Miracle-dz/UniFAR-FTUs huggingface dataset:
Structural Domains Involved in the Regulation of Transmitter Release by Synapsins

Synapsins are a family of neuron-specific phosphoproteins that regulate neurotransmitter release by associating with synaptic vesicles. Synapsins consist of a series of conserved and variable structural domains of unknown function. We performed a systematic structure-function analysis of the various domains of synapsin by assessing the actions of synapsin fragments on neurotransmitter release, presynaptic ultrastructure, and the biochemical interactions of synapsin. Injecting a peptide derived from domain A into the squid giant presynaptic terminal inhibited neurotransmitter release in a phosphorylation-dependent manner. This peptide had no effect on vesicle pool size, synaptic depression, or transmitter release kinetics. In contrast, a peptide fragment from domain C reduced the number of synaptic vesicles in the periphery of the active zone and increased the rate and extent of synaptic depression. This peptide also slowed the kinetics of neurotransmitter release without affecting the number of docked vesicles. The domain C peptide, as well as another peptide from domain E that is known to have identical effects on vesicle pool size and release kinetics, both specifically interfered with the binding of synapsins to actin but not with the binding of synapsins to synaptic vesicles. This suggests that both peptides interfere with release by preventing interactions of synapsins with actin. Thus, interactions of domains C and E with the actin cytoskeleton may allow synapsins to perform two roles in regulating release, whereas domain A has an actin-independent function that regulates transmitter release in a phosphorylation-sensitive manner.
Contribution of Pannexin 1 and Connexin 43 Hemichannels to Extracellular Calcium–Dependent Transport Dynamics in Human Blood-Brain Barrier Endothelial Cells

Dysregulation of blood-brain barrier (BBB) transport function is thought to exacerbate neuronal damage in acute ischemic stroke. The purpose of this study was to clarify the characteristics of pannexin (Px) and/or connexin (Cx) hemichannel(s)-mediated transport of organic anions and cations in human BBB endothelial cell line hCMEC/D3 and to identify inhibitors of hemichannel opening in hCMEC/D3 cells in the absence of extracellular Ca2+, a condition mimicking acute ischemic stroke. In the absence of extracellular Ca2+, the cells showed increased uptake and efflux transport of organic ionic fluorescent dyes. Classic hemichannel inhibitors markedly inhibited the enhanced uptake and efflux. Quantitative targeted absolute proteomics confirmed Px1 and Cx43 protein expression in plasma membrane of hCMEC/D3 cells. Knockdown of Px1 and Cx43 with the small interfering RNAs significantly inhibited the enhanced uptake and efflux of organic anionic and cationic fluorescent dyes. Clinically used cilnidipine and progesterone, which have neuroprotective effects in animal ischemia models, were identified as inhibitors of hemichannel opening. These findings suggest that altered transport dynamics at the human BBB in the absence of extracellular Ca2+ is at least partly attributable to opening of Px1 and Cx43 hemichannels. Therefore, we speculate that Px1 and Cx43 may be potential drug targets to ameliorate BBB transport dysregulation during acute ischemia.
Retail internationalization and retail failure: issues from the case of Marks and Spencer

Retail internationalization has attracted much attention in recent years as the scale and nature of the activity has changed. Most analysis of retail internationalization however is based on market entry and mainly successful businesses. Here, the internationalization strategy of Marks and Spencer over 30 years is examined. Its recent large-scale withdrawal from such activity is considered in the light of theories about internationalization and business failure. The complexity of market exit in retailing is emphasized. It is suggested that market exit and failure are important underresearched dimensions of retail internationalization. More detailed and careful work on market entry and withdrawal (failure? ) is needed to adequately conceptualize the subject area.
Culture shock

The ability to communicate well in a foreign culture is considered as a set of learnable social skills. The notion of culture shock is introduced to cover a broad range of psychological and social reactions to immersion in another culture, many of them detrimental to communication. Programs aimed at reducing the harmful effects of culture shock are examined in terms of the strategies adopted: (1) information giving, (2) cultural sensitization, (3) isomorphic attribution, (4) learning by doing, and (5) social skills training (SST). The latter, it is argued, is the most effective.
Multi-period mean-variance portfolio optimization with markov switching parameters

In this paper we deal with a multi-period mean-variance portfolio selection problem with the market parameters subject to Markov random regime switching. We analytically derive an optimal control policy for this mean-variance formulation in a closed form. Such a policy is obtained from a set of interconnected Riccati difference equations. Additionally, an explicit expression for the efficient frontier corresponding to this control law is identified and numerical examples are presented.
Spectrum of geometric phases in a driven impact oscillator

