Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanisms mediating cholinergic antral circular smooth muscle contraction in rats.

AIM To investigate the pathway (s) mediating rat antral circular smooth muscle contractile responses to the cholinomimetic agent, bethanechol and the subtypes of muscarinic receptors mediating the cholinergic contraction. METHODS Circular smooth muscle strips from the antrum of Sprague-Dawley rats were mounted in muscle baths in Krebs buffer. Isometric tension was recorded. Cumulative concentration-response curves were obtained for (+)-cis-dioxolane (cD), a nonspecific muscarinic agonist, at 10(-8)-10(-4) mol/L, in the presence of tetrodotoxin (TTX, 10(-7) mol/L). Results were normalized to cross sectional area. A repeat concentration-response curve was obtained after incubation of the muscle for 90 min with antagonists for M1 (pirenzepine), M2 (methoctramine) and M3 (darifenacin) muscarinic receptor subtypes. The sensitivity to PTX was tested by the ip injection of 100 mg/kg of PTX 5 d before the experiment. The antral circular smooth muscles were removed from PTX-treated and non-treated rats as strips and dispersed smooth muscle cells to identify whether PTX-linked pathway mediated the contractility to bethanechol. RESULTS A dose-dependent contractile response observed with bethanechol, was not affected by TTX. The pretreatment of rats with pertussis toxin decreased the contraction induced by bethanechol. Lack of calcium as well as the presence of the L-type calcium channel blocker, nifedipine, also inhibited the cholinergic contraction, with a reduction in response from 2.5+/-0.4 g/mm2 to 1.2+/-0.4 g/mm(2) (P<0.05). The dose-response curves were shifted to the right by muscarinic antagonists in the following order of affinity: darifenacin (M(3))>methocramine (M(2)) >pirenzepine (M(1)). CONCLUSION The muscarinic receptors-dependent contraction of rat antral circular smooth muscles was linked to the signal transduction pathway(s) involving pertussis-toxin sensitive GTP-binding proteins and to extracellular calcium via L-type voltage gated calcium channels. The presence of the residual contractile response after the treatment with nifedipine, suggests that an additional pathway could mediate the cholinergic contraction. The involvement of more than one muscarinic receptor (functionally predominant type 3 over type 2) also suggests more than one pathway mediating the cholinergic contraction in rat antrum.
Automated observation: heart rate variability and its relationship with performance-related psychological variables in young swimmers

Título: Observación automatizada: la variabilidad de la frecuencia cardíaca y su relación con las variables psicológicas determinantes del rendimiento en nadadores jóvenes. Resumen: La correcta interpretación de los marcadores de rendimiento desde una perspectiva psicofisiológica es importante para el desarrollo de los atletas en etapas formativas. Este trabajo contiene dos objetivos. El primero es analizar la relación de la variabilidad de la frecuencia cardíaca (VFC) con las variables psicológicas: calidad de sueño, autoestima y estados de ánimo en jóvenes nadadores de una escuela profesional. El segundo objetivo es estudiar la relación de la VFC y determinantes psicológicos con el rendimiento. Esta se compuso 9 nadadores (11.7 ± 1.4 años) basada en un método de muestreo a propósito. Las mediciones fueron efectuadas una vez por semana durante tres semanas de entrenamiento. El análisis estadístico muestra como la dimensión de ansiedad correlacionó negativamente con el logaritmo natural de banda de alta frecuencia (Ln HF) y positivamente con el logaritmo natural de la banda de muy baja frecuencia (Ln VLF) de forma significativa. No se encontraron relaciones para las variables autoestima y calidad de sueño. El tiempo en la prueba de rendimiento fue asociado negativamente con indicadores de la actividad parasimpática. Estos resultados sugieren que la VFC podría ser una herramienta válida para la predicción del rendimiento y mejora de la interpretación de la ansiedad. Palabras clave: Calidad de sueño; estados de ánimo; autoestima; rendimiento. Abstract: Correct interpretation of performance markers from a psychophysiological perspective is important in young developing athletes. This study had two objectives. The first was to analyze the relationship between heart rate variability (HRV) and the psychological variables sleep quality, self-esteem, and mood states in young swimmers from a professional swimming club. The second was to study the relationship between performance and HRV and psychological determinants. The sample was composed of nine swimmers (11.7±1.4 years) base on purposive sampling method. Data were collected once a week during training sessions for 3 weeks. The statistical analysis showed that anxiety was negatively correlated with the high frequency component of HRV (Ln HF) and positively correlated with the very low frequency component (Ln LVF). No significant correlations were observed for self-esteem or sleep quality. Performance in a 200-m freestyle event was negatively correlated with the parasympathetic HRV indices. Our results suggest that HRV could be a valid tool for predicting performance and improving interpretation of psychometric tests.
Unstable Repeat Expansion in Neurodegenerative Dementias: Mechanisms of Disease

