Miracle-dz/UniFAR-FTUs huggingface dataset:
Inward Rectification by Polyamines in Mouse Kir2.1 Channels: Synergy between Blocking Components

We recently characterized two distinct mechanisms by which the polyamine spermine blocks Kir2.1 channels: (1) by reduction of negative surface charges in the cytoplasmicpore, thereby reducing single‐channel conductance, and (2) by direct open channel transmembrane pore block. The extent to which the surface charge reduction component is mediated by passive surface charge screening versus binding of polyamines to these charges, as well as the extent to which the surface charge reduction and pore block mechanisms are synergistic, versus simply additive, was not established. To address these issues, macroscopic currents were recorded from inside‐out giant patches from Xenopus oocytes and from single‐channel currents from COS7 cells expressing wild‐type and mutant Kir2.1 channels, during exposure to polyamines of varying length and charge. The surface charge reduction component was decreased when polyamine charge (at constant length) was decreased from 4 (spermine) to 2 (diamine 10, DA10). Moreover, the surface charge reduction component of block involved more than passive surface charge screening and required binding of polyamines to the cytoplasmic pore, since it was eliminated when polyamine length was shortened below six alkyl groups. Loss of surface charge reduction also dramatically affected open channel pore block. The latter consisted of two subcomponents with fast and slow kinetics, respectively. The slow subcomponent decreased as blocker length decreased (DA10, DA8 and DA6), whereas the fast subcomponent was sensitive to blocker charge (spermine vs. DA10). Neutralization of E224 and E299, which eliminated the surface charge reduction component of block, also eliminated the fast subcomponent of pore block. Neutralization of D172 had no effect on the surface charge reduction component, but weakened both of the subcomponents of pore block. These findings can be accounted for by a model in which the negative charges at E224, E299 and D172 act in a concerted manner to coordinate the surface charge reduction and open channel components of polyamine block. In this model, the binding of polyamines to surface charges E224 and E299 pre‐positions them in the cytoplasmic pore in a manner that directly facilitates their entry and exit from a transmembrane pore‐occluding site involving D172. A molecular model using the recently reported 1.8 Å resolution structure of the inward‐rectifier cytoplasmic pore, adapted to Kir2.1, is consistent with longer polyamines binding at their positively charged ends to the E224 and E299 positions in the same subunit, potentially accommodating four polyamine molecules per channel.
Prediction of patient‐specific risk of early preterm delivery using maternal history and sonographic measurement of cervical length: a population‐based prospective study

To develop a model for calculating the patient‐specific risk of spontaneous early preterm delivery by combining maternal factors and the transvaginal sonographic measurement of cervical length at 22 + 0 to 24 + 6 weeks, and to compare the detection rate of this method to that achieved from screening by cervical length or maternal characteristics alone.
Sensing Urban with Wi-Fi and Satellite: Functional Region Discovery across Cities

Modern urbanization is featured with rapid development and collective intelligence, for which how to effectively utilize multimodal urban sensory data is a hot topic. In this paper, we focus on automatically recognizing functional urban regions by fusing two important sensory media, including collective behavioral information reflected by Wi-Fi accessing records collected from large populations as well as high-resolution satellite urban imaging. An aggregation algorithm is firstly applied to identify candidate functional regions characterized by geographical clusters of Wi-Fi access points. Semantic behavioral and visual features are extracted from two heterogeneous sensory data respectively, from which multi-functional properties are recognized by combining decision trees with boosting method. Finally, a transfer learning algorithm derived from AdaBoost is proposed to adapt the trained model to other cities with different feature distribution. Experimental results on real data sets demonstrate the efficacy of the proposed model in terms of recognition accuracy.
Systematic review and meta-analysis of exercise tolerance and physical functioning in dialysis patients treated with erythropoiesis-stimulating agents.

