Miracle-dz/UniFAR-FTUs huggingface dataset:
University of Groningen Mechanosensitive membrane channels in action

The tension-driven gating process of MscL from Mycobacterium tuberculosis, Tb-MscL, has been addressed at near-atomic detail using coarse-grained molecular dynamics simulations. To perform the simulations, a novel coarse-grained peptide model based on a thermodynamic parameterization of the amino-acid side chains has been applied. Both the wild-type Tb-MscL and its gain-of-function mutant V21D embedded in a solvated lipid bilayer have been studied. To mimic hypoosmotic shock conditions, simulations were performed at increasing levels of membrane tension approaching the rupture threshold of the lipid bilayer. Both the wild-type and the mutant channel are found to undergo significant conformational changes in accordance with an irislike expansion mechanism, reaching a conducting state on a microsecond timescale. The most pronounced expansion of the pore has been observed for the V21D mutant, which is consistent with the experimentally shown gain-of-function phenotype of the V21D mutant.
Parallel Chemical Protein Synthesis on a Surface Enables the Rapid Analysis of the Phosphoregulation of SH3 Domains.

Analysis of postranslationally modified protein domains is complicated by an availability problem, as recombinant methods rarely allow site-specificity at will. Although total synthesis enables full control over posttranslational and other modifications, chemical approaches are limited to shorter peptides. To solve this problem, we herein describe a method that combines a) immobilization of N-terminally thiolated peptide hydrazides by hydrazone ligation, b) on-surface native chemical ligation with self-purified peptide thioesters, c) radical-induced desulfurization, and d) a surface-based fluorescence binding assay for functional characterization. We used the method to rapidly investigate 20 SH3 domains, with a focus on their phosphoregulation. The analysis suggests that tyrosine phosphorylation of SH3 domains found in Abl kinases act as a switch that can induce both the loss and, unexpectedly, gain of affinity for proline-rich ligands.
Switching LPV Controllers for a Variable Speed Pitch Regulated Wind Turbine

This paper deals with the control of a variable speed, pitch regulated wind turbine in the whole plant operating area. The wind turbine operating area can be divided into several zones, depending on the wind speed, and the control objectives are different for each operating zone. A hybrid control system composed by several LPV controllers which switches during transitions from one operating area to another is designed in order to ensure asymptotic stability and a good level of performances in the whole operating area. The LPV controllers are calculated from a convex LMI formulation of the problem in order to minimize an H2/Hinfin criteria that optimizes the energy conversion of the system and that reduces the mechanical fatigue of the plant mechanical structure. The proposed controller is finally compared with two more conventional ones
A Black-Box Approach to Latency and Throughput Analysis

To enable fast and reliable delivery of mobile text messages (SMS), special bidirectional protocols are often used. Measuring the achieved throughput and involved latency is however non-trivial, due to the complexity of these protocols. Modifying an existing system would incur too much of a risk, so instead a new tool was created to analyse the log files containing information about this traffic in a black-box fashion. When the produced raw data was converted into graphs, they gave new insights into the behaviour of both the protocols and the remote systems involved.
Comparison of a two-handed interface to a wand interface and a mouse interface for fundamental 3D tasks

This paper describes a two-handed interface that enables intuitive interaction with 3D multimedia environments. Two user studies demonstrated the effectiveness of the two-handed interface in fundamental 3D object manipulation and viewpoint manipulation tasks. Trained participants docked and constructed 3D objects 4.5-4.7 times as fast as a standard mouse interface and 1.3-2.5 times as fast as a standard one-handed wand interface. 19 of 20 participants preferred the two-handed interface over the mouse and wand interfaces. 16 participants felt very comfortable with the two-handed interface and 4 felt comfortable. No statistically significant differences in performance were found between monoscopic and stereoscopic displays although 17 of 20 participants preferred the stereoscopic display over the monoscopic display.
Keyframe selection for motion capture using motion activity analysis

Motion capture data acquired from high definition cameras creates accurate human motion representation but introduces many redundant frames which pose a problem in data storage and motion retrieval purposes. In this paper, a keyframing approach is proposed to reduce the motion data by extracting keyframes using motion analysis approach in sampling windows. Motion changes in sampling windows for original motion without frame skipping and with frame skipping are computed. The difference in the motion changes is the main aspect in deciding whether the frames in sampling windows are possible candidates for keyframe selection. Simulation results showed that the proposed method is able to achieve an overall good visual quality for different types of motion. It also gives an improvement of up to 52% in terms of mean square error measurement, as compared to the existing keyframe extraction method, which is curve simplification method.
Cyclo-oxygenase-2 (COX-2) expression at the site of recent myocardial infarction: friend or foe?

