Miracle-dz/UniFAR-FTUs huggingface dataset:
Type 1 IP3 receptors activate BKCa channels via local molecular coupling in arterial smooth muscle cells

Plasma membrane large-conductance Ca2+-activated K+ (BKCa) channels and sarcoplasmic reticulum inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) are expressed in a wide variety of cell types, including arterial smooth muscle cells. Here, we studied BKCa channel regulation by IP3 and IP3Rs in rat and mouse cerebral artery smooth muscle cells. IP3 activated BKCa channels both in intact cells and in excised inside-out membrane patches. IP3 caused concentration-dependent BKCa channel activation with an apparent dissociation constant (Kd) of ∼4 µM at physiological voltage (−40 mV) and intracellular Ca2+ concentration ([Ca2+]i; 10 µM). IP3 also caused a leftward-shift in BKCa channel apparent Ca2+ sensitivity and reduced the Kd for free [Ca2+]i from ∼20 to 12 µM, but did not alter the slope or maximal Po. BAPTA, a fast Ca2+ buffer, or an elevation in extracellular Ca2+ concentration did not alter IP3-induced BKCa channel activation. Heparin, an IP3R inhibitor, and a monoclonal type 1 IP3R (IP3R1) antibody blocked IP3-induced BKCa channel activation. Adenophostin A, an IP3R agonist, also activated BKCa channels. IP3 activated BKCa channels in inside-out patches from wild-type (IP3R1+/+) mouse arterial smooth muscle cells, but had no effect on BKCa channels of IP3R1-deficient (IP3R1−/−) mice. Immunofluorescence resonance energy transfer microscopy indicated that IP3R1 is located in close spatial proximity to BKCa α subunits. The IP3R1 monoclonal antibody coimmunoprecipitated IP3R1 and BKCa channel α and β1 subunits from cerebral arteries. In summary, data indicate that IP3R1 activation elevates BKCa channel apparent Ca2+ sensitivity through local molecular coupling in arterial smooth muscle cells.
Peer social status and friendship: independent contributors to children's social and academic adjustment

Peer social status, friendships, and adjustment were measured for 326 school-aged children (M age = 8 years, 8 months). Although status and friendship were related, they were not redundant. Some rejected and neglected children had friends; and some popular and average children did not have friends. Both peer social status and friendship were found to contribute uniquely to children's socio-emotional adjustment, academic competence, and self-concept. These results argue for the functional importance of both types of peer relationships for school-aged children
Prior exposure to freezing stress enhances the survival and recovery of Poa pratensis exposed to severe drought.

PREMISE OF THE STUDY Both freezing and drought cause cellular dehydration, and they elicit similar increases in protective compounds, which suggests that these stresses could potentially interact. We examined whether the physiological changes that occur in response to freezing in the fall and spring could affect subsequent survival and growth after summer drought. METHODS We froze Poa pratensis tillers in the late fall, early spring, or late spring at 0, -5, or -10°C for 3 d and then subjected them to no drought (-0.025 MPa), moderate drought (-0.140 MPa), or severe drought (-0.250 MPa) for 3 wk in the summer. We quantified survival and total biomass after a 3-wk recovery period, and we determined leaf soluble sugar concentrations before and then 0, 30, and 55 d after freezing. KEY RESULTS For survival and biomass, there were significant interactions between freezing and drought. Spring frozen tillers had the highest biomass and survival following severe drought, whereas fall freezing did not significantly increase the biomass of tillers following the severe drought. Increased drought tolerance after spring freezing did not appear to be associated with increased soluble sugar content, given that the freezing effects on leaf glucose, fructose, and sucrose content were absent 55 d post freezing. CONCLUSIONS Our results demonstrate that multiple stresses that occur over different seasons can interact; this interaction is highly relevant to herbaceous species in northern temperate regions that are experiencing more intense and frequent stress as a result of changes in snow cover and extreme climatic events.
Antigen-Specific Induction of Regulatory T Cells for Type 1 Diabetes Therapy