BACKGROUND The role of erythropoiesis-stimulating agents (ESAs) in treating the anemia of chronic kidney disease has been reevaluated in view of recent studies suggesting that the use of these agents may be associated with increased morbidity and mortality. This potential increased risk needs to be weighed against the potential benefit of ESAs in improving various aspects of health-related quality of life, in particular, exercise tolerance and physical functioning. STUDY DESIGN A systematic review and meta-analysis of exercise tolerance and physical functioning. SETTING & PARTICIPANTS Adults on maintenance dialysis therapy. SELECTION CRITERIA FOR STUDIES Outcomes measured before and after ESA treatment were required. Studies of physical function were required to include at least 25 participants. INTERVENTION Treatment with any ESA. OUTCOMES Exercise tolerance measured using VO(2peak) (oxygen consumption per minute at the peak workload during the test), duration of exercise, or 6-minute walk distance or physical functioning assessed using > or = 1 patient- or clinician-reported outcome measure that included a physical function domain. RESULTS 28 articles met criteria for inclusion for evaluation of exercise tolerance, and 14 articles, for physical function. Meta-analysis showed a 23.8% increase in VO(2peak) from before to after erythropoietin therapy initiation (15 studies) and a nonsignificant 8.2% increase comparing a higher with a lower hemoglobin target (3 studies). For physical functioning, 4 studies met criteria for inclusion in the meta-analysis: there was a 10.5% increase in Karnofsky score from before to after erythropoietin therapy initiation. LIMITATIONS Many studies of exercise tolerance did not include control groups. A wide variety of instruments was used to assess physical function. CONCLUSIONS Partial correction of anemia through ESA treatment has a consistent and positive impact on VO(2peak). ESA treatment improves patient- and clinician-assessed physical functioning.
Investor herding behaviour in globally listed shipping stocks

ABSTRACT This study undertakes one of the first empirical attempts to investigate and contribute a set of innovative findings to investor herding behavior and herding spillover effects in globally listed shipping company stock returns. Distinguishing between OECD and Non-OECD markets, herding behavior is tested on a diversified set of shipping companies traded in international equity markets, over different business cycle phases, financial crises, and external shocks. A set of dynamic models, well established in the relevant behavioral finance literature, is implemented. Empirical evidence indicates investor herding behavior in shipping stock returns and herding spillover effects between different shipping sectors, albeit not robust in all cases. These challenging findings can have a material impact on efficient investment and financing decisions of shipping market players.
Assessing the Current and Future State of Arctic Governance: A Study of Academic Approaches to Arctic Law Development

In recent years, climate change’s impact on the Arctic ecosystem and the increasing interests in developing the Arctic natural resources and shipping routes have raised a question of the future of Arctic governance. Although the concept of governance is rather new, several scholars (Exner-Pirot 2012; Koivurova 2008) point out that the questions of Arctic governance had been discussed already during the Cold War period. As an example, the authors talk about the 1973 “Agreement on the Conservation of Polar Bears” and the 1987 Mikhail Gorbachev’s Murmansk speech. Drawing on these cases, one could suggest that the elaboration of Arctic governance has evolved as a topdown process. However, several authors (Pelaudeix 2015) mention that quite a few academic work1 on Arctic governance were already published in the 1980s. In this view, the vision of
Assessing the effect of an antimicrobial wound dressing on biofilms

To date the effect of silver‐containing wound dressings on biofilms, known to be present in chronic wounds, has not been determined or documented. In this current study, we aimed to determine the antimicrobial effect of a silver‐containing dressing on biofilms grown in a chambered slide model. Before the addition of a wound dressing onto a 24‐hour biofilm, composed of either Pseudomonas aeruginosa, Enterobacter cloacae, Staphylococcus aureus, or a mixed bacterial community, a fluorescent dye was applied. This enabled the viability of sessile bacteria to be monitored in real‐time, using a rapid form of confocal laser scanning microscopy over a contact time period of 48 hours. By analyzing all the three‐dimensional data generated from the confocal time‐lapse sequences, 90% of all sessile bacteria within the biofilm were observed to progressively turn red (i.e., died) within 24 hours. Total bacterial kill in the biofilm was achieved after 48 hours. This research has shown that the dressing was effective in killing the tested bacteria evident in both the tested mono and polymicrobial biofilms, which provides valuable evidence that this dressing may have an effect on biofilms found in recalcitrant chronic wounds.
Proteolytic cleavage of the E2 glycoprotein of murine coronavirus: host-dependent differences in proteolytic cleavage and cell fusion

