Miracle-dz/UniFAR-FTUs huggingface dataset:
Interleukin 2 Activates Brain Microvascular Endothelial Cells Resulting in Destabilization of Adherens Junctions*

The pleiotropic cytokine interleukin 2 (IL2) disrupts the blood-brain barrier and alters brain microcirculation, underlying vascular leak syndrome that complicates cancer immunotherapy with IL2. The microvascular effects of IL2 also play a role in the development of multiple sclerosis and other chronic neurological disorders. The mechanism of IL2-induced disruption of brain microcirculation has not been determined previously. We found that both human and murine brain microvascular endothelial cells express constituents of the IL2 receptor complex. Then we established that signaling through this receptor complex leads to activation of the transcription factor, nuclear factor κB, resulting in expression of proinflammatory interleukin 6 and monocyte chemoattractant protein 1. We also discovered that IL2 induces disruption of adherens junctions, concomitant with cytoskeletal reorganization, ultimately leading to increased endothelial cell permeability. IL2-induced phosphorylation of vascular endothelial cadherin (VE-cadherin), a constituent of adherens junctions, leads to dissociation of its stabilizing adaptor partners, p120-catenin and β-catenin. Increased phosphorylation of VE-cadherin was also accompanied by a reduction of Src homology 2 domain-containing protein-tyrosine phosphatase 2, known to maintain vascular barrier function. These results unravel the mechanism of deleterious effects induced by IL2 on brain microvascular endothelial cells and may inform the development of new measures to improve IL2 cancer immunotherapy, as well as treatments for autoimmune diseases affecting the central nervous system.
Prediction of Solvation Sites at the Interface of Src SH2 Domain Complexes Using Molecular Dynamics Simulations

Src Homology 2 (SH2) domains are ∼100 amino acid domains that mediate recognition of tyrosine‐phosphorylated sites by signalling proteins. Structures of SH2 domains with bound ligands indicate a potentially important role of water in influencing the binding thermodynamics. In this study, we used molecular dynamics (MD) simulation methods to evaluate solvation sites at the binding interface of the Src SH2 domain. We designed a software, WaRP (Water Residency Potential), to compute the positions of hydration sites from coordinates data of MD simulations and studied the impact of the computed positions on the prediction of the thermodynamics of Src SH2 domain binding to phosphorylated peptides using a method based on accessible surface area buried upon association. Two dually phosphorylated ligands and one monophosphorylated ligand were studied. We showed that the software predicted between 70% and 85% of the crystallographic water molecules depending on complexes. Comparison of the predicted water structures of both the bound and unbound binding partners led to a thorough evaluation of water behaviour during the binding reaction. We also showed that the predicted water structures of all ligand‐SH2 domain structures investigated may be used to derive the entropy change provided that the heat capacity change is known. This study is the first to examine the dynamics of the water structure around the SH2 domain binding interface and contributes to our understanding of binding thermodynamics in SH2 domains.
Communities of Practice (CoP): Implementation challenges of e-working

In this paper, results from action research on communities of practice (CoP) concerning e-working in Canada are discussed. It highlights the main conditions and challenges of e-working as well as their gender characteristics. It does this on the basis of seven case studies analysed in detail. Participant commitment and motivation in the project, dynamism and continuity of leadership, recognition of employee involvement and organizational support appear to be key elements in the success of this form of e-work. Some of these variables have also presented interesting differences in terms of gender and age. In this paper, we question the objective of using such devices as CoP for developing new forms of e-working. Beyond the formal objectives of innovation and knowledge sharing in CoP, could the enrolment of individuality and mobilization of identities be barriers for implementation of eworking in organizations?
[Study on the extraction process of polysaccharide from Lycium barbarum].