Since their discovery decades ago, regulatory T (Treg) cells have prompted many investigations into their potential role in the generation or prevention of autoimmune disorders such as type 1 diabetes (T1D). Initially identified based on their ability to maintain tolerance to self-antigens in peripheral organs, Treg cells have since been efficiently induced therapeutically and shown to prevent the progression of T1D as well as other autoimmune diseases. Beneficial modification of immunity through the induction of Treg cells has been successfully achieved by antigen-based therapy as well as non-antigen-specific (systemic) treatments. In the current article, we review different strategies that have proved effective in preventing autoimmune diabetes and analyze them with respect to translation into clinical applications. Current evidence indicates that antigen-specific induction of potent regulatory mechanisms is influenced by the systemic milieu, suggesting that systemic modulation might be an essential prerequisite for antigen-based therapy and the successful maintenance or reestablishment of tolerance.
Single Na+ channels activated by veratridine and batrachotoxin

Voltage-sensitive Na+ channels from rat skeletal muscle plasma membrane vesicles were inserted into planar lipid bilayers in the presence of either of the alkaloid toxins veratridine (VT) or batrachotoxin (BTX). Both of these toxins are known to cause persistent activation of Na+ channels. With BTX as the channel activator, single channels remain open nearly all the time. Channels activated with VT open and close on a time scale of 1-10 s. Increasing the VT concentration enhances the probability of channel opening, primarily by increasing the rate constant of opening. The kinetics and voltage dependence of channel block by 21-sulfo-11-alpha-hydroxysaxitoxin are identical for VT and BTX, as is the ionic selectivity sequence determined by bi-ionic reversal potential (Na+ approximately Li+ greater than K+ greater than Rb+ greater than Cs+). However, there are striking quantitative differences in open channel conduction for channels in the presence of the two activators. Under symmetrical solution conditions, the single channel conductance for Na+ is about twice as high with BTX as with VT. Furthermore, the symmetrical solution single channel conductances show a different selectivity for BTX (Na+ greater than Li+ greater than K+) than for VT (Na+ greater than K+ greater than Li+). Open channel current-voltage curves in symmetrical Na+ and Li+ are roughly linear, while those in symmetrical K+ are inwardly rectifying. Na+ currents are blocked asymmetrically by K+ with both BTX and VT, but the voltage dependence of K+ block is stronger with BTX than with VT. The results show that the alkaloid neurotoxins not only alter the gating process of the Na+ channel, but also affect the structure of the open channel. We further conclude that the rate-determining step for conduction by Na+ does not occur at the channel's "selectivity filter," where poorly permeating ions like K+ are excluded.
Satellites in our pockets: an object positioning system using smartphones

This paper attempts to solve the following problem: can a distant object be localized by looking at it through a smartphone. As an example use-case, while driving on a highway entering New York, we want to look at one of the skyscrapers through the smartphone camera, and compute its GPS location. While the problem would have been far more difficult five years back, the growing number of sensors on smartphones, combined with advances in computer vision, have opened up important opportunities. We harness these opportunities through a system called Object Positioning System (OPS) that achieves reasonable localization accuracy. Our core technique uses computer vision to create an approximate 3D structure of the object and camera, and applies mobile phone sensors to scale and rotate the structure to its absolute configuration. Then, by solving (nonlinear) optimizations on the residual (scaling and rotation) error, we ultimately estimate the object's GPS position. We have developed OPS on Android NexusS phones and experimented with localizing 50 objects in the Duke University campus. We believe that OPS shows promising results, enabling a variety of applications. Our ongoing work is focused on coping with large GPS errors, which proves to be the prime limitation of the current prototype.
Reticulon‐1C acts as a molecular switch between endoplasmic reticulum stress and genotoxic cell death pathway in human neuroblastoma cells

