Miracle-dz/UniFAR-FTUs huggingface dataset:
The Neuroactive Steroid Pregnenolone Sulfate Stimulates Trafficking of Functional N-Methyl D-Aspartate Receptors to the Cell Surface via a Noncanonical, G Protein, and Ca2+-Dependent Mechanism

N-methyl D-aspartate (NMDA) receptors (NMDARs) mediate fast excitatory synaptic transmission and play a critical role in synaptic plasticity associated with learning and memory. NMDAR hypoactivity has been implicated in the pathophysiology of schizophrenia, and clinical studies have revealed reduced negative symptoms of schizophrenia with a dose of pregnenolone that elevates serum levels of the neuroactive steroid pregnenolone sulfate (PregS). This report describes a novel process of delayed-onset potentiation whereby PregS approximately doubles the cell’s response to NMDA via a mechanism that is pharmacologically and kinetically distinct from rapid positive allosteric modulation by PregS. The number of functional cell-surface NMDARs in cortical neurons increases 60–100% within 10 minutes of exposure to PregS, as shown by surface biotinylation and affinity purification. Delayed-onset potentiation is reversible and selective for expressed receptors containing the NMDAR subunit subtype 2A (NR2A) or NR2B, but not the NR2C or NR2D, subunits. Moreover, substitution of NR2B J/K helices and M4 domain with the corresponding region of NR2D ablates rapid allosteric potentiation of the NMDA response by PregS but not delayed-onset potentiation. This demonstrates that the initial phase of rapid positive allosteric modulation is not a first step in NMDAR upregulation. Delayed-onset potentiation by PregS occurs via a noncanonical, pertussis toxin–sensitive, G protein–coupled, and Ca2+-dependent mechanism that is independent of NMDAR ion channel activation. Further investigation into the sequelae for PregS-stimulated trafficking of NMDARs to the neuronal cell surface may uncover a new target for the pharmacological treatment of disorders in which NMDAR hypofunction has been implicated.
Towards open science: the myExperiment approach

By making research content more reusable, and providing a social infrastructure that facilitates sharing, the human aspects of the scholarly knowledge cycle may be accelerated and ‘time‐to‐discovery’ reduced. We propose that the key to this is the sharing of methods and processes. We present myExperiment, a social web site for discovering, sharing and curating Scientific Workflows and experiment plans, and describe how myExperiment facilitates the management and sharing of research workflows, supports a social model for content curation tailored to the researcher and community, and supports Open Science by exposing content and functionality to the users' tools and applications. Based on this, we introduce the notion of the Research Object—the work objects that are built, transformed and published in the course of scientific experiments—and suggest that by encapsulating methods with results we can achieve research that is more reusable and repeatable and hence rapid and robust. Copyright © 2010 John Wiley & Sons, Ltd.
Drying stress and damage processes in human stratum corneum

The drying stresses that develop in stratum corneum (SC) are crucial for its mechanical and biophysical function, its cosmetic feel and appearance, and play a central role in processes of dry skin damage. However, quantitative methods to characterize these stresses are lacking and little understanding exists regarding the effects of drying environment, chemical exposures and moisturizing treatments. We describe the application of a substrate curvature technique adapted for biological tissue to accurately characterize SC drying stresses as a function of time following environmental pre‐conditioning and chemical treatment in a range of drying environments. SC stresses were observed to increase to stress levels of up to ∼ 3 MPa over periods of 8 h depending on pretreatment and drying environment. A unique relationship between the SC stress and water in the drying environment was established. The effect of glycerol on lowering SC stresses and damaging surfactants on elevating SC stresses were quantified. Extensions of the method to continuous monitoring of SC stresses in response to changes in environmental moisture content and temperature are reported. Finally, a biomechanics framework to account for the SC drying stress as a mechanical driving force for dry skin damage is presented.
Project Characteristics, Incentives and Team Production

