Miracle-dz/UniFAR-FTUs huggingface dataset:
Too Much Inhibition Leads to Excitation in Absence Epilepsy

Enhanced Tonic GABAA Inhibition in Typical Absence Epilepsy. Cope DW, Di Giovanni G, Fyson SJ, Orbán G, Errington AC, Lorincz ML, Gould TM, Carter DA, Crunelli V. Nat Med 2009;(12):1392–1398. The cellular mechanisms underlying typical absence seizures, which characterize various idiopathic generalized epilepsies, are not fully understood, but impaired γ-aminobutyric acid (GABA)-ergic inhibition remains an attractive hypothesis. In contrast, we show here that extrasynaptic GABAA receptor–dependent ‘tonic’ inhibition is increased in thalamocortical neurons from diverse genetic and pharmacological models of absence seizures. Increased tonic inhibition is due to compromised GABA uptake by the GABA transporter GAT-1 in the genetic models tested, and GAT-1 is crucial in governing seizure genesis. Extrasynaptic GABAA receptors are a requirement for seizures in two of the best characterized models of absence epilepsy, and the selective activation of thalamic extrasynaptic GABAA receptors is sufficient to elicit both electrographic and behavioral correlates of seizures in normal rats. These results identify an apparently common cellular pathology in typical absence seizures that may have epileptogenic importance and highlight potential therapeutic targets for the treatment of absence epilepsy.
Coupling between arterial pressure, cerebral blood velocity, and cerebral tissue oxygenation with spontaneous and forced oscillations

We tested the hypothesis that transmission of arterial pressure to brain tissue oxygenation is low under conditions of arterial pressure instability. Two experimental models of hemodynamic instability were used in healthy human volunteers; (1) oscillatory lower body negative pressure (OLBNP) (N = 8; 5 male, 3 female), and; (2) maximal LBNP to presyncope (N = 21; 13 male, 8 female). Mean arterial pressure (MAP), middle cerebral artery velocity (MCAv), and cerebral tissue oxygen saturation (ScO2) were measured non-invasively. For the OLBNP protocol, between 0 and −60 mmHg negative pressure was applied for 20 cycles at 0.05 Hz, then 20 cycles at 0.1 Hz. For the maximal LBNP protocol, progressive 5 min stages of chamber decompression were applied until the onset of presyncope. Spectral power of MAP, mean MCAv, and ScO2 were calculated within the VLF (0.04–0.07 Hz), and LF (0.07–0.2 Hz) ranges, and cross-spectral coherence was calculated for MAP-mean MCAv, MAP-ScO2, and mean MCAv-ScO2 at baseline, during each OLBNP protocol, and at the level prior to pre-syncope during maximal LBNP (sub-max). The key findings are (1) both 0.1 Hz OLBNP and sub-max LBNP elicited increases in LF power for MAP, mean MCAv, and ScO2 (p ≤ 0.08); (2) 0.05 Hz OLBNP increased VLF power in MAP and ScO2 only (p ≤ 0.06); (3) coherence between MAP-mean MCAv was consistently higher (≥0.71) compared with MAP-ScO2, and mean MCAv-ScO2 (≤0.43) during both OLBNP protocols, and sub-max LBNP (p ≤ 0.04). These data indicate high linearity between pressure and cerebral blood flow variations, but reduced linearity between cerebral tissue oxygenation and both arterial pressure and cerebral blood flow. Measuring arterial pressure variability may not always provide adequate information about the downstream effects on cerebral tissue oxygenation, the key end-point of interest for neuronal viability.
An internet portal for the development of community oriented entrepreneurship

In conjunction with the Dutch Ministry of Economic Affairs, Agriculture and Innovation an internet portal ‘community oriented entrepreneurship’ was developed. The portal is meant to develop entrepreneurial skills of (future) farmers and enable them to maintain their licence to operate in an increasingly complex and urban society, with competing claims on agricultural areas and production methods. The portal contains tools, experiences and information, that can be used by farmers directly, but the main target user group are intermediaries, such as teachers and advisors. Feedback on the portal prototype changed the portal to a more simplified structure, focussing on content that delivers practical results for the entrepreneur and their business strategy. In order to continuously meet the demands of the users of the portal, it is preferable to transfer ownership of the portal to farmers organisations or teachers associations, so that continuous improvement of the portal can be operationalized by the user community itself.
Inhibition of cap (m7GpppXm)-dependent endonuclease of influenza virus by 4-substituted 2,4-dioxobutanoic acid compounds