Inam Neuroscience Research Center, Department of Neurology, Sanbon Medical Center, College of Medicine, Wonkwang University, Gunpo, Korea The majority of neurodegenerative dementias are thought to result primarily from the misfolding, aggregation and accumulation of proteins which interfere with protein homeostasis in the brain. Some of them are caused by the expansion of unstable nucleotide repeats, which include Huntington’s disease as a prototype. Other neurodevelopmental or neurodegenerative disorders, such as fragile X syndrome, some spinocerebellar ataxias and myotonic dystrophies exhibit cognitive or behavioral deficits as parts of their clinical manifestations. Unstable repeat expansions include trinucleotide, tetranucleotide, and pentanucleotide. Recently hexanucleotide repeat expansion in frontotemporal dementia and amyotrophic lateral sclerosis was identified. The pathogenic mechanisms for these repeat disorders include either loss of protein function or gain of function at the protein or RNA levels. The aim of this article is to review proposed mechanisms by which unstable repeat expansions give rise to degeneration of brain with the hope of understanding the diseases and providing insights into the areas of therapeutic intervention. We will review these potential mechanisms in the context of fragile X syndrome, Huntington’s disease, spinocerebellar ataxias, myotonic dystrophy, and frontotemporal dementia and amyotrophic lateral sclerosis. We will also discuss the potential targets for therapeutic intervention. Received: February 17, 2011 Revision received: March 7, 2011 Accepted: March 7, 2011
Zinc finger E‐box binding factor 1 plays a central role in regulating Epstein‐Barr virus (EBV) latent‐lytic switch and acts as a therapeutic target in EBV‐associated gastric cancer

The role of Epstein‐Barr virus (EBV) infection in gastric carcinogenesis remains largely unknown. The authors studied the effects of zinc finger E‐box binding factor 1 (ZEB1) on latent‐lytic switch of EBV infection in gastric cancer and explored the importance of EBV in gastric carcinogenesis.
The Algebraic Intersection Type Unification Problem

The algebraic intersection type unification problem is an important component in proof search related to several natural decision problems in intersection type systems. It is unknown and remains open whether the algebraic intersection type unification problem is decidable. We give the first nontrivial lower bound for the problem by showing (our main result) that it is exponential time hard. Furthermore, we show that this holds even under rank 1 solutions (substitutions whose codomains are restricted to contain rank 1 types). In addition, we provide a fixed-parameter intractability result for intersection type matching (one-sided unification), which is known to be NP-complete. We place the algebraic intersection type unification problem in the context of unification theory. The equational theory of intersection types can be presented as an algebraic theory with an ACI (associative, commutative, and idempotent) operator (intersection type) combined with distributivity properties with respect to a second operator (function type). Although the problem is algebraically natural and interesting, it appears to occupy a hitherto unstudied place in the theory of unification, and our investigation of the problem suggests that new methods are required to understand the problem. Thus, for the lower bound proof, we were not able to reduce from known results in ACI-unification theory and use game-theoretic methods for two-player tiling games.
Compiling Ramification Constraints into Effect Axioms

We present a method to derive a solution to the combined frame and ramification problems for certain classes of theories of action written in the situation calculus. The theories of action considered include the causal laws of the domain, in the form of a set of effect axioms, as well as a set of ramification state constraints. The causal laws state the direct effects that actions have on the world, and ramification state constraints allow one to derive indirect effects of actions on the domain.
Alpha-synuclein’s degradation in vivo

