Miracle-dz/UniFAR-FTUs huggingface dataset:
Atrophic Remodeling of the Heart In Vivo Simultaneously Activates Pathways of Protein Synthesis and Degradation

Background—Mechanical unloading of the heart results in atrophic remodeling. In skeletal muscle, atrophy is associated with inactivation of the mammalian target of rapamycin (mTOR) pathway and upregulation of critical components of the ubiquitin proteosome proteolytic (UPP) pathway. The hypothesis is that mechanical unloading of the mammalian heart has differential effects on pathways of protein synthesis and degradation. Methods and Results—In a model of atrophic remodeling induced by heterotopic transplantation of the rat heart, we measured gene transcription, protein expression, polyubiquitin content, and regulators of the mTOR pathway at 2, 4, 7, and 28 days. In atrophic hearts, there was an increase in polyubiquitin content that peaked at 7 days and decreased by 28 days. Furthermore, gene and protein expression of UbcH2, a ubiquitin conjugating enzyme, was also increased early in the course of unloading. Transcript levels of TNF-&agr;, a known regulator of UbcH2-dependent ubiquitin conjugating activity, were upregulated early and transiently in the atrophying rat heart. Unexpectedly, p70S6K and 4EBP1, downstream components of mTOR, were activated in atrophic rat heart. This activation was independent of Akt, a known upstream regulator of mTOR. Rapamycin treatment of the unloaded rat hearts inhibited the activation of p70S6K and 4EBP1 and subsequently augmented atrophy in these hearts compared with vehicle-treated, unloaded hearts. Conclusions—Atrophy of the heart, secondary to mechanical unloading, is associated with early activation of the UPP. The simultaneous activation of the mTOR pathway suggests active remodeling, involving both protein synthesis and degradation.
Tobacco Smoking Leads to Extensive Genome-Wide Changes in DNA Methylation

Environmental factors such as tobacco smoking may have long-lasting effects on DNA methylation patterns, which might lead to changes in gene expression and in a broader context to the development or progression of various diseases. We conducted an epigenome-wide association study (EWAs) comparing current, former and never smokers from 1793 participants of the population-based KORA F4 panel, with replication in 479 participants from the KORA F3 panel, carried out by the 450K BeadChip with genomic DNA obtained from whole blood. We observed wide-spread differences in the degree of site-specific methylation (with p-values ranging from 9.31E-08 to 2.54E-182) as a function of tobacco smoking in each of the 22 autosomes, with the percent of variance explained by smoking ranging from 1.31 to 41.02. Depending on cessation time and pack-years, methylation levels in former smokers were found to be close to the ones seen in never smokers. In addition, methylation-specific protein binding patterns were observed for cg05575921 within AHRR, which had the highest level of detectable changes in DNA methylation associated with tobacco smoking (–24.40% methylation; p = 2.54E-182), suggesting a regulatory role for gene expression. The results of our study confirm the broad effect of tobacco smoking on the human organism, but also show that quitting tobacco smoking presumably allows regaining the DNA methylation state of never smokers.
Induction of Porcine Host Defense Peptide Gene Expression by Short-Chain Fatty Acids and Their Analogs

