Miracle-dz/UniFAR-FTUs huggingface dataset:
Alterations in DNA methylation patterns and gene expression in spermatozoa of subfertile males

This study was designed to evaluate the DNA methylation patterns and gene expression in spermatozoa from subfertile males. Thirty samples were subjected to 450K arrays as a screening study to evaluate the variation in sperm DNA methylation levels between cases and controls groups, and then three CpG sites (cg07227024, cg05813498 and cg23081194) have the highest difference in methylation levels and located within ALS2CR12, GAA and UBE2G2 genes respectively; these were selected for further analysis using deep bisulphite sequencing and qPCR in 136 samples (64 proven fertile males “controls” and 72 subfertile males “cases”). A significant difference in the methylation level was found between cases and controls at two CpGs, six CpGs and three CpGs in ALS2CR12, GAA and UBE2G2 gene‐related amplicon respectively. Besides, the qPCR results showed a significant change in the expression levels of GAA, UBE2G2 and ALS2CR12 gene in cases compared to the controls (p ≤ .00001). In conclusion, the methylation levels at CpGs in GAA, UBE2G2 and ALS2CR12 gene amplicons were significantly different in subfertile compared to proven fertile males. In addition, a significantly different was showed in the expression levels of GAA, UBE2G2 and ALS2CR12 genes in subfertile males compared to proven fertile males.
Genomics pipelines and data integration: challenges and opportunities in the research setting

ABSTRACT Introduction: The emergence and mass utilization of high-throughput (HT) technologies, including sequencing technologies (genomics) and mass spectrometry (proteomics, metabolomics, lipids), has allowed geneticists, biologists, and biostatisticians to bridge the gap between genotype and phenotype on a massive scale. These new technologies have brought rapid advances in our understanding of cell biology, evolutionary history, microbial environments, and are increasingly providing new insights and applications towards clinical care and personalized medicine. Areas covered: The very success of this industry also translates into daunting big data challenges for researchers and institutions that extend beyond the traditional academic focus of algorithms and tools. The main obstacles revolve around analysis provenance, data management of massive datasets, ease of use of software, interpretability and reproducibility of results. Expert commentary: The authors review the challenges associated with implementing bioinformatics best practices in a large-scale setting, and highlight the opportunity for establishing bioinformatics pipelines that incorporate data tracking and auditing, enabling greater consistency and reproducibility for basic research, translational or clinical settings.
Uncovering state-dependent relationships in shallow lakes using Bayesian latent variable regression.

Ecosystems sometimes undergo dramatic shifts between contrasting regimes. Shallow lakes, for instance, can transition between two alternative stable states: a clear state dominated by submerged aquatic vegetation and a turbid state dominated by phytoplankton. Theoretical models suggest that critical nutrient thresholds differentiate three lake types: highly resilient clear lakes, lakes that may switch between clear and turbid states following perturbations, and highly resilient turbid lakes. For effective and efficient management of shallow lakes and other systems, managers need tools to identify critical thresholds and state-dependent relationships between driving variables and key system features. Using shallow lakes as a model system for which alternative stable states have been demonstrated, we developed an integrated framework using Bayesian latent variable regression (BLR) to classify lake states, identify critical total phosphorus (TP) thresholds, and estimate steady state relationships between TP and chlorophyll a (chl a) using cross-sectional data. We evaluated the method using data simulated from a stochastic differential equation model and compared its performance to k-means clustering with regression (KMR). We also applied the framework to data comprising 130 shallow lakes. For simulated data sets, BLR had high state classification rates (median/mean accuracy >97%) and accurately estimated TP thresholds and state-dependent TP-chl a relationships. Classification and estimation improved with increasing sample size and decreasing noise levels. Compared to KMR, BLR had higher classification rates and better approximated the TP-chl a steady state relationships and TP thresholds. We fit the BLR model to three different years of empirical shallow lake data, and managers can use the estimated bifurcation diagrams to prioritize lakes for management according to their proximity to thresholds and chance of successful rehabilitation. Our model improves upon previous methods for shallow lakes because it allows classification and regression to occur simultaneously and inform one another, directly estimates TP thresholds and the uncertainty associated with thresholds and state classifications, and enables meaningful constraints to be built into models. The BLR framework is broadly applicable to other ecosystems known to exhibit alternative stable states in which regression can be used to establish relationships between driving variables and state variables.
Relationship between serum bilirubin levels and cardiovascular disease

