Miracle-dz/UniFAR-FTUs huggingface dataset:
Suppression of Viral RNA Binding and the Assembly of Infectious Hepatitis C Virus Particles In Vitro by Cyclophilin Inhibitors

ABSTRACT Nonstructural protein 5A (NS5A) of hepatitis C virus (HCV) is an indispensable component of the HCV replication and assembly machineries. Although its precise mechanism of action is not yet clear, current evidence indicates that its structure and function are regulated by the cellular peptidylprolyl isomerase cyclophilin A (CyPA). CyPA binds to proline residues in the C-terminal half of NS5A, in a distributed fashion, and modulates the structure of the disordered domains II and III. Cyclophilin inhibitors (CPIs), including cyclosporine (CsA) and its nonimmunosuppressive derivatives, inhibit HCV infection of diverse genotypes, both in vitro and in vivo. Here we report a mechanism by which CPIs inhibit HCV infection and demonstrate that CPIs can suppress HCV assembly in addition to their well-documented inhibitory effect on RNA replication. Although the interaction between NS5A and other viral proteins is not affected by CPIs, RNA binding by NS5A in cell culture-based HCV (HCVcc)-infected cells is significantly inhibited by CPI treatment, and sensitivity of RNA binding is correlated with previously characterized CyPA dependence or CsA sensitivity of HCV mutants. Furthermore, the difference in CyPA dependence between a subgenomic and a full-length replicon of JFH-1 was due, at least in part, to an additional role that CyPA plays in HCV assembly, a conclusion that is supported by experiments with the clinical CPI alisporivir. The host-directed nature and the ability to interfere with more than one step in the HCV life cycle may result in a higher genetic barrier to resistance for this class of HCV inhibitors.
Importance of calcitonin gene‐related peptide, adenosine and reactive oxygen species in cerebral autoregulation under normal and diseased conditions

1. Mechanisms regulating cerebral circulation, including autoregulation of cerebral blood flow (CBF), have been widely investigated. Vasodilators such as nitric oxide, prostacyclin, calcitonin gene‐related peptide (CGRP) and K+ channel openers are well known to have important roles in the physiological and pathophysiological control of CBF autoregulation. In the present review, the focus is on the mechanism(s) of altered CBF autoregulation after traumatic brain injury and subarachnoid haemorrhage (SAH) and on the effect of adenovirus‐mediated transfer of Cu/Zn superoxide dismutase (SOD)‐1 in amelioration of impaired CBF autoregulation.
Heart failure-a growing epidemic in Asia.

In Asia, rapid economic development, increasing industrialisation and urbanisation, and improving living standards have led to a marked change in lifestyle—namely, reduced levels of exercise; increased intake of calories, fat, and salt; and increased cigarette smoking. The consequence has been an increased incidence in obesity, high blood pressure, diabetes mellitus, and vascular disease particularly affecting the coronary and cerebrovascular circulations. The resulting coronary artery disease and hypertension lead to accumulated myocardial damage and eventually heart failure, which is now a global disease with an increasing incidence. Hypertension is a common cause of heart failure in Asia (often with diabetes) and probably accounts for the high proportion (about 50%) of cases of heart failure that have a relatively normal left ventricular ejection fraction—a condition labelled ‘diastolic heart failure’. Coronary artery disease, however, is soon likely to become the major cause of heart failure in South Asia and China, where more than half the world’s population lives. In addition, death from coronary heart disease will have risen by an estimated 115% to 127% in India and by 81% to 110% in China between 1990 and 2020. These estimates are based on demographic changes alone and do not take into account the expected major increases in effects from risk factors.
Single layer centrifugation of stallion spermatozoa consistently selects the most robust spermatozoa from the rest of the ejaculate in a large sample size.