Dietary modulation of the synthesis of endogenous host defense peptides (HDPs) represents a novel antimicrobial approach for disease control and prevention, particularly against antibiotic-resistant infections. However, HDP regulation by dietary compounds such as butyrate is species-dependent. To examine whether butyrate could induce HDP expression in pigs, we evaluated the expressions of a panel of porcine HDPs in IPEC-J2 intestinal epithelial cells, 3D4/31 macrophages, and primary monocytes in response to sodium butyrate treatment by real-time PCR. We revealed that butyrate is a potent inducer of multiple, but not all, HDP genes. Porcine β-defensin 2 (pBD2), pBD3, epididymis protein 2 splicing variant C (pEP2C), and protegrins were induced markedly in response to butyrate, whereas pBD1 expression remained largely unaltered in any cell type. Additionally, a comparison of the HDP-inducing efficacy among saturated free fatty acids of different aliphatic chain lengths revealed that fatty acids containing 3–8 carbons showed an obvious induction of HDP expression in IPEC-J2 cells, with butyrate being the most potent and long-chain fatty acids having only a marginal effect. We further investigated a panel of butyrate analogs for their efficacy in HDP induction, and found glyceryl tributyrate, benzyl butyrate, and 4-phenylbutyrate to be comparable with butyrate. Identification of butyrate and several analogs with a strong capacity to induce HDP gene expression in pigs provides attractive candidates for further evaluation of their potential as novel alternatives to antibiotics in augmenting innate immunity and disease resistance of pigs.
Menopause and the metabolic syndrome: the Study of Women's Health Across the Nation.

BACKGROUND Cross-sectional studies suggest that prevalence of the metabolic syndrome (MetS) increases from premenopause to postmenopause in women, independent of age. Little is known about why. We hypothesized that the incidence of the MetS increases with progression through menopause and that this increase is explained by the progressive androgenicity of the hormonal milieu. METHODS This longitudinal, 9-year study of 949 participants in the Study of Women's Health Across the Nation investigates the natural history of the menopausal transition. Participants of 5 ethnicities at 7 geographic sites were recruited when they were premenopausal or early perimenopausal and were eligible for this study if they (1) reached menopause during the study; (2) had never taken hormone therapy, and (3) did not have diabetes mellitus or the MetS at baseline. The primary outcome was the presence of MetS using National Cholesterol Education Program Adult Treatment Panel III criteria. Secondary outcomes were the components of the MetS. RESULTS By the final menstrual period, 13.7% of the women had new-onset MetS. Longitudinal analyses, centered at the final menstrual period, were adjusted for age at menopause, ethnicity, study site, marital status, education, body mass index, smoking, and aging. Odds of developing the MetS per year in perimenopause were 1.45 (95% confidence interval, 1.35-1.56); after menopause, 1.24 (95% confidence interval, 1.18-1.30). These odds were significantly different (P < .001). An increase in bioavailable testosterone or a decrease in sex hormone-binding globulin levels increased the odds. CONCLUSIONS As testosterone progressively dominates the hormonal milieu during the menopausal transition, the prevalence of MetS increases, independent of aging and other important covariates. This may be a pathway by which cardiovascular disease increases during menopause.
Structure of Drosophilidae Assemblage (Insecta, Diptera) in Pampa Biome (São Luiz Gonzaga, RS)

The Brazilian Pampa (the southernmost end of the country) is currently a highly modified environment because of increasing agricultural activities. In many places, only small parts of grasslands remain inside an agricultural landscape. Drosophilidae (Diptera) have been widely used as a potential bioindicators to monitor the effects of anthropogenic changes in natural environments. However, the fauna of Drosophilidae in the Pampa Biome from natural and disturbed environments, still remains largely unknown. The present study represents one of the first attempts to fill this gap, showing results from monthly collections in the municipality of Sao Luiz Gonzaga (28o24'28"S, 54o57'39"W), in the Brazilian Pampa. A species inventory was carried out in two contrasting environments, an urban zone and a forest remnant (rural zone). In both areas banana-baited traps were used to capture adult drosophilids. The identification was made using external morphology and male terminalia. In total, 13,379 drosophilids were analyzed (rural zone: N = 8,812 and Sobs = 25; urban zone: N = 4,567 and Sobs = 16). In the present study, 16 (60%) out of 26 species were found exclusively or preferentially in the forest. The period of highest richness was between the months of June to November (roughly winter and spring), and the period of lowest richness was from December to May (roughly summer and autumn). An analysis of cluster by the Coefficient of Jaccard showed that species composition slightly changes when the period of the year with higher temperatures (from January to May) is compared with the period with lower temperatures (from June to October). The species abundances were also highly affected by seasonality, as revealed by the Morisita Index, since the samples clustered into similar groups in consecutive periods and in the same season, showing the seasonal preference of some species. The time component was a determinant in the diversity of the assemblage, surpassing the spatial effect. The strong reduction in diversity in the urban area when compared to a small forest patch is evidence of the importance of the natural environments in maintaining the diversity in the Pampa biome, currently a highly disturbed landscape.
Performance of ESPRIT for Estimating Mixtures of Complex Exponentials Modulated by Polynomials