We study the geometric phases underlying the time evolution of the quantum wavefunction of a driven nonlinear oscillator which exhibits periodic, quasiperiodic as well as chaotic dynamics. In the asymptotic limit, irrespective of the classical dynamics, the geometric phases are found to increase linearly with time. Interestingly, the fingerprints of the classical motion are present in the bounded fluctuations that are superimposed on the monotonically growing phases, as well as in the difference between the geometric phases of two neighbouring quantum states.
Use of the mouse ear vesicant model to evaluate the effectiveness of ebselen as a countermeasure to the nitrogen mustard mechlorethamine

Previous studies in this and other laboratories have demonstrated that ebselen (EB‐1), an organoselenium compound, spares cells from mechlorethamine (HN2) toxicity in vitro. In the present study, the hypothesis that EB‐1 will reduce dermal toxicity of HN2 in vivo is put forward and found to have merit. Using the mouse ear vesicant model (MEVM), HN2, applied topically, showed a dose‐dependent effect upon ear swelling and thickness 24 h after treatment; whereas tissue injury consistent with vesication was observed at the higher test doses of HN2 (≥ 0.250 µmol per ear). To examine HN2 countermeasure activity using the MEVM, either hydrocortisone (HC), as a positive control, or EB‐1, the test countermeasure, was administered as three topical treatments 15 min, 4 and 8 h after HN2 exposure. Using this approach, both HC and EB‐1 were found to reduce tissue swelling associated with HN2 toxicity 24 h after exposure to the vesicant. Taken together, these data demonstrate for the first time the effectiveness of EB‐1 as a vesicant countermeasure in a relevant in vivo model. Copyright © 2013 John Wiley & Sons, Ltd.
Safety of teriflunomide for the management of relapsing-remitting multiple sclerosis

Introduction: Teriflunomide is a new oral disease-modifying drug (DMD), recently approved for the first-line treatment of relapsing multiple sclerosis (MS). Since MS is a chronic disease, which often necessitates long-term treatment, data not only on efficacy but also on long-term safety, including pregnancy-related issues, are very important. Areas covered: In this review article, we outline the key preclinical and clinical data on teriflunomide with a focus on its safety profile. We summarize adverse events observed in the Phase II and III clinical trials and the safety data from the long-term extension phases as well as the > 15-year post-marketing experience with the parent drug, leflunomide. We also consider the evidence regarding immune competence and potential fetal risks of the drug. Expert opinion: Teriflunomide has the advantage of a convenient once-daily oral administration scheme and a large body of evidence suggesting a manageable safety profile (clinical development program with > 6800 patient-years of exposure and post-marketing experience with leflunomide). Further post-marketing data, especially regarding pregnancy outcomes and risks of infections, will help to define the exact place of teriflunomide in the treatment of MS in the future, especially compared with the other oral DMDs.
Analytical Physical-Based Drain-Current Model of Amorphous InGaZnO TFTs Accounting for Both Non-Degenerate and Degenerate Conduction

In this letter, we propose a physical-based analytical drain current model for amorphous indium-gallium-zinc oxide thin-film transistors (a-IGZO TFTs). As a key feature, the model accounts for both the non-degenerate and the degenerate conduction regimes, including the contributions of trapped and free charges. These two conduction regimes as well as the trapped and free charges are essential to consistently describe a-IGZO TFTs. The model is compared with both exact numerical calculations and measurements. It is continuous, symmetric, simple, and accurate. The model enables to gain physical insight on the material and device properties, and it is a valuable tool for fast process optimization and circuit design.
Using question words or asking yes/no questions: Failure and success in clarifying the intentions of a boy with high‐functioning autism

This paper examined the processes that resulted in an adult failing to comprehend the intentions of a boy with high‐functioning autism. In a dyadic conversation between an adult and a young boy, the adult used questions to elicit clarification of intentions. The boy's responses were examined frame‐by‐frame using videotape microanalysis. Two causes of adult misunderstanding were formulaic use of words that confused the listener and directional gaze away from the listener. Questions that used interrogatives often failed to clarify the intention of the boy and yes/no questions appeared suitable to clarify his intention. However, success or failure to clarify an intention was not based solely on differences in the question format. Differences in question content may also have been relevant. Yes/no questions were mainly used to ask about specific actions. On the other hand, interrogative questions were used to handle cognitive or meta‐cognitive matters.
What Ties Return Volatilities to Price Valuations and Fundamentals?

Stock and Treasury bond comovement, volatilities, and their relations to their price valuations and fundamentals change stochastically over time, in both magnitude and direction. These stochastic changes are explained by a general equilibrium model in which agents learn about composite economic and inflation regimes. We estimate our model using both fundamentals and asset prices and find that inflation news signal either positive or negative future real economic growth depending on the times, thereby affecting the direction of stock-bond comovement. The learning dynamics generate strong nonlinearities between volatilities and price valuations. We find empirical support for numerous predictions of the model.
The intriguing metabolically healthy but obese phenotype: cardiovascular prognosis and role of fitness.