Damage or stress in many organelles may trigger apoptosis by several not yet fully elucidated mechanisms. A cell death pathway is induced by endoplasmic reticulum (ER) stress elicited by the unfolded protein response and/or by aberrant Ca2+ signalling. Reticulon‐1C (RTN‐1C) belongs to the reticulon family, neuroendocrine‐specific proteins localized primarily on the ER membrane. In the present study, we demonstrate that RTN‐1C is able to modulate, in a mutually exclusive way, the cellular sensitivity to different apoptosis pathways in human neuroblastoma cells. In fact, the increase of RTN‐1C protein levels per se results in ER stress‐induced cell death, mediated by an increase of cytosolic Ca2+, and significantly sensitizes cells to different ER stress inducers. In line with these findings, the reduction of RTN‐1C, by antisense DNA expression, reduced the sensitivity to ER‐stressors. In the presence of high RTN‐1C levels, genotoxic drugs become ineffective as a consequence of the cytoplasm translocation of p53 protein, while the silencing of endogenous RTN‐1C results in the potentiation of the genotoxic drugs action. These data indicate that RTN‐1C is able to modulate the cellular sensitivity to different apoptotic pathways representing a promising molecular target for new drug development.
Understanding Two Types of Technological Diversity and their Effects on the Technological Value of Outcomes from Bilateral Inter-firm R&D Alliances

This study investigates the relationship between the technological value of collaborative research and development (R&D) outcomes and technological diversity in inter-firm R&D alliances. We differentiate technological diversity into two types—relational technological diversity (RTD) and distributional technological diversity (DTD)—and relate them to distinct mechanisms. By empirically analyzing 18,575 granted U.S. patent applications from 1993 to 2002, we find that RTD and DTD is negatively associated and positively associated, respectively, with the technological value of R&D outcomes. In addition, we consider two hypothesized moderators—team size and exploratory degree—in order to examine the moderation effects. The results show that the negative effect of RTD becomes stronger when team size is larger, and the positive effect of DTD becomes greater when an alliance attempts to invent in a less familiar technological field where the exploratory degree is higher. Moreover, we find that RTD and DTD interact in their influences on outcomes.
Point Mutations in the Transmembrane Region of the Clic1 Ion Channel Selectively Modify Its Biophysical Properties

Chloride intracellular Channel 1 (CLIC1) is a metamorphic protein that changes from a soluble cytoplasmic protein into a transmembrane protein. Once inserted into membranes, CLIC1 multimerises and is able to form chloride selective ion channels. Whilst CLIC1 behaves as an ion channel both in cells and in artificial lipid bilayers, its structure in the soluble form has led to some uncertainty as to whether it really is an ion channel protein. CLIC1 has a single putative transmembrane region that contains only two charged residues: arginine 29 (Arg29) and lysine 37 (Lys37). As charged residues are likely to have a key role in ion channel function, we hypothesized that mutating them to neutral alanine to generate K37A and R29A CLIC1 would alter the electrophysiological characteristics of CLIC1. By using three different electrophysiological approaches: i) single channel Tip-Dip in artificial bilayers using soluble recombinant CLIC1, ii) cell-attached and iii) whole-cell patch clamp recordings in transiently transfected HEK cells, we determined that the K37A mutation altered the single-channel conductance while the R29A mutation affected the single-channel open probability in response to variation in membrane potential. Our results show that mutation of the two charged amino acids (K37 and R29) in the putative transmembrane region of CLIC1 alters the biophysical properties of the ion channel in both artificial bilayers and cells. Hence these charged residues are directly involved in regulating its ion channel activity. This strongly suggests that, despite its unusual structure, CLIC1 itself is able to form a chloride ion channel.
A compact dual-band branch-line coupler based on the interdigital transmission line

A dual-band (DB) microstrip branch-line coupler with quadrature phase difference based on the interdigital transmission line (TL) is presented. Interdigital TLs are realized by cascading interdigital capacitors (cells of the structure) in series. The design procedure to reach the dual-band interdigital transmission lines at two arbitrary frequencies is presented. Dual-band operation for branch-line coupler is achieved by implementing the interdigital TLs with 3 cells in each branch to provide a phase of −90° at the lower operation frequency band (2GHz) and −270° phase shift at the upper frequency band (3GHz). Branches length is approximately 0.8 λg and as compared to the conventional DB composite right/left handed (CRLH) branch-line couplers, the proposed structure achieves smaller dimension. Also, simulation results show that the dual-band proposed coupler exhibits an amplitude balance of ±2 dB from 1.9 GHz to 2.2 GHz in the lower band and from 2.8 GHz to 3.2 GHz in the upper band. Moreover, at mentioned frequency bands, the phase difference between the coupled and through ports is 90° ± 10°.
Neurological Soft Signs in the Clinical Course of Schizophrenia: Results of a Meta-Analysis