Progressive accumulation of α-synuclein is key to the pathology of many neurodegenerative diseases, including Parkinson disease and dementia with Lewy bodies. Increased intracellular levels of α-synuclein may be caused by enhanced expression or alterations in protein degradation pathways. Here we review our recent study showing that the ubiquitin-proteasome system and the autophagy-lysosomal pathway are differentially involved in α-synuclein's degradation in vivo. We discuss the key findings obtained with our novel in vivo approach and also present a model for the progression of protein aggregation and dysfunctional degradation in Parkinson disease.
The 2005 dengue epidemic in Singapore: epidemiology, prevention and control.

INTRODUCTION We investigated the 2005 outbreak of dengue fever (DF)/dengue haemorrhagic fever (DHF) to determine its epidemiological, virological and entomological features to further understand the unprecedented resurgence. MATERIALS AND METHODS All physician-diagnosed, laboratory-confirmed cases of DF/DHF notified to the Ministry of Health, Singapore during the outbreak as well as entomological and virological data were analysed retrospectively. RESULTS A total of 14,006 cases of DF/DHF comprising 13,625 cases of DF and 381 cases of DHF, including 27 deaths were reported, giving an incidence rate of 322.6 per 100,000 and a case-fatality rate of 0.19%. The median age of the cases and deaths were 32 and 59.5 years, respectively. The incidence rate of those living in compound houses was more than twice that of residents living in public and private apartments. The distribution of DF/DHF cases was more closely associated with Aedes aegypti compared to Aedes albopictus breeding sites and the overall Aedes premises index was 1.15% (2.28% in compound houses and 0.33% to 0.8% in public and private apartments). The predominant dengue serotype was DEN-1. A significant correlation between weekly mean temperature and cases was noted. The correlation was strongest when the increase in temperature preceded rise in cases by a period of 18 weeks. CONCLUSION The resurgence occurred in a highly densely populated city-state in the presence of low Aedes mosquito population. Factors contributing to this resurgence included lower herd immunity and change in dominant dengue serotype from DEN-2 to DEN-1. There was no evidence from gene sequencing of the dengue viruses that the epidemic was precipitated by the introduction of a new virulent strain. The current epidemiological situation is highly conducive to periodic dengue recurrences. A high degree of vigilance and active community participation in source reduction should be maintained.
Review of the formulation of present-generation stratospheric chemistry-climate models and associated external forcings

The goal of the Chemistry-Climate Model Validation (CCMVal) activity is to improve understanding of chemistry-climate models (CCMs) through process-oriented evaluation and to provide reliable projections of stratospheric ozone and its impact on climate. An appreciation of the details of model formulations is essential for understanding how models respond to the changing external forcings of greenhouse gases and ozone-depleting substances, and hence for understanding the ozone and climate forecasts produced by the models participating in this activity. Here we introduce and review the models used for the second round (CCMVal-2) of this intercomparison, regarding the implementation of chemical, transport, radiative, and dynamical processes in these models. In particular, we review the advantages and problems associated with approaches used to model processes of relevance to stratospheric dynamics and chemistry. Furthermore, we state the definitions of the reference simulations performed, and describe the forcing data used in these simulations. We identify some developments in chemistry-climate modeling that make models more physically based or more comprehensive, including the introduction of an interactive ocean, online photolysis, troposphere-stratosphere chemistry, and non-orographic gravity-wave deposition as linked to tropospheric convection. The relatively new developments indicate that stratospheric CCM modeling is becoming more consistent with our physically based understanding of the atmosphere.
Etude de la paroi intestinale dans un modèle murin d'interruption intestinale : rôles des cellules du SNE et des cellules neuroendocrines

