Miracle-dz/UniFAR-FTUs huggingface dataset:
[Ca2+]i Elevations Detected by BK Channels during Ca2+ Influx and Muscarine-Mediated Release of Ca2+ from Intracellular Stores in Rat Chromaffin Cells

Submembrane [Ca2+]ichanges were examined in rat chromaffin cells by monitoring the activity of an endogenous Ca2+-dependent protein: the large conductance Ca2+- and voltage-activated K+ channel (also known as the BK channel). The Ca2+ and voltage dependence of BK current inactivation and conductance were calibrated first by using defined [Ca2+]i salines. This information was used to examine submembrane [Ca2+]i elevations arising out of Ca2+ influx and muscarine-mediated release of Ca2+ from intracellular stores. During Ca2+ influx, some BK channels are exposed to [Ca2+]i of at least 60 μm. However, the distribution of this [Ca2+]i elevation is highly nonuniform so that the average [Ca2+]i detected when all BK channels are activated is only ∼10 μm. Intracellular dialysis with 1 mm or higher EGTA spares only the BK channels activated by the highest [Ca2+]i during influx, whereas dialysis with 1 mm or higher BAPTA blocks activation of all BK channels. Submembrane [Ca2+]i elevations fall rapidly after termination of short (5 msec) Ca2+influx steps but persist above 1 μm for several hundred milliseconds after termination of long (200 msec) influx steps. In contrast to influx, the submembrane [Ca2+]i elevations produced by release of intracellular Ca2+ by muscarinic actetylcholine receptor (mAChR) activation are much more uniform and reach peak levels of 3–5 μm. Our results suggest that during normal action potential activity only 10–20% of BK channels in each chromaffin cell see sufficient [Ca2+]i to be activated.
Differences in Perception of Risk Between People Who Have and Have Not Experienced Salmonella Food Poisoning

It is believed that food hygiene precautions in domestic kitchens are an important strategy in efforts to reduce the incidence of sporadic food poisoning, but recent research has shown that people who have suffered food poisoning handle the same types of foods and adopt similar food hygiene precautions in their kitchens to the rest of the population. This suggests the need to examine other factors. A case‐control study of sporadic Salmonella food poisoning was conducted to investigate several domestic kitchen risk factors. Measures of perception of risk, knowledge, and control associated with food poisoning in case and control respondents are reported here. It was found that perceived personal risk from food poisoning in the home was less than perceived risk to other people. In contrast, ratings of personal knowledge about food poisoning and personal control over food poisoning in the home were seen to be greater than other people's knowledge and control. There were no differences between the cases and the controls in their ratings of knowledge about food poisoning or their control over food poisoning. However, cases perceived their personal risk from food poisoning to be higher than controls. Both case and control samples exhibited optimistic bias but this was reduced in the case sample, suggesting that experience with food poisoning may reduce optimistic bias.
Interleukin-7 retroviruses transform pre-B cells by an autocrine mechanism not evident in Abelson murine

In this study, we have constructed retroviral vectors expressing the interleukin-7 (IL-7) cDNA and have used infection with these retroviruses to express this cytokine endogenously in an IL-7-dependent pre-B-cell line. Infection with IL-7 retroviruses, but not with a control retrovirus, resulted in the conversion of the cells to IL-7 independence. The frequency at which this occurred, together with data on vector expression levels, indicated that secondary events were required for factor independence in this system. Southern analysis showed that the IL-7-dependent clones harbored unrearranged copies of the vector proviruses. The factor-independent cells produced variable quantities of IL-7 as measured by an IL-7-specific bioassay, and their proliferation could be substantially inhibited by a neutralizing antibody directed against IL-7, indicating that a classical autocrine-mechanism was responsible for their transformation. These IL-7-independent cells were tumorigenic, in contrast to the parental IL-7-dependent cells or those infected with a control vector. These results showed that IL-7 could participate in the malignant transformation of pre-B cells. However, neither of two Abelson murine leukemia virus (A-MuLV)-transformed pre-B-cell lines expressed detectable IL-7 mRNA, at a level of sensitivity corresponding to less than one molecule of mRNA per cell. Moreover, the proliferation of the A-MuLV transformants was unaffected by addition of the IL-7 antisera under conditions in which parallel experiments with IL-7 virus-infected cells resulted in greater than 70% growth inhibition. Thus, transformation of pre-B cells by A-MuLV was not associated with a demonstrable autocrine loop of IL-7 synthesis. These results show that IL-7 can participate in the malignant transformation of pre-B cells and suggest studies aimed at assessing the role of autocrine production of IL-7 in the generation of human leukemias and lymphomas.
EFFECTS OF HERBAL EXTRACTS ON THE FUNCTION OF HUMAN ORGANIC ANION-TRANSPORTING POLYPEPTIDE OATP-B