High-resolution (HR) methods are known to provide accurate frequency estimates for discrete spectra. The polynomial amplitude complex exponentials (PACE) model, also called quasi-polynomial model in the literature, was presented as the most general model tractable by HR methods. A subspace-based estimation scheme was recently proposed, derived from the classical ESPRIT algorithm. In this paper, we focus on the performance of this estimator. We first present some asymptotic expansions of the estimated parameters, obtained at the first order under the assumption of a high signal-to-noise ratio (SNR). Then the performance of the generalized ESPRIT algorithm for estimating the parameters of this model is analyzed in terms of bias and variance, and compared to the Cramer-Rao bounds (CRB). This performance is studied in an asymptotic context, and it is proved that the efficiency of undamped single poles estimators is close to the optimality. Moreover, our results show that the best performance is obtained for a proper dimensioning of the data. To illustrate the practical capabilities of the generalized ESPRIT algorithm, we finally propose an application to ARMA filter synthesis, in the context of system conversion from continuous time to discrete time.
Fiscal Multipliers and the Labour Market in the Open Economy

Several contributions have recently assessed the size of fiscal multipliers both in RBC models and New Keynesian models. None of the studies considers a model with frictional labour markets which is a crucial element, particularly at times in which much of the fiscal stimulus has been directed toward labour market measures. We use an open economy model (more specifically, a currency area calibrated to the European Monetary Union) with labour market frictions in the form of labour turnover costs and workers’ heterogeneity to measure fiscal multipliers. We compute short and long run multipliers and open economy spillovers for five types of fiscal packages: pure demand stimuli and consumption tax cuts return very small multipliers; income tax cuts and hiring subsidies deliver larger multipliers, as they reduce distortions in sclerotic labour markets; short-time work (German "Kurzarbeit") returns negative short-run multipliers, but stabilises employment. Our model highlights a novel dimension through which multipliers operate, namely the labour demand stimulus which occurs in a model with non-walrasian labour markets.
Complete and incomplete neutralisation in Fuzhou tone sandhi

This is a study of incomplete neutralisation using Fuzhou tone sandhi as a test case. In Fuzhou Min, Tone 44 and Tone 232 undergo putative neutralisation into Tone 53 preceding a set of low tones, while T44 and T53 are neutralised into T44 preceding T53. Data from 10 Fuzhou speakers show the former neutralisation to be acoustically incomplete, with the sandhi tone of underlying Tone 44 having a higher pitch onset, while the latter appears to be acoustically complete. This result expands the typology of incomplete neutralisation by showing that two distinct phonological objects can incompletely neutralise (A / B → C) into a third object, as previous studies predominantly feature neutralisation of one object into another: A / B → B, e.g. Beijing tone sandhi T2/T3 → T2 / __ T3. It is argued that a hybrid model with both abstract categories and stored exemplars can best account for the data (Pierrehumbert, 2002 & 2006).
Please Wait, Processing: A Selective Literature Review of the Neurological Understanding of Emotional Processing in ASD and Its Potential Contribution to Neuroeducation

Autism spectrum disorder (ASD) and its corresponding conditions have been investigated from a multitude of perspectives resulting in varying understandings of its origin, its outplay, its prognosis, and potential methods of intervention and education for individuals with the disorder. One area that has contributed significantly to providing a different type of understanding is that of neuroscience, and specifically neuroimaging. This paper will offer a selective literature review of research that investigates the role of emotional processing in ASD, and how a deepening of this line of understanding can be used to inform more comprehensive educational practices.
Analysis and spectral characteristics of a spread-spectrum technique for conducted EMI suppression