Background: Cyclo-oxygenase-2 (COX-2) is induced in cardiomyocytes only in response to stress, such as ischaemia. Objective: To assess COX-2 expression at the site of recent myocardial infarction. Methods: COX-2 expression was evaluated by specific immunostaining in cardiomyocytes from 23 subjects who died 10–60 days after acute myocardial infarction. The relation between COX-2 myocardial expression and apoptotic rate was investigated. Cardiomyocyte apoptotic rate was defined as the number of cells co-expressing in situ end labelling of DNA fragmentation (TUNEL) and immunostaining for activated caspase-3. Results: COX-2 expression was found in cardiomyocytes at the site of infarction in nine of 23 cases (39%). It was associated with fivefold higher apoptotic rates (median 17.9% (interquartile range 11.0–25.4%) v 3.7% (0.6–12.8%); p = 0.016), and apoptotic rate increased progressively from mild to intense COX-2 staining (p for trend 0.009). COX-2 expression co-localised with TUNEL nuclear staining in myocytes, and there was a high concordance between COX-2 and hypoxia induced factor 1-α staining (78%, p = 0.021) and between COX-2 and bax (83%, p = 0.014). Subjects showing myocardial COX-2 expression were more likely to have enlarged hearts (p = 0.050), and intense COX-2 staining was strictly associated with symptomatic heart failure (p = 0.035). Conclusions: COX-2 is expressed in cardiomyocytes in nearly 40% of cases at the site of recent acute myocardial infarction, even late after the index event. Its expression was associated with extremely high apoptotic rates. These findings suggest a potential cause–effect link between COX-2 expression and enhanced myocardial apoptosis in ischaemic cardiomyopathy.
Estimates of aseismic slip associated with small earthquakes near San Juan Bautista, CA

Postseismic slip observed after large (M > 6) earthquakes typically has an equivalent moment of a few tens of percent of the coseismic moment. Some observations of the recurrence intervals of repeating earthquakes suggest that postseismic slip following small ( M≲4 ) earthquakes could be much larger—up to 10 or 100 times the coseismic moment. We use borehole strain data from U.S. Geological Survey strainmeter SJT to analyze deformation in the days before and after 1000 1.9 < M < 5 earthquakes near San Juan Bautista, CA. We find that on average, postseismic strain is roughly equal in magnitude to coseismic strain for the magnitude range considered, suggesting that postseismic moment following these small earthquakes is roughly equal to coseismic moment. This postseismic to coseismic moment ratio is larger than typically observed in earthquakes that rupture through the seismogenic zone but is much smaller than was hypothesized from modeling repeating earthquakes. Our results are consistent with a simple, self‐similar model of earthquakes.
Structure of the Exon Junction Core Complex with a Trapped DEAD-Box ATPase Bound to RNA

In higher eukaryotes, a multiprotein exon junction complex is deposited on spliced messenger RNAs. The complex is organized around a stable core, which serves as a binding platform for numerous factors that influence messenger RNA function. Here, we present the crystal structure of a tetrameric exon junction core complex containing the DEAD-box adenosine triphosphatase (ATPase) eukaryotic initiation factor 4AIII (eIF4AIII) bound to an ATP analog, MAGOH, Y14, a fragment of MLN51, and a polyuracil mRNA mimic. eIF4AIII interacts with the phosphate-ribose backbone of six consecutive nucleotides and prevents part of the bound RNA from being double stranded. The MAGOH and Y14 subunits lock eIF4AIII in a prehydrolysis state, and activation of the ATPase probably requires only modest conformational changes in eIF4AIII motif I.
The Bacterial Endotoxin Lipopolysaccharide has the Ability to Target the Brain in Upregulating Its Membrane CD14 Receptor Within Specific Cellular Populations