Synthesis of influenza virus mRNA is primed by capped and methylated (cap 1, m7GpppXm) RNAs which the virus derives by endonucleolytic cleavage from RNA polymerase II transcripts in host cells. The conserved nature of the endonucleolytic processing provides a unique target for the development of antiviral agents for influenza viruses. A series of 4-substituted 2,4-dioxobutanoic acid compounds has been identified as selective inhibitors of this activity in both influenza A and B viruses. These inhibitors exhibited 50% inhibitory concentrations in the range of 0.2 to 29.0 microM for cap-dependent influenza virus transcription and had no effect on the activity of other viral and cellular polymerases when tested at 100- to 500-fold higher concentrations. The compounds did not inhibit the initiation or elongation of influenza virus mRNA synthesis but specifically inhibited the cleavage of capped RNAs by the influenza virus endonuclease and were not inhibitory to the activities of other nucleases. Additionally, the compounds specifically inhibited replication of influenza A and B viruses in cell culture with potencies comparable to the 50% inhibitory concentrations obtained for transcription.
Shear Wave Spectroscopy for In Vivo Quantification of Human Soft Tissues Visco-Elasticity

In vivo assessment of dispersion affecting the propagation of visco-elastic waves in soft tissues is key to understand the rheology of human tissues. In this paper, the ability of the supersonic shear imaging (SSI) technique to generate planar shear waves propagating in tissues is fully exploited. First, by strongly limiting shear wave diffraction in the imaging plane, this imaging technique enables to discriminate between the usually concomitant influences of both medium rheological properties and diffraction affecting the shear wave dispersion. Second, transient propagation of these plane shear waves in soft tissues can be measured using echographic images acquired at very high frame. In vitro and in vivo experiments demonstrate that dispersion curves, which characterize the rheological behavior of tissues by measuring the frequency dependence of shear wave speed and attenuation, can be recovered in the 75-600 Hz frequency range. Based on a phase difference algorithm, the dispersion curves are computed in 1 cm2 regions of interest from the acquired propagation movie. In vivo measurements in biceps brachii muscle and liver of three healthy volunteers show important differences in the rheological behavior of these different tissues. Liver tissue appears to be much more dispersive with a phase velocity ranging from ~ 1.5 m/s at 75 Hz to ~ 3 m/s at 500 Hz whereas muscle tissue shows an important anisotropy, shear waves propagating longitudinally to the muscular fibers are almost nondispersive while those propagating transversally are very dispersive with a shear wave speed ranging from 0.5 to 2 m/s between 75 and 500 Hz. The estimation of dispersion curves is local and can be performed separately in different regions of the organ. This signal processing approach based on the SSI modality introduces the new concept of In vivo shear wave spectroscopy (SWS) that could become an additional tool for tissue characterization. This paper demonstrates the in vivo ability of this SWS to quantify both local shear elasticity and dispersion in real time.
The independent relationship of epicardial adipose tissue with carotid intima-media thickness and endothelial functions: the association of pulse wave velocity with the active facilitated arterial conduction concept