Frequency modulation (FM) and random switching methods have been used for reducing conducted electromagnetic interference (EMI) in power converters. Limited theoretical studies and comparisons of these schemes, however, are available. In this paper, a detailed analysis and the spectral characteristics of a random carrier-frequency (RCF) technique for suppressing conducted EMI in an offline switched-mode power supply are presented. The analysis provides a theoretical platform for studying the characteristics of this random switching scheme. The level of randomness is defined for the RCF scheme and varied in the converter example so that the effects on the power spectra can be demonstrated. Theoretical predictions of the spectral characteristics of this scheme are confirmed with measurements. The RCF scheme has been compared with the standard constant-frequency pulsewidth modulation (PWM) scheme and the FM scheme. Comparisons of their spectral performance show that the RCF scheme has better conducted EMI suppression than the FM and standard PWM schemes.
Fatty acid oxidation enzyme gene expression is downregulated in the failing heart.

BACKGROUND During the development of heart failure (HF), the chief myocardial energy substrate switches from fatty acids to glucose. This metabolic switch, which recapitulates fetal cardiac energy substrate preferences, is thought to maintain aerobic energetic balance. The regulatory mechanisms involved in this metabolic response are unknown. METHODS AND RESULTS To characterize the expression of genes involved in mitochondrial fatty acid beta-oxidation (FAO) in the failing heart, levels of mRNA encoding enzymes that catalyze the first and third steps of the FAO cycle were delineated in the left ventricles (LVs) of human cardiac transplant recipients. FAO enzyme and mRNA levels were coordinately downregulated (> 40%) in failing human LVs compared with controls. The temporal pattern of this alteration in FAO enzyme gene expression was characterized in a rat model of progressive LV hypertrophy (LVH) and HF [SHHF/Mcc-facp (SHHF) rat]. FAO enzyme mRNA levels were coordinately downregulated (> 70%) during both the LVH and HF stages in the SHHF rats compared with controls. In contrast, the activity and steady-state levels of medium-chain acyl-CoA dehydrogenase, which catalyzes a rate-limiting step in FAO, were not significantly reduced until the HF stage, indicating additional control at the translational or post-translational levels in the hypertrophied but nonfailing ventricle. CONCLUSIONS These findings identify a gene regulatory pathway involved in the control of cardiac energy production during the development of HF.
Inhibition of L-type calcium currents by magnesium sulfate on the rat basilar artery smooth muscle cells

Objective: Vasospasm remains the leading cause of cerebral damage after aneurysmal subarachnoid hemorrhage. Although magnesium regulates the calcium influx in vascular smooth muscle and endothelial cells, it has not been reported whether L-type calcium channels are involved in magnesiuminduced vascular relaxation in rat basilar artery. So, the effect of magnesium sulfate on L-type calcium currents in freshly isolated smooth muscle cells from rat basilar artery was investigated. Methods: The smooth muscle cells were isolated from rabbit basilar artery by enzyme treatment. L-type Ca 2+ currents were identified using cesium chloride, a potassium channel blocker and Bay K8644, an activator of L-type Ca 2+ channel. Currents were recorded under step pulse whole cell patch clamp technique. Results: In the presence of cesium chloride (in pipette solution), inward currents were observed by depolarizing step pulses. The inward currents were significantly reduced by nimodipine (n=4, p<0.05), an L-type Ca 2+ channel blocker and increased by Bay K8644 (n=5, p<0.05), an L-type Ca 2+ channel activator. The L-type calcium currents (156±17.0 pA, n=12) were significantly reduced by the application of 5 mM magnesium sulfate (53.8±7.0 pA, n=12, p<0.01). Conclusion: These results suggest that magnesium may relax cerebral vessel of rat basilar artery through decreasing intracellular Ca 2+ ion by inhibition of L-type Ca 2+ channels.
Similarity between Words Computed by Spreading Activation on an English Dictionary