We develop a model to show how agency conflicts, free-rider effects, and monitoring costs interact to affect optimal team size and workers’ incentive contracts. Team size increases with project risk, decreases with profitability, and decreases with monitoring costs as a proportion of output. Our predictions are consistent with empirical evidence that firm-specific risk has increased over time, average corporate earnings have declined, and firms’ organizational structures have also flattened. The predicted effects of monitoring costs on team size are supported by evidence that improvements in information technology likely to lower monitoring costs lead to larger teams. Further, firms with relatively more intangible assets, where monitoring costs are likely to be higher, are smaller. Optimal incentive intensities decrease with risk and increase with profitability. The endogenous determination of team size accentuates the positive effects of a decline in risk and an increase in profitability on incentives. This paper was accepted by Gustavo Manso, finance.
Reputation and Financial Intermediation: An Empirical Investigation of the Impact of IPO Mispricing on Underwriter Market Value

Abstract This paper investigates the empirical significance of underwriter reputation capital by analyzing the impact of initial returns of IPOs on lead-underwriter market value. Consistent with reputation costs, overpriced offerings are associated with a decrease in lead-underwriter market value significantly in excess of estimated direct costs. For moderately underpriced offerings, however, underwriter wealth effects are positive. Consistent with higher reputation costs, these wealth effects are insignificant when the IPO underpricing is more extreme. In jointly managed offerings, it is lead-underwriters that are primarily affected by IPO initial performance. Journal of Economic Literature Classification Numbers: G24, G32.
An updated computational model of rabbit sinoatrial action potential to investigate the mechanisms of heart rate modulation

• Computational models of the electrical activity of sinoatrial cells (SANCs) have been proposed to gain a deeper understanding of the cellular basis of cardiac pacemaking. • However, they fail to reproduce a number of experimental data, among which are effects measured after modifications of the ‘funny’ (If) current. • We developed a novel SANC mathematical model by updating the description of membrane currents and intracellular mechanisms on the basis of experimental acquisitions, in an attempt to reproduce pacemaker activity and its physiological and pharmacological modulation. • Our model describes satisfactorily experimental data on pacemaking regulation due to neural modulation, If block and inhibition of the intracellular Ca2+ handling. • Computer simulation results suggest that a detailed description of the intracellular Ca2+ fluxes is fully compatible with the observation that If is a major component of pacemaking and heart rate modulation.
Analysis of school failure based on Portuguese micro data

In this article we investigate the main causes of school failure in the primary public schools in Lisbon. Poisson count-data models are used to analyse the relationship between the number of failures and a wide set of explanatory variables. However heterogeneity due to unobserved differences in intellectual abilities of the students is of primary concern. Neglecting it causes biased estimates and therefore a proper method is required to accommodate it. In this article we suggest a finite mixture of Poisson's. We found that variables associated to gender, ethnicity, family dimension, parent's level of education and income poverty are the most important observable determinants of school failure.
The balanced scorecard

Gives a comparative analysis about the differences between the balanced scorecard and other, more traditional, financial accounting measures, such as ROI and EPS that may give misleading signals. Advocates that the balanced scorecard's advantages — such as giving managers the ability to view performance simultaneously in several areas. Itemizes the four main perspectives as: the customer; the internal; innovation and learning; and financial. Cautions that the four goals and measures must be reflective of the company's specific view of the world and what its own critical success factors must be, though even with these excellent balanced scorecard measures a winning strategy is not guaranteed.
Liposomal bupivacaine versus interscalene nerve block for pain control after shoulder arthroplasty

Background: Postoperative pain control after total shoulder arthroplasty (TSA) can be challenging. Liposomal bupivacaine and interscalene nerve block are 2 common pain control protocol for TSA patients. However, whether liposomal bupivacaine was superior than interscalene nerve block was unknown. This meta-analysis aimed to illustrate the efficacy liposomal bupivacaine versus interscalene nerve block for pain control in patients undergoing TSA. Methods: In May 2017, a systematic computer-based search was conducted in PubMed, EMBASE, Web of Science, Cochrane Database of Systematic Reviews, and Google database. Data on patients prepared for TSA in studies that compared liposomal bupivacaine versus interscalene nerve block were retrieved. The endpoints were the visual analogue scale (VAS) at 4 hours, 8 hours, 12 hours, 24 hours, and 2 weeks, total morphine consumption at 24 hours, and the length of hospital stay. Software of Stata 12.0 was used for pooling the final outcomes. Results: Five clinical studies with 573 patients (liposomal bupivacaine group = 239, interscalene nerve block group = 334) were ultimately included in the meta-analysis. There was no significant difference between the VAS at 4 hours, 8 hours, and 2 weeks between liposomal bupivacaine group and interscalene nerve block group (P > .05). Compared with interscalene nerve block group, liposomal bupivacaine was associated with a reduction of VAS score at 12 hours, 24 hours by appropriately 3.31 points and 6.42 points respectively on a 100-point VAS. Furthermore, liposomal bupivacaine was associated with a significantly reduction of the length of hospital stay by appropriately by 0.16 days compared with interscalene nerve block group. Conclusion: Current meta-analysis indicates that compared with interscalene nerve block, liposomal bupivacaine had comparative effectiveness on reducing both pain scores and the length of hospital stay. However, studies with more patients and better-designed methods are needed to establish the optimal regimen and the safety of liposomal bupivacaine in TSA patients.
Defying Gravity: Costly Signaling to Mislead or to Inform?

While it is generally maintained that earnings management can occur to inform as well as to mislead, evidence that earnings management informs has been scarce, and evidence that credibility increases with signal costliness inexistent. We provide evidence that firms use discretion over financial reporting and real activities to report higher earnings on lower sales from continuing operations. Although these firms defy gravity artificially, we show that the upwards earnings management informs rather than misleads investors. We find that firms that defy gravity (1) report higher future earnings and cash flows, (2) earn higher one-year-ahead abnormal returns, (3) have a positive market reaction to the defying gravity earnings announcement, and (4) their CEOs are more likely to be net buyers in the year preceding the defying gravity event. We also show that the upwards earnings management signal is more credible when it is more costly to achieve: Defying gravity firms perform better when they bear the opportunity loss of not taking a big bath in times of crisis — years where poorer performance can be blamed on economy-wide shocks, and when they have fewer degrees of freedom to report higher earnings.
Multiplex PCR for molecular screening of Borrelia burgdorferi sensu lato, Anaplasma spp. and Babesia spp.

INTRODUCTION Ticks transmit a great variety of pathogenic microorganisms to humans and animals. The detection of tick-borne pathogens (TBP) is mainly by molecular techniques based on polymerase chain reactions (PCR). OBJECTIVE To design and evaluate a multiplex PCR for the molecular screening of zoonotic TBP for exploratory studies. MATERIAL AND METHODS Control DNA from reference strains, DNA from experimentally-infected biological specimens, and from Rhipicephalus sanguineus ticks collected from domestic and homeless dogs were used. A multiplex PCR assay to detect the presence of Borrelia burgdorferi sensu lato, Anaplasma spp. and Babesia spp. was designed and optimized using primers previously reported for B. burgdorferi sensu lato and Anaplasma spp. , while for Babesia spp. they were designed in silico. The multiplex PCR was evaluated on the DNA from biological samples. RESULTS A new set of specific primers for Babesia spp. was designed. Adjustment of the master mix reactive concentrations and amplification conditions for the multiplex PCR allowed the successful amplification of the specific amplicons for each microbial group from the control DNA and experimentally-infected biological specimens. The efficiency of the multiplex PCR amplifying three DNA targets was confirmed. Individual and co-infection of Anaplasma spp. and Babesia spp. were detected in the R. sanguineus ticks from dogs. CONCLUSIONS A multiplex PCR assay for the screening of three TBP is available. By using it, B. burgdorferi sensu lato, Anaplasma spp. and Babesia spp. can be detected accurately in one PCR reaction.
Tactile motion activates the human middle temporal/V5 (MT/V5) complex

The human middle temporal/V5 complex (hMT/V5) plays a central role in the perception of visual motion. This region is considered a unimodal visual area with little direct involvement of other sensory modalities. The current study uses H215O PET to test whether tactile motion influences the activity of hMT/V5. Regional cerebral blood flow (rCBF) within hMT/V5 was estimated in eight subjects in separate tactile motion and visual motion conditions, each contrasted with a resting, control. The tactile motion condition involved a brush stroked proximal‐to‐distal along the volar forearm and palm, while the subject attended to the stimulus with closed eyes. The visual motion condition consisted of low contrast, grey‐scale rings radiating at 15°/s from a central point, upon which the subject was instructed to fixate. The location of hMT/V5 was defined for each subject separately as the local maximum of rCBF change during the visual motion condition (vs. control). The average change in rCBF within spherical regions of interest at each peak revealed significant bilateral activation of hMT/V5 in the tactile motion condition contrasted with a second, independent set of control scans. Additionally, a single subject received a sufficient number of scans to perform a pixel‐wise, within‐subject analysis. His functional images were coregistered to his anatomical MRI. In this subject, tactile motion produced a significant increase in rCBF that directly overlapped a region activated by visual motion at the posterior continuance of the inferior temporal sulcus, consistent with the known location of hMT/V5. These results suggest involvement of the hMT/V5 complex in tactile motion processing.
MM-wave cylindrical dielectric lens antenna for full azimuth scanning coverage

This paper proposed a 360° azimuth scanning cylindrical dielectric lens antenna at mm-waves. The antenna system consists of Rexolite (∊r=2.54) cylindrical lens, tapered slot antenna (TSA) array and circular parallel conductor plates. A combined ray-optics method and CST-MWS are used to analyze and optimize this cylindrical dielectric lens antenna at 30GHz. A total of 60 TSAs are used to launch 60 beams, each with 3dB beamwidth of 6° leading to a 360° scan coverage.
The properties of mesoporous silica nanoparticles functionalized with different PEG-chain length via the disulfide bond linker and drug release in glutathione medium

Abstract In this paper, a novel drug-loaded material (MSNs-SS-PEG) was obtained by grafting the thiol-linked methoxy polyethylene glycol (MeOPEG-SH) onto the thiol-functionalized mesoporous silica nanoparticles (MSNs-SH) via the disulfide bond linker. In our designed experiment, three different chain lengths of PEG (PEG1000, PEG5000, and PEG1000-PEG5000) were used. The silica materials were characterized by Fourier transform infrared spectroscopy (FT-IR), dynamic light scattering, field emission scanning electron microscopy, transmission electron microscopy, nitrogen adsorption–desorption measurements, and X-ray diffraction. The morphology of the MSNs-SS-PEG was spherical with an average diameter of about 150 nm. Due to the covalent modification of hydrophilic MeOPEG, the MSNs-SS-PEG was coated by a thin polymer shell, showing stable and inerratic MCM-41 type mesoporous structure as well as high specific surface areas and large pore volumes. Moreover, the releases of doxorubicin hydrochloride (DOX) from these materials at 10 mM of glutathione were investigated. The PEG functionalization could effectively cap drugs in the mesoporous channels. The release of DOX from the MSNs-SS-PEGn revealed redox-responsive characteristic. The obtained results showed that the MSNs-SS-PEG might be promising drug delivery carrier materials, which could play an important role in the development of drug delivery.
On the Deployment of Healthcare Applications over Fog Computing Infrastructure

Fog computing is considered as the most promising enhancement of the traditional cloud computing paradigm in order to handle potential issues introduced by the emerging Interned of Things (IoT) framework at the network edge. The heterogeneous nature, the extensive distribution and the hefty number of deployed IoT nodes will disrupt existing functional models, creating confusion. However, IoT will facilitate the rise of new applications, with automated healthcare monitoring platforms being amongst them. This paper presents the pillars of design for such applications, along with the evaluation of a working prototype that collects ECG traces from a tailor-made device and utilizes the patient's smartphone as a Fog gateway for securely sharing them to other authorized entities. This prototype will allow patients to share information to their physicians, monitor their health status independently and notify the authorities rapidly in emergency situations. Historical data will also be available for further analysis, towards identifying patterns that may improve medical diagnoses in the foreseeable future.
An Optimal Product Mix for Hedging Longevity Risk in Life Insurance Companies: The Immunization Theory Approach

This article investigates the natural hedging strategy to deal with longevity risks for life insurance companies. We propose an immunization model that incorporates a stochastic mortality dynamic to calculate the optimal life insurance–annuity product mix ratio to hedge against longevity risks. We model the dynamic of the changes in future mortality using the well-known Lee–Carter model and discuss the model risk issue by comparing the results between the Lee–Carter and Cairns–Blake–Dowd models. On the basis of the mortality experience and insurance products in the United States, we demonstrate that the proposed model can lead to an optimal product mix and effectively reduce longevity risks for life insurance companies.
Secure group key distribution in constrained environments with IKEv2

Group communication is an important means for communication in todays interconnected world, where multiple endpoints need exchange of data in the most efficient and concurrently secure way. The resulting complexity represents a substantial challenge, especially in the constrained environments introduced through the Internet-of-Things and sensor networks. An in-depth analysis of existing work shows that the problem of secure key distribution within groups requires novel approaches. Instead of designing yet another (group) key distribution scheme, this paper offers a minimal client based on the well-known Group Internet-Key-Exchange protocol G-IKEv2. The evaluation of this first open client with real-life observations and corresponding measurements proves its applicability for secure group key distribution and will serve as the basis for implementing group and identity management.
Validation of the Flexible Electrogoniometer for Measuring Thoracic Kyphosis

Study Design. Three experiments to validate the use of the flexible electrogoniometer (FEG) as a tool to measure thoracic kyphosis. Objective. To investigate the accuracy, test-retest reliability, and concurrent validity of the FEG as applied to the thoracic spine. Summary of Background Data. Thoracic kyphosis is commonly measured by the Cobb angle from lateral radiograph. Other less-invasive tools have been developed, but all yield only static measurements or are restricted to the laboratory. The FEG, which can record joint angles over time outside the laboratory, has been used to measure other joints but has not yet been validated for measurement of the thoracic spine. Methods. First, the FEG was bench-tested against a plurimeter for accuracy. Second, 12 subjects performed 7 functional activities 1 week apart to assess the test-retest reliability. Finally, to examine concurrent validity, 12 subjects underwent radiography in “upright” and “slumped” standing with the FEG attached to the skin over their thoracic spine. Three Cobb angles, which corresponded with the inner, mid, and outer margins, respectively, of the overlying FEG end blocks were compared with the FEG angles. Results. The correlation between the FEG and the plurimeter was excellent (r > 0.99, P < 0.0001), although some accuracy was lost at extremes of range. The mean correlation between the first and second measurements was very strong (intraclass correlation coefficient2,1 0.92, P < 0.0001; range, 0.89–0.95). The mid-Cobb angle showed the least absolute angular difference from, and was highly correlated with, the FEG angle (r = 0.81, P < 0.01). Conclusion. The FEG demonstrated excellent accuracy and test-retest reliability and correlated very well with the Cobb angle. The FEG measurement seemed to correspond most closely with the Cobb angle measured between the middle of the FEG end blocks.
Trends in Australian rehabilitation: Reviving its humanitarian core

Purpose. This paper discusses how vocational rehabilitation (VR) in Australia has been captured by economic concerns, leading to its failure to deliver promised outcomes. Both public and private sector VR in Australia have undergone significant changes over the last two decades. The demise of non-profit and socially-based rehabilitation in favour of fixed funding models (e.g., managed care or case-base funding), coupled with the growing emphasis on cost containment has placed many VR providers in an unfamiliar environment dominated by bureaucratic, legal, economic and political imperatives. Although it was expected that VR would address rising injury costs, its inability to do so has jeopardized its existence. Conclusion. Ironically, it is economic imperatives that are now prompting the re-invention of old concepts that appear to offer the same cost-containment possibilities rehabilitation offered in the 1990s. The most significant among these trends are self-management, coordinated care, community rehabilitation and welfare-to-work incentives. Perhaps the major challenge now, however, is to define a new dimension for rehabilitation and capture the essence of these trends to ensure that they contribute to a possible revival of a model of VR that focuses on the client's broad social context and responds to client-centred goals.