OBJECTIVE To choose the optimum extration process of polysaccharide from Lycium barbarum L. METHODS The optimal water extration process is selected with the orthogonal design. The yield and the content of polysaccharide were used to evaluate the factor levels. RESULTS The ideal extraction process is: the polysaccharide is extracted with water for 3 times,with solvent volume 8 times amount each time (10 times amount for the first time), extraction time 1 h each time and stired 10 min each hour. CONCLUSION The experimental results provide the basis for the water extration process of polysaccharide from Lycium barbarum L.
Grounding effect on transient earth voltage signal induced by partial discharge in metal box model

This paper deals with advancement of insulation diagnosis technology for high voltage equipment by partial discharge (PD) detection using transient earth voltage (TEV) detection method. Our previous study showed that detected TEV signal contains both high-frequency and low-frequency components around 500 MHz and 30 MHz, respectively. To further investigate the principle of detecting the low frequency components, this paper presents experiment and finite difference time domain analysis of TEV signal propagation. Results revealed that the signal intensity detected by TEV sensor with grounding is about five to six times as much as that without the grounding. Furthermore, when grounded, the low frequency components tend to be strongly detected. In other words, it is suggested that PD current including the low frequency component is induced on the surface of the metal box via the ground line, and this component greatly influences the TEV detection intensity.
Lower Extremity Peripheral Artery Disease and Quality of Life Among Older Individuals in the Community

Background Evidence regarding the association of lower extremity peripheral arterial disease with quality of life (QOL) is mainly from selected clinical populations or relatively small clinical cohorts. Thus, we investigated this association in community‐derived populations. Methods and Results Using data of 5115 participants aged 66 to 90 years from visit 5 (2011‐2013) of the Atherosclerosis Risk in Communities Study, we quantified the associations of ankle‐brachial index (ABI) with several QOL parameters, including 12‐item Short‐Form Health Survey (SF‐12), after accounting for potential confounders using linear and logistic regression models. Peripheral arterial disease defined by an ABI <0.90 (n=402), was independently associated with a low SF‐12 Physical Component Summary score (−3.26 [95% CI −5.60 to −0.92]), compared to the ABI reference 1.10 to 1.19 (n=1900) but not with the Mental Component Summary score (−0.07 [−2.21 to 2.06]). A low ABI was significantly associated with poorer status of all SF‐12 physical domains (physical functioning, role‐physical, bodily pain, and general health) but only vitality out of 4 mental domains. Similarly, low ABI values were more consistently associated with other physically related QOL parameters (leisure‐time exercise/activity/walking) than mentally related parameters (significant depressive symptoms and hopeless feeling). Lower physical QOL was observed even in individuals with borderline low ABI (0.90 to 0.99; n=426). Conclusions Low ABI (even borderline) was independently associated with poor QOL, especially for physical components, in community‐dwelling older adults. QOL is a critical element for older adults, and thus, further studies are warranted to assess whether peripheral arterial disease‐specific management can improve QOL in older populations.
Periocular routes for retinal drug delivery

Despite numerous scientific efforts, delivery of therapeutic amounts of a drug to the retina remains a challenge. This challenge is compounded if chronic therapy is desired. The inability or inefficiency of topical and systemic routes for retinal delivery of existing drugs is now widely accepted. Although the intravitreal route offers high local concentrations in the vitreous and, hence, retina, these advantages are offset by side effects, such as cataracts, endophthalmitis and retinal detachment, following repeated intravitreal injections, or intravitreal placement of sustained-release implants. As discussed in this review, periocular routes, including subconjunctival, sub-tenon, retrobulbar, peribulbar and posterior juxtascleral routes, potentially offer a more promising alternative for enhanced drug delivery to the retina compared with topical and systemic routes. Periocular routes exploit the permeability of sclera for retinal drug delivery, and they are particularly useful for administering sustained-release systems of potent drugs. This review discusses the various periocular routes with respect to their anatomical location, pharmacokinetics, safety and mechanisms of drug delivery. In the coming years, several innovations in absorption enhancement, drug delivery systems and drug administration devices are anticipated for improving retinal drug delivery via periocular routes.
Specific binding of the activator Mga to promoter sequences of the emm and scpA genes in the group A streptococcus