AIMS Current knowledge on the prognosis of metabolically healthy but obese phenotype is limited due to the exclusive use of the body mass index to define obesity and the lack of information on cardiorespiratory fitness. We aimed to test the following hypotheses: (i) metabolically healthy but obese individuals have a higher fitness level than their metabolically abnormal and obese peers; (ii) after accounting for fitness, metabolically healthy but obese phenotype is a benign condition, in terms of cardiovascular disease and mortality. METHODS AND RESULTS Fitness was assessed by a maximal exercise test on a treadmill and body fat per cent (BF%) by hydrostatic weighing or skinfolds (obesity = BF% ≥ 25 or ≥ 30%, men or women, respectively) in 43 265 adults (24.3% women). Metabolically healthy was considered if meeting 0 or 1 of the criteria for metabolic syndrome. Metabolically healthy but obese participants (46% of the obese subsample) had a better fitness than metabolically abnormal obese participants (P < 0.001). When adjusting for fitness and other confounders, metabolically healthy but obese individuals had lower risk (30-50%, estimated by hazard ratios) of all-cause mortality, non-fatal and fatal cardiovascular disease, and cancer mortality than their metabolically unhealthy obese peers; while no significant differences were observed between metabolically healthy but obese and metabolically healthy normal-fat participants. CONCLUSIONS (i) Higher fitness should be considered a characteristic of metabolically healthy but obese phenotype. (ii) Once fitness is accounted for, the metabolically healthy but obese phenotype is a benign condition, with a better prognosis for mortality and morbidity than metabolically abnormal obese individuals.
The effect of limb length discrepancy on health-related quality of life: is the ‘2 cm rule’ appropriate?

The primary goal of surgical equalization of lower extremity limb length discrepancy is to enhance the quality of life of patients by improving their function, gait, appearance, and pain secondary to compensation for the limb length discrepancy. While many surgeons use a cutoff point of 2 cm as an indication for intervention, little attention has been given to the effect of limb length discrepancy on quality of life. Therefore, the purpose of this study was to determine the relationship between limb length discrepancy and health-related quality of life and to assess whether the commonly accepted 2 cm cutoff serves to predict patients with and without quality of life perturbations. The Child Health Questionnaire was used to collect information from the parents of 76 children diagnosed with limb length discrepancy, and these data were compared with data from scanograms. Differences in quality of life became more apparent with increasing limb length discrepancy, especially among psychosocial health domains. As expected, patients with a limb length discrepancy of 2 cm or below generally fared better than patients with larger discrepancies, but no discrete cutoff could be identified within this group.
Downregulation of mu opioid receptor by RNA interference in the ventral tegmental area reduces ethanol consumption in mice

Pharmacological and genetic studies have implicated the mu opioid receptor (MOR) in the regulation of ethanol intake in animal models and humans. Non‐specific antagonists of opioid receptors have been shown to affect ethanol consumption when infused directly into the ventral tegmental area (VTA) of rats. However, administration of MOR‐selective antagonists into the VTA has yielded mixed results. We used RNA interference (RNAi) to specifically decrease levels of MOR messenger RNA in the VTA of mice and examined the effect on ethanol consumption in a two‐bottle choice paradigm. Mice were injected in the VTA with lentivirus expressing either a small hairpin RNA (shRNA) targeting MOR or a control shRNA. One week after virus injection, mice were examined for ethanol consumption in a two‐bottle choice experiment with increasing concentrations of ethanol over the course of 1 month. Expression of an shRNA targeting MOR in the VTA led to a significant reduction in ethanol consumption. These results strengthen the hypothesis that MOR in the VTA is one of the key brain substrates mediating alcohol consumption. The RNAi combined with lentiviral delivery can be used successfully in brain to effect a sustained reduction in expression of specific genes for behavioral analysis.
"Thermal" SiO radio line emission towards M-type AGB stars: A probe of circumstellar dust formation and dynamics

