Miracle-dz/UniFAR-FTUs huggingface dataset:
The association between resting heart rate, cardiovascular disease and mortality: evidence from 112,680 men and women in 12 cohorts

Background: Multiple studies have examined the relationship between heart rate and mortality; however, there are discrepancies in results. Our aim was to describe the relationship between resting heart rate (RHR) and both major cardiovascular (CV) outcomes, as well as all-cause mortality in the Asia-Pacific region. Design and methods: Individual data from 112,680 subjects in 12 cohort studies were pooled and analysed using Cox models, stratified by study and sex, and adjusted for age and systolic blood pressure. Results: During a mean 7.4 years follow-up, 6086 deaths and 2726 fatal or nonfatal CV events were recorded. There was a continuous, increasing association between having a RHR above approximately 65 beats/min and the risk of both CV and all-cause mortality, yet there was no evidence of associations below this threshold. The hazard ratio (95% CI) comparing the extreme quarters of RHR (80+ v <65 beats/min) was 1.44 (1.29–1.60) for CV and 1.54 (1.43–1.66) for total mortality. These associations were not materially changed by adjustment for other risk factors and exclusion of the first 2 years of follow-up. Hazard ratios of a similar magnitude were found for ischemic and hemorrhagic stroke, but the hazard ratio for heart failure was higher (2.08, 95% CI 1.07–4.06) and for Coronary Heart Disease (CHD) was lower (1.11, 95% CI 0.93–1.31) than for stroke. Conclusions: RHR of above 65 beats/min has a strong independent effect on premature mortality and stroke, but a lesser effect on CHD. Lifestyle and pharmaceutical regimens to reduce RHR may be beneficial for people with moderate to high levels of RHR.
Resilience of an embedded architecture using hardware redundancy

In the last decade the dominance of the general computing systems market has being replaced by embedded systems with billions of units manufactured every year. Embedded systems appear in contexts where continuous operation is of utmost importance and failure can be profound. Nowadays, radiation poses a serious threat to the reliable operation of safety-critical systems. Fault avoidance techniques, such as radiation hardening, have been commonly used in space applications. However, these components are expensive, lag behind commercial components with regards to performance and do not provide 100% fault elimination. Without fault tolerant mechanisms, many of these faults can become errors at the application or system level, which in turn, can result in catastrophic failures. In this work we study the concepts of fault tolerance and dependability and extend these concepts providing our own definition of resilience. We analyse the physics of radiation-induced faults, the damage mechanisms of particles and the process that leads to computing failures. We provide extensive taxonomies of 1) existing fault tolerant techniques and of 2) the effects of radiation in state-of-the-art electronics, analysing and comparing their characteristics. We propose a detailed model of faults and provide a classification of the different types of faults at various levels. We introduce an algorithm of fault tolerance and define the system states and actions necessary to implement it. We introduce novel hardware and system software techniques that provide a more efficient combination of reliability, performance and power consumption than existing techniques. We propose a new element of the system called syndrome that is the core of a resilient architecture whose software and hardware can adapt to reliable and unreliable environments. We implement a software simulator and disassembler and introduce a testing framework in combination with ERA’s assembler and commercial hardware simulators.
A Multiobjective Distribution-Pricing Model for Multiperiod Price-Sensitive Demands

In this paper, a new multiobjective model is proposed in order to determine the pricing and distribution plans for a wholesaler and its local distributors. Each local distributor has its own price-sensitive demand over the planning horizon. The model illustrates the conflict between the objectives pursued by the wholesaler (total profit maximization) and the local distributors (maximization of service levels). The model considers selling price, realized demand, production quantity, inventory levels, shortages, and inventory deterioration. The exact relationship between the two objectives is extracted. The model is applied to a case study of a wholesaler that distributes supplementary nutrition items to a set of local distributors. A new solution method is proposed for practically obtaining a set of global Pareto-optimal solutions of the problem. Each Pareto-optimal solution can be considered as a negotiation scenario between the wholesaler and the local distributors. The proposed solution is capable of finding all global Pareto-optimal solutions of the problem in certain conditions. Also, the proposed heuristic determines the most favorable solution among the set of Pareto-optimal solutions obtained. Finally, the computational results of the real case study are highlighted along with conclusions and future research directions.
Privacy and Security Requirements for RFID Applications

