Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of aerobic training on baseline expression of signaling and respiratory proteins in human skeletal muscle

Most studies examining the molecular mechanisms underlying adaptation of human skeletal muscles to aerobic exercise focused on the response to acute exercise. Here, we examined the effect of a 2‐month aerobic training program on baseline parameters in human muscle. Ten untrained males performed a one‐legged knee extension exercise for 1 h with the same relative intensity before and after a 2‐month aerobic training program. Biopsy samples were taken from vastus lateralis muscle at rest before and after the 2 month training program (baseline samples). Additionally, biopsy samples were taken from the exercised leg 1 and 4 h after the one‐legged continuous knee extension exercise. Aerobic training decreases baseline phosphorylation of FOXO1Ser256, increases that of CaMKIIThr286, CREB1Ser133, increases baseline expression of mitochondrial proteins in respiratory complexes I–V, and some regulators of mitochondrial biogenesis (TFAM, NR4A3, and CRTC2). An increase in the baseline content of these proteins was not associated with a change in baseline expression of their genes. The increase in the baseline content of regulators of mitochondrial biogenesis (TFAM and NR4A3) was associated with a transient increase in transcription after acute exercise. Contrariwise, the increase in the baseline content of respiratory proteins does not seem to be regulated at the transcriptional level; rather, it is associated with other mechanisms. Adaptation of human skeletal muscle to regular aerobic exercise is associated not only with transient molecular responses to exercise, but also with changes in baseline phosphorylation and expression of regulatory proteins.
Weight-Independent Mechanisms of Glucose Control After Roux-en-Y Gastric Bypass

Roux-en-Y gastric bypass results in large and sustained weight loss and resolution of type 2 diabetes in 60% of cases at 1–2 years. In addition to calorie restriction and weight loss, various gastro-intestinal mediated mechanisms, independent of weight loss, also contribute to glucose control. The anatomical re-arrangement of the small intestine after gastric bypass results in accelerated nutrient transit, enhances the release of post-prandial gut hormones incretins and of insulin, alters the metabolism and the entero-hepatic cycle of bile acids, modifies intestinal glucose uptake and metabolism, and alters the composition and function of the microbiome. The amelioration of beta cell function after gastric bypass in individuals with type 2 diabetes requires enteric stimulation. However, beta cell function in response to intravenous glucose stimulus remains severely impaired, even in individuals in full clinical diabetes remission. The permanent impairment of the beta cell may explain diabetes relapse years after surgery.
The CCHamide1 Neuropeptide Expressed in the Anterior Dorsal Neuron 1 Conveys a Circadian Signal to the Ventral Lateral Neurons in Drosophila melanogaster

The fruit fly Drosophila melanogaster possesses approximately 150 brain clock neurons that control circadian behavioral rhythms. Even though individual clock neurons have self-sustaining oscillators, they interact and synchronize with each other through a network. However, little is known regarding the factors responsible for these network interactions. In this study, we investigated the role of CCHamide1 (CCHa1), a neuropeptide expressed in the anterior dorsal neuron 1 (DN1a), in intercellular communication of the clock neurons. We observed that CCHa1 connects the DN1a clock neurons to the ventral lateral clock neurons (LNv) via the CCHa1 receptor, which is a homolog of the gastrin-releasing peptide receptor playing a role in circadian intercellular communications in mammals. CCHa1 knockout or knockdown flies have a generally low activity level with a special reduction of morning activity. In addition, they exhibit advanced morning activity under light-dark cycles and delayed activity under constant dark conditions, which correlates with an advance/delay of PAR domain Protein 1 (PDP1) oscillations in the small-LNv (s-LNv) neurons that control morning activity. The terminals of the s-LNv neurons show rather high levels of Pigment-dispersing factor (PDF) in the evening, when PDF is low in control flies, suggesting that the knockdown of CCHa1 leads to increased PDF release; PDF signals the other clock neurons and evidently increases the amplitude of their PDP1 cycling. A previous study showed that high-amplitude PDP1 cycling increases the siesta of the flies, and indeed, CCHa1 knockout or knockdown flies exhibit a longer siesta than control flies. The DN1a neurons are known to be receptive to PDF signaling from the s-LNv neurons; thus, our results suggest that the DN1a and s-LNv clock neurons are reciprocally coupled via the neuropeptides CCHa1 and PDF, and this interaction fine-tunes the timing of activity and sleep.
Alpha 2-Adrenergic Receptor Agonist Brimonidine Stimulates ERK1/2 and AKT Signaling via Transactivation of EGF Receptors in the Human MIO-M1 Müller Cell Line

ABSTRACT Purpose: Alpha 2-adrenergic receptor (α2-ADR) agonists are used clinically for a range of indications including reducing elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. Animal experiments show that α2-ADR agonists attenuate the injury-induced Müller cell dedifferentiation by a mechanism that involves activation and regulation of extracellular signal-regulated kinase (ERK) 1/2 leading to transactivation of epidermal growth factor receptors (EGFRs). The purpose of this study was to study and corroborate the activation of this system in human cells. Material and Methods: The human Müller cell line MIO-M1 was treated with the α2A-ADR agonist brimonidine in combination with inhibitors for Src-kinase, EGFR-kinase, matrix metalloproteinase (MMP) as well as small interfering RNAs (siRNAs) for the EGFR. The cells were analyzed using immunocytochemistry, quantitative PCR and western blot techniques. Results: Our results show that human MIO-M1 cells express α2A-ADRs and that stimulation of these receptors caused a robust increase of ERK1/2 and protein kinase B (PKB/AKT) (Thr-308) phosphorylation in MIO-M1 cells. P-ERK1/2 and P-AKT (Thr-308) signaling was mediated by Src-kinase and associated with phosphorylation of tyrosine residue of epidermal growth factor receptor (P-EGFR Y1173). In addition, the agonist caused activation of MMPs. These effects could be blocked by Src-kinase inhibitors (PP1, PP2), EGFR-kinase inhibitor (AG1478), EGFR-siRNA and a MMP inhibitor (GM6001). Conclusion: The results confirm that this human Müller cell line responds to ADR stimulation with phosphorylation of ERK and AKT, which suggests that it is possible to pharmacologically target ADR to modulate the early events in human Müller cell dedifferentiation in a similar fashion as been shown for chicken Müller cells. Abbreviations: CRALBP: cellular retinaldehyde binding protein; EGFR: epidermal growth factor receptor; ERK1/2: extracellular signal-regulated kinase 1/2; GS: glutamine synthetase; GPCR: G protein-coupled receptor; IR: immunoreactivity; MAPK: mitogen-activated protein kinase; MMP: matrix metalloproteinase; P-ERK1/2: phospho-ERK1/2; qRT-PCR: quantitative reverse transcriptase PCR
A survey of high dimension low sample size asymptotics

Peter Hall's work illuminated many aspects of statistical thought, some of which are very well known including the bootstrap and smoothing. However, he also explored many other lesser known aspects of mathematical statistics. This is a survey of one of those areas, initiated by a seminal paper in 2005, on high dimension low sample size asymptotics. An interesting characteristic of that first paper, and of many of the following papers, is that they contain deep and insightful concepts which are frequently surprising and counter‐intuitive, yet have mathematical underpinnings which tend to be direct and not difficult to prove.
Microscopic and Proteomic Analysis of Dissected Developing Barley Endosperm Layers Reveals the Starchy Endosperm as Prominent Storage Tissue for ER-Derived Hordeins Alongside the Accumulation of Barley Protein Disulfide Isomerase (HvPDIL1-1)

Barley (Hordeum vulgare) is one of the major food sources for humans and forage sources for animal livestock. The average grain protein content (GPC) of barley ranges between 8 and 12%. Barley hordeins (i.e., prolamins) account for more than 50% of GPC in mature seeds and are important for both grain and flour quality. Barley endosperm is structured into three distinct cell layers: the starchy endosperm, which acts essentially as storage tissue for starch; the subaleurone, which is characterized by a high accumulation of seed storage proteins (SSPs); and the aleurone, which has a prominent role during seed germination. Prolamins accumulate in distinct, ER-derived protein bodies (PBs) and their trafficking route is spatio-temporally regulated. The protein disulfide isomerase (PDI) has been shown to be involved in PB formation. Here, we unravel the spatio-temporal proteome regulation in barley aleurone, subaleurone, and starchy endosperm for the optimization of end-product quality in barley. We used laser microdissection (LMD) for subsequent nanoLC-MS/MS proteomic analyses in two experiments: in Experiment One, we investigated the proteomes of dissected barley endosperm layers at 12 and at ≥20 days after pollination (DAP). We found a set of 10 proteins that were present in all tissues at both time points. Among these proteins, the relative protein abundance of D-hordein, B3-hordein and HvPDIL1-1 significantly increased in starchy endosperm between 12 and ≥20 DAP, identifying the starchy endosperm as putative major storage tissue. In Experiment Two, we specifically compared the starchy endosperm proteome at 6, 12, and ≥20 DAP. Whereas the relative protein abundance of D-hordein and B3-hordein increased between 6 and ≥20 DAP, HvPDIL1-1 increased between 6 and 12 DAP, but remained constant at ≥20 DAP. Microscopic observations showed that these relative protein abundance alterations were accompanied by additional localization of hordeins at the periphery of starch granules and a partial re-localization of HvPDIL1-1 from PBs to the periphery of starch granules. Our data indicate a spatio-temporal regulation of hordeins and HvPDIL1-1. These results are discussed in relation to the putative role of HvPDIL1-1 in end-product quality in barley.
When are the cardiovascular and stroke risks too high? Pharmacotherapy for stroke prophylaxis

ABSTRACT Introduction: Stroke is a significant source of morbidity and mortality in developed countries. Cardioembolic strokes represent approximately 15–30% of all ischemic strokes. They are frequently related to atrial fibrillation (AF) and have a worse prognosis and high recurrence rates when compared to other causes (e.g. atherosclerosis). Areas covered: This review includes a summary of general and specific scores to assess cardiovascular and stroke risks, with a focus on specific scores available in AF. Recommendations for antithrombotic therapy are also reviewed. Expert opinion: Several scores are available for the evaluation of stroke risk. They are useful to identify the risk factors that trigger the need for medical interventions. Integrated risk scores with visual interfaces showing the risk of events, with and without the proposed interventions, can aid decision-making. The risk of stroke can definitely be considered too high in those patients with a history of stroke/transient ischemic attack, who need antiplatelet therapy (after a non-cardioembolic stroke) or anticoagulant therapy (after a cardioembolic stroke). For primary prevention of stroke, antiplatelet therapy is not usually recommended, while anticoagulation should be considered if the patient has concomitant AF and at least one additional risk factor unrelated to sex.
Microfluidics Devices Manufacturing and Biomedical Applications

Microfluidics technology is growing field emerged late 1950. It became popular passing through different historical events, contributing to the inception and growth of the field. From the beginning of inkjets to current enormous medical and industrial applications. It focus on handling fluids in the micro, Nano, Pico even femto liter level through utilizing the physical properties they exhibit while miniaturized. According to our study class of materials are available for microfluidics device fabrication and there are factors to consider in application specific design and microfabrication. In microfabrication technique, we can implement lithography, laser induced selective etching, powder blasting and molding found for fabrication. The medical and research application of microfluidics devices includes Cardiovascular System, Respiratory system, Nervous System, Digestive+Excretory System, Endocrine System, Integumentary System, cell culturing and preparation of scaffolds, therapeutics, diagnostics and preventive system. Multiples channels of biomaterials, which is biocompatible platforms to regenerate and rehabilitate Physiological and pathological conditions of complex tissues and organs. The aim of this paper is to present a paper reviewing on material selection, microfluidics fabrication, medical application and suggesting future prospects of the fields and possible microfluidics device implementation in biomedical field.
Inhibition of the aryl hydrocarbon receptor/polyamine biosynthesis axis suppresses multiple myeloma