This paper proposes a method for measuring semantic similarity between words as a new tool for text analysis. The similarity is measured on a semantic network constructed systematically from a subset of the English dictionary, LDOCE (Longman Dictionary of Contemporary English). Spreading activation on the network can directly compute the similarity between any two words in the Longman Defining Vocabulary, and indirectly the similarity of all the other words in LDOCE. The similarity represents the strength of lexical cohesion or semantic relation, and also provides valuable information about similarity and coherence of texts.
Effects of Genotype and Child Abuse on DNA Methylation and Gene Expression at the Serotonin Transporter

Altered regulation of the serotonin transporter (SLC6A4) is hypothesized to be a key event in many forms of neuropsychiatric illness, yet our understanding of the molecular mechanisms through which changes in gene function could lead to illness remains incomplete. In prior studies, we and others have demonstrated that methylation of CpG residues in the promoter associated CpG island alters SLC6A4 gene expression, that the extent of that DNA methylation in child abuse is genotype dependent, and that adverse childhood experiences such as child sex abuse are related to methylation. However, we have not examined whether these effects are splice variant specific, whether the association of methylation to gene expression varies as a function of genotype, and whether methylation in other SLC6A4 gene regions are more likely candidates for GxE effects. In the current investigation we measured methylation in lymphoblast DNA from 158 female subjects in the Iowa Adoption Studies at 16 CpG residues spread across the SLC6A4 locus, and analyzed their relationship to gene expression for two SLC6A4 splice variants. Methylation of two CpG residues in the shore of the CpG island (cg22584138 and cg05951817), a location immediately upstream from exon 1A, predicted gene expression for the splice variant containing Exon 1A + 1B. Methylation at two residues in the CpG island itself (cg 25769822 and cg05016953) was associated with total SLC6A4 expression. Examination of these four CpG residues indicated that methylation of cg22584138 was influenced by both genotype and sex abuse, whereas methylation of cg05016953 was influenced only by sex abuse history. Factors influencing methylation at other CpG dinucleotide pairs were not identified. We conclude that methylation effects on transcription may vary as a function of underlying gene motif and splice variant, and that the shore of CpG islands, upstream of TSS, may be of particular interest in examining environmental effects on methylation.
Journal of the International Aids Society the Fields of Hiv and Disability: Past, Present and Future

This article provides an historic overview of the fields of disability and HIV. We describe this area of concern in terms of "fields" versus "a single field" because of the two related but distinct trends that have evolved over time. The first field involves people living with HIV and their experiences of disability, disablement and rehabilitation brought on by the disease and its treatments. The second involves people with disabilities and their experiences of vulnerability to and life with HIV. These two fields have evolved relatively independently over time. However, in the final section of this article, we argue that the divide between these fields is collapsing, and that this collapse is beginning to produce a new understanding about shared concerns, cross-field learning and the mutual benefits that might be realized from integrating policy and programmatic responses. We close by identifying directions that we expect these merging fields to take in the coming years.
Selection and parameter optimization of SVM kernel function for underwater target classification

The identification and classification of noise sources in the ocean has become a key task of modern underwater acoustic signal processing and because of the ever changing and complicated oceanic environment, underwater target classification has become a demanding task. An underwater acoustic target classification system identifies the acoustic target from the characteristic acoustic signature. The characteristic acoustic signatures are patterned by feature recognition algorithms operating on data captured by hydrophone. In this paper, an SVM classifier works on the acoustic signatures of four different target types. The performance of the classifier depends on a variety of factors, of which SVM parameter tuning is very important. Several attempts have been made for automatic kernel selection and parameter optimization, including meta-heuristic algorithms such as genetic algorithms (GA) and particle swarm optimization (PSO). This paper attempts towards selection of SVM parameters, kernel and kernel parameter optimization using the BAT algorithm. The results indicate higher classification accuracy when compared to PSO based selection and optimization.