We tested the hypothesis that higher levels of bilirubin, a bile pigment with antioxidant properties, are associated with a decreased risk of cardiovascular disease (CVD). This study analyzed data from the Korean Health and Genome Study to examine the association between serum total bilirubin (TB) on CVD and CVD death. Serum TB was measured in a total of 8,844 subjects (4,196 males and 4,648 females) and evaluated for the development of new onset CVD from 2001 to 2012 (mean 8.1 years of follow-up). During the follow-up period, 689 cases of incident CVD (7.8%) were identified, and the prevalence of metabolic syndrome (MetS) at baseline was 26.1%. The prevalence of MetS decreased across bilirubin tertile categories. In addition to MetS itself, individual components of MetS significantly decreased with increased bilirubin tertiles. Moreover, the incidence of CVD decreased across bilirubin tertile categories. The hazard ratios (HRs) for developing coronary heart disease (CHD, HR 0.769, 95% CI 0.655–1.000) and CVD death (HR 0.513, 95% CI 0.267–0.985) was significantly lower in the highest tertile group (> 0.63 mg/dL) in comparison to the lowest tertile group (< 0.44 mg/dL) after adjusting for all confounding variables. In the present longitudinal study, a significant negative relationship was demonstrated between baseline bilirubin levels and incident CHD and CVD death.
Evaluation of Allelic Expression of Imprinted Genes in Adult Human Blood

Background Imprinted genes are expressed from only one allele in a parent-of-origin dependent manner. Loss of imprinted (LOI) expression can result in a variety of human disorders and is frequently reported in cancer. Biallelic expression of imprinted genes in adult blood has been suggested as a useful biomarker and is currently being investigated in colorectal cancer. In general, the expression profiles of imprinted genes are well characterised during human and mouse fetal development, but not in human adults. Methodology/Principal Findings We investigated quantitative expression of 36 imprinted genes in adult human peripheral blood leukocytes obtained from healthy individuals. Allelic expression was also investigated in B and T lymphocytes and myeloid cells. We found that 21 genes were essentially undetectable in adult blood. Only six genes were demonstrably monoallelic, and most importantly, we found that nine genes were either biallelic or showed variable expression in different individuals. Separated leukocyte populations showed the same expression patterns as whole blood. Differential methylation at each of the imprinting control loci analysed was maintained, including regions that contained biallelically expressed genes. This suggests in some cases methylation has become uncoupled from its role in regulating gene expression. Conclusions/Significance We conclude that only a limited set of imprinted genes, including IGF2 and SNRPN, may be useful for LOI cancer biomarker studies. In addition, blood is not a good tissue to use for the discovery of new imprinted genes. Finally, lymphocyte DNA methylation status in the adult may not always be a reliable indicator of monoallelic gene expression.
Icariin Attenuates Interleukin-1β-Induced Inflammatory Response in Human Nucleus Pulposus Cells.