Polyamine inhibition for cancer therapy is, conceptually, an attractive approach but has yet to meet success in the clinical setting. The aryl hydrocarbon receptor (AHR) is the central transcriptional regulator of the xenobiotic response. Our study revealed that AHR also positively regulates intracellular polyamine production via direct transcriptional activation of 2 genes, ODC1 and AZIN1, which are involved in polyamine biosynthesis and control, respectively. In patients with multiple myeloma (MM), AHR levels were inversely correlated with survival, suggesting that AHR inhibition may be beneficial for the treatment of this disease. We identified clofazimine (CLF), an FDA-approved anti-leprosy drug, as a potent AHR antagonist and a suppressor of polyamine biosynthesis. Experiments in a transgenic model of MM (Vk*Myc mice) and in immunocompromised mice bearing MM cell xenografts revealed high efficacy of CLF comparable to that of bortezomib, a first-in-class proteasome inhibitor used for the treatment of MM. This study identifies a previously unrecognized regulatory axis between AHR and polyamine metabolism and reveals CLF as an inhibitor of AHR and a potentially clinically relevant anti-MM agent.
Integration of two herbivore‐induced plant volatiles results in synergistic effects on plant defence and resistance

Abstract Plants can use induced volatiles to detect herbivore‐ and pathogen‐attacked neighbors and prime their defenses. Several individual volatile priming cues have been identified, but whether plants are able to integrate multiple cues from stress‐related volatile blends remains poorly understood. Here, we investigated how maize plants respond to two herbivore‐induced volatile priming cues with complementary information content, the green leaf volatile (Z)‐3‐hexenyl acetate (HAC) and the aromatic volatile indole. In the absence of herbivory, HAC directly induced defence gene expression, whereas indole had no effect. Upon induction by simulated herbivory, both volatiles increased jasmonate signalling, defence gene expression, and defensive secondary metabolite production and increased plant resistance. Plant resistance to caterpillars was more strongly induced in dual volatile‐exposed plants than plants exposed to single volatiles. Induced defence levels in dual volatile‐exposed plants were significantly higher than predicted from the added effects of the individual volatiles, with the exception of induced plant volatile production, which showed no increase upon dual‐exposure relative to single exposure. Thus, plants can integrate different volatile cues into strong and specific responses that promote herbivore defence induction and resistance. Integrating multiple volatiles may be beneficial, as volatile blends are more reliable indicators of future stress than single cues.
Tensor Ring Decomposition with Rank Minimization on Latent Space: An Efficient Approach for Tensor Completion

In tensor completion tasks, the traditional low-rank tensor decomposition models suffer from the laborious model selection problem due to their high model sensitivity. In particular, for tensor ring (TR) decomposition, the number of model possibilities grows exponentially with the tensor order, which makes it rather challenging to find the optimal TR decomposition. In this paper, by exploiting the low-rank structure of the TR latent space, we propose a novel tensor completion method which is robust to model selection. In contrast to imposing the low-rank constraint on the data space, we introduce nuclear norm regularization on the latent TR factors, resulting in the optimization step using singular value decomposition (SVD) being performed at a much smaller scale. By leveraging the alternating direction method of multipliers (ADMM) scheme, the latent TR factors with optimal rank and the recovered tensor can be obtained simultaneously. Our proposed algorithm is shown to effectively alleviate the burden of TR-rank selection, thereby greatly reducing the computational cost. The extensive experimental results on both synthetic and real-world data demonstrate the superior performance and efficiency of the proposed approach against the state-of-the-art algorithms.
ETUDE DU BRAYLATOR PAR LA METHODE DE CLARKE

La methode de Clarke est utilisee pour etudier la stabilite de l'etat stationnaire du Braylator, forme simplifiee de notre mecanisme de la reaction de Bray. L'utilisation des parametres de Clarke au lieu des constantes cinetiques simplifie notablement les calculs et la recherche des termes dominants dans l'equation caracteristique. Lorsque l'etat stationnaire est instable le Braylator donne des oscillations semblables a celles obtenues experimentalement
Risk Assessment in Chinese Hospitalized Patients Comparing the Padua and Caprini Scoring Algorithms

The current venous thromboembolism (VTE) guidelines recommend all patients to be assessed for the risk of VTE using risk assessment models (RAMs). The study was to evaluate the performance of the Caprini and Padua RAMs among Chinese hospitalized patients. We reviewed data from 189 patients with deep venous thrombosis (DVT) and 201 non-DVT patients. Deep venous thrombosis risk factors were obtained from all patients. The sensitivity and specificity of the Caprini and Padua scores for all patients were calculated. The receiver operating curve (ROC) and the area under the ROC curve (AUC) were used to evaluate the performance of each score. We documented that age, acute infection, prothrombin time (PT), D-dimer, erythrocyte sedimentation rate, blood platelets, and anticoagulation were significantly associated with the occurrence of DVT (P < .05). These results were true for all medical and surgical patients group (G1), as well as the analysis of medical versus surgical patients (G2). Finally, analysis of the scores in patients with and without cancer was also done (G3). The Caprini has a higher sensitivity but a lower specificity than the Padua (P < .05). Caprini has a better predictive ability for the first 2 groups (P < .05). We found Caprini and Padua scores have a similar predictive value for patients with cancer (P > .05), while Caprini has a higher predictive ability for no cancer patients in G3 than Padua (P < .05). For Chinese hospitalized patients, Caprini has a higher sensitivity but a lower specificity than Padua. Overall, Caprini RAM has a better predictive ability than Padua RAM.
A new sRNA‐mediated posttranscriptional regulation system for Bacillus subtilis

Many genetic tools for gene regulation have been developed during the past decades. Some of them edit genomic DNA, such as nucleotides deletions and insertions, while the others interfere with the gene transcriptions or messenger RNA translation. Here, we report a posttranscriptional regulation tool which is termed “Modulation via the small RNA (sRNA)‐dependent operation system: MS‐DOS” by engineering the type I toxin–antitoxin system in Bacillus subtilis. MS‐DOS depends simply on insertion of an operation region (OPR; partial toxin‐encoding region) downstream of a genomic open reading frame of interest and overexpression of the coupling antitoxin sRNA from a plasmid. Pairing between the OPR and the sRNA will trigger the RNAse degradation of the transcripts of selected genes. MS‐DOS allows for the quantitative, specific, and reversible knockdown of single or multiple genomic genes in B. subtilis. We also showed that the truncated antitoxin SR4 with 53 nt length is sufficient to repress gene expression. Superior to other existing RNA based interfering systems, MS‐DOS allows simultaneous knockdown of multiple genes with effortless expression of a single antitoxin RNA. This sRNA‐guided repression system will further enrich the gene regulation tools and expand the gene regulation flexibility.
End-to-End Analysis of In-Browser Cryptojacking

In-browser cryptojacking involves hijacking the CPU power of a website's visitor to perform CPU-intensive cryptocurrency mining, and has been on the rise, with 8500% growth during 2017. While some websites advocate cryptojacking as a replacement for online advertisement, web attackers exploit it to generate revenue by embedding malicious cryptojacking code in highly ranked websites. Motivated by the rise of cryptojacking and the lack of any prior systematic work, we set out to analyze malicious cryptojacking statically and dynamically, and examine the economical basis of cryptojacking as an alternative to advertisement. For our static analysis, we perform content-, currency-, and code-based analyses. Through the content-based analysis, we unveil that cryptojacking is a wide-spread threat targeting a variety of website types. Through a currency-based analysis we highlight affinities between mining platforms and currencies: the majority of cryptojacking websites use Coinhive to mine Monero. Through code-based analysis, we highlight unique code complexity features of cryptojacking scripts, and use them to detect cryptojacking code among benign and other malicious JavaScript code, with an accuracy of 96.4%. Through dynamic analysis, we highlight the impact of cryptojacking on system resources, such as CPU and battery consumption (in battery-powered devices); we use the latter to build an analytical model that examines the feasibility of cryptojacking as an alternative to online advertisement, and show a huge negative profit/loss gap, suggesting that the model is impractical. By surveying existing countermeasures and their limitations, we conclude with long-term countermeasures using insights from our analysis.
Optimizing deep video representation to match brain activity

The comparison of observed brain activity with the statistics generated by artificial intelligence systems is useful to probe brain functional organization under ecological conditions. Here we study fMRI activity in ten subjects watching color natural movies and compute deep representations of these movies with an architecture that relies on optical flow and image content. The association of activity in visual areas with the different layers of the deep architecture displays complexity-related contrasts across visual areas and reveals a striking foveal/peripheral dichotomy.