Miracle-dz/UniFAR-FTUs huggingface dataset:
Arginase Inhibition Improves Microvascular Endothelial Function in Patients With Type 2 Diabetes Mellitus.

OBJECTIVES The development of microvascular complications in diabetes is a complex process in which endothelial dysfunction is important. Emerging evidence suggests that arginase is a key mediator of endothelial dysfunction in type 2 diabetes mellitus by reciprocally regulating nitric oxide bioavailability. The aim of this prospective intervention study was to test the hypothesis that arginase activity is increased and that arginase inhibition improves microvascular endothelial function in patients with type 2 diabetes and microvascular dysfunction. DESIGN Microvascular endothelium-dependent and -independent dilatation was determined in patients with type 2 diabetes (n = 12) and healthy age-matched control subjects (n = 12) with laser Doppler flowmetry during iontophoretic application of acetylcholine and sodium nitroprusside, respectively, before and after administration of the arginase inhibitor Nω-hydroxy-nor-L-arginine (120 min). Plasma ratios of amino acids involved in arginase and nitric oxide synthase activities were determined. The laser Doppler flowmetry data were the primary outcome variable. RESULTS Microvascular endothelium-dependent dilatation was impaired in subjects with type 2 diabetes (P < .05). After administration of Nω-hydroxy-nor-L-arginine, microvascular endothelial function improved significantly in patients with type 2 diabetes to the level observed in healthy controls. Endothelium-independent vasodilatation did not change significantly. Subjects with type 2 diabetes had higher levels of ornithine and higher ratios of ornithine/citrulline and ornithine/arginine (P < .05), suggesting increased arginase activity. CONCLUSION Arginase inhibition improves microvascular endothelial function in patients with type 2 diabetes and microvascular dysfunction. Arginase inhibition may represent a novel therapeutic strategy to improve microvascular endothelial function in patients with type 2 diabetes.
Probing the Relative Importance of Molecular Oscillations in the Circadian Clock

Circadian (∼24 hr) rhythms of behavior and physiology are driven by molecular clocks that are endogenous to most organisms. The mechanisms underlying these clocks are remarkably conserved across evolution and typically consist of auto-regulatory loops in which specific proteins (clock proteins) rhythmically repress expression of their own genes. Such regulation maintains 24-hr cycles of RNA and protein expression. Despite the conservation of these mechanisms, however, questions are now being raised about the relevance of different molecular oscillations. Indeed, several studies have demonstrated that oscillations of some critical clock genes can be eliminated without loss of basic clock function. Here, we describe the multiple levels at which clock gene/protein expression and function can be rhythmically regulated—transcription, protein expression, post-translational modification, and localization—and speculate as to which aspect of this regulation is most critical. While the review is focused on Drosophila, we include some discussion of mammalian clocks to indicate the extent to which the questions concerning clock mechanisms are similar, regardless of the organism under study.
Logic-based Speciﬁcation and Veriﬁcation of Homogeneous Dynamic Multi-agent Systems

We develop a logic-based framework for formal speciﬁcation and algorithmic veriﬁcation of homogeneous and dynamic concurrent multi-agent transition systems (HDMAS). Homogeneity means that all agents have the same available actions at any given state and the actions have the same eﬀects regardless of which agents perform them. The state transitions are therefore determined only by the vector of numbers of agents performing each action and are speciﬁed symbolically, by means of conditions on these numbers deﬁnable in Presburger arithmetic. The agents are divided into controllable (by the system supervisor/controller) and uncontrollable , representing the environment or adversary. Dynam-icity means that the numbers of controllable and uncontrollable agents may vary throughout the system evolution, possibly at every transition. As a language for formal speciﬁcation we use a suitably extended version of Alternating-time Temporal Logic (ATL), where one can specify properties of the type “a coalition of (at least) n controllable agents can ensure against (at most) m uncontrollable agents that any possible evolution of the system satisﬁes a given objective γ ”, where γ is speciﬁed again as a formula of that language and each of n and m is either a ﬁxed number or a variable that can be quantiﬁed over. We provide formal semantics to our logic L hdmas and deﬁne normal form of its formulae. We then prove that every formula in L hdmas is equivalent in the ﬁnite to one in a normal form and develop an algorithm for global model checking of formulae in normal form in ﬁnite HDMAS models, which invokes model checking truth of Presburger formulae. We establish worst case complexity estimates for the model checking algorithm and illustrate it on a running example.
Hopf-Frobenius Algebras and a Simpler Drinfeld Double

The zx-calculus and related theories are based on so-called interacting Frobenius algebras, where a pair of dagger-special commutative Frobenius algebras jointly form a pair of Hopf algebras. In this setting we introduce a generalisation of this structure, Hopf-Frobenius algebras, starting from a single Hopf algebra which is not necessarily commutative or cocommutative. We provide a few necessary and sufficient conditions for a Hopf algebra to be a Hopf-Frobenius algebra, and show that every Hopf algebra in the category of finite dimensional vector spaces is a Hopf-Frobenius algebra. In addition, we show that this construction is unique up to an invertible scalar. Due to this fact, Hopf-Frobenius algebras provide two canonical notions of duality, and give us a "dual" Hopf algebra that is isomorphic to the usual dual Hopf algebra in a compact closed category. We use this isomorphism to construct a Hopf algebra isomorphic to the Drinfeld double, but has a much simpler presentation.
“Influence sketching”: Finding influential samples in large-scale regressions

There is an especially strong need in modern large-scale data analysis to prioritize samples for manual inspection. For example, the inspection could target important mislabeled samples or key vulnerabilities exploitable by an adversarial attack. In order to solve the “needle in the haystack” problem of which samples to inspect, we develop a new scalable version of Cook's distance, a classical statistical technique for identifying samples which unusually strongly impact the fit of a regression model (and its downstream predictions). In order to scale this technique up to very large and high-dimensional datasets, we introduce a new algorithm which we call “influence sketching. ” Influence sketching embeds random projections within the influence computation; in particular, the influence score is calculated using the randomly projected pseudo-dataset from the post-convergence General Linear Model (GLM). We validate that influence sketching can reliably and successfully discover influential samples by applying the technique to a malware detection dataset of over 2 million executable files, each represented with almost 100,000 features. For example, we find that randomly deleting approximately 10% of training samples reduces predictive accuracy only slightly from 99.47% to 99.45%, whereas deleting the same number of samples with high influence sketch scores reduces predictive accuracy all the way down to 90.24%. Moreover, we find that influential samples are especially likely to be mislabeled. In the case study, we manually inspect the most influential samples, and find that influence sketching pointed us to new, previously unidentified pieces of malware.
Magnesium and calciprotein particles in vascular calcification: the good cop and the bad cop.

PURPOSE OF REVIEW Vascular calcification is a major contributor to increased cardiovascular mortality in chronic kidney disease (CKD). Recently, calciprotein particles (CPP) were identified to drive the calcification process. CPP may explain the effects of high phosphate on vascular calcification. Magnesium is a promising novel therapeutic approach to halt vascular calcification, because it inhibits CPP maturation and is associated with reduced cardiovascular mortality in CKD. We aim to examine the current evidence for the role of CPP in the calcification process and to explain how magnesium prevents calcification. RECENT FINDINGS A recent meta-analysis concluded that reducing high phosphate levels in CKD patients does not associate with lowering cardiovascular mortality. Inhibition of CPP formation prevents phosphate-induced calcification in vitro. Consequently, delaying CPP formation and maturation may be a clinical approach to reduce calcification. Magnesium inhibits CPP maturation and vascular calcification. Clinical pilot studies suggest that magnesium is a promising intervention strategy against calcification in CKD patients. SUMMARY CPP induce vascular calcification and are modulated by serum phosphate and magnesium concentrations. Magnesium is a strong inhibitor of CPP maturation and therefore, a promising therapeutic approach to reduce vascular calcification in CKD. Currently, several studies are being performed to determine the clinical outcomes of magnesium supplementation in CKD.
Classification by pain pattern for patients with cervical spine radiculopathy

ABSTRACT Objectives A prospective observational cohort study was conducted to (1) report the prevalence of Mechanical Diagnosis and Therapy (MDT) classifications, Centralization (CEN), and Non-CEN among patients with Cervical Spine Radiculopathy (CSR), and (2) describe the association between classification via CEN and Non-CEN and clinical outcomes at follow-up. Methods Data were collected from 680 consecutive patients who presented to outpatient, orthopedic physical therapy clinics with primary complaints of neck pain with and without radiculopathy; thirty-nine patients (6%) met the physical examination inclusion criteria for CSR. First examination and follow-up data were completed by 19 patients. Results Seventy-nine percent of patients’ conditions were classified as Reducible Derangement at first examination and 21% were classified as either Irreducible Derangement, Entrapment, or Mechanically Inconclusive. The prevalence of CEN and Non-CEN was 36.8% and 47.4%, respectively. All patients treated via MDT methods made clinically significant improvements in disability, but not pain intensity, at follow-up. The magnitude of change in clinical outcomes was greatest for patients who exhibited CEN; however, the changes in disability and pain intensity at follow-up were not statistically significant compared to patients who exhibited Non-CEN at first examination. Patients who exhibited CEN were discharged, on average, ten days earlier and had one less treatment visit compared to patients who exhibited Non-CEN. Discussion The findings of this study show that patients with CSR can be classified and treated via MDT methods and experienced clinically significant improvements in disability, but not pain intensity, at follow-up. Providers should consider MDT classification and treatment to improve clinical outcomes for their patients affected by CSR.
TAGOOS: genome-wide supervised learning of non-coding loci associated to complex phenotypes

Abstract Genome-wide association studies (GWAS) associate single nucleotide polymorphisms (SNPs) to complex phenotypes. Most human SNPs fall in non-coding regions and are likely regulatory SNPs, but linkage disequilibrium (LD) blocks make it difficult to distinguish functional SNPs. Therefore, putative functional SNPs are usually annotated with molecular markers of gene regulatory regions and prioritized with dedicated prediction tools. We integrated associated SNPs, LD blocks and regulatory features into a supervised model called TAGOOS (TAG SNP bOOSting) and computed scores genome-wide. The TAGOOS scores enriched and prioritized unseen associated SNPs with an odds ratio of 4.3 and 3.5 and an area under the curve (AUC) of 0.65 and 0.6 for intronic and intergenic regions, respectively. The TAGOOS score was correlated with the maximal significance of associated SNPs and expression quantitative trait loci (eQTLs) and with the number of biological samples annotated for key regulatory features. Analysis of loci and regions associated to cleft lip and human adult height phenotypes recovered known functional loci and predicted new functional loci enriched in transcriptions factors related to the phenotypes. In conclusion, we trained a supervised model based on associated SNPs to prioritize putative functional regions. The TAGOOS scores, annotations and UCSC genome tracks are available here: https://tagoos.readthedocs. io.
Characterizing Attention Cascades in WhatsApp Groups

An important political and social phenomena discussed in several countries, like India and Brazil, is the use of WhatsApp to spread false or misleading content. However, little is known about the information dissemination process in WhatsApp groups. Attention affects the dissemination of information in WhatsApp groups, determining what topics or subjects are more attractive to participants of a group. In this paper, we characterize and analyze how attention propagates among the participants of a WhatsApp group. An attention cascade begins when a user asserts a topic in a message to the group, which could include written text, photos, or links to articles online. Others then propagate the information by responding to it. We analyzed attention cascades in more than 1.7 million messages posted in 120 groups over one year. Our analysis focused on the structural and temporal evolution of attention cascades as well as on the behavior of users that participate in them. We found specific characteristics in cascades associated with groups that discuss political subjects and false information. For instance, we observe that cascades with false information tend to be deeper, reach more users, and last longer in political groups than in non-political groups.
Cache efficiency based dynamic bypassing technique for improving GPU performance