This paper surveys recent technical researches on the problems of privacy and security for various applications in radio frequency identification (RFID). Most RFID system try to design a high level security, but not all of the RFID applications need it. The cost will increase if the privacy and security simultaneously improve, thus, how to balance the two issues are important. This paper provides an insight into the privacy and security requirements for RFID applications by the industrial processes. We will discuss and compare privacy and security in various cases. The results of our surveys are helpful for security engineers, who are responsible for the design and development in RFID.
The Prophylactic Use of Acidifiers as Antibacterial Agents in Swine

In recent decades, acidifiers have emerged as viable alternatives to antibiotics in swine diets, in order to stimulate optimal growth performance and prevent various enteric diseases. Antimicrobials have been used for more than 50 years to enhance growth performance and prevent various pig diseases (Gustafson & Bowen, 1997). There is growing public awareness of the relationship between the feed medication with antimicrobials as growth promoters in livestock diets and the risk of developing cross-resistance of pathogens to antibiotics, threatening animals and human health (Corpet, 1996; Mathew et al. 2007; Hunter et al. 2010). During the last few years, as the use of antibiotics in pig diets has decreased, the use of acidifiers has increased.
Discovery of a Novel Mycobacterium tuberculosis Lineage That Is a Major Cause of Tuberculosis in Rio de Janeiro, Brazil

ABSTRACT The current study evaluated Mycobacterium tuberculosis isolates from Rio de Janeiro, Brazil, for genomic deletions. One locus in our panel of PCR targets failed to amplify in ∼30% of strains. A single novel long sequence polymorphism (>26.3 kb) was characterized and designated RDRio. Homologous recombination between two similar protein-coding genes is proposed as the mechanism for deleting or modifying 10 genes, including two potentially immunogenic PPE proteins. The flanking regions of the RDRio locus were identical in all strains bearing the deletion. Genetic testing by principal genetic group, spoligotyping, variable-number tandem repeats of mycobacterial interspersed repetitive units (MIRU-VNTR), and IS6110-based restriction fragment length polymorphism analysis cumulatively support the idea that RDRio strains are derived from a common ancestor belonging solely to the Latin American-Mediterranean spoligotype family. The RDRio lineage is therefore the predominant clade causing tuberculosis (TB) in Rio de Janeiro and, as indicated by genotypic clustering in MIRU-VNTR analysis, the most significant source of recent transmission. Limited retrospective reviews of bacteriological and patient records showed a lack of association with multidrug resistance or specific risk factors for TB. However, trends in the data did suggest that RDRio strains may cause a form of TB with a distinct clinical presentation. Overall, the high prevalence of this genotype may be related to enhanced virulence, transmissibility, and/or specific adaptation to a Euro-Latin American host population. The identification of RDRio strains outside of Brazil points to the ongoing intercontinental dissemination of this important genotype. Further studies are needed to determine the differential strain-specific features, pathobiology, and worldwide prevalence of RDRioM. tuberculosis.
Validity of PEC approximation for on-body propagation

Many articles on on-body propagation assumes that the human body can be approximated by a perfect electric conductor (PEC) instead of the actual constitutive parameters of the human body, which is that of a lossy dielectric. This assumption is investigated in this article through comparison of the scattering of a plane wave at oblique incidence by a PEC and a lossy dielectric cylinder. The investigation shows that the validity of the assumption depends on the polarization of the plane wave, the angle of incidence, and the region of interest.
Pharmaceutical nanotechnology: polymeric vesicles for drug and gene delivery