REASONS FOR PERFORMING STUDY An improvement in sperm quality after single layer centrifugation (SLC) has been seen in previous studies using small sample sizes (for example, n = 10 stallions). There is a need to investigate whether this improvement is repeatable over several breeding seasons with a larger number of stallions (n ≥ 30 stallions). OBJECTIVE To make a retrospective analysis of the results of SLC performed on more than 250 sperm samples (176 ejaculates) from 31 stallions in 3 consecutive breeding seasons. METHODS Sperm quality (motility, proportion of morphologically normal spermatozoa and the proportion of spermatozoa with undamaged chromatin) was assessed before and after SLC. RESULTS All parameters of sperm quality examined were significantly better in sperm samples after SLC than in their unselected counterparts (P<0.001 for each parameter). The yield of spermatozoa obtained after SLC was influenced by the type of extender used and also by the concentration of spermatozoa in the original ejaculate, with fewer spermatozoa being recovered when the loading dose contained a high concentration of spermatozoa. The optimal concentration was approximately 100 × 10⁶/ml. Sperm concentration in the samples loaded on to the colloid influenced the sperm yield while the type of semen extender affected sperm quality and survival. Furthermore, the scaled-up SLC method was found to be suitable for use with a range of ejaculates, with similar sperm kinematics being observed for standard and scaled-up preparations. CONCLUSIONS SLC consistently improved the quality of stallion sperm samples from a large number of ejaculates. The method could be scaled-up, allowing larger volumes of ejaculate to be processed easily from a wide range of stallions.
Postprandial plasma incretin hormones in exercise-trained versus untrained subjects.

INTRODUCTION After food ingestion, the incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are secreted by the intestines into circulation where they act on the pancreas to promote insulin secretion. We evaluated the hypothesis that low postprandial plasma insulin levels in lean exercise-trained individuals are associated with low concentrations of incretin hormones. METHODS A cross-sectional study was performed to compare postprandial incretin hormone levels in lean endurance exercise-trained individuals (EX; n = 14, ≥40 yr) and age- and sex-matched, nonobese, sedentary control subjects (CON, n = 14). The main outcome measures were GLP-1, GIP, insulin, and glucose incremental areas under the curve (AUC) as measured in plasma samples collected during a 2-h,75-g oral glucose tolerance test (OGTT). RESULTS The EX group had lower body fat percentage (14.6% ± 1.1% vs 23.3% ± 1.7%, P = 0.0002) and higher maximal oxygen uptake (53 ± 2 vs 34 ± 2, P < 0.0001) than CON. Glucose AUC did not differ between groups (P = 0.20). Insulin AUC was lower in EX (2.5 ± 0.5 vs 4.2 ± 1.2 μU·mL·1000 min, P = 0.02). No differences were observed between groups (EX and CON, respectively) for GLP-1 AUC (3.5 ± 0.7 vs 4.1 ± 1.1 pmol·min·100 L, P = 0.61) or GIP AUC (19.2 ± 1.4 vs 18.0 ± 1.4 pg·min·1000 mL; P = 0.56). In CON, insulin AUC was correlated with AUC for GLP-1 (r = 0.53, P = 0.05) and GIP (r = 0.71, P = 0.004), but no such correlations were observed in EX (both P ≥ 0.67). CONCLUSIONS Low postprandial insulin levels in lean exercise-trained individuals are not attributable to lower incretin hormone concentrations. However, exercise may decrease the dependency of postprandial insulin levels on incretin hormones.
Effects of Physical Exercise on the Photoplethysmogram Waveform

Photoplethysmography is a non-invasive method which is suitable to estimate vascular compliance. Photoplethysmogram (PPG) waveform has been used to evaluate vascular characteristic changes due to exercise. Quantification of the primary and secondary peak position is of interest as a potential objective, individualized measure of the level of exercise that a subject has achieved with respect to a baseline status, prior to the beginning of the exercise session. The modified bicycle ergonomic protocol was selected for this experiment. Two different signal processing methods were employed in processing the PPG waveform to characterize its changes through a single parameter. Both, the visual inspection of the recorded PPG and the results of the analyses reinforce our opinion about the existence of continuous changes in PPG waveform through an exercise session. The experiment results confirm that PPG can be a potential approach in quantifying cardiovascular characteristics or properties of an individual.
Algoritmo de caminho mınimo para grafos coloridos aplicado a redes de transporte multimodal

Este trabalho apresenta um algoritmo para o problema de caminho minimo em grafos coloridos baseado no algoritmo classico de Ford-Moore-Bellman e aplicado a redes de transporte multimodal, onde cada modo de transporte considerado e representado por uma cor, podendo ter varios arcos entre dois nos do grafo. Durante o procedimento de resolucao, o metodo detecta se houve mudanca de modo e um custo referente a esta mudanca e acrescentado no caminho, ao final temos um caminho minimo multimodal com informacao de qual modo foi utilizado para percorrer cada arco do caminho. Testes computacionais foram feitos a fim de comprovar a viabilidade do algoritmo proposto.
Plasma levels of adrenomedullin, a newly identified hypotensive peptide, in patients with hypertension and renal failure.

Adrenomedullin is a potent hypotensive peptide newly discovered in pheochromocytoma tissue by monitoring its elevating activity on platelet cAMP. We measured plasma concentration of adrenomedullin in patients with essential hypertension and chronic renal failure. As compared with normal subjects, plasma adrenomedullin was increased by 26% (P < 0.05) in hypertensives without organ damage and by 45% (P < 0.005) in those with organ damage. The increase in plasma adrenomedullin was more prominent in renal failure than in hypertension. Renal failure patients with plasma creatinine of 1.5-3, 3-6, and > 6 mg/dl had higher plasma adrenomedullin levels than healthy subjects by 78% (P < 0.05), 131% (P < 0.001), and 214% (P < 0.001), respectively. Moreover, adrenomedullin showed intimate correlations with norepinephrine, atrial natriuretic peptide, and cAMP in plasma (r = 0.625, P < 0.001; r = 0.656, P < 0.001; and r = 0.462, P < 0.001; respectively). Thus, plasma adrenomedullin is supposed to increase in association with changes in sympathetic nervous activity and body fluid volume in hypertension and renal failure. Considering its potent vasodilator effect, adrenomedullin may be involved in the defense mechanism preserving the integrity of the cardiovascular system in these disorders.
Pitolisant, an Inverse Agonist of the Histamine H3 Receptor: An Alternative Stimulant for Narcolepsy-Cataplexy in Teenagers With Refractory Sleepiness

ObjectiveNarcolepsy is a rare disabling sleep disorder characterized by excessive daytime sleepiness and cataplexy (sudden loss of muscle tone). Drugs such as pitolisant, which block histamine H3 autoreceptors, constitute a newly identified class of stimulants because they increase brain histamine and enhance wakefulness in animal and human adult narcolepsy. MethodsWe report our experience with the off-label use of pitolisant in 4 teenagers with narcolepsy/cataplexy with severe daytime sleepiness, refractory to available treatments (modafinil, methylphenidate, mazindol, sodium oxybate, and D-amphetamine). ResultsAll teenagers developed their disease during childhood (11.3 ± 2.4 years; 50% boys) and were 17.3 ± 0.8 years old at the time of pitolisant therapy. Pitolisant treatment was increased from 10 to 30 mg (n = 1) and 40 mg (n = 3). The adapted Epworth Sleepiness Score decreased from 14.3 ± 1.1 to 9.5 ± 2.9 (P = 0.03) with pitolisant alone to 7 ± 3.4 when combined with mazindol (n = 1), methylphenidate (n = 1), or sodium oxybate plus modafinil (n = 1). Mean sleep onset latency increased from 31 ± 14 minutes to 36 ± 8 minutes (P = 0.21) on the maintenance of wakefulness test. The severity and frequency of cataplexy were slightly improved. Adverse effects were minor (insomnia, headache, hot flushes, leg pain, and hallucinations) and transitory, except for insomnia, which persisted in 2 teenagers. The benefit was maintained after a mean of 13 months. ConclusionsPitolisant could constitute an acceptable alternative for the treatment of refractory sleepiness in teenagers with narcolepsy.
Phenotype MicroArray Analysis of Escherichia coli K-12 Mutants with Deletions of All Two-Component Systems