Most known interactions between herbal extracts and drugs involve the inhibition of drug-metabolizing enzymes, but little is yet known about the possible role of transporters in these interactions. In this study, we have examined the effects of herbal extracts used in dietary supplements on the function of organic anion-transporting polypeptide B (OATP-B; OATP2B1), which is expressed on human intestinal epithelial cells and is considered to be involved in the intestinal absorption of various drugs. Specifically, the effects of 15 herbal extracts on uptake of estrone-3-sulfate, a typical OATP-B substrate, by human embryonic kidney 293 cells stably expressing OATP-B were evaluated. At concentration levels considered likely to be attainable in the human intestine, extracts of bilberry, echinacea, green tea, banaba, grape seed, ginkgo, and soybean potently inhibited estrone-3-sulfate uptake by 75.5, 55.5, 82.1, 61.1, 64.5, 85.4, and 66.8%, respectively (P < 0.01). The inhibitory effect of ginkgo leaf extract was concentration-dependent (IC50 = 11.2 ± 3.3 μg/ml) and reversible. Moreover, flavonol glycosides and catechins significantly inhibited the function of OATP-B, suggesting that the inhibitory effects of the herbal extracts on OATP-B may be primarily attributable to flavonoids. The extracts of mulberry, black cohosh, and Siberian ginseng moderately (but significantly) inhibited estrone-3-sulfate uptake by 39.1, 47.2, and 49.2%, respectively (P < 0.05). Extracts of barley, Job's tears, rutin, rafuma, and passionflower were ineffective. These results suggest that coadministration of some dietary supplements may decrease the absorption of orally administered substrates of OATP-B.
Behavioural consequences of oligodendrocyte progenitor cell transplantation into experimental demyelinating lesions in the rat spinal cord

Glial cell transplantation has the potential to be developed into a clinical treatment for human demyelinating diseases because of its demonstrated efficacy in remyelinating experimentally demyelinated axons. As a step towards clinical application it is necessary to demonstrate that the procedure is safe and efficacious in promoting behavioural recovery. In this study we transplanted glial cell progenitors into demyelinating lesions induced by intraspinal injection of ethidium bromide in the rat. Locomotor function after transplantation was assessed using a beam‐walking test that has previously been shown able to detect deficits associated with demyelination in the dorsal funiculus of the rat spinal cord. Two groups of animals with transplants were examined. In one group, spontaneous remyelination was prevented by exposure of the lesion to 40 Gy of X‐irradiation; in the other, male glial cells were transplanted into nonirradiated female receipients, permitting their identification by use of a probe specific to the rat Y chromosome. Following transplantation, there was severe axon loss in a large proportion of the irradiated animals and those affected did not recover normal behavioural function. In contrast, both the small proportion of the irradiated group that sustained only mild axon loss and the nonirradiated recipients of transplants recovered normal function on our behavioural test. We conclude that glial cell transplantation is able to reverse the functional deficits associated with demyelination, provided axonal loss is minimal.
The nonproton ligand of acid-sensing ion channel 3 activates mollusk-specific FaNaC channels via a mechanism independent of the native FMRFamide peptide