Transcription of the surface-associated virulence factors of the group A streptococcus (GAS) Streptococcus pyogenes, M protein (emm) and the C5a peptidase (scpA), is activated by a protein called Mga (formerly Mry or VirR). To determine whether Mga binds directly to the promoters of the genes it regulates, a protein resulting from the fusion of Mga to the C-terminal end of maltose-binding protein was purified from Escherichia coli. Specific binding to the promoter regions of the scpA and emm alleles of the type M6 GAS strain JRS4 was demonstrated by electrophoresis of the DNA-protein complex. Competition studies showed that the region upstream of scpA bound MBP-Mga with a slightly higher affinity than did the region upstream of emm. DNase I protection experiments identified a single 45-bp binding site immediately upstream of and overlapping the -35 region of both promoters. Sequences homologous to the protected regions were found in the promoters of many emm, scp, and emm-like genes from strains of different serotypes of GAS, and a consensus Mga binding site was deduced.
The proteome of the phytopathogenic fungus Sclerotinia sclerotiorum

In order to gain a more thorough understanding of the phytopathogenic fungus, Sclerotinia sclerotiorum, we initiated a proteome‐level study of the fungal mycelia and secretome. To our knowledge, this is the first comprehensive proteome‐level study of this fungus. Extracted mycelial proteins and secreted proteins collected from liquid culture were separated using 2‐DE and annotated following ESI‐q‐TOF MS/MS. Fifty‐two secreted proteins were reproducibly present in three biological replicates and 18 of them were identified by MS/MS while over 200 mycelial proteins were reproducibly present in three independent extractions and approximately half of them were identified. Many of the annotated secreted proteins were cell wall degrading enzymes that had been previously identified as pathogenicity or virulence factors of S. sclerotiorum; however, the contribution to the virulence of S. sclerotiorum of one of the identified proteins, alpha‐L‐arabinofuranosidase, is yet to be analyzed. Furthermore, previous comprehensive EST studies did not detect the presence of the alpha‐L‐arabinofuranosidase transcript, which demonstrates the merit of performing proteome‐level research. All of the secreted and mycelial proteins identified were functionally classified, and the known and proposed roles in disease initiation or progression for many of them are discussed.
Accounting for uncertainty in search operations using AUVs

Traditional coverage path planners create lawnmower-type paths in the operating area completely ignoring the uncertainty in the vehicle's position. However, in the presence of significant uncertainty in localization estimates, one can no longer guarantee that the vehicle will cover all the area according to plan. Aiming to bridge this gap, we present a coverage path planning technique for search operations which takes into account the vehicle's position and detection performance uncertainties and tries to minimize this uncertainty along the planned path. The objective is to plan paths, using a localization error model as input, to reduce as much uncertainty as possible and to minimize the extra path length (swath overlap) while satisfying mission feasibility constraints. We introduce an algorithm that calculates what will be the best moments for bringing the vehicle to surface to ensure a bounded position error. We also consider time and energy constraints that may influence the planned trajectory as path overlap is increased to account for uncertainty. Additionally we challenge the assumption frequently seen in coverage algorithms where two observations of the same target are considered independent.
Deterrence's Element of Sanction Certainty: Friendships, Vicarious Experiences, and Underage Alcohol Use