BACKGROUND Low back pain is a common problem, mainly caused by intervertebral disc degeneration (IDD). An important pathophysiological characteristic of IDD is the loss of homeostatic balance of the extracellular matrix metabolism. Interleukin-1β (IL-1β) is one of the inflammatory mediators stimulating the degradation of extracellular matrix in the nucleus pulposus (NP) and contributing to IDD pathogenesis. Icariin, which is isolated from Epimedium brevicornum, acts as an anti-inflammatory drug. OBJECTIVE This study aimed to explore the pharmacological effects of icariin in IDD by simulating NP inflammation in vitro. METHOD Human NP cells were isolated and cultured in vitro. NP cells were pretreated with icariin (0.1, 1 and 10 µM) and stimulated by IL-1β (10 ng/ml). The concentration of Prostaglandin E2 was determined by enzymelinked immunosorbent assay. Nitric oxide was determined by Griess reagent assay. The expression of cyclooxygenase- 2 (COX-2), inducible nitric oxide synthase (iNOS), degrading enzymes, collagen II, aggrecan, mitogenactivated protein kinase (MAPK), and nuclear factor-kappa B (NF-κB)-related signaling molecules was assessed via western blotting. RESULTS IL-1β induced pronounced expression of COX-2 and iNOS, and stimulated production of prostaglandin E2 and nitric oxide. Icariin exhibited significant anti-inflammatory effect, inhibiting IL-1β-induced production of degrading enzymes, as well as extracellular matrix reduction. Finally, icariin suppressed IL-1β-induced activation of MAPK- and NF-κB-related signaling pathways. CONCLUSION The present findings suggest that icariin may have a protective effect on NP cells. The antiinflammatory effect may contribute to the therapeutic action of icariin in IDD.
Achieving social-ecological fit through bottom-up collaborative governance: an empirical investigation

Significant benefits can arise from collaborative forms of governance that foster self-organization and flexibility. Likewise, governance systems that fit with the extent and complexity of the system under management are considered essential to our ability to solve environmental problems. However, from an empirical perspective the fundamental question of whether self-organized (bottom-up) collaborative forms of governance are able to accomplish adequate fit is unresolved. We used new theory and methodological approaches underpinned by interdisciplinary network analysis to address this gap by investigating three governance challenges that relate to the problem of fit: shared management of ecological resources, management of interconnected ecological resources, and cross-scale management. We first identified a set of social-ecological network configurations that represent the hypothesized ways in which collaborative arrangements can contribute to addressing these challenges. Using social and ecological data from a large-scale biodiversity conservation initiative in Australia, we empirically determined how well the observed patterns of stakeholder interactions reflect these network configurations. We found that stakeholders collaborate to manage individual parcels of native vegetation, but not for the management of interconnected parcels. In addition, our data show that the collaborative arrangements enable management across different scales (local, regional, supraregional). Our study provides empirical support for the ability of collaborative forms of governance to address the problem of fit, but also suggests that in some cases the establishment of bottom-up collaborative arrangements would likely benefit from specific guidance to facilitate the establishment of collaborations that better align with the ways ecological resources are interconnected across the landscape. In our case study region, this would improve the capacity of stakeholders to detect both the intended and unintended off-site impacts of management actions. Our approach offers an avenue for empirical evaluations of collaborative governance so that preconditions for effectiveness of environmental programs can be enhanced.
Dengue and chikungunya viruses in plasma are effectively inactivated after treatment with methylene blue and visible light

Arboviruses, such as dengue viruses (DENV) and chikungunya virus (CHIKV), pose a risk to the safe transfusion of blood components, including plasma. Pathogen inactivation is an approach to manage this transfusion transmission risk, with a number of techniques being used worldwide for the treatment of plasma. In this study, the efficacy of the THERAFLEX MB‐Plasma system to inactivate all DENV serotypes (DENV‐1, DENV‐2, DENV‐3, DENV‐4) or CHIKV in plasma, using methylene blue and light illumination at 630 nm, was investigated.
The Effects of Ramadan Intermittent Fasting (RIF) on Spirometric Data of Stable COPD Patients: A Pilot Study