The degenerin/epithelial sodium channel (DEG/ENaC) superfamily of ion channels contains subfamilies with diverse functions that are fundamental to many physiological and pathological processes, ranging from synaptic transmission to epileptogenesis. The absence in mammals of some DEG/ENaCs subfamily orthologues such as FMRFamide peptide–activated sodium channels (FaNaCs), which have been identified only in mollusks, indicates that the various subfamilies diverged early in evolution. We recently reported that the nonproton agonist 2-guanidine-4-methylquinazoline (GMQ) activates acid-sensing ion channels (ASICs), a DEG/ENaC subfamily mainly in mammals, in the absence of acidosis. Here, we show that GMQ also could directly activate the mollusk-specific FaNaCs. Differences in ion selectivity and unitary conductance and effects of substitutions at key residues revealed that GMQ and FMRFamide activate FaNaCs via distinct mechanisms. The presence of two activation mechanisms in the FaNaC subfamily diverging early in the evolution of DEG/ENaCs suggested that dual gating is an ancient feature in this superfamily. Notably, the GMQ-gating mode is still preserved in the mammalian ASIC subfamily, whereas FMRFamide-mediated channel gating was lost during evolution. This implied that GMQ activation may be essential for the functions of mammalian DEG/ENaCs. Our findings provide new insights into the evolution of DEG/ENaCs and may facilitate the discovery and characterization of their endogenous agonists.
Effects of alterations in cellular iron on biosynthesis of the transferrin receptor in K562 cells

Treatment of K562 cells, a human erythroleukemia cell line, with desferrioxamine raised the levels of the receptor for transferrin (Tf) two- to threefold over that of the control cells. The levels of receptor were reduced by at least 50 and 35% of that of the control in cells treated with diferric Tf and ferric ammonium citrate, respectively. These changes were of total cellular receptors with no alteration in the proportion of receptors found on the cell surface. The half-lives of the receptor were identical in cells treated with desferrioxamine, diferric Tf, or ferric ammonium citrate. Cells metabolically labeled with [35S]methionine showed a 2.5-fold increase in the rate of receptor synthesis when treated with desferrioxamine and a 35 and 65% decrease when treated with ferric ammonium citrate and diferric Tf, respectively. In vitro translations of polyadenylated mRNA isolated from cells incubated with desferrioxamine showed a 2.5-fold increase in translatable mRNA for the receptor, whereas treatment of cells with ferric ammonium citrate and diferric Tf resulted in a 25 and 50% reduction, respectively, in translatable mRNA for this receptor.
Verified Hormone Therapy Improves Episodic Memory Performance in Healthy Postmenopausal Women

ABSTRACT Studies of hormone therapy (HT) and cognition have yielded conflicting results. The aim of this observational study was to examine the effect of estradiol, via serum verified HT (estradiol, estriol, progesterone) and endogenous estradiol, on 108 healthy postmenopausal women's cognitive performance. The results demonstrated that the 43 HT-users performed at a significantly higher level than non-users on episodic memory tasks and on a verbal fluency task, whereas HT-users and non-users did not differ on tasks assessing semantic memory and spatial visualization. In addition, there was a positive relationship between serum estradiol level and episodic memory performance, indicating that postmenopausal HT is associated with enhanced episodic memory and verbal fluency, independent of age and education. These observational results suggest that HT use may be sufficient to exert small, yet positive effects on female sensitive cognitive tasks. Hormone therapy compliance and formulation is discussed as confounding factors in previous research.
Intestinal absorption of the intact peptide carnosine in man, and comparison with intestinal permeability to lactulose.

1. Healthy humans ingested the dipeptide carnosine (L‐beta‐alanyl‐L‐histidine). Their plasma levels and urinary outputs of carnosine and beta‐alanine were monitored over the following 5 h. 2. Large amounts of intact carnosine (up to 14% of the ingested dose) were recovered in the urine over the 5 h after ingestion. However, carnosine was undetectable in the plasma unless precautions were taken to inhibit blood carnosinase activity ex vivo during and after blood collection. 3. The amount of carnosine recovered in urine varied substantially between subjects. It correlated negatively with carnosinase enzymic activity in the plasma. Highest carnosinase activities were observed in those subjects who regularly underwent physical training. 4. Urinary recovery of the disaccharide lactulose also varied considerably between subjects, but was substantially lower than that of carnosine. There was no significant correlation between the recoveries of carnosine and lactulose. 5. When lactulose was ingested with a hypertonic solution, the urinary recovery of lactulose was generally increased. When carnosine was ingested with a hypertonic solution, the urinary recovery of carnosine was reduced: hence the paracellular route probably is not dominant for absorption of intact carnosine. 6. Intact carnosine must have crossed the intestine to an extent much greater than hitherto recognized. Rapid post‐absorptive hydrolysis is a severe obstacle to quantification of intact peptide absorption.
Plug and play bench: Simplifying big data benchmarking using containers