Improving the therapeutic index of medicines is a goal of drug delivery. Employing nanosystems that control drug biodistribution is one way of achieving therapeutic improvements, and polymeric bilayer vesicles are one such nanosystem. Polymeric vesicles, with the ability to transport drugs or genes, are prepared in one of two ways: i) the self-assembly of amphiphilic polymers and ii) the polymerisation of monomers, following self-assembly (polymerised vesicles). There are two types of self-assembling amphiphilic polymers: water-soluble polymers derivatised with hydrophobic pendant groups and amphiphilic block copolymers. Amphiphilic alkenes and alkynes are the main compounds that are used to make polymerised vesicles. This review discusses polymer architecture fundamentals that govern the self-assembly of polymers into vesicles, the fine control on vesicle size that is achievable with polymeric vesicles and the application of the vesicles to drug delivery.
Scalable Design of Heterogeneous Networks

A systematic approach to the analysis and design of a class of large dynamical systems is presented. The approach allows decentralized control laws to be designed independently using only local subsystem models. Design can be conducted using standard techniques, including loopshaping based on Nyquist and Popov plots, <inline-formula> <tex-math notation="LaTeX">$\mathbf{H}_\infty$</tex-math></inline-formula> methods, and <inline-formula> <tex-math notation="LaTeX">$\mu$</tex-math></inline-formula>-synthesis procedures. The approach is applied to a range of network models, including those for consensus, congestion control, electrical power systems, and distributed optimization algorithms subject to delays.
Bayesian Hierarchical Kernelized Probabilistic Matrix Factorization

We present a Bayesian analysis framework for matrix-variate normal data with dependency structures induced by rows and columns. This framework of matrix normal models includes prior specifications, posterior computation using Markov chain Monte Carlo methods, evaluation of prediction uncertainty, model structure search, and extensions to multidimensional arrays. Compared with Bayesian probabilistic matrix factorization, which integrates a Gaussian prior for single row of the data matrix, our proposed model, namely Bayesian hierarchical kernelized probabilistic matrix factorization, imposes Gaussian Process priors over multiple rows of the matrix. Hence, the learned model explicitly captures the underlying correlation among the rows and the columns. In addition, our method requires no specific assumptions like independence of latent factors for rows and columns, which obtains more flexibility for modeling real data compared to existing works. Finally, the proposed framework can be adapted to a wide range of applications, including multivariate analysis, times series, and spatial modeling. Experiments highlight the superiority of the proposed model in handling model uncertainty and model optimization.
High glucose downregulates myocardin expression in rat glomerular mesangial cells via the ERK signaling pathway

Mesangial cells (MCs), which are vascular smooth muscle-derived cells, occupy the central position in the glomerulus. Diabetic nephropathy (DN) is one of the most common diabetes complications and is likely attributed to the loss of MC contractility. Myocardin stimulates downstream vascular smooth muscle genes and regulates the contractility of vascular smooth muscle cells. Therefore, we hypothesized that myocardin is expressed in MCs and that high glucose is involved in the regulation of myocardin and downstream contractile genes in the context of DN. Confocal microscopy revealed that myocardin is expressed in rat MCs. Western blot and RT-qPCR analyses showed that treatment with 30 mM D-glucose significantly downregulated the mRNA and protein levels of myocardin and downstream SM α-actin. As an isotonic contrast, 30 mM mannitol did not affect myocardin mRNA levels but did downregulate myocardin protein levels. Treatment with 30 mM mannitol also downregulated SM α-actin mRNA and protein levels. Conversely, as another isotonic contrast, 30 mM L-glucose also had no effect on myocardin and SM α-actin expression in MCs. The extracellular signal-regulated kinase (ERK) pathway was activated by treatment with 30 mM D-glucose or mannitol, while specific inhibitors of the ERK pathway (PD98059) compromised the downregulation of myocardin and SM α-actin triggered by high glucose or mannitol. Thus we revealed that myocardin is expressed in MCs and that high glucose downregulates myocardin expression and downstream contractile protein SM α-actin via the ERK pathway. Our results suggest a novel mechanism for high glucose inhibition of MC contraction, which contributes to DN pathogenesis.
Rapidly cleared episodes of herpes simplex virus reactivation in immunocompetent adults.