Neurological soft signs (NSS) comprise subtle deficits in sensory integration, motor coordination, and sequencing of complex motor acts, which are typically observed in the majority of schizophrenia patients, including chronic cases and neuroleptic-naïve first-episode patients. However, recent studies clearly demonstrate that NSS are not a static feature of schizophrenia but vary in the clinical course of the disorder. This effect was investigated in a meta-analysis based on 17 longitudinal studies published between 1992 and 2012. Studies included between 10 and 93 patients with schizophrenia spectrum disorders (total number 787) with follow-up periods between 2 and 208 weeks. Beside the Neurological Examination Scale, the Cambridge Neurological Inventory and the Heidelberg NSS Scale were used to assess NSS. All but three studies found NSS to decrease in parallel with remission of psychopathological symptoms. This effect was more pronounced in patients with a remitting compared to a non-remitting, chronic course (Cohen’s d 0.81 vs. 0.15) and was significantly correlated with length of the follow-up period (r = −0.64) but not with age (r = 0.28). NSS scores did not decrease to the level typically observed in healthy controls. From a clinical perspective, NSS may therefore be used to identify subjects at risk to develop schizophrenia and to monitor disease progression.
Potential fitness for genetic programming

We introduce potential fitness, a variant of fitness function that operates in the space of schemata and is applicable to tree-based genetic programing. The proposed evaluation algorithm estimates the maximum possible gain in fitness of an individual's direct offspring. The value of the potential fitness is calculated by analyzing the context semantics and subtree semantics for all contexts (schemata) of the evaluated tree. The key feature of the proposed approach is that a tree is rewarded for the correctly classified fitness cases, but it is not penalized for the incorrectly classified ones, provided that such errors are recoverable by substitution of an appropriate subtree (which is however not explicitly considered by the algorithm). The experimental evaluation on a set of seven boolean benchmarks shows that the use of potential fitness may lead to better convergence and higher success rate of the evolutionary run.
Image classification based on bag of visual graphs

This paper proposes the Bag of Visual Graphs (BoVG), a new approach to encode the spatial relationships of visual words through a codebook of visual-word arrangements, represented by graphs. This graph-based codebook defines a descriptor for image representations that not only considers the frequency of occurrence of visual words, but also their spatial relationships. Experiments demonstrate that BoVG yields high-accuracy scores in classification tasks on the traditional Caltech-101 and Caltech-256 datasets.
Numerical investigation on the effects of six control rods arranged in equilateral triangular configurations on fluid flow and forced convection heat transfer from a circular cylinder

The present work deals with heat transfer characteristics as well as fluid flow patterns in laminar flow regime for a circular cylinder with six control rods arranged in equilateral triangular geometries. The computations have been carried out by a finite volume approach using the overset grid method. The unsteady flow at Re= 200 and Pr= 0.7 and 7.0 was examined. The effect of the control rods on suppression of the fluid forces applied on a main cylinder has been investigated by numerical solution of the Navier-Stokes equations. Based on the results obtained, the arrangement employed in this study indicated the significant performance in reducing the oscillatory force coefficients of the primary cylinder. Except for some gap ratios, it is indicated that both drag and lift coefﬁcients are much lower than that for a single cylinder. Moreover, forced convection heat transfer was calculated using local and mean Nusselt numbers at the surface of the cylinders. The instantaneous streamlines, the vortices and isothermal contours were presented in order to analyze the temperature field and flow field around the cylinders.
Soluble Interleukin-6 Receptor-Mediated Innate Immune Response to DNA and RNA Viruses

