Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of Binding Sites in the Nicotinic Acetylcholine Receptor for [3H]Azietomidate, a Photoactivatable General Anesthetic*

To identify binding domains in a ligand-gated ion channel for etomidate, an intravenous general anesthetic, we photolabeled nicotinic acetylcholine receptor (nAChR)-rich membranes from Torpedo electric organ with a photoactivatable analog, [3H]azietomidate. Based upon the inhibition of binding of the noncompetitive antagonist [3H]phencyclidine, azietomidate and etomidate bind with 10-fold higher affinity to nAChRs in the desensitized state (IC50 = 70 μm) than in the closed channel state. In addition, both drugs between 0.1 and 1 mm produced a concentration-dependent enhancement of [3H]ACh equilibrium binding affinity, but they inhibited binding at higher concentrations. UV irradiation resulted in preferential [3H]azietomidate photoincorporation into the nAChR α and δ subunits. Photolabeled amino acids in both subunits were identified in the ion channel domain and in the ACh binding sites by Edman degradation. Within the nAChR ion channel in the desensitized state, there was labeling of αGlu-262 and δGln-276 at the extracellular end and δSer-258 and δSer-262 toward the cytoplasmic end. Within the acetylcholine binding sites, [3H]azietomidate photolabeled αTyr-93, αTyr-190, and αTyr-198 in the site at the α-γ interface and δAsp-59 (but not the homologous position, γGlu-57). Increasing [3H]azietomidate concentration from 1.8 to 150 μm increased the efficiency of incorporation into amino acids within the ion channel by 10-fold and in the ACh sites by 100-fold, consistent with higher affinity binding within the ion channel. The state dependence and subunit selectivity of [3H]azietomidate photolabeling are discussed in terms of the structures of the nAChR transmembrane and extracellular domains.
The hidden stressor of child welfare workers: client confidentiality as a barrier for coping with emotional work demands

Studies show that client confidentiality can inhibit proper adaptation to emotional work stress, which can affect health and well-being among help service professionals. There is a lack of knowledge on the link between confidentiality and symptoms of ill health. It is likely that confidentiality can be a hidden stressor that modifies coping strategies necessary for healthy adaptation to emotional work demands. The aim of the current paper was to investigate the influence of client confidentiality on different modes of coping among child welfare workers and possible variation according to proximity to clients and years of experience. The study included survey data among all child welfare workers (n = 142) situated at six office locations in a Norwegian city with a population of >150 000. The analyses included descriptive statistics, t-test, analysis of variance and multiple linear regressions. The results showed that client confidentiality can interfere with a range of coping strategies which are important to reduce stress from emotionally demanding work experiences among child welfare workers. This was prominent among workers with less experience or high proximity to clients. The results imply that confidentiality can interfere with adaptation to work stress, which can affect the health and well-being of child welfare workers.
Gaze-Centered Remapping of Remembered Visual Space in an Open-Loop Pointing Task

Establishing a coherent internal reference frame for visuospatial representation and maintaining the integrity of this frame during eye movements are thought to be crucial for both perception and motor control. A stable headcentric representation could be constructed by internally comparing retinal signals with eye position. Alternatively, visual memory traces could be actively remapped within an oculocentric frame to compensate for each eye movement. We tested these models by measuring errors in manual pointing (in complete darkness) toward briefly flashed central targets during three oculomotor paradigms; subjects pointed accurately when gaze was maintained on the target location (control paradigm). However, when steadily fixating peripheral locations (static paradigm), subjects exaggerated the retinal eccentricity of the central target by 13.4 ± 5.1%. In the key “dynamic” paradigm, subjects briefly foveated the central target and then saccaded peripherally before pointing toward the remembered location of the target. Our headcentric model predicted accurate pointing (as seen in the control paradigm) independent of the saccade, whereas our oculocentric model predicted misestimation (as seen in the static paradigm) of an internally shifted retinotopic trace. In fact, pointing errors were significantly larger than were control errors (p ≤ 0.003) and were indistinguishable (p ≥ 0.25) from the static paradigm errors. Scatter plots of pointing errors (dynamic vs static paradigm) for various final fixation directions showed an overall slope of 0.97, contradicting the headcentric prediction (0.0) and supporting the oculocentric prediction (1.0). Varying both fixation and pointing-target direction confirmed that these errors were a function of retinotopically shifted memory traces rather than eye position per se. To reconcile these results with previous pointing experiments, we propose a “conversion-on-demand” model of visuomotor control in which multiple visual targets are stored and rotated (noncommutatively) within the oculocentric frame, whereas only select targets are transformed further into head- or bodycentric frames for motor execution.
Video matching using binary signature