BACKGROUND Herpes simplex virus (HSV) remains latent in nerve root ganglia of infected persons and is thought to reactivate several times yearly. Recent in situ data show the localization of HSV-specific CD8(+) T cells at the dermal epidermal junction next to peripheral sensory nerve endings, suggesting that viral reactivation may occur more frequently than previously appreciated. METHODS Twenty-five HSV-2-seropositive and 18 HSV-1-seropositive healthy adults collected anogenital and oral swabs, respectively, 4 times per day for 60 days. Swabs were assayed for HSV, using a quantitative polymerase chain reaction assay. RESULTS Twenty-four percent of anogenital reactivations and 21% of oral reactivations lasted < or =6 h, and 49% of anogenital reactivations and 39% of oral reactivations lasted < or =12 h. Lesions were reported in only 3 (7%) of 44 anogenital reactivations and 1 (8%) of 13 oral reactivations lasting < or =12 h. The median HSV DNA levels at initial and last detection were 10(3.5) and 10(3.3) copies/mL, respectively, during anogenital reactivation and 10(3.7) and 10(3.0) copies/mL, respectively, during oral reactivation. CONCLUSIONS This high frequency of short subclinical HSV reactivation in immunocompetent hosts strongly suggests that the peripheral mucosal immune system plays a critical role in clearing HSV reactivations.
Pharmacotherapy for children and adolescents with epilepsy

Introduction: Childhood epilepsies are the most frequent neurological problems that occur in children. Despite the introduction of new antiepileptic drugs (AEDs) 25 – 30% of children with epilepsy remain refractory to medical therapy. Areas covered: This review aims to highlight the main published data on the treatment of childhood epilepsy. The electronic database, PubMed, and abstract proceedings were used to identify studies. The aim of antiepileptic therapy should be to provide complete seizure control, if possible without the burden of any side effect. Since 1993, new agents have been approved for use as an antiepileptic. Although there are few published data (especially in pediatric populations) to establish that the second-generation AEDs are more efficacious than the older AEDs, they appear to have better tolerability. Expert opinion: Old AEDs are efficacious agents that continue to play a major role in the current treatment of epilepsy. These agents actually remain the first-line treatment for many specific seizure types or epileptic syndromes. The new AEDs were initially approved as adjunct agents and – subsequently – as monotherapy for various seizure types in the adult and children. Despite these improvements, few AEDs are now considered to be a first-choice for the treatment of epilspsy in children.
Peak oxygen uptake and regional oxygenation in response to a 10‐day confinement to normobaric hypoxia

We investigated the effect of hypoxic acclimatization per se, without any concomitant influence of strenuous physical activity on muscle and cerebral oxygenation. Eight healthy male subjects participated in a crossover‐designed study. In random order, they conducted a 10‐day normoxic (CON) and a 10‐day hypoxic (EXP) confinement. Pre and post both CON and EXP confinements, subjects conducted two incremental‐load cycling exercises to exhaustion; one under normoxic, and the other under hypoxic (FIO2 = 0.154) conditions. Oxygen uptake ( V ˙ O 2 ), ventilation ( V ˙ E ), and relative changes in regional hemoglobin oxygenation (Δ([HbO2]) in the cerebral cortex and in the serratus anterior (SA) and vastus lateralis (VL) muscles were measured. No changes were observed in the CON confinement. Peak work rate and V ˙ O 2 p ⁢ e a k were similar pre and post in the EXP confinement, whereas V ˙ E increased in the EXP post normoxic and hypoxic trials (P < 0.05). The exercise‐induced drop in VL Δ[HbO2] was less in the post‐ than pre‐EXP trial by 4.0 ± 0.4 and 4.2 ± 0.6 μM during normoxic and hypoxic exercise, respectively. No major changes were observed in cerebral or SA oxygenation. These results demonstrate that a 10‐day hypoxic exposure without any concomitant physical activity had no effect on normoxic or hypoxic V ˙ O 2 p ⁢ e a k , despite the enhanced VL oxygenation.
Hantavirus Nucleocapsid Protein Oligomerization