Systemic injection of the bacterial endotoxin lipopolysaccharide (LPS) provides a very good mean for increasing the release of proinflammatory cytokines by circulating monocytes and tissue macrophages. There is now considerable evidence that LPS exerts its action on mononuclear phagocytes via the cell surface receptor CD14. The aim of the present study was to verify the hypothesis that the brain has also the ability to express the gene encoding the LPS receptor, which may allow a direct action of the endotoxin onto specific cellular populations during blood sepsis. Adult male Sprague‐Dawley rats were sacrificed 1, 3, 6 and 24 h after systemic (i.v. or i.p.) injection of LPS or the vehicle solution. Brains were cut from the olfactory bulb to the medulla in 30‐μm coronal sections and mRNA encoding rat CD14 was assayed by in situ hybridization histochemistry using a specific 35S‐labeled riboprobe. The results show low levels of CD14 mRNA in the leptomeninges, choroid plexus and along blood vessels of the brain microvasculature under basal conditions. Systemic injection of the bacterial endotoxin caused a profound increase in the expression of the gene encoding CD14 within these same structures as well as in the circumventricular organs (CVOs) the organum vasculosum of the lamina terminalis, subfornical organ, median eminence and area postrema. In most of these structures, the signal for CD14 mRNA was first detected at 1 h, reached a peak at 3 h post‐injection, declined at 6 h, and return to basal levels 24 h after LPS treatment. Quite interestingly, a migratory‐like pattern of CD14 positive cells was observed from all sensorial CVOs to deeper parenchymal brain 3 and 6 h after LPS injection. At 6 h post‐challenge, small positive cells were found throughout the entire parenchymal brain and dual‐labeling procedure indicated that different cells of myeloid origin have the ability to express CD14 in response to systemic LPS. These included CVO microglia, choroid plexus and leptomeninge macrophages, parenchymal and perivascular‐associated microglial cells, although specific nonmyeloid cells were also positive for the LPS receptor. These results provide the very first evidence of a direct role of LPS on specific cell populations of the central nervous system, which is likely to be responsible for the transcription of proinflammatory cytokines; first within accessible structures from the blood and thereafter through scattered parenchymal cells during severe sepsis.
Cleavage of Poly(A)-Binding Protein by Coxsackievirus 2A Protease In Vitro and In Vivo: Another Mechanism for Host Protein Synthesis Shutoff?

ABSTRACT Infection of cells by picornaviruses of the rhinovirus, aphthovirus, and enterovirus groups results in the shutoff of host protein synthesis but allows viral protein synthesis to proceed. Although considerable evidence suggests that this shutoff is mediated by the cleavage of eukaryotic translation initiation factor eIF4G by sequence-specific viral proteases (2A protease in the case of coxsackievirus), several experimental observations are at variance with this view. Thus, the cleavage of other cellular proteins could contribute to the shutoff of host protein synthesis and stimulation of viral protein synthesis. Recent evidence indicates that the highly conserved 70-kDa cytoplasmic poly(A)-binding protein (PABP) participates directly in translation initiation. We have now found that PABP is also proteolytically cleaved during coxsackievirus infection of HeLa cells. The cleavage of PABP correlated better over time with the host translational shutoff and onset of viral protein synthesis than did the cleavage of eIF4G. In vitro experiments with purified rabbit PABP and recombinant human PABP as well as in vivo experiments withXenopus oocytes and recombinant Xenopus PABP demonstrate that the cleavage is catalyzed by 2A protease directly. N- and C-terminal sequencing indicates that cleavage occurs uniquely in human PABP at482VANTSTQTM↓GPRPAAAAAA500, separating the four N-terminal RNA recognition motifs (80%) from the C-terminal homodimerization domain (20%). The N-terminal cleavage product of PABP is less efficient than full-length PABP in restoring translation to a PABP-dependent rabbit reticulocyte lysate translation system. These results suggest that the cleavage of PABP may be another mechanism by which picornaviruses alter the rate and spectrum of protein synthesis.
Sodium and Chloride Ion‐Dependent Transport of β‐Alanine Across the Blood‐Brain Barrier

Abstract: The characteristics of β‐alanine transport at the blood‐brain barrier were studied by using primary cultured bovine brain capillary endothelial cells. Kinetic analysis of the β‐[3H]alanine transport indicated that the transporter for β‐alanine functions with Kt of 25.3 ± 2.5 µM and Jmax of 6.90 ± 0.48 nmol/30 min/mg of protein in the brain capillary endothelial cells. β‐[3H]Alanine uptake is mediated by an active transporter, because metabolic inhibitors (2,4‐dinitrophenol and NaN3) and low temperature reduced the uptake significantly. Furthermore, the uptake of β‐[3H]alanine required Na+ and Cl− in the external medium. Stoichiometric analysis of the transport demonstrated that two sodium ions and one chloride ion are associated with one β‐alanine molecule. The Na+ and Cl−‐dependent uptake of β‐[3H]alanine was stimulated by a valinomycin‐induced inside‐negative K+‐diffusion potential. β‐Amino acids (β‐alanine, taurine, and hypotaurine) inhibited strongly the uptake of β‐[3H]alanine, whereas α‐ and γ‐amino acids had little or no inhibitory effect. In ATP‐depleted cells, the uptake of β‐[3H]alanine was stimulated by preloading of β‐alanine or taurine but not l‐leucine. These results show that β‐alanine is taken up by brain capillary endothelial cells, via the secondary active transport mechanism that is common to β‐amino acids.
Health Care CIOs: Assessing Their Fit in the Organizational Hierarchy and Their Influence on Information Technology Capability

Despite the continuing interest in the importance of health care information technology adoption, very little is known about chief information officers (CIOs), the individuals who manage this effort. The present study surveyed hospital CIOs to understand their backgrounds, their organizational status, and their influence in hospital health care information technology adoption. Survey responses from 98 organizations suggest that the CIO position varies significantly according to the profit status of the hospital. Further, regression analyses suggest that CIO tenure is associated with greater health care information technology adoption, whereas the reporting structure of the CIO is not. Management implications of the findings are discussed.
Competitive Pressure and Technology Adoption: Evidence from a Policy Reform in Western Canada