An extensive radiative transfer analysis of circumstellar SiO "thermal" radio line emission from a large sample of M-type AGB stars has been performed. The sample contains 18 irregulars of type Lb (IRV), 7 and 34 semiregulars of type SRa and SRb (SRV), respectively, and 12 Miras. New observational data, which contain spectra of several ground vibrational state SiO rotational lines, are presented. The detection rate was about 60% (44% for the IRVs, and 68% for the SRVs). SiO fractional abundances have been determined through radiative transfer modelling. The abundance distribution of the IRV/SRV sample has a median value of 6 × 10 −6 , and a minimum of 2 × 10 −6 and a maximum of 5 × 10 −5 . The high mass-loss rate Miras have a much lower median abundance, <10 −6 . The derived SiO abundances are in all cases well below the abundance expected from stellar atmosphere equilibrium chemistry, on average by a factor of ten. In addition, there is a trend of decreasing SiO abundance with increasing mass-loss rate. This is interpreted in terms of depletion of SiO molecules by the formation of silicate grains in the circumstellar envelopes, with an efficiency which is high already at low mass-loss rates and which increases with the mass-loss rate. The high mass-loss rate Miras appear to have a bimodal SiO abundance distribution, a low abundance group (on average 4 × 10 −7 ) and a high abundance group (on average 5 × 10 −6 ). The estimated SiO envelope sizes agree well with the estimated SiO photodissociation radii using an unshielded photodissociation rate of 2.5 × 10 −10 s −1 . The SiO and CO radio line profiles differ in shape. In general, the SiO line profiles are narrower than the CO line profiles, but they have low-intensity wings which cover the full velocity range of the CO line profile. This is interpreted as partly an effect of selfabsorption in the SiO lines, and partly (as has been done also by others) as due to the influence of gas acceleration in the region which produces a significant fraction of the SiO line emission. Finally, a number of sources which have peculiar CO line profiles are discussed from the point of view of their SiO line properties.
Human balancing of an inverted pendulum: is sway size controlled by ankle impedance?

1 Using the ankle musculature, subjects balanced a large inverted pendulum. The equilibrium of the pendulum is unstable and quasi‐regular sway was observed like that in quiet standing. Two main questions were addressed. Can subjects systematically change sway size in response to instruction and availability of visual feedback? If so, do subjects decrease sway size by increasing ankle impedance or by some alternative mechanism? 2 The position of the pendulum, the torque generated at each ankle and the soleus and tibialis anterior EMG were recorded. 3 Results showed that subjects could significantly reduce the mean sway size of the pendulum by giving full attention to that goal. With visual feedback sway size could be minimised significantly more than without visual feedback. In changing sway size, the frequency of the sways was not changed. 4 Results also revealed that ankle impedance and muscle co‐contraction were not significantly changed when the sway size was decreased. As the ankle impedance and sway frequency do not change when the sway size is decreased, this implies no change in ankle stiffness or viscosity. 5 Increasing ankle impedance, stiffness or viscosity are not the only methods by which sway size could be reduced. A reduction in torque noise or torque inaccuracy via a predictive process which provides active damping could reduce sway size without changing ankle impedance and is plausible given the data. Such a strategy involving motion recognition and generation of an accurate motor response may require higher levels of control than changing ankle impedance by altering reflex or feedforward gain.
Improving double-layer space trusses collapse behavior by strengthening compression layer and weakening tension layer members

Progressive collapse is a chain of local failures leading to the collapse of either the entire or a part of the structure. The double-layer space trusses are susceptible to progressive collapse due to sudden buckling of compression members. The method of strengthening the compression layer members along with weakening the tension layer members is an effective method for retrofitting the double-layer space truss behavior against progressive collapse. In this study, the method is applied on offset double-layer space truss models with different support conditions, members’ geometrical imperfections, height, and shapes, and the effectiveness in increasing the structure’s ductility and load-bearing capacity is demonstrated. The results show that the method converted the sudden collapse of the structures into a beneficial gradual (progressive) collapse. More specifically, for double-layer space trusses comprising members with similar geometrical imperfection, strengthening the compression layer chords along with weakening the tension layer chords within 30%–40% will significantly improve the ductility and load-bearing capacity. In addition, the results show that the method can decrease the weight of the structures and consequently provide more economical structures.
The role of accessibility in a universal web

"Universal design" is the process of creating products that are usable by people with the widest possible range of abilities, operating within the widest possible range of situations; whereas "accessibility" primarily refers to design for people with disabilities. While the focus of accessibility is disabilities, research and development in accessibility brings benefits to everyone, particularly users with situational limitations, including device limitations and environmental limitations. Awareness and understanding of the benefits of web accessibility to users without disabilities is growing in some areas with the rapid increase of web-enabled devices such as mobile phones, tablets, televisions, and more; with the increasing focus on the growing number of older web users; and with wider web reach in areas with high incidence of low literacy, low bandwidth, older technology, etc. Although there is significant overlap between designing for accessibility and designing for situational limitations, addressing one set of needs does not necessarily provide sufficient solutions for other needs. Keeping accessibility focused on disabilities encourages research and development on meeting the specific needs of people with disabilities. This communications paper explains the importance of "accessibility" continuing to focus on people with disabilities, while further integrating accessibility with web design, development, and research in other areas, including those covered under universal design and design for all. It also describes how the World Wide Web Consortium (W3C) and Web Accessibility Initiative (WAI) are working to address accessibility and related user needs throughout the technologies of the Web, and invites all interested parties to participate in research and development to further integrate accessibility for people with disabilities in ways that benefit all.