BackgroundHypertension, identifiable by elevated blood pressure (BP), is a heterogeneous multifactorial disorder. Epicardial adipose tissue (EAT), a special fat depot that is related to visceral fat rather than total adiposity, shares the same microcirculation with myocardial tissue and coronary vessels. Recent studies have identified EAT as an active organ, which secretes several mediators, called adipokines, affecting the vascular system. The aim of this study was to evaluate the potential association between EAT and BP, endothelial function, carotid intima-media thickness (CIMT), and pulse wave velocity (PWV) independent of conventional and novel metabolic risk factors in patients with previously untreated hypertension. Patients and methodsOur study, which has a cross-sectional design, included 107 consecutive untreated hypertensive patients. Vascular status and functions were evaluated using CIMT, PWV, and flow-mediated dilation (FMD) of the brachial artery. The values of BP were obtained both by the traditional auscultatory method using a sphygmomanometer in an office and by ambulatory BP measurement. ResultsWhen we stratified the patients into three groups according to increased EAT values, CIMT (P<0.001), presence of carotid plaque (P=0.026), and BP values (P=0.001) were increased in the higher tertile compared with the lower tertile. FMD of the brachial artery decreased significantly with increasing EAT thickness (P<0.001). There was a significant, strong, and negative association between CIMT and FMD (r=−0.604, P<0.001). CIMT correlated positively to age (r=0.404, P<0.001), EAT (r=0.517, P<0.001), office systolic BP (r=0.241, P=0.016), ambulatory systolic BP (r=0.419, P<0.001), and diastolic BP (r=0.360, P=0.002). FMD correlated negatively to age (r=−0.390, P<0.001), EAT (r=−0.495, P<0.001), ambulatory systolic (r=−0.338, P=0.006), and diastolic BP (r=−0.281, P=0.024). Multivariate linear regression analyses, carried out to identify predictors of CIMT and FMD, showed only age, EAT, and mean ambulatory BP as independent predictors of both CIMT and FMD. ConclusionOur study showed that EAT is an independent factor of adverse changes in CIMT, FMD, and PWV. Future studies, investigating the vascular influence of EAT at the molecular level, may provide therapeutic options to prevent its adverse vascular interactions.
Aberrant Salience and Probabilistic Reasoning in Distressing Attenuated Positive Psychotic Symptoms: An Examination of a Two Factor Model

Theoretical psychological models of positive psychotic symptoms have increasingly emphasized the interaction of multiple cognitive factors. Research into delusions in particular has focused on the interaction of two factors; a perceptual anomaly that gives rise to a need for explanation, and a bias toward premature acceptance of a hypothesis. Recently this two factor approach has been applied to positive psychotic symptoms more broadly. Two candidate factors have received extensive theoretical and empirical interest. The aberrant salience hypothesis posits that salience regulation, mediated by dopamine, goes awry in psychosis, giving rise to a generalized sense of undue significance that is applied to neutral perceptual stimuli. For the person who experiences it, this unwarranted sense of significance seems to demand an explanation. A second candidate factor, the jumping to conclusions bias has come to be regarded as one of the most stable findings in psychosis research. Reliably associated with the presence of delusions, but also associated with positive symptoms more broadly, the bias is seen when psychotic participants make a probabilistic decision on the basis of less evidence than controls. These factors may work in concert to establish unrealistic conclusions about the nature of perceptual inputs, giving rise to psychotic explanations. In a quasi-experimental study, individuals who endorsed an unusually high level of distressing attenuated positive psychotic symptoms (DAPPS) were compared with controls who endorse a lower than average number. Participants completed one behavioral and one self-report measure of aberrant salience, and a commonly used task for assessing the presence of bias in probabilistic reasoning. Results: Preliminary analyses revealed that participants in the current study did not respond in the expected way to the behavioral measure of aberrant salience. It is possible that the task used is insufficiently sensitive to detect subtle variations in salience processing among non-clinical individuals. In terms of the main results, multiple independent samples t-tests (corrected for multiple comparisons) revealed a group difference only on the self-report measure of aberrant salience. Groups showed no significant difference on the test of probabilistic reasoning, though the group with elevated rates of DAPPS requested more evidence than controls. Logistic regression models predicting group membership from the experimental variables suggested that while the inclusion of aberrant salience significantly improved predictive accuracy, neither probabilistic reasoning nor the interaction between aberrant salience and probabilistic reasoning increased predictive accuracy. This result is a consistent with an interpretation on which distressing attenuated positive psychotic symptoms are associated with aberrant salience attribution but not with probabilistic reasoning deficits. Further research is needed to establish whether these variables interact in clinical
The Compact Modeling of Channel Potential in Sub-30-nm NAND Flash Cell String

This letter presents a compact model of nand Flash strings in which complex characteristics of scaled-down Flash cells can be captured very accurately through simple circuit simulation. Different from previous modeling studies, the proposed model has detailed physical descriptions for channel potential of Flash cell so that various program disturbances due to leakages in nand string can be easily analyzed. The compact model of channel potential is fully compatible with BSIM4 SPICE model. By applying compact model to the 30-nm nand product, many phenomena in the device were realized with more than 95% accuracy at the expense of only a few minutes.
Papulonecrotic Tuberculide