ABSTRACT The interleukin-6 (IL-6) receptor, which exists as membrane-bound and soluble forms, plays critical roles in the immune response. The soluble IL-6 receptor (sIL6R) has been identified as a potential therapeutic target for preventing coronary heart disease. However, little is known about the role of this receptor during viral infection. In this study, we show that sIL6R, but not IL-6, is induced by viral infection via the cyclooxygenase-2 pathway. Interestingly, sIL6R, but not IL-6, exhibited extensive antiviral activity against DNA and RNA viruses, including hepatitis B virus, influenza virus, human enterovirus 71, and vesicular stomatitis virus. No synergistic effects on antiviral action were observed by combining sIL6R and IL-6. Furthermore, sIL6R mediated antiviral action via the p28 pathway and induced alpha interferon (IFN-α) by promoting the nuclear translocation of IFN regulatory factor 3 (IRF3) and NF-κB, which led to the activation of downstream IFN effectors, including 2′,5′-oligoadenylate synthetase (OAS), double-stranded RNA-dependent protein kinase (PKR), and myxovirus resistance protein (Mx). Thus, our results demonstrate that sIL6R, but not IL-6, plays an important role in the host antiviral response.
Using a predefined passphrase to evaluate a speaker verification system

This article presents a standardized and repeatable process used to evaluate the performance of a speaker verification system.Through the use of a common passphrase and a subset of extracted feature vectors that outperforms other combinations, thestudy limits the exposure to potential experimental flaws, while measuring true biometric performance more effectively thanexisting evaluation methodologies. After collecting a dataset of 33 participants, the researchers achieved a performance rate of99.8% for the 22 users who contributed at least 20 text-dependent samples. The primary focus of the research, however, was toillustrate a variety of testing techniques that can be used to efficiently analyze the performance of a speaker verification systemand advocate the use of a common passphrase in this process.
Genetic Signatures of Asthma Exacerbation

Asthma exacerbation (AE) usually denotes worsening of asthma symptoms that requires intense management to prevent further deterioration. AE has been reported to correlate with clinical and demographic factors, such as race, gender, and treatment compliance as well as environmental factors, such as viral infection, smoking, and air pollution. In addition, recent observations suggest that there are likely to be genetic factors specific to AE. Understanding genetic factors specific to AE is essential to develop therapy tailored for exacerbation-prone asthma. Here, we summarize the results of studies involving genetic risk factors for AE. To simplify and enhance understanding, we reviewed the studies according to the following categories: hypothesis-driven approaches, hypothesis-free approaches, gene-environment interactions, and pharmacogenetics.
Refined and Incremental Centroid-based approach for Genre Categorization of Web pages

In this paper, I propose a refined and incremental centroid-based approach for genre categorization of web pages. My approach is based on the construction of genre centroids using a set of training web pages. These centroids will be used to classify new web pages. The originality of my approach is the implementation of two new aspects, which are refining and incrementing. My approach is based on the combination of three information sources, which are the URL address, the logical structure and the hypertext structure. Conducted experiments show that the proposed approach is very fast and provide micro-average accuracy more than 95%, which is better than those obtained by other works on genre categorization of web pages and other machine learning techniques.
Conditional brain-specific knockdown of MAPK using Cre/loxP regulated RNA interference

In the last years, RNA interference (RNAi)-mediated gene knockdown has developed into a routine method to assess gene function in cultured mammalian cells in a fast and easy manner. For the use of this technique in developing or adult mice, short hairpin (sh)RNA vectors expressed stably from the genome are a faster alternative to conventional knockout approaches. Here we describe an advanced strategy for conditional gene knockdown in mice, where we used the Cre/loxP system to activate RNAi in a time and tissue dependent manner in the adult mouse brain. By placing conditional RNAi constructs into the defined genomic Rosa26 locus and by using recombinase mediated cassette exchange (RMCE) instead of laborious homologous recombination, we developed a fast, easy and reproducible approach to assess gene function in adult mice. We applied this technique to three genes of the MAPK signaling pathway—Braf, Mek1 and Mek2—and demonstrate here the potential of this new tool in mouse mutagenesis.