GPUs utilize parallel HW resources to provide good performance for graphics as well as general purpose programs. There have been many researches to improve performance by using GPUs. However, due to the problems such as cache contention, it is not always possible to fully utilize hardware resources in GPUs. In this paper, we propose a simple cache bypassing technique to enhance the resource utilization in GPUs. The proposed bypassing technique that selectively caches memory requests can mitigate these problems. According to our simulation results, the proposed technique reduces the number of accesses to the L1 data cache, which improves performance and reduces power consumption. Compared to baseline GPU architecture, the proposed scheme can increase the average performance by about 100%.
Modern QFD-based requirements analysis for enterprise modelling: enterprise-QFD

Competitiveness and globalisation force enterprises quickly to adapt to changing conditions of markets. Enterprises employ modelling methodologies to organise their strategic knowledge to cope with this change, which results in an enterprise (data) model. Requirements discovery and analysis is the most important phase in creating the enterprise model because any mistake in the requirements discovery deteriorates the validity of the model, resulting in user dissatisfaction. Quality function deployment (QFD) is a well-known and integrated approach used in converting the requirements of users into final product specifications. This paper modifies QFD for enterprise modelling, and proposes Enterprise-QFD, which provides a common platform to be integrated with any methodology for discovering and analysing customer requirements. The modified QFD tables involve some required columns added and unnecessary ones deleted based on enterprise modelling. A novel matrix content and sequence is also proposed.
Hormone Metabolism Genes and Mammographic Density in Singapore Chinese Women

Background: Female steroid hormone levels and exogenous hormone use influence breast cancer risk. We investigated the association between genetic variation in the hormone metabolism and signaling pathway and mammographic density, a strong predictor of breast cancer risk. Methods: We genotyped 161 SNPs in 15 hormone metabolism pathway gene regions and evaluated mammographic density in 2,038 Singapore Chinese women. Linear regression analysis was used to investigate single-nucleotide polymorphism (SNP) and mammographic density association. An overall pathway summary was obtained using the adaptive ranked truncated product test. Results: We did not find any of the individually tested SNPs to be associated with mammographic density after a multiple testing correction. There was no evidence of an overall effect on mammographic density of genetic variation in the hormone metabolism pathway. Conclusions: In this cross-sectional study, genetic variation in hormone metabolism pathway was not associated with mammographic density in Singapore Chinese women. Impact: Consistent with existing data from Caucasian populations, polymorphisms in hormone pathway genes are not likely to be strong predictors of mammographic density in Asian women. Cancer Epidemiol Biomarkers Prev; 22(5); 984–6. ©2013 AACR.
Transforming Growth Factor-β1 (TGF-β1) Regulates Cell Junction Restructuring via Smad-Mediated Repression and Clathrin-Mediated Endocytosis of Nectin-like Molecule 2 (Necl-2)