ABSTRACT Hantaviruses are enveloped, negative-strand RNA viruses which can be lethal to humans, causing either a hemorrhagic fever with renal syndrome or a hantaviral pulmonary syndrome. The viral genomes consist of three RNA segments: the L segment encodes the viral polymerase, the M segment encodes the viral surface glycoproteins G1 and G2, and the S segment encodes the nucleocapsid (N) protein. The N protein is a 420- to 430-residue, 50-kDa protein which appears to direct hantavirus assembly, although mechanisms of N protein oligomerization, RNA encapsidation, budding, and release are poorly understood. We have undertaken a biochemical and genetic analysis of N protein oligomerization. Bacterially expressed N proteins were found by gradient fractionation to associate not only as large multimers or aggregates but also as dimers or trimers. Chemical cross-linking of hantavirus particles yielded N protein cross-link products with molecular masses of 140 to 150 kDa, consistent with the size of an N trimer. We also employed a genetic, yeast two-hybrid method for monitoring N protein interactions. Analyses showed that the C-terminal half of the N protein plus the N-terminal 40 residues permitted association with a full-length N protein fusion. These N-terminal 40 residues of seven different hantavirus strains were predicted to form trimeric coiled coils. Our results suggest that coiled-coil motifs contribute to N protein trimerization and that nucleocapsid protein trimers are hantavirus particle assembly intermediates.
Visualization of transcription-dependent association of imprinted genes with the nuclear matrix.

Genomic imprinting is characterized by allele-specific gene expression as a biological phenomenon. To analyze the participation of the nuclear matrix in the expression of imprinted genes, we first examined the allelic expression state of genes by simultaneously visualizing their primary transcripts and the gene sequences in individual cell nuclei using fluorescence in situ hybridization (FISH). We confirmed that each imprinted gene, SNRPN and UBE3A in human lymphocytes and Igf2 and H19 in mouse embryonic fibroblasts, mainly expressed from one allele, although some nuclei showed biallelic expression. We next visualized the gene sequences on the nuclear matrix by FISH with a tyramide signal amplification technique. Interestingly, we predominantly observed one DNA signal of imprinted genes on the nuclear matrix preparation, closely correlated with their expression patterns. Using patient cells, we confirmed that both the transcription and the binding to the nuclear matrix of the SNRPN gene occurred at the paternal allele. Our results suggest that the nuclear matrix plays an important role in gene expression, including imprinted genes, and that the FISH technique used here allows us to visualize the behaviors of genes at an individual cell level.
Nelfinavir Plasma Levels Under Twice-Daily and Three-Times-Daily Regimens: High Interpatient and Low Intrapatient Variability

Nelfinavir has been recently approved as a twice-daily (BID) dose regimen, but no evaluation of the influence of this regimen change on patients' protease inhibitor exposure has been published. The aim of this study was to compare trough plasma concentrations of nelfinavir obtained under the 1250-mg b.i. d regimen with the levels achieved with the original 750-mg three-times-daily (TID) regimen in 56 HIV-infected patients. Blood samples were obtained at steady state before the morning dose of nelfinavir. Plasma levels were measured by high-performance liquid chromatography. Eleven and 45 patients were following TID and BID regimens, respectively. Trough concentrations ranged from 0.14 to 11.74 mg/L and from 0.36 to 10.57 mg/L under TID and BID regimens, respectively. Large interpatient (coefficient of variation: 153%) and modest intrapatient (45%) variabilities of nelfinavir levels were observed. Twenty-one patients (38%) and six patients (11%) had levels above and below, respectively, the trough nelfinavir range (1.0–3.0 mg/L) recommended by the manufacturer. Trough levels are not affected by the dosing regimen; they mainly reflect the important interindividual variability, while remaining fairly stable over time. Many subjects had plasma levels repeatedly outside the assumed therapeutic range. Dose adjustment based on therapeutic drug monitoring may contribute to optimizing antiretroviral therapy.
GPU-based Volume Ray-casting supporting Specular Reflection and Refraction

Nowadays mostly local illumination models are used when rendering volumetric data. When computing global light effects, interactive frame rates are usually hard to achieve. We present an extension of GPU-based volume ray-casting, which allows to compute specular reflection and refraction effects at interactive frame rates on current commodity graphics hardware. In contrast to other techniques proposed for integrating these effects into volume rendering, our technique does not constrain the type of rendering used, i. e. , it can be used with DVR as well as isosurface rendering.