But de l’etudeL’atresie intestinale est une anomalie congenitale definie par une perte de la continuite digestive. Malgre une restauration chirurgicale precoce de cette continuite, surviennent durant les premiers mois de vie des troubles de la motilite digestive et des surinfections bacteriennes chez un tiers des patients. Ces troubles fonctionnels etaient attribues jusque la principalement a des alterations du systeme nerveux enterique. Le but de cette etude etait de confirmer cette hypothese mais egalement d’elargir le champ des explorations aux autres composants du tube digestif.Materiel et methodesLe modele animal de l’atresie chez le rat initialement decrit dans notre equipe a ete utilise pour caracteriser les anomalies d’expression genique par transcriptomique. L’etude portait egalement sur la maturation digestive chez des fœtus de rat controle entre un stade de developpement embryonnaire E15 et E21. Des modifications en amont et en aval de l’obstruction ont ete etudiees en prelevant deux segments successifs de 1 cm par cette approche globale transcriptomique puis precisees par RT-PCRq et confirmees par des techniques immunohistochimiques et de microscopie electronique. ResultatsChez les fœtus temoins, l’expression genique montre une decroissance physiologique pour le SNE et une augmentation pour les systemes neuroendocrine et epithelial de E15 a E21. Concernant les fœtus avec atresie, les modifications concernent quasi exclusivement le segment d’amont avec une augmentation du calibre intestinal, de l’epaisseur musculaire et une acceleration globale de la maturation. Une redistribution des sous types neuronaux est constatee dans le segment d’amont ainsi qu’une augmentation de l’expression du systeme neuro endocrine. Pour ces deux systemes, le segment d’aval est peu modifie. Des modifications importantes du systeme epithelial sont observees en amont comme en aval avec pour consequence probable une alteration de la barriere intestinale et du systeme anti infectieux.ConclusionCes resultats montrent que les changements predominent dans le segment en amont de l’atresie alors que le segment d’aval etait parfois considere comme le plus pathologique. De plus, il a ete retrouve des changements inattendus du systeme neuroendocrine et epithelial qui sous tendent une implication non exclusive du SNE. D’autres recherches sont necessaires pour confirmer ces donnees et les exploiter dans une demarche therapeutique.
Una concepción del tiempo no-lineal en dos lenguas: el maya yucateco colonial y actual y la lengua de señas maya yucateca

En este trabajo se plantea la existencia una concepcion del tiempo propiamente maya (yucateca) en la cual el tiempo no es metaforicamente lineal y puede ser concebido como “estructuralmente ciclico”. Usare ejemplos de dos lenguas que podemos considerar como pertenecientes a una misma cultura maya yucateca. La primera es el maya yucateco y se considera en una perspectiva diacronica, tomando ejemplos del maya actual pero tambien del maya colonial, en particular extractos de varios textos del Chilam Balam. La segunda lengua es la lengua de senas maya yucateca; una nueva lengua que surgio en pueblos mayas en los cuales nacieron personas sordas. Para comunicarse sin la ayuda del canal oral, los sordos juntos con sus familiares inventaron un lenguaje senado que tiene caracteristicas similares en diferentes pueblos. Este trabajo se enfoca en el analisis de las metaforas que se usan para hablar del tiempo y se argumenta que no hubo una influencia de la concepcion lineal occidental del tiempo (por lo menos hasta muy recientemente) en la concepcion maya del tiempo.
Treating cancer by targeting the immune system.

There is currently great interest in the targeted therapy of cancer. Antibodies that target specific antigens on the surface of cancer cells — such as rituximab, which binds to CD20 on lymphoid tumors, and trastuzumab, which blocks HER2 on breast-cancer cells — were early successes. However, a novel method of using antibodies to stimulate an antitumor response was pioneered in the mid-1990s by James Allison and colleagues.1 Because the body's immune response, if left unchecked, can result in autoimmunity, we have evolved a number of immune “checkpoints” that work as braking mechanisms to counterbalance immune activation. Studies in animals have .
Gaussian process based recursive system identification