We measure the impact of the removal of a railway transportation subsidy on the adoption of technology for Western Canadian farms, using a unique combination of Census and freight rate data. We exploit the large regional variation in these one-time freight rate increases in order to identify causal effects of increased competitive pressure. Using a difference-in-differences methodology we find that higher freights rates – and hence lower farm gate prices – induced farmers to adopt new, more efficient production technology. We also find that farmers experiencing the greatest transportation cost increases also increased fertilizer usage and made significant land use changes.
Crowd-sourced data coding for the social sciences : massive non-expert coding of political texts

A large part of empirical social science relies heavily on data that are not observed in the field, but are generated by researchers sitting at their desks, raising obvious issues of both reliability and validity. This paper addresses these issues for a widely used type of coded data, derived from the content analysis of political text. Comparing estimates derived from multiple “expert” and crowd-sourced codings of the same texts, as well as other independent estimates of the same latent quantities, we investigate whether we can analyze political text in a reliable and valid way using the cheap and scalable method of crowd sourcing. Our results show that, contrary to naive preconceptions and reflecting concerns often swept under the carpet, a set of expert coders is also a crowd. We find that deploying a crowd of non-expert coders on the same texts, with careful specification and design to address issues of coder quality, offers the prospect of cheap, scalable and replicable human text coding. Even as computational text analysis becomes more effective, human coding will always be needed, both to validate and interpret computational results and to calibrate supervised methods. While our specific findings here concern text coding, they have implications for all expert coded data in the social sciences.
Boundary Stabilization for a Class of Hyperbolic PDEs with a Free End

In this paper, the problem of boundary feedback stabilization for a class of hyperbolic partial differential equations (PDEs) is considered by using the backstepping approach. We show that, under certain mathematical conditions the closed-loop system could become stable exponentially at a given decay rate. The mappings between the original and the transformed systems are constructed, in which the boundary conditions of the kernel functions are discussed.
RNA-Sequencing Quantification of Hepatic Ontogeny of Phase-I Enzymes in Mice

Phase-I drug metabolizing enzymes catalyze reactions of hydrolysis, reduction, and oxidation of drugs and play a critical role in drug metabolism. However, the functions of most phase-I enzymes are not mature at birth, which markedly affects drug metabolism in newborns. Therefore, characterization of the expression profiles of phase-I enzymes and the underlying regulatory mechanisms during liver maturation is needed for better estimation of using drugs in pediatric patients. The mouse is an animal model widely used for studying the mechanisms in the regulation of developmental expression of phase-I genes. Therefore, we applied RNA sequencing to provide a “true quantification” of the mRNA expression of phase-I genes in the mouse liver during development. Liver samples of male C57BL/6 mice at 12 different ages from prenatal to adulthood were used for defining the ontogenic mRNA profiles of phase-I families, including hydrolysis: carboxylesterase (Ces), paraoxonase (Pon), and epoxide hydrolase (Ephx); reduction: aldo-keto reductase (Akr), quinone oxidoreductase (Nqo), and dihydropyrimidine dehydrogenase (Dpyd); and oxidation: alcohol dehydrogenase (Adh), aldehyde dehydrogenase (Aldh), flavin monooxygenases (Fmo), molybdenum hydroxylase (Aox and Xdh), cytochrome P450 (P450), and cytochrome P450 oxidoreductase (Por). Two rapidly increasing stages of total phase-I gene expression after birth reflect functional transition of the liver during development. Diverse expression patterns were identified, and some large gene families contained the mRNA of genes that are enriched at different stages of development. Our study reveals the mRNA abundance of phase-I genes in the mouse liver during development and provides a valuable foundation for mechanistic studies in the future.
Real-time path tracking with torque limits by using a disturbance observer

When the minimum-time trajectory of a manipulator along a geometrically prescribed path is planned, considering the manipulator's dynamics and actuators' torque limits, at least one of the joints is at the torque limit. The execution of such a trajectory by a conventional feedback scheme results in torque saturation. Consequently, the tracking error cannot be suppressed and the manipulator may deviate from the desired path. We propose a feedback control method for path tracking which takes the torque saturation into account. A "path coordinate system" is defined, which is composed of the component along the desired path and the components normal to the path. Control of the components normal to the path is given priority in order to keep the motion of the manipulator on the path. A disturbance observer is used to estimate nonlinear dynamics instead of calculating them directly. This method can reduce real-time computations and can also reject unmodeled disturbances. The simulations of a two-degree-of-freedom manipulator show the effectiveness of the method. <<ETX>>