ABSTRACT Background: Underage drinking remains a pressing issue on college campuses across the United States. Though the most common form of addressing underage alcohol use on campuses is through deterrence-based policies, evidence suggests deterrence-based methods are ineffective and may produce negative outcomes. Objectives: Using dyadic data, the objective of this study is to use a friendship-informed perspective on deterrence theory to examine how an individual's and his/her friend's perceptions of sanction certainty relate to self-reported underage alcohol use. Results: Using multilevel mixed models which fall under the actor-partner interdependence modeling class, results demonstrate that respondents who perceive high levels of sanction certainty drink and heavily use alcohol more frequently than those who perceive low levels of sanction certainty. Additionally, those who have friends who perceive high levels of sanction certainty tend to drink at young ages significantly more frequently and in more dangerous patterns than those who have friends who perceive a low sanction certainty. The dyad members' levels of sanction certainty do not interact in relation to alcohol use. Conclusions: The significant relationships of the friends' sanction certainty support the notion of friendship-based deterrence. However, the consistent positive direction of all sanction certainty measures is the opposite of what deterrence theory hypothesizes. As such, it appears that deterrence is not only ineffective at stopping underage alcohol use on college campuses, but may be harmful due to increased rates of both drinking and high-risk drinking.
Self‐rated health and associated factors among older people living alone in Shanghai

Self‐rated health is a reliable and important health measure related to older people's mortality and quality of life. Few studies regarding the self‐rated health of older people living alone have been carried out in Mainland China. The present study aimed to investigate the self‐rated health of older people living alone in Shanghai and its associated factors.
Pancreatic Cell Lines: A Review

Pancreatic cancer has an extremely poor prognosis and lacks early diagnostic and therapeutic possibilities, mainly because of its silent course and explosive fatal outcome. The histogenesis of the disease and early biochemical and genetic alterations surrounding carcinogenesis are still controversial. In vitro studies offer a useful tool to study physiologic, pathophysiologic, differentiation, and transformation processes of cells and to understand some of these shortcomings. The extreme difficulties in isolating individual pancreatic cells and their purification by maintaining their native characteristics have limited research in this area. This review is intended to present and discuss the current availability of rodent and pancreatic cell lines, their differences as well as the difficulties, limitations, and characteristics of these cultured cells. Discussed are in vitro models; ductal, islet, and acinar cell culture; cell differentiation; cell transformation, including genetic and chromosomal alterations; as well as tumor cell markers. Also addressed are the advantages and problems associated with the cell culture in humans and rodents. Advancements in tissue culture technique and molecular biology offer steady progress in this important line of research. The improved methods not only promise the establishment of &bgr;-cell cultures for the treatment of diabetes, but also for studying sequential genetic alterations during pancreatic carcinogenesis and in understanding the tumor cell origin.
Unidirectional error detection, localization and correction for DRAMs: Application to on-line DRAM repair strategies

A novel family of codes for the detection, localization and correction of unidirectional errors for DRAMs in proposed. For DRAM memories, multi-bit soft and hard errors are a growing concern, as the cell sizes continue to decrease with aggressive scaling down. As a result, the classical error detection/correction codes become less efficient to deal with multiple errors in a single word [16]. Berger codes are effective in detecting 100% of the unidirectional errors, but introduce considerable delay and does not provide any error correction feature. In order to decrease the computing time of the code check bits and, at the same time, to provide the possibility to localize the segment(s) where single or multiple errors have occurred, a modification of the Berger code is proposed, called Carry Save K Berger code (CS-K Berger). Basically consists in using Carry Save representations of the partial additions of the word segments. The number of check bits increases as compared with Berger code and consequently the code redundancy overhead increases but the delay in computing the check bits and the corresponding checking is drastically reduced. In addition, some patterns of unidirectional errors become correctable. The proposed CS-K Berger codes for different values of K are analyzed for different word lengths. The hardware required for code generation and verification is discussed as well, as the possibility of using this code for word segment replacement in online applications of DRAMs.
Multiple Laser System for High-Resolution Thomson Scattering Diagnostics on the EAST Tokamak