This paper is concerned with the problem of recursive system identification using nonparametric Gaussian process model. Non-linear stochastic system in consideration is affine in control and given in the input-output form. The use of recursive Gaussian process algorithm for non-linear system identification is proposed to alleviate the computational burden of full Gaussian process. The problem of an online hyper-parameter estimation is handled using proposed ad-hoc procedure. The approach to system identification using recursive Gaussian process is compared with full Gaussian process in terms of model error and uncertainty as well as computational demands. Using Monte Carlo simulations it is shown, that the use of recursive Gaussian process with an ad-hoc learning procedure offers converging estimates of hyper-parameters and constant computational demands.
A new DC voltage balancing method for cascaded multilevel inverter based STATCOM

It has been mentioned in the literature that, among the multilevel inverter topologies used for STATCOM applications, the cascaded multilevel topology is the most advantageous and economical one. On the other hand, the main problem of this topology comes out to be the difficulty of sustaining the DC capacitors' mean voltages. This issue is very important for obtaining an output voltage with low THD and having equal device stresses. In this work, a new DC voltage balancing method (Selective- Swapping Algorithm) for cascaded multilevel inverter based STATCOM applications is investigated and the results are given. Moreover, these results are compared with the ones obtained for the other DC voltage equalization methods given in the literature.
Long‐term outcome in adolescent‐onset generalized genetic epilepsies

Until now, it has been unclear if the three subsyndromes of adolescent‐onset generalized genetic epilepsy (GGE) differ in long‐term prognosis. Therefore, this study aimed to compare long‐term seizure outcome in juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy (JME), and epilepsy with generalized tonic–clonic seizures alone (EGTCS).
Covariance functions across herd production levels for test day records on milk, fat, and protein yields.

Multiple-trait BLUP evaluations of test day records require a large number of genetic parameters. This study estimated covariances with a reduced model that included covariance functions in two dimensions (stage of lactation and herd production level) and all three yield traits. Records came from all six states in Australia, were evenly distributed across the herd production levels, but decreased with increasing lactation stage from 9693 records for the 1st mo of lactation to 4199 records for the 10th mo. Using the variance component estimation package and a bivariate animal model, 1176 genetic (co)variances and 312 environmental (co)variances were estimated for 48 traits (1, 4, 7, and 10 mo of lactation; herd production levels of < 20, 20 to 22, 22 to 24, > 24 kg of milk/d; and milk, fat, and protein yields). The genetic (co)variances could be predicted by a multiplicative model that included 1) a term dependent on which yields (milk, fat, or protein) were involved in the covariance, 2) the covariance functions for month of lactation and herd production level, and 3) a covariance function for the interaction between these. This model required only 27 parameters instead of the 1176 (co)variances. For the environmental (co)variances, a model was fitted that contained several additional covariance functions. This model reduced the number of parameters from 312 to 71. For the same trait at the same production level, genetic correlations between test days ranged from 0.59 to 1, and environmental correlations ranged from 0.17 to 0.48. Genetic correlations between milk and fat, milk and protein, and fat and protein were 0.38, 0.83, 0.59, respectively, and correlations between the herd production levels ranged from 0.79 to 0.97. Failure to consider herd production level in a test day model evaluation might result, for instance, in overweighting of early lactation information from high production herds compared with information coming from bulls tested across all production levels.
Inhibition of Rift Valley Fever Virus Replication and Perturbation of Nucleocapsid-RNA Interactions by Suramin

ABSTRACT Rift Valley fever virus (RVFV) is an emerging infectious pathogen that causes severe disease in humans and livestock and has the potential for global spread. There are currently no proven safe and effective treatment options for RVFV infection. Inhibition of RNA binding to RVFV nucleocapsid protein (N) represents an attractive antiviral therapeutic strategy because several essential steps in the RVFV replication cycle involve N binding to viral RNA. In this study, we demonstrate the therapeutic potential of the drug suramin by showing that it functions well as an inhibitor of RVFV replication at multiple stages in human cell culture. Suramin has been used previously to treat trypanosomiasis in Africa. We characterize the dynamic and cooperative nature of N-RNA binding interactions and the dissociation of high-molecular-mass ribonucleoprotein complexes using suramin, which we previously identified as an N-RNA binding inhibitor in a high-throughput screen. Finally, we elucidate the molecular mechanism used by suramin in vitro to disrupt both specific and nonspecific binding events important for ribonucleoprotein formation.