The recent boom of big data, coupled with the challenges of its processing and storage gave rise to the development of distributed data processing and storage paradigms like MapReduce, Spark, and NoSQL databases. With the advent of cloud computing, processing and storing such massive datasets on clusters of machines is now feasible with ease. However, there are limited tools and approaches, which users can rely on to gauge and comprehend the performance of their big data applications deployed locally on clusters, or in the cloud. Researchers have started exploring this area by providing benchmarking suites suitable for big data applications. However, many of these tools are fragmented, complex to deploy and manage, and do not provide transparency with respect to the monetary cost of benchmarking an application. In this paper, we present Plug And Play Bench (PAPB1): an infrastructure aware abstraction built to integrate and simplify the deployment of big data benchmarking tools on clusters of machines. PAPB automates the tedious process of installing, configuring and executing common big data benchmark workloads by containerising the tools and settings based on the underlying cluster deployment framework. Our proof of concept implementation utilises HiBench as the benchmark suite, HDP as the cluster deployment framework and Azure as the cloud platform. The paper further illustrates the inclusion of cost metrics based on the underlying Microsoft Azure cloud platform.
A different approach of using Personas in human-robot interaction: Integrating Personas as computational models to modify robot companions' behaviour

The current paper focuses on a novel integration of the Personas technique into HRI studies, and the definition of a Persona-Based Computational Behaviour Model for achieving socially intelligent robot companions in living environments. Our core interest is the creation of companions adapted to users' needs to support their activities of daily living. The aim is to create a mechanism that allows us to develop initial robot behaviour, i.e. behaviour when first encountering the user, which is already adapted to each user without the necessity of collecting in advance a large dataset to train the system. A persona represents the specific needs of many individuals for a particular scenario. This technique helps us develop initial robot behaviour adapted to user needs, and so reduces the amount of trials that participants have to perform during early stages of the system development. The paper describes how this behaviour model has been created and integrated into a functional architecture, and presents the motivation, background and conceptual framework for this new research direction. Future empirical studies will validate this approach and expand the initial definition of our model.
Prevalence and Genotype Distribution of Pneumocystis jirovecii in Cuban Infants and Toddlers with Whooping Cough

ABSTRACT This study describes the prevalence and genotype distribution of Pneumocystis jirovecii obtained from nasopharyngeal (NP) swabs from immunocompetent Cuban infants and toddlers with whooping cough (WC). A total of 163 NP swabs from 163 young Cuban children with WC who were admitted to the respiratory care units at two pediatric centers were studied. The prevalence of the organism was determined by a quantitative PCR (qPCR) assay targeting the P. jirovecii mitochondrial large subunit (mtLSU) rRNA gene. Genotypes were identified by direct sequencing of mtLSU ribosomal DNA (rDNA) and restriction fragment length polymorphism (RFLP) analysis of the dihydropteroate synthase (DHPS) gene amplicons. qPCR detected P. jirovecii DNA in 48/163 (29.4%) samples. mtLSU rDNA sequence analysis revealed the presence of three different genotypes in the population. Genotype 2 was most common (48%), followed in prevalence by genotypes 1 (23%) and 3 (19%); mixed-genotype infections were seen in 10% of the cases. RFLP analysis of DHPS PCR products revealed four genotypes, 18% of which were associated with resistance to sulfa drugs. Only contact with coughers (prevalence ratio [PR], 3.51 [95% confidence interval {CI}, 1.79 to 6.87]; P = 0.000) and exposure to tobacco smoke (PR, 1.82 [95% CI, 1.14 to 2.92]; P = 0.009) were statistically associated with being colonized by P. jirovecii. The prevalence of P. jirovecii in infants and toddlers with WC and the genotyping results provide evidence that this population represents a potential reservoir and transmission source of P. jirovecii.
Surgery Goes Social: The Extent and Patterns of Social Media Utilization by Major Trauma, Acute and Critical Care Surgery Societies