Cell fusion induced by infection with mouse hepatitis virus strain A59 (MHV-A59) varied markedly in extent and time course in four different murine cell lines. When inoculated at a multiplicity of 3 to 5 PFU per cell, the Sac-, L2, and DBT cell lines began to fuse by 7 h, were fused into confluent syncytia by 9 to 12 h, and peeled from the substrate by 10 to 14 h. These virulent virus-cell interactions were in striking contrast to the moderate interaction of MHV-A59 with the 17 Cl 1 cell line, in which only small syncytia were observed 18 h postinoculation, and greater than 50% of the cells remained unfused by 24 h. The yield of infectious virus produced by 17 Cl 1 cells was 10-fold higher than the yields from the other three cell lines. The processing of the nucleocapsid protein, the membrane glycoprotein E1, and the peplomeric glycoprotein E2 were found to differ significantly in the four cell lines. Since the E2 glycoprotein is responsible for virus-induced cell fusion, we attempted to correlate differences in cellular processing of E2 with differences in fusion of infected cells. The predominant intracellular form of E2 in all cell lines was the 180K species. Pulse-chase experiments showed that a small portion of the 17 Cl 1 cell-associated 180K E2 was cleaved by 1 h after synthesis to yield 90K E2, shown in the preceding paper to consist of two different glycoproteins called 90A and 90B (L. S. Sturman, C. S. Ricard, and K. V. Holmes, J. Virol. 56:904-911, 1985). This cleavage occurred shortly before the release of virions from cells, as shown by pulse-chase experiments. After budding at intracellular membranes, virions released into the medium by the four cell lines contained different ratios of 180K to 90K E2. Virions from Sac- cells, which contained 100% 90K E2, fused L2 cells rapidly without requiring virus replication, whereas virions from 17 Cl 1 cells, which had 50% 90K E2, required trypsin activation to induce rapid fusion (Sturman et al., J. Virol. 56:904-911, 1985). The addition of protease inhibitors to the medium markedly delayed L2 cell fusion induced by MHV infection. The extent of coronavirus-induced cell fusion does not depend solely upon the percent cleavage of the E2 glycoprotein by cellular proteases, since extensive fusion was induced by infection of L2 and DBT cells but not 17 Cl 1 cells, although all three cell lines cleaved E2 to the same extent. (ABSTRACT TRUNCATED AT 400 WORDS)
An Activity Systems Model for Estimating Human Exposure to 60 Hz Electric Fields

This paper describes a methodology that can be used to develop estimates of exposure to 60 Hz electric fields of transmission lines for a variety of human activities. The method, called an Activity Systems Model, is used to characterize human activities in situations where exposure to electric fields is possible. The model provides the framework that combines electric field maps, activity maps, and experimentally determined ``activity factors'' to produce histograms of time spent in various levels of electric field strength. An assortment of 74 activity factors based on 725 individual measurements are provided in the paper. Results of an activity systems model can be used to quantify public exposure to electric fields. (This work was supported by EPRI, RP799-16.)
Steady-State Plasma Membrane Expression of Human Cytomegalovirus gB Is Determined by the Phosphorylation State of Ser900