No previous study has raised the effects of RIF on lung function data of chronic obstructive pulmonary disease (COPD) patients. The objective of the present study was to assess the effects of RIF on spirometric data measured in male patients with a stable COPD. Sixteen patients with stable COPD (mean ± SD of age: 64 ± 7 years) who fasted during Ramadan volunteered to the study. Three sessions (Before-R, End-R, and After-R) were selected for spirometry tests that were consistently performed 2.5–4.5 hr before fasting break. Assessment sessions comprised: forced vital capacity (FVC), 1st s forced expiratory volume (FEV1), FEV1/FVC, peak expiratory flow (PEF), maximal mid-expiratory flow (MMEF), and forced expiratory flow rate at the x% of FVC to be exhaled (FEFx%). A reversibility test was performed only during the Before-Ramadan session. Spirometric data were expressed in percentages of local reference values. Findings were analyzed by applying repeated measures analysis of variance. The mean ± SD of the postbronchodilator FEV1/FVC ratio and the FEV1 were, respectively, 0.52 ± 0.14 and 48 ± 19%. The mean ± SD of FEV1 (Before-R: 47 ± 19, End-R: 45 ± 18, After-R: 44 ± 19%), FVC (Before-R: 73 ± 18, End-R: 71 ± 16, After-R: 69 ± 17%), FEV1/FVC (Before-R: 67 ± 16, End-R: 66 ± 16, After-R: 65 ± 16%), PEF (Before-R: 46 ± 19, End-R: 47 ± 22, After-R: 45 ± 21%), MMEF (Before-R: 19 ± 10, End-R: 18 ± 8, After-R: 18 ± 9%), FEF25% (Before-R: 16 ± 6, End-R: 16 ± 5, After-R: 15 ± 5%), FEF50% (Before-R: 21 ± 14, End-R: 20 ± 12, After-R: 20 ± 12%) and FEF75% (Before-R: 27 ± 19, End-R: 27 ± 19, After-R: 27 ± 19%) were not significantly influenced by RIF. RIF did not bring about any significant changes in the spirometric data of stable COPD male patients fasting the 2016 holy month of Ramadan.
Microwave-assisted synthesis of isosorbide-derived diols for the preparation of thermally stable thermoplastic polyurethane

Abstract In order to prepare thermally stable isosorbide-derived thermoplastic polyurethane, the synthesis of two new chiral exo–exo configured diols, prepared from isosorbide, and two types of diphenols (bisphenol A and thiodiphenol) was described. The synthesis conditions were optimized under conventional heating and microwave irradiations. To prove their suitability in polymerization, these monomers were successfully polymerized using 4,4′-diphenylmethane diisocyanate (MDI) and hexamethylene diisocyanate (HDI). Both monomers and polymers have been studied by NMR, FT-IR, TGA, DSC; intrinsic viscosity of polymers has also been determined. The results showed the effectiveness of the synthetic strategy proposed; moreover, a dramatic reduction of the reaction time and an important improvement of the monomers yield using microwave irradiation have been demonstrated. The monomers, as well as the polymers, showed excellent thermal stability both in air and nitrogen. It was also shown that the introduction of sulphur in the polyurethane backbone was effective in delaying the onset of degradation as well as the degradation rate.
Intercellular Variability in Protein Levels from Stochastic Expression and Noisy Cell Cycle Processes

Inside individual cells, expression of genes is inherently stochastic and manifests as cell-to-cell variability or noise in protein copy numbers. Since proteins half-lives can be comparable to the cell-cycle length, randomness in cell-division times generates additional intercellular variability in protein levels. Moreover, as many mRNA/protein species are expressed at low-copy numbers, errors incurred in partitioning of molecules between two daughter cells are significant. We derive analytical formulas for the total noise in protein levels when the cell-cycle duration follows a general class of probability distributions. Using a novel hybrid approach the total noise is decomposed into components arising from i) stochastic expression; ii) partitioning errors at the time of cell division and iii) random cell-division events. These formulas reveal that random cell-division times not only generate additional extrinsic noise, but also critically affect the mean protein copy numbers and intrinsic noise components. Counter intuitively, in some parameter regimes, noise in protein levels can decrease as cell-division times become more stochastic. Computations are extended to consider genome duplication, where transcription rate is increased at a random point in the cell cycle. We systematically investigate how the timing of genome duplication influences different protein noise components. Intriguingly, results show that noise contribution from stochastic expression is minimized at an optimal genome-duplication time. Our theoretical results motivate new experimental methods for decomposing protein noise levels from synchronized and asynchronized single-cell expression data. Characterizing the contributions of individual noise mechanisms will lead to precise estimates of gene expression parameters and techniques for altering stochasticity to change phenotype of individual cells.
Effects of Fertilizer Treatments on Soil Chemical Properties and Crop Yields in a Cassava-based Cropping System

A study was carried out to examine the effect of inorganic and organic fertilizers on soil chemical properties and crop yields in a cassava-based cropping system. The treatments were organic fertilizer -5 t/ha/year; inorganic fertilizer - 400 kg/ha NPK 15-15-15; inorganic + organic fertilizer - 200 kg/ha NPK 15-15-15 and 2.5 t/ha organic fertilizer and a control (no fertilizer). The crops planted were cassava, maize, melon and cowpea. The result showed that fertilizer treatments had no significant effects on soil pH after cropping for two years. The level of organic C decreased by about 17, 44, 47 and 59% under organic fertilizer, inorganic + organic fertilizer, no fertilizer and inorganic fertilizer respectively. Total N decreased in all the plots after cropping. Available P reduced from initial value of 4.72 mg/kg to 3.37 mg/kg where no fertilizer was added but increased by 8% and 9% under inorganic + organic and inorganic fertilizers. Exchangeable K decreased in all the plots irrespective of fertilizer type and the changes ranged between 25% under organic fertilizer and 53% under inorganic fertilizer treatment. Addition of Organic fertilizer increased Effective Cation Exchange Capacity (ECEC) by 16% while it reduced in all other plots. Though the yields of crops were increased by application of inorganic and organic fertilizers in this experiment but the changes in soil nutrient status after cropping have shown there might be need to increase the level of organic material added to sustain the fertility of the soil.
Stability Analysis of Oscillatory Systems Subject to Large Delays: A Synchronization Point of View

The behavior of the rightmost characteristic roots of linear time-delay systems as a function of the delay parameter is studied for small values of a gain parameter. The results explain the qualitative behavior of the stability regions in the delay parameter space of oscillatory systems subjected to large delays, and shed new light on the corresponding stabilization problem. In particular, for a chain of multiple oscillators the determination of a stabilizing value of the delay parameter is interpreted as a phase synchronization problem. The results are illustrated with the output feedback stabilization of an oscillator and the stability analysis of a gyroscopic system.
Decoding-History-Based Adaptive Control of Attention for Neural Machine Translation

Attention-based sequence-to-sequence model has proved successful in Neural Machine Translation (NMT). However, the attention without consideration of decoding history, which includes the past information in the decoder and the attention mechanism, often causes much repetition. To address this problem, we propose the decoding-history-based Adaptive Control of Attention (ACA) for the NMT model. ACA learns to control the attention by keeping track of the decoding history and the current information with a memory vector, so that the model can take the translated contents and the current information into consideration. Experiments on Chinese-English translation and the English-Vietnamese translation have demonstrated that our model significantly outperforms the strong baselines. The analysis shows that our model is capable of generating translation with less repetition and higher accuracy. The code will be available at this https URL
The Coda of the Transient Response in a Sensitive Cochlea: A Computational Modeling Study

In a sensitive cochlea, the basilar membrane response to transient excitation of any kind–normal acoustic or artificial intracochlear excitation–consists of not only a primary impulse but also a coda of delayed secondary responses with varying amplitudes but similar spectral content around the characteristic frequency of the measurement location. The coda, sometimes referred to as echoes or ringing, has been described as a form of local, short term memory which may influence the ability of the auditory system to detect gaps in an acoustic stimulus such as speech. Depending on the individual cochlea, the temporal gap between the primary impulse and the following coda ranges from once to thrice the group delay of the primary impulse (the group delay of the primary impulse is on the order of a few hundred microseconds). The coda is physiologically vulnerable, disappearing when the cochlea is compromised even slightly. The multicomponent sensitive response is not yet completely understood. We use a physiologically-based, mathematical model to investigate (i) the generation of the primary impulse response and the dependence of the group delay on the various stimulation methods, (ii) the effect of spatial perturbations in the properties of mechanically sensitive ion channels on the generation and separation of delayed secondary responses. The model suggests that the presence of the secondary responses depends on the wavenumber content of a perturbation and the activity level of the cochlea. In addition, the model shows that the varying temporal gaps between adjacent coda seen in experiments depend on the individual profiles of perturbations. Implications for non-invasive cochlear diagnosis are also discussed.