Blood-count (4.3.44). -Total white cells 10,600 per c.mm. Differential white count: Polys. 74%, lymphos. 180%, monos. 7%, eosinophils. 1% Blood sedimentationz rate (3.3.44). -52 mm. at 1 hr. (Westergren). Treatment. -As the blood sedimentation rate was rather high it was thought better to give Alepol 3% intramuscularlv twice a week rather than to give any intravenous or intradermal preparation for fear of provoking a lepra reaction. Nineteen injections were given commencing with 0-2 c.c. and gradually increasing to 5 c.c. Comment. -At no time did he show any fever and only experienced a slight sweat the night after an injection whiclh was given at midday. There was no pain in the nodules during treatment. He has not developed any fresh lesions, neither has there been any obvious regression of the nodules. The hands are slightly cyanotic, but no patches of anmsthesia or diminution in pain sense have become evident. There was very slight nasal discharge one month ago, now none. I should like to have the opinion of the Section as regards further treatment and possibly prognosis. If one can get the sedimentation rate down to about 10 mm. (first hour) I think the prognosis is favourable. The Kahn test was positive on two occasions. A Wassermann reaction was not performed but there is no history of syphilis.
Dramatic synergistic anticancer effect of clinically achievable doses of lovastatin and troglitazone

Lovastatin (an HMG‐CoA reductase inhibitor) and troglitazone (a PPAR‐γ agonist) have been intensively studied prospectively for their application in cancer treatment. However, clinical trials of lovastatin or troglitazone in cancer treatment resulted in only limited responses. To improve their efficacy, lovastatin and troglitazone have, respectively, been tried to combine with other anticancer agents with varied outcomes. In our study, we found a dramatic synergism between lovastatin and troglitazone in anticancer at clinically achievable concentrations. This synergism was found in far majority of cell lines tested including DBTRG 05 MG (glioblastoma) and CL1‐0 (lung). This amazing synergism was accompanied by synergistic modulation of E2F‐1 and p27Kip1, which were reported to mediate the anticancer activities of lovastatin and troglitazone, respectively, and other cell cycle regulating proteins such as CDK2, cyclin A and RB phosphorylation status. With this dramatic combination effect of lovastatin and troglitazone, a promising regimen of cancer therapy may be materialized in the future. © 2005 Wiley‐Liss, Inc.
The Institutional Arrangements between Airlines, Airports, and Handling Companies — A Transaction Cost Assessment

Die Dissertationsschrift analysiert die institutionellen Arrangements zwischen Fluggesellschaften, Flughäfen und Abfertigungsunternehmen unter Anwendung der Transaktionskostentheorie. Der entwickelte Erklärungsansatz und die Fallstudienergebnisse belegen, dass die Unterschiede bei vertikalen Vertragsbeziehungen und Organisationsformen zwischen Fluggesellschaften und Flughäfen mit dem Volumen der spezifischen Investitionen und dem bilateralen Anpassungsbedarf erklärt werden können. Des Weiteren wird die Vertragsgestaltung zwischen Fluggesellschaften und Abfertigungsunternehmen in der Arbeit untersucht. Die qualitativen und quantitativen Ergebnisse zeigen, dass dedizierte Investitionen und die Standardisierung von Vertragselementen die Gestaltung von Abfertigungsverträgen maßgeblich beeinflussen. Die Wahl von effizienten Vertragsund Organisationsformen wird jedoch durch die Vergabe von Lizenzen an neue Wettbewerber in der EU behindert. Schlüsselwörter: Transaktionskostentheorie, Vertrag, Deregulierung, Luftverkehr Abstract: This thesis draws on transaction cost economics to analyze the institutional arrangements between airlines, airports, and handling companies. The developed explanatory framework and the presented case study evidence corroborate the proposition that contractual and organizational arrangements between airlines and airports vary with the amount of relationship-specific investments and the bilateral need for adaptation. In addition, we analyze the contract design decision between airlines and handling companies in this thesis. Our qualitative and quantitative results show that dedicated asset specificity and the degree of standardization of contract provisions explain the contract design decision. The award of temporary licenses to new entrants in the EU is shown to impede efficient contractual and organizational arrangements. This thesis draws on transaction cost economics to analyze the institutional arrangements between airlines, airports, and handling companies. The developed explanatory framework and the presented case study evidence corroborate the proposition that contractual and organizational arrangements between airlines and airports vary with the amount of relationship-specific investments and the bilateral need for adaptation. In addition, we analyze the contract design decision between airlines and handling companies in this thesis. Our qualitative and quantitative results show that dedicated asset specificity and the degree of standardization of contract provisions explain the contract design decision. The award of temporary licenses to new entrants in the EU is shown to impede efficient contractual and organizational arrangements.
The Baby-Friendly Hospital Initiative as an Intervention to Improve Breastfeeding Rates: A Review of the Literature.