ABSTRACT Human cytomegalovirus (HCMV) infection of an astrocytoma cell line (U373) or human fibroblast (HF) cells results in a differential cell distribution of the major envelope glycoprotein gB (UL55). This 906-amino-acid type I glycoprotein contains an extracellular domain with a signal sequence, a transmembrane domain, and a 135-amino-acid cytoplasmic tail with a consensus casein kinase II (CKII) site located at Ser900. Since phosphorylation of proteins in the secretory pathway is an important determinant of intracellular trafficking, the state of gB phosphorylation in U373 and HF cells was examined. Analysis of cells expressing wild-type gB and gB with site-specific mutations indicated that the glycoprotein was equally phosphorylated at a single site, Ser900, in both U373 and HF cells. To assess the effect of charge on gB surface expression in U373 cells, Ser900 was replaced with an aspartate (Asp) or alanine (Ala) residue to mimic the phosphorylated and nonphosphorylated states, respectively. Expression of the Asp but not the Ala gB mutation resulted in an increase in the steady-state expression of gB at the plasma membrane (PM) in U373 cells. In addition, treatment of U373 cells with the phosphatase inhibitor tautomycin resulted in the accumulation of gB at the PM. Interestingly, the addition of a charge at Ser900 trapped gB in a low-level cycling pathway at the PM, preventing trafficking of the protein to thetrans-Golgi network or other intracellular compartments. Therefore, these results suggest that a tautomycin-sensitive phosphatase regulates cell-specific PM retrieval of gB to intracellular compartments.
Pyridostigmine treatment trial in neurogenic orthostatic hypotension.

BACKGROUND Midodrine hydrochloride is the only drug demonstrated in a placebo-controlled treatment trial to improve orthostatic hypotension (OH) but it significantly worsens supine hypertension. By enhancing ganglionic transmission, pyridostigmine bromide can potentially ameliorate OH without worsening supine hypertension. OBJECTIVE To evaluate the efficacy of a single 60-mg dose of pyridostigmine bromide, alone or in combination with a subthreshold (2.5 mg) or suprathreshold (5 mg) dose of midodrine hydrochloride, compared with placebo. DESIGN We report a double-blind, randomized, 4-way cross-over study of pyridostigmine in the treatment of neurogenic OH. A total of 58 patients with neurogenic OH were enrolled. After 1 day of baseline measurements, patients were given 4 treatments (3 active treatments [60 mg of pyridostigmine bromide; 60 mg of pyridostigmine bromide and 2.5 mg of midodrine hydrochloride; 60 mg of pyridostigmine bromide and 5 mg of midodrine hydrochloride] and a placebo) in random order on successive days. Blood pressure (BP) and heart rate were measured, both supine and standing, immediately before treatment and hourly for 6 hours after the treatment was given. RESULTS No significant differences were seen in the supine BP, either systolic (P = .36) or diastolic (P = .85). In contrast, the primary end point of the fall in standing diastolic BP was significantly reduced (P = .02) with treatment. Pairwise comparison showed significant reduction by pyridostigmine alone (BP fall of 27.6 mm Hg vs 34.0 mm Hg with placebo; P = .04) and pyridostigmine and 5 mg of midodrine hydrochloride (BP fall of 27.2 mm Hg vs 34.0 mm Hg with placebo; P = .002). Standing BP improvement significantly regressed with improvement in OH symptoms. CONCLUSIONS Pyridostigmine significantly improves standing BP in patients with OH without worsening supine hypertension. The greatest effect is on diastolic BP, suggesting that the improvement is due to increased total peripheral resistance.
Defense against impersonating attackers: An efficient RFID mutual authentication protocol based on standard

As the RFID based Internet of Things (loT) gets worldwide attention, to prepare for the rapidly increasing applications in daily life, various security protocols are proposed. But, these protocols, most of which are limited by the tag processing capacity and dangerous exposure during transmission, could only be applied in certain fields. Previously, Chen and Deng's mutual authentication and privacy protection protocol which conforming EPC Class 1 Generation 2 Standards stands out for low cost as well as little requirements of the tag processing capacity. However, currently reported by others, this system faces up with severe dangers of tracking or cloning tags via impersonating attacks. After scrutiny, we found out that these vulnerabilities lie in the insufficient protections of random numbers, and we reconstruct the request and response based on the original protocol by making message unrepeatable, key elements secret and adding small storage for comparisons. The security of our protocol, proved by Ban logic analysis, is ensured by double protections — secret key pairs and dynamic random numbers. Our comparisons show that our protocol not only is safe under traditional attacks guaranteed by the original protocol but also overcomes impersonating attacks which represents the inherent weakness of information exposure in public.
Progress in predicting inter‐residue contacts of proteins with neural networks and correlated mutations