Automated video matching and recognition has emerged in many applications in recent years. Computer recognition of TV commercials is one of interesting areas. One of critical challenges in automatic recognition of TV commercials is to generate a unique, robust and compact signature. As amount of video data is stored in large quantities, it is necessary to propose an efficient technique for video seeking and matching. In this paper, we present a binary signature based method BOC for TV matching. Experimental results on a real large commercial video database show that our novel approach delivers a significantly better performance comparing to the existing methods.
Purification and Three-Dimensional Electron Microscopy Structure of the Neisseria meningitidis Type IV Pilus Biogenesis Protein PilG

ABSTRACT Type IV pili are surface-exposed retractable fibers which play a key role in the pathogenesis of Neisseria meningitidis and other gram-negative pathogens. PilG is an integral inner membrane protein and a component of the type IV pilus biogenesis system. It is related by sequence to the extensive GspF family of secretory proteins, which are involved in type II secretion processes. PilG was overexpressed and purified from Escherichia coli membranes by detergent extraction and metal ion affinity chromatography. Analysis of the purified protein by perfluoro-octanoic acid polyacrylamide gel electrophoresis showed that PilG formed dimers and tetramers. A three-dimensional (3-D) electron microscopy structure of the PilG multimer was determined using single-particle averaging applied to samples visualized by negative staining. Symmetry analysis of the unsymmetrized 3-D volume provided further evidence that the PilG multimer is a tetramer. The reconstruction also revealed an asymmetric bilobed structure approximately 125 Å in length and 80 Å in width. The larger lobe within the structure was identified as the N terminus by location of Ni-nitrilotriacetic acid nanogold particles to the N-terminal polyhistidine tag. We propose that the smaller lobe corresponds to the periplasmic domain of the protein, with the narrower “waist” region being the transmembrane section. This constitutes the first report of a 3-D structure of a member of the GspF family and suggests a physical basis for the role of the protein in linking cytoplasmic and periplasmic protein components of the type II secretion and type IV pilus biogenesis systems.
Comparing an Iconic Interface to a Text-based and Virtual Paths Interface for Effective Interaction in an Interactive Workspace

ARIS is an iconic interface that enables users to relocate applications and redirect input in an interactive workspace. We compared the use of ARIS to a text-based and virtual paths (VP) interface for relocating applications and redirecting input. Results showed that the iconic interface was more effective than the text-based interface and almost as effective as the VP interface. Since the use of text-based interfaces is common, the use of an iconic interface enables relocation and redirection tasks to be performed more effectively than today. Though it imposes a small additional cost, an iconic interface also supports features useful for interactive spaces that a VP interface does not.
The EGG/YOLK reliability hierarchy: semantic data integration using sorts with prototypes

Integration of disparate heterogeneous databases requires translation of types. Because a type in one system often has no exact counterpart in the others, fully reliable integration requires deep understanding of the subject domain, with conceptual analysis of type meanings. So far, reliable translation has had to be done by hand. In practice, few types are so crucial as to require full reliability. The EGG/YOLK hierarchy ranks types by the tolerable rashness in translation, based on prototypes in each type. Each defined class (EGG) has a subclass of typical members (YOLK) defined. We exploit Cui, Cohn and Randell's Qualitative Spatial Simulation program to create the hierarchy of all possible relations between source and target EGG/YOLK types, ranked by reliability. Our eventual ranking is based on a poset combining four different preference criteria.
Protoporphyrin (PPIX) efflux by the MacAB-TolC pump in Escherichia coli

In most organisms, heme biosynthesis is strictly controlled so as to avoid heme and heme precursor accumulation, which is toxic. Escherichia coli regulates heme biosynthesis by a feedback loop involving heme‐induced proteolytic cleavage of HemA, glutamyl‐tRNA reductase, which is the first enzyme in the heme biosynthetic pathway. We show here that heme homeostasis can be disrupted by overproduction of YfeX, a cytoplasmic protein that captures iron from heme that we named deferrochelatase. We also show that it is disrupted by iron chelation, which reduces the intracellular iron concentration necessary for loading iron into protoporphyrin IX (PPIX, the immediate heme precursor). In both cases, we established that there is an increased PPIX concentration and we demonstrate that this compound is expelled by the MacAB‐TolC pump, an efflux pump involved in E. coli and Salmonella for macrolide efflux. The E. coli macAB and tolC mutants accumulate PPIX and are sensitive to photo‐inactivation. The MacAB‐TolC pump is required for Salmonella typhimurium survival in macrophages. We propose that PPIX is an endogenous substrate of the MacAB‐TolC pump in E. coli and S. typhimurium and that this compound is produced inside bacteria when natural heme homeostasis is disrupted by iron shortