationship between bone mineral density (BMD) and blood pressure (BP) could be generalizable to the general elderly population. We used data from the fourth and fifth Korea National Health and Nutrition Examination Survey. The study sample consisted of 8439 men and postmenopausal women aged 50 years and older. We evaluated the relationship between BMD and BP. When adjusted for covariates, femur neck T-score [coefficient = −0.391, 95% confidence interval (CI) −0.766 to −0.016, p = 0.041] had an inverse relationship with diastolic BP (DBP), whereas lumbar spine BMD (coefficient = 0.395, 95% CI 0.058–7.752, p = 0.047) and T-score (coefficient = 0.458, 95% CI 0.005–0.911, p = 0.047) had a positive relationship with systolic BP (SBP). When adjusted for confounding factors, SBP (128.67 ± 0.979 mmHg versus 126.36 ± 0.545 mmHg, p = 0.026) and DBP (78.8 ± 0.622 mmHg versus 77.27 ± 0.283 mmHg, p = 0.016) were significantly higher in femur neck osteoporosis subjects than non-osteoporosis subjects. However, there were no differences in BP in relation to lumbar spine osteoporosis. Femur neck osteoporosis (odds ratio = 1.422, 95% CI 1.107–1.827, p = 0.006) had a significant and positive relationship with hypertension, whereas the other parameters of BMD were not significantly related to hypertension. In conclusion, higher BP and hypertension were significantly and positively correlated with femur neck osteoporosis in men and postmenopausal women aged 50 years and older.
Androgen Receptor Splice Variants Are Not Substrates of Nonsense‐Mediated Decay

Androgen receptor (AR) splice variants have been clinically associated with progressive cancer, castration‐resistance, and resistance to AR antagonists and androgen synthesis inhibitors. AR variants can be generated by genomic alterations and alternative splicing, and their expression is androgen‐regulated. There has been a suggestion that AR variants bearing premature termination codons and coding for truncated proteins should be regulated by the nonsense‐mediated decay (NMD) mRNA surveillance pathway, suggesting that either the NMD pathway is dysfunctional in variant‐expressing cell lines or that variants are somehow able to evade degradation by NMD.
Assessment of genetic and epigenetic variations in potato somatic hybrids by Methylation-sensitive ISSR and RAPD markers

Genetic and epigenetic changes (DNA methylation) in the mother plants of somatic hybrids (1st cycle) and their regenerants (30th cycles sub-cultured) were analyzed using methylation-sensitive ISSR and RAPD markers. ISSR and RAPD profiles and their cluster analyses based on the Jaccard’s similarity coefficient revealed 100% genetic similarity among the mother plant and their regenerants. While for the epigenetic changes in the samples, the MS-ISSR markers detected DNA methylation (2.7%) in the regenerants compared to the mother plant (1%), whereas MS-RAPD markers detected a little methylation patterns in the regeneratns (0.6%) compared to the mother plants (0.4%). DOI: http://dx.doi. org/10.3329/bjb.v44i1. 22722 Bangladesh J. Bot. 44 (1): 45-50, 2015 (March)
Down-regulation of Death-associated Protein Kinase-2 Is Required for β-Catenin-induced Anoikis Resistance of Malignant Epithelial Cells*

Resistance of solid tumor cells to anoikis, apoptosis induced by cell detachment from the extracellular matrix, is thought to be critical for the ability of these cells to grow anchorage independently within thee-dimensional tumor masses and from metastases. β-Catenin, a major oncoprotein, can inhibit anoikis of cancer cells via unknown mechanisms. In an effort to identify these mechanisms we found that β-catenin blocks anoikis of malignant kidney and intestinal epithelial cells and promotes their anchorage-independent growth by down-regulating death-associated protein kinase-2 (DAPk-2), a pro-apoptotic protein whose cellular functions have so far remained unexplored. We found that β-catenin-induced down-regulation of DAPk-2 requires the presence of the transcription factor Tcf-4, a known mediator of β-catenin signaling. We also observed that DAPk-2 contributes to the execution of anoikis of the non-malignant epithelial cells. Thus, β-catenin-induced down-regulation of DAPk-2 represents a novel signaling mechanism by which β-catenin promotes the survival of malignant epithelial cells following their detachment from the ECM and enables these cells to grow in an anchorage-independent manner.
Covariate measurement error correction methods in mediation analysis with failure time data

Mediation analysis is important for understanding the mechanisms whereby one variable causes changes in another. Measurement error could obscure the ability of the potential mediator to explain such changes. This article focuses on developing correction methods for measurement error in the mediator with failure time outcomes. We consider a broad definition of measurement error, including technical error, and error associated with temporal variation. The underlying model with the “true” mediator is assumed to be of the Cox proportional hazards model form. The induced hazard ratio for the observed mediator no longer has a simple form independent of the baseline hazard function, due to the conditioning event. We propose a mean‐variance regression calibration approach and a follow‐up time regression calibration approach, to approximate the partial likelihood for the induced hazard function. Both methods demonstrate value in assessing mediation effects in simulation studies. These methods are generalized to multiple biomarkers and to both case‐cohort and nested case‐control sampling designs. We apply these correction methods to the Women's Health Initiative hormone therapy trials to understand the mediation effect of several serum sex hormone measures on the relationship between postmenopausal hormone therapy and breast cancer risk.
Commutativity, comonotonicity, and Choquet integration of self-adjoint operators

In this work, we propose a definition of comonotonicity for elements of [Formula: see text], i.e. bounded self-adjoint operators defined over a complex Hilbert space [Formula: see text]. We show that this notion of comonotonicity coincides with a form of commutativity. Intuitively, comonotonicity is to commutativity as monotonicity is to bounded variation. We also define a notion of Choquet expectation for elements of [Formula: see text] that generalizes quantum expectations. We characterize Choquet expectations as the real-valued functionals over [Formula: see text] which are comonotonic additive, [Formula: see text]-monotone, and normalized.
Soft switched boost converter for a battery operated electric wehicle

Electric vehicles are considered less practical because, huge batteries are required to provide the power for acceleration. High voltage can be obtained with the help of DC-DC boosters. A soft switched DC-DC converter with high efficiency is proposed in this paper. A theoretical analysis of a soft switched boost converter is carried out and its operating principles are presented and the same is verified through simulation results.
Feature extraction of SERS spectrum of honey using Principal Component Analysis

Honey purity can be identified using combinations of Surface-Enhanced Raman Spectroscopy (SERS), digital signal processing and Principal Component Analysis. This paper focuses on the revelation of honey composition and extraction of honey features. The honey was diluted before it was passed to Surface Enhanced Raman Spectroscopy to enhance its spectrum. After the spectrum was processed by removing background interferences, the honey features were then extracted and analyzed using Principal Component Analysis. The significant features were selected for future classification using eigenvalue one criterion. It was found that coefficients 1 to 9 of all honey samples are significant and can be used as input to a classifier.
Streptomycin – Like Antibiotic from Streptomyces spp. Isolated from Mount Everest Base Camp

Streptomyces spp. (Lob18.2b), isolated from soil sample from Everest Base Camp, was obtained from Research Laboratory for Biotechnology and Biochemistry (RLABB). The isolate was found to inhibit Salmonella paratyphi, Salmonella typhi, Proteus mirabilis, Proteus vulgaris, Shigella sonnei, Klebsiella pneumoniae, Klebsiella oxytoca, Escherichia coli, Bacillus subtilis and Staphylococcus aureus on primary screening. Secondary screening was done using fermented starch casein broth of the streptomycete to its stationary phase culture. The antibacterial agent was highly effective against all susceptible Gram negative bacteria except Proteus spp. Gram positive bacteria were relatively lesser sensitive. Pseudomonas aeruginosa was resistant to the agent. Antibacterial activity of aqueous fraction obtained from fermented broth of streptomycete culture was more effective than that of organic fraction of same extract. Thin layer chromatography revealed that the test compound was relatively nonpolar compared to the known antibiotics. Among the tested standard antibiotics, the chemical characteristic of the antibacterial agent was comparable to streptomycin. Key words: aminoglycoside; antibacterial agent; fermentation; secondary screening; thin layer chromatography DOI: 10.3126/njst.v9i0. 3168 Nepal Journal of Science and Technology 9 (2008) 73-77
Risk factors for Clostridium difficile infection in the community: a case-control study in patients in general practice, Denmark, 2009–2011

SUMMARY To identify risk factors for Clostridium difficile infection (CDI) in Danish patients consulting general practice with gastrointestinal symptoms, a prospective matched case-control study was performed; cases (N = 259) had positive cultures for toxigenic C. difficile and controls (N = 455) negative cultures. Data were analysed by conditional logistic regression. In patients aged ⩾2 years (138 cases), hospitalization [odds ratio (OR) 8·4, 95% confidence interval (CI) 3·1–23], consumption of beef (OR 5·5, 95% CI 2·0–15), phenoxymethylpenicillin (OR 15, 95% CI 2·7–82), dicloxacillin (OR 27, 95% CI 3·6–211), and extended spectrum penicillins (OR 9·2, 95% CI 1·9–45) were associated with CDI. In patients aged <2 years none of these were associated with CDI, but in a subgroup analysis contact with animals was associated with CDI (OR 8·1, 95% CI 1·0–64). This study emphasizes narrow-spectrum penicillins, and suggests beef consumption, as risk factors for CDI in adults, and indicates a different epidemiology of CDI in infants.
The aim of this study is to examine the effect of predisposing , enabling , and need factors on subsequent physician and hospital use among older Mexican Americans

Results: After two years of follow-up, predisposing and enabling factors accounted for ,5% of the variance in physician and hospital use. Need factors explained 21% of the variance in physician use and 7% of the variance in hospital use. Older age; being female; insurance coverage; having arthritis, diabetes, heart attack, hypertension, stroke, or cancer; and number of medications were factors associated with higher physician utilization. Subjects with arthritis, diabetes, hip fracture, high depressive symptoms, activities of daily living (ADL) disability, or high number of medications increased the odds of having any hospitalization. Subjects with diabetes, heart attack, hip fracture, ADL disabled, and high number of medications had a greater number of hospital nights than their counterparts.
Serum adipokines levels in patients with systemic sclerosis: A meta-analysis

Abstract Background: Systemic sclerosis is an chronic inflammatory autoimmune diseases. Adipokine has been reported to play an important role in modulating immune responses. Recent studies suggest that adipokine also plays some roles in the pathogenesis of systemic sclerosis (SSc). However, published data regarding the relationship between plasma/serum adipokine levels and SSc are contradictory. The aim of this study was at performing a meta-analysis to derive a more accurate estimation and further investigate the association of plasma/serum leptin and adiponectin levels with SSc patients. Methods: PubMed, and Web of Science databases (up to Feb 20, 2016) were used to obtain all relative published literatures. The study quality was assessed by the Newcastle–Ottawa scale. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by random-effect model analysis. Results: A total of fourteen studies were finally included in this meta-analysis. Among them, six of which were studied for the serum adiponectin levels in SSc patients, six of which were studied for the serum leptin levels in SSc patients, and two of them were studied both for serum adiponectin levels and serum leptin levels in SSc patients. The meta-analysis results showed that the serum adiponectin levels in SSc patients were significantly lower than that in normal controls (SMD = −0.608 ng/ml, 95% CI = −1.029 to −0.186, p = 0.005). However, there were no significant differences in serum leptin levels between SSc patients and healthy controls (SMD = −0.990 ng/ml, 95% CI = −2.340 to 0.359, p = 0.150). The subgroup analysis showed that Asia SSc patients with age less than 50 years old had lower plasma/serum adiponectin levels when compared with controls. Conclusion: The serum adiponectin levels, but not serum leptin levels, in SSc patients were significantly lower than that in normal controls.
Detection of Significant Bacteriuria by Use of the iQ200 Automated Urine Microscope

ABSTRACT In the microbiology laboratory, there is an augmented need for rapid screening methods for the detection of bacteria in urine samples, since about two-thirds of these samples will not yield any bacteria or will yield insignificant growth when cultured. Thus, a reliable screening method can free up laboratory resources and can speed up the reporting of a negative urine result. In this study, we have evaluated the detection of leukocytes, bacteria, and a new sediment indicator, the “all small particles” (ASP), by an automated instrument, the iQ200 urine analyzer, to detect negative urine samples that can be excluded from culture. A coupled automated strip reader (iChem Velocity), enabling the detection of nitrite and leukocyte esterase, was tested in parallel. In total, 963 urine samples were processed through both conventional urine culture and the iQ200/iChem Velocity workstation. Using the data, a multivariate regression model was established, and the predicted specificity and the possible reduction in urine cultures were calculated for the indicators and their respective combinations (leukocytes plus bacteria plus ASP and leukocyte esterase plus nitrite). Among all options, diagnostic performance was best using the whole microscopic content of the sample (leukocytes plus bacteria plus ASP). By using a cutoff value of ≥104 CFU/ml for defining a positive culture, a given sensitivity of 95% resulted in a specificity of 61% and a reduction in urine cultures of 35%. By considering the indicators alone, specificity and the culture savings were both much less satisfactory. The regression model was also used to determine possible cutoff values for running the instrument as part of daily routine. By using a graphical representation of all combinations possible, we derived cutoff values for leukocyte, bacterial, and ASP count, which should enable the iQ200 microscope to screen out approximately one-third of the urine samples, significantly reducing the workload in the microbiology laboratory.
Isolation of cDNAs encoding the Drosophila GAGA transcription factor

To investigate the mechanisms involved in expression of the Drosophila melanogaster engrailed gene, we purified GAGA protein, one of several putative transcriptional activator proteins that binds to the proximal region of the engrailed promoter. Antibodies raised against GAGA protein were used to demonstrate that the protein is present in all nuclei of young embryos. We isolated cDNA clones encoding GAGA protein in which a putative 519-codon open reading frame contains general sequence motifs characteristic of other transcription factors. These include stretches of polyglutamine, a 60-amino-acid region with 18 (30%) lysine or arginine residues, and a single putative zinc finger motif. In addition, a 120-residue N-terminal region shares significant sequence homology with several other known Drosophila transcription factors, including those encoded by Broad Complex and tramtrack. Up to 35-fold GAGA protein-dependent stimulation of transcription in Schneider line 2 tissue culture cells was observed after transfection of GAGA protein-encoding sequences. The GAGA gene is present in one copy in the Drosophila genome, at cytological location 70EF, and it encodes RNAs which vary in size between 2.4 and 4.4 kb.
Translation of Vascular Endothelial Growth Factor mRNA by Internal Ribosome Entry: Implications for Translation under Hypoxia

ABSTRACT Vascular endothelial growth factor (VEGF) is a hypoxia-inducible angiogenic growth factor that promotes compensatory angiogenesis in circumstances of oxygen shortage. The requirement for translational regulation of VEGF is imposed by the cumbersome structure of the 5′ untranslated region (5′UTR), which is incompatible with efficient translation by ribosomal scanning, and by the physiologic requirement for maximal VEGF production under conditions of hypoxia, where overall protein synthesis is compromised. Using bicistronic reporter gene constructs, we show that the 1,014-bp 5′UTR of VEGF contains a functional internal ribosome entry site (IRES). Efficient cap-independent translation is maintained under hypoxia, thereby securing efficient production of VEGF even under unfavorable stress conditions. To identify sequences within the 5′UTR required for maximal IRES activity, deletion mutants were analyzed. Elimination of the majority (851 nucleotides) of internal 5′UTR sequences not only maintained full IRES activity but also generated a significantly more potent IRES. Activity of the 163-bp long “improved” IRES element was abrogated, however, following substitution of a few bases near the 5′ terminus as well as substitutions close to the translation start codon. Both the full-length 5′UTR and its truncated version function as translational enhancers in the context of a monocistronic mRNA.
Anatomical study of the auditory region of Arctotherium tarijense (Ursidae, Tremarctinae), an extinct short‐faced bear from the Pleistocene of South America

Here we present the most detailed morphological study of the auditory region of a tremarctinae bear, Arctotherium tarijense Ameghino. In addition, we provide new anatomical information of the Tremarctinae inner ear, such as coplanarity and deviation from orthogonality of the semicircular canals, as an approach to infer the head movements which encountered the extinct forms in locomotion. Based on morphological comparisons, A. tarijense exhibits the following particular features: the cavum tympani presents the highest relative volume compared with other ursids; the processus paraoccipitalis has a foramen that is absent in other tremarctines; there is only one (ventral) recess in the anterior region of the cavum tympani; and the recessus epytimpanicus is the smallest for all ursids studied. In relation to the inner ear, A. tarijense shows the lowest values of orthogonality deviation and highest scores of locomotor agility. Based on this, is possible to make a preliminary proposal that this species had a relative high vestibular sensibility and therefore a better ability to explore different kind of habitats. However, this hypothesis might be contrasted among bears taking into account the orientation of each semicircular canal in a phylogenetic framework.