ABSTRACT Two-component systems are the most common mechanism of transmembrane signal transduction in bacteria. A typical system consists of a histidine kinase and a partner response regulator. The histidine kinase senses an environmental signal, which it transmits to its partner response regulator via a series of autophosphorylation, phosphotransfer, and dephosphorylation reactions. Much work has been done on particular systems, including several systems with regulatory roles in cellular physiology, communication, development, and, in the case of bacterial pathogens, the expression of genes important for virulence. We used two methods to investigate two-component regulatory systems in Escherichia coli K-12. First, we systematically constructed mutants with deletions of all two-component systems by using a now-standard technique of gene disruption (K. A. Datsenko and B. L. Wanner, Proc. Natl. Acad. Sci. USA 97:6640-6645, 2000). We then analyzed these deletion mutants with a new technology called Phenotype MicroArrays, which permits assays of nearly 2,000 growth phenotypes simultaneously. In this study we tested 100 mutants, including mutants with individual deletions of all two-component systems and several related genes, including creBC-regulated genes (cbrA and cbrBC), phoBR-regulated genes (phoA, phoH, phnCDEFGHIJKLMNOP, psiE, and ugpBAECQ), csgD, luxS, and rpoS. The results of this battery of nearly 200,000 tests provided a wealth of new information concerning many of these systems. Of 37 different two-component mutants, 22 showed altered phenotypes. Many phenotypes were expected, and several new phenotypes were also revealed. The results are discussed in terms of the biological roles and other information concerning these systems, including DNA microarray data for a large number of the same mutants. Other mutational effects are also discussed.
Geographical association between livestock density and human Shiga toxin-producing Escherichia coli O157 infections

SUMMARY Shiga toxin-producing Escherichia coli (STEC) bacteria can cause outbreaks and sporadic cases of gastroenteritis in humans. Ruminants are seen as the main reservoir. The aim of this study was to evaluate the spatial association between reported human STEC O157 infections in The Netherlands and different livestock densities. Data were collected at the municipality level and a spatial regression analysis was performed. Between April 1999 and December 2008, 409 symptomatic sporadic cases were registered. Adding an interaction term between season, age, and livestock density showed an increased risk of STEC cases in summer for living in areas with cattle, in particular for young children. In conclusion, cattle, but not pigs or poultry, are indicated as an important source for human STEC O157 infections in rural areas. The association is probably due to direct or indirect contact with cattle, resulting in symptomatic infections, especially in young children.
Reduktion prooxidativer und Stärkung antioxidativer Prozesse - ein verbindendes Element der Kneipp'schen Therapie

Die Kneipp'schen Therapieverfahren und damit zentrale Inhalte der klassischen Naturheilverfahren zeichnen sich durch ein breites Wirkungsspektrum aus. Es ist naheliegend, dass diesen Verfahren auch gemeinsame Wirkungsmechanismen auf der Basis ubiquitärer Substanzen und Reaktionsmechanismen zugrunde liegen. Hier wurden die Wirkungen von reaktiven Sauerstoffspezies (ROS), von Lipid peroxidations(LPO)-Produkten und von antioxidativen Schutzmechanismen untersucht. Die Bilanz von prooxidativen und antioxidativen Prozessen, die das Mass für einen oxidativen Stress angibt, hat eine immense Auswirkung auf Gesundheit, Krankheit, Wohlbefinden und Leistungsfähigkeit. Die Übersicht über Resultate zu allen fünf Säulen der Kneipp-Therapie - Hydrotherapie, Phytotherapie, Ernährungstherapie, Bewegungstherapie und Ordnungstherapie - liefert klare Hinweise auf die bessere Bewältigung von oxidativem Stress durch die Kneipp'schen Therapieformen. Es wird deutlich aufgezeigt, dass eine verminderte Bildung freier Radikale und/oder deren bessere Bewältigung ein verbindendes Element der klassischen Naturheilverfahren ist.
NCAM‐derived peptides function as agonists for the fibroblast growth factor receptor

The neural cell adhesion molecule (NCAM) directly interacts with the fibroblast growth factor receptor (FGFR). Both fibronectin type III (FN3) modules of NCAM are involved in this interaction. One of the NCAM–FGFR contact sites has been localized recently to the upper N‐terminal part of the second NCAM FN3 module encompassing the F and G β‐strands and the interconnecting loop region. Here, we investigated whether any of the six putative strand‐loop‐strand regions in the first NCAM FN3 module are involved in FGFR interactions. Peptide sequences encompassing these regions, termed encamins, were synthesized and tested for their ability to bind and activate FGFR. Encamins localized to the N‐terminal part of the first FN3 module did not interact with FGFR, whereas encamins localized to the C‐terminal part, termed EncaminA, C and E, bound to and activated FGFR. The encamins induced FGFR‐dependent neurite outgrowth, and EncaminC and E promoted neuronal survival and enhanced pre‐synaptic function. In conclusion, the interaction between NCAM and FGFR probably involves multiple contact sites at an interface formed by the two NCAM FN3 modules and FGFR, and encamins could constitute important pharmacological tools for the study of specific functional aspects of NCAM, including neuroprotection and modulation of plasticity.
The constructivist museum and the web