INTRODUCTION The Baby-Friendly Hospital Initiative (BFHI) is considered to be an evidence-based program that improves breastfeeding outcomes, but primary research on the topic has been limited. The purpose of this review was to evaluate the literature and synthesize findings to determine the effectiveness of the BFHI as an intervention to improve breastfeeding initiation, duration, and exclusivity. METHODS A review of literature published from 1991 to October 2014 using MEDLINE, CINAHL, PsycINFO, and Web of Knowledge with the search term "Baby-Friendly Hospital Initiative. " The 724 titles initially identified were reviewed using these inclusion criteria: English language, primary research, and available electronically or via interlibrary loan. Studies were excluded if they explicitly stated that they had omitted specific portions of the BFHI or did not fully implement the intervention; considered breastfeeding rather than the BFHI as an intervention; used the BFHI to improve neonatal intensive care unit outcomes specifically; or measured outcomes other than breastfeeding initiation, duration, or exclusivity. This yielded 25 studies for review. RESULTS There are more studies that support the BFHI as an intervention to increase breastfeeding than there are studies that demonstrate no effect of the intervention. However, design weaknesses, settings outside the United States, and disparate methods impede the ability to reach firm conclusions regarding the effectiveness of the BFHI in improving breastfeeding initiation, duration, and exclusivity rates in the United States. DISCUSSION Many of the studies regarding the effectiveness of the BFHI have been hampered by weak designs or methodologic limitations. Research conducted in the United States and employing experimental designs would help to more conclusively determine the effectiveness of the BFHI as an intervention to improve breastfeeding rates.
A Dominant Negative Mutant of Helicobacter pyloriVacuolating Toxin (VacA) Inhibits VacA-induced Cell Vacuolation*

Most Helicobacter pyloristrains secrete a toxin (VacA) that causes structural and functional alterations in epithelial cells and is thought to play an important role in the pathogenesis of H. pylori-associated gastroduodenal diseases. The amino acid sequence, ultrastructural morphology, and cellular effects of VacA are unrelated to those of any other known bacterial protein toxin, and the VacA mechanism of action remains poorly understood. To analyze the functional role of a unique strongly hydrophobic region near the VacA amino terminus, we constructed an H. pylori strain that produced a mutant VacA protein (VacA-(Δ6–27)) in which this hydrophobic segment was deleted. VacA-(Δ6–27) was secreted by H. pylori, oligomerized properly, and formed two-dimensional lipid-bound crystals with structural features that were indistinguishable from those of wild-type VacA. However, VacA-(Δ6–27) formed ion-conductive channels in planar lipid bilayers significantly more slowly than did wild-type VacA, and the mutant channels were less anion-selective. Mixtures of wild-type VacA and VacA-(Δ6–27) formed membrane channels with properties intermediate between those formed by either isolated species. VacA-(Δ6–27) did not exhibit any detectable defects in binding or uptake by HeLa cells, but this mutant toxin failed to induce cell vacuolation. Moreover, when an equimolar mixture of purified VacA-(Δ6–27) and purified wild-type VacA were added simultaneously to HeLa cells, the mutant toxin exhibited a dominant negative effect, completely inhibiting the vacuolating activity of wild-type VacA. A dominant negative effect also was observed when HeLa cells were co-transfected with plasmids encoding wild-type and mutant toxins. We propose a model in which the dominant negative effects of VacA-(Δ6–27) result from protein-protein interactions between the mutant and wild-type VacA proteins, thereby resulting in the formation of mixed oligomers with defective functional activity.