Nectin-like molecule-2 (Necl-2), a junction molecule, is exclusively expressed by spermatogenic cells. It mediates homophilic interaction between germ cells and heterophilic interaction between Sertoli and germ cells. Knockout studies have shown that loss of Necl-2 causes male infertility, suggesting Necl-2-based cell adhesion is crucial for spermatogenesis. Transforming growth factor-βs (TGF-βs) are crucial for regulating cell junction restructuring that are required for spermatogenesis. In the present study, we aim to investigate the mechanism on how TGF-β1 regulates Necl-2 expression to achieve timely junction restructuring in the seminiferous epithelium during spermatogenesis. We have demonstrated that TGF-β1 reduces Necl-2 mRNA and protein levels at both transcriptional and post-translational levels. Using inhibitor and clathrin shRNA, we have revealed that TGF-β1 induces Necl-2 protein degradation via clathrin-dependent endocytosis. Endocytosis assays further confirmed that TGF-β1 accelerates the internalization of Necl-2 protein to cytosol. Immunofluorescence staining also revealed that TGF-β1 effectively removes Necl-2 from cell-cell interface. In addition, TGF-β1 reduces Necl-2 mRNA via down-regulating Necl-2 promoter activity. Mutational studies coupled with knockdown experiments have shown that TGF-β1-induced Necl-2 repression requires activation of Smad proteins. EMSA and ChIP assays further confirmed that TGF-β1 promotes the binding of Smad proteins onto MyoD and CCAATa motifs in vitro and in vivo. Taken together, TGF-β1 is a potent cytokine that provides an effective mechanism in controlling Necl-2 expression in the testis via Smad-dependent gene repression and clathrin-mediated endocytosis.
Permanent pacing and conduction recovery in patients undergoing cardiac surgery for active infective endocarditis in an Australian Tertiary Center

Postoperative heart block is common among patients undergoing surgery for infective endocarditis (IE). Limited data exists allowing cardiologists to predict who will require permanent pacemaker (PPM) implantation postoperatively. We aimed to determine the rate of postoperative PPM insertion, predictors for postoperative PPM, and describe PPM utilization and rates of device‐related infection during follow‐up.
Climatology of aerosol optical properties in Northern Norway and Svalbard

Abstract. We present comparisons between estimates of the aerosol optical thickness and the Angstrom exponent in Northern Norway and Svalbard based on data from AERONET stations at Andenes (69° N, 16° E, 379 m altitude) and Hornsund (77° N, 15° E, 10 m altitude) for the period 2008–2010. The three-year annual mean values for the aerosol optical thickness at 500 nm τ(500) at Andenes and Hornsund were 0.11 and 0.10, respectively. At Hornsund, there was less variation of the monthly mean value of τ(500) than at Andenes. The annual mean values of the Angstrom exponent α at Andenes and Hornsund were 1.18 and 1.37, respectively. At Andenes and Hornsund α was found to be larger than 1.0 in 68% and 93% of the observations, respectively, indicating that fine-mode particles were dominating at both sites. Both sites had a similar seasonal variation of the aerosol size distribution although one site is in an Arctic area while the other site is in a sub-arctic area.
Adult newborn neurons interfere with fear discrimination in a protocol‐dependent manner

Significant enhancement of neurogenesis is known to occur in response to a variety of brain insults such as traumatic brain injury. Previous studies have demonstrated that injury‐induced newborn neurons are required for hippocampus‐dependent spatial learning and memory tasks like the Morris water maze, but not in contextual fear conditioning that requires both the hippocampus and amygdala. Recently, the dentate gyrus, where adult hippocampal neurogenesis occurs, has been implicated in processing information to form specific memory under specific environmental stimuli in a process known as pattern separation.
Liver, Kidney, and Thoracic Organ Transplantation Under FK 506

The new immunosuppressive drug FK 506 was used from the outset with low doses of prednisone to treat 120 recipients of primary liver grafts and 20 more patients undergoing liver retransplantation. The patient survival rate after 2 to 8 months in the primary liver transplantation series is 93.3%, with original graft survival of 87.5%. Of the 20 patients in the hepatic retransplant series, 17 (85%) are living. Almost all of the surviving patients have good liver function. In addition 11 hearts, 2 double lungs, and a heart-lung have been transplanted under FK 506, with survival of all 14 patients. With all of the organ systems so far tested, including the kidney (which has been reported elsewhere), rejection usually has been controlled without additional drugs and with lower average steroid doses than in the past. Nephrotoxicity has been observed, but not to an alarming degree, and there has been a notable absence of hypertension. There is a suggestion that serum cholesterol may be lowered by FK 506, but this is unproved. Although the adverse reactions of FK 506 and the immunosuppressive mechanisms resemble those of cyclosporine, our preliminary observations suggest that FK 506 may have a more advantageous therapeutic index.