This article presents recent progress in predicting inter‐residue contacts of proteins with a neural network‐based method. Improvement over the results obtained at the previous CASP3 competition is attained by using as input to the network a complex code, which includes evolutionary information, sequence conservation, correlated mutations, and predicted secondary structures. The predictor was trained and cross‐validated on a data set comprising the contact maps of 173 non‐homologous proteins as computed from their well‐resolved three‐dimensional structures. The method could assign protein contacts with an average accuracy of 0.21 and with an improvement over a random predictor of a factor greater than 6, which is higher than that previously obtained with methods only based either on neural networks or on correlated mutations. Although far from being ideal, these scores are the highest reported so far for predicting protein contact maps. On 29 targets automatically predicted by the server (CORNET) the average accuracy is 0.14. The predictor is poorly performing on all‐α proteins, not represented in the training set. On all‐β and mixed proteins (22 targets) the average accuracy is 0.16. This set comprises proteins of different complexity and different chain length, suggesting that the predictor is capable of generalization over a broad number of features. Proteins 2001;Suppl 5:157–162. © 2002 Wiley‐Liss, Inc.
Premedication with Oral and Transdermal Clonidine Provides Safe and Efficacious Postoperative Sympatholysis

We studied 61 patients undergoing elective major non-cardiac surgery in a randomized, double-blind, placebo-control clinical trial to test the hypothesis that the addition of clonidine to a standardized general anesthetic could safely provide postoperative sympatholysis for patients with known or suspected coronary artery disease. Patients were allocated randomly to receive either placebo (n = 31) or clonidine (n = 30). The treatment group received premedication with a trans-dermal clonidine system (0.2 mg/d) the night prior to surgery, which was left in place for 72 h, and 0.3 mg oral clonidine 60–90 min before surgery. Clonidine reduced enflurane requirements, intraoperative tachycardia, and myocardial ischemia (1/28 clonidine patients vs 5/24 placebo, P = 0.05). However, clonidine decreased heart rates only during the first five postoperative hours; the incidence of postoperative myocardial ischemia (6/28 clonidine vs 5/26 placebo) did not differ between the two groups. Patients who experienced postoperative myocardial ischemia tended to have higher heart rates after surgery. Clonidine significantly reduced the plasma levels of epinephrine (P = 0.009) and norepinephrine (P = 0.026) measured on the first postoperative morning. There were no differences in the need for intravenous fluid therapy or antihypertensive therapy after surgery. The number of hours spent in an intensive care setting and the number of days spent in hospital were not different between the two groups. These results suggest that larger doses of clonidine should be investigated for their ability to decrease postoperative tachycardia and myocardial ischemia. (Anesth Analg 1994;79:1133–40)
The End Is the Beginning: Parkinson’s Disease in the Light of Brain Imaging

Parkinson’s disease (PD), the most common neurodegenerative disorder, is characterized by abnormal accumulation of α-synuclein aggregates known as Lewy bodies (LB) and loss of nigrostriatal dopaminergic neurons. Recent neuroimaging studies suggest that in the early phases of PD, synaptic and axonal damage anticipate the onset of a frank neuronal death. Paralleling, even post mortem studies on the brain of affected patients and on animal models support that synapses might represent the primary sites of functional and pathological changes. Indeed, α-synuclein microaggregation and spreading at terminals, by dysregulating the synaptic junction, would block neurotransmitter release, thus triggering a retrograde neurodegenerative process ending with neuronal cell loss by proceeding through the axons. Rather than neurodegeneration, loss of dopaminergic neuronal endings and axons could thus underlie the onset of connectome dysfunction and symptoms in PD and parkinsonisms. However, the manifold biases deriving from the interpretation of human brain imaging data hinder the validation of this hypothesis. Here, we present pivotal evidence supporting that novel comparative brain imaging studies, in patients and experimental models of PD in preliminary stages of disease, could be instrumental for proving whether synaptic endings are the sites where degeneration begins and initiating the factual achievement of disease modifying approaches. The need for such investigations is timely to define an early therapeutic window of intervention to attempt disease halting by terminal and/or axonal healing.