A multiple laser system for high-resolution Thomson scattering diagnostics has been developed in ASIPP. The system includes laser controller, high-energy lasers, transfer optics, focusing lens, and beam alignment system. Each Nd:YAG laser can be fired for measuring the electron temperature and density profiles periodically at 10 Hz, and consequently, four lasers can be fired alternately for an average measurement frequency of 40 Hz. In order to measure transient events, they will be fired in rapid succession, and produce a burst of pulses. After about one month trial running on the superconducting EAST tokamak, the system was proven to be capable of working well with improved time resolution. The system setup and analysis are described in detail, as well as the measurement capability, spatial and temporal resolutions ~7 mm and tens kilohertz, respectively. So as to monitor and adjust the laser beam, two beam position sensitive detectors are installed in the 40-m beam path. Finally, the experimental results are presented.
The Incremental Value of RT Three‐Dimensional TEE in the Evaluation of Prosthetic Mitral Valve Ring Thrombosis Complicated with Thromboembolism

Purpose: Although nonobstructive prosthetic valve thrombosis (PVT) does not develop hemodynamic compromise, it carries potential risk for thromboembolism. Real time three‐dimensional transesophageal echocardiography (RT‐3DTEE), has emerged as a complementary tool in depicting “en face” views of prosthesis compared with two‐dimensional transesophageal echocardiography (2DTEE). We aimed to evaluate the utility of RT‐3DTEE in assessment of mitral ring‐located thrombosis. Method: We present 3 cases of mechanical mitral valve thrombosis complicated by thromboembolism, who were all examined and followed‐up by 2D transthoracic echocardiography (TTE), 2DTEE, and RT‐3DTEE. Result: The consequencies of thromboembolism in the patients were coronary embolism, transient ischemic attack, and ischemic stroke, respectively. They were all inadequately anticoagulated at the time of admission. 2DTTE and TEE examination was unsatisfactory; RT‐3DTEE depicted nonobstructive mitral ring thrombosis in each of the patients. The patients were followed up under effective anticoagulation and antiplatelet therapy. RT‐3DTEE was able to demonstrate the evolution of thrombus size in each of the patients. Conclusion: Nonobstructive ring‐located PVT which poses risk for thromboembolism, may be diagnosed with certainty and imaged with clarity utilizing RT‐3DTEE.
When Playing the Woman Card is Playing Trump: Assessing the Efficacy of Framing Campaigns as Historic

ABSTRACT Candidate gender has become a major theme in the 2016 presidential campaign. Secretary Clinton appears to be emphasizing her gender to a greater degree than she did in 2008, even invoking gender in primary debates as something that separates her from the political establishment. Her opponent in the general election, Donald Trump, claimed that Clinton was playing the “woman card” and that Clinton has little to offer as a candidate beyond her sex. However, scholars have little sense of the effectiveness of playing the woman card by emphasizing the historic first associated with a candidacy, a strategy with inherent risks. This project examines the effect of playing the woman card by emphasizing the historic nature of a female executive candidate, and demonstrates that playing the woman card may actually benefit female candidates among certain subsets of voters. Playing the gender card appeals to voters traditionally underrepresented in politics and to weak Democrats and independents. These findings suggest that playing the gender card may benefit female candidates, especially Democrats, in elections.
Serum prealbumin as an effective prognostic indicator for determining clinical status and prognosis in patients with hemorrhagic stroke

Serum prealbumin is a recognized marker of malnutrition, but its prognostic role in patients with hemorrhagic stroke remains unclear. In this study, we retrospectively reviewed the records of 105 patients with hemorrhagic stroke admitted to Renmin Hospital of Wuhan University, China, from January to December 2015. We collected demographic and radiological data, and recorded serum prealbumin levels at admission and on days 1, 3, 6, 9, and 14–21. The existence of infections and gastrointestinal hemorrhage, and clinical condition at discharge were also recorded. Serum prealbumin levels during hospitalization were significantly lower in patients with infections compared with those without infections, and also significantly lower in patients with gastrointestinal hemorrhage compared with those without. Serum prealbumin levels at discharge were significantly higher in patients with good recovery than in those with poor recovery. We conclude that regular serum prealbumin measurements in patients with hemorrhagic stroke may be a useful indicator for determining clinical status and prognosis, which may therefore help to guide clinical decision-making.