Context and Aims: The evolving influence of social media in trauma, acute, and critical care surgery (TACCS) cannot be ignored. We sought to investigate the extent and patterns of use of social networks by major regional, national and international TACCS societies. Materials and Methods: The two leading social networking sites, Facebook (FB) and Twitter (TW), were thoroughly examined for the presence of official accounts for each of the major TACCS societies. An official FB or TW account was defined as one which has a blue verified badge and/or is linked the society's official website. For societies with confirmed official accounts, the extent and patterns of use of the two platforms were systematically examined over a 2-week period through: (1) manual inspection of the societies' FB and TW pages, (2) the SQLite database containing downloaded samples of posts, and (3) the TW analytics database, symplur.com. Standardized social media metrics were calculated for each society. Posted content was categorized as being: (1) society news updates, (2) event announcements, or (3) general medical information. Results: From a total of 64 TACCS societies, only 27 (42%) had FB and/or TW accounts. Ten out of the 12 American societies had accounts compared to 13/39 of European, 2/9 of Australasian, and 0/2 of international societies. For the societies with social media presence, the mean numbers of monthly tweets and FB posts per society were 22 and 8, respectively. We summarize the FB and TW activity of the studied TACCS societies. Most tweets/posts were society news updates and event announcements intended to the society's constituents not the general public. A text cloud was constructed to summarize the major featured topics. Conclusion: Less than half of the TACCS societies are currently using social media; those that do are arguably underutilizing its potential. Non-American societies in particular lag behind in their use of social networking.
MICA/NKG2D-mediated immunogene therapy of experimental gliomas.

The failure of conventional cancer therapy renders glioblastoma an attractive target for immunotherapy. Tumor cells expressing ligands of the activating immunoreceptor NKG2D stimulate tumor immunity mediated by natural killer (NK), gammadelta T, and CD8(+) T cells. We report that human glioma cells express the NKG2D ligands MICA, MICB, and members of the UL16-binding protein family constitutively. However, glioma cells resist NK cell cytolysis because of high MHC class I antigen expression. Plasmid-mediated or adenovirus-mediated overexpression of MICA in glioma cells enhances their sensitivity to NK and T-cell responses in vitro and markedly delays the growth of s.c. and intracerebral LN-229 human glioma cell xenografts in nude mice and of SMA-560 gliomas in syngeneic VMDk mice. Glioma cells forming progressive tumors after implantation of stably MICA-transfected human LN-229 cells lost MICA expression, indicating a strong selection against MICA expression in vivo. Rejection of MICA-expressing SMA-560 cells in VMDk mice resulted in protective immunity to a subsequent challenge with wild-type tumor cells. Finally, the growth of syngeneic intracerebral SMA-560 tumors is inhibited by peripheral vaccination with adenovirus-mediated, MICA-infected irradiated tumor cells, and vaccination results in immune cell activation in the NK and T-cell compartments in vivo. These data commend MICA immunogene therapy as a novel experimental treatment for human malignant gliomas.
DETERMINANTES DEL VOTO SWING EN ESPAÑA

Swing voter es aquel elector que vota a dos formaciones diferentes en dos elecciones consecutivas del mismo nivel. Este estudio revela la existencia de este tipo de votantes dentro del electorado espanol. Aproximadamente, los swing voters representaron el 20% del electorado efectivo en la legislatura 2004/8. Tras su identificacion, el estudio discute en base a que factores estos votantes deciden el sentido final de su voto. El analisis estadistico sugiere que los swing voters emplean valoraciones prospectivas y retrospectivas del gobierno y la oposicion en este proceso. Estas evaluaciones se demostraran sistematicamente menos sesgadas que las del resto de votantes, lo que sugiere una mayor exigencia por parte de este colectivo hacia las acciones y promesas de los partidos politicos. El estudio dedica una especial atencion a la reaccion de los swing voters ante las estrategias de la oposicion encaminadas a desgastar al partido en el gobierno y a capturar el voto de aquellos electores mas susceptibles de prestarles su apoyo. Por ultimo, el estudio reflexiona sobre el dilema distributivo que podria surgir en caso de que el apoyo de los swing voters resultase una condicion necesaria para alcanzar mayorias suficientes para gobernar.