As long as there have been museum collections they have been interpreted and displayed according to the prevailing philosophy of their time. In the post-modern period many schools of thought have influenced museum interpretation, amongst them Constructivism. The model of the Constructivist Museum is one where visitors are involved in the process of interpretation and the construction of knowledge. Though examples of this have been rare in the world of physical museum display, with advances in technology and the development of the World Wide Web, visitors to online museums have more opportunity for participation. This paper examines how and if the concept of the Constructivist Museum is manifesting itself in the world of museums and the Web. Using several online projects as examples, it seeks to discover how user-generated content is being incorporated into museums and why there is a reticence amongst the public to dispute or edit official interpretation. It examines issues of trust, authority and the challenges to the traditional hierarchy of knowledge that arise in its doing so. This paper contends that whilst user-generated content is often encouraged on museum websites it is rarely allowed to infiltrate the official museum interpretative process and suggests that reluctance amongst museum professionals and curators to relinquish power and control might be responsible. It also suggests that museums might need to review the way they interact with their users in terms of presenting content on existing internet platforms.
Performance analysis of an evolutionary algorithm for fault detection in t-diagnosable multi-processor systems

In this paper, we present a performance analysis of an evolutionary approach for fault identification in t-diagnosable systems, i.e. systems in which the set of t permanently faulty units could be unambiguously identified. The proposed algorithm is based on evolutionary/genetic computing and is shown to correctly identify the set of faulty units. Simulation results are more than encouraging and should stimulate future research.
Consideraciones de Diseño para Receptores Móviles

I. INTRODUCCION Con un crecimiento anual de 40% las comunicaciones moviles continuan su desarrollo exponencial comparado con un 1% en el caso de las comunicaciones fijas [1]. Estas condiciones del mercado han impulsado el florecimiento de multiples dispositivos y sistemas moviles para responder a la demanda. La disponibilidad de la informacion en todo lugar y en todo momento, paradigma de la plataforma movil, traera como consecuencia una complejidad superior de los sistemas moviles incrementado los problemas inherentes a la plataforma, tales como las como interferencias, la eficiencia espectral, el compromiso entre la capacidad y la calidad, la cobertura y otros factores. Todas estas consideraciones son el objeto de investigaciones de multiples organismos gubernamentales y /o industriales de normalizacion y de concepcion a fin de lograr una plataforma movil universal.
Pain: Its Modes and Functions

Professor Buytendijk, a well-known Dutch biologist-turned-psychologist, manages, in 5 compactly-written chapters, to present a wealth of accurate information and much discerning thought on pain and suffering. In the first chapter, Buytendijk sets the tone of the book by placing his inquiry into an existential-phenomenological framework. He notes, with regret, that modern society tries hard to distract man from experiencing pain, and hence also from dwelling on its meaning. Yet, despite remarkable advances in medicine and surgery, men have not rid themselves of the fear of pain,
Propuesta de Modelo de Gobierno TI para Empresa de Servicios Sanitarios de Chile

La implementacion de un gobierno de TI efectivo en las empresas es un gran desafio para los gerentes de informatica. La mayoria de los marcos existentes de gobierno TI comprenden elementos que no son aplicables para cierto tipo de empresas, o bien, adolecen de otros elementos que se deberian considerar. El reto para las instituciones es, por tanto, poder adecuar los modelos existentes de acuerdo a sus propias necesidades. En este estudio, se revisan dos modelos: COBIT en sus versiones 4.1 y 5 y la norma ISO38500. Luego de recopilar informacion en una importante empresa de servicios sanitarios de Chile, se propone un modelo de gobierno TI especifico basado en los modelos antes mencionados. La propuesta contempla la implementacion del modelo en una etapa posterior y su refinacion para ser utilizado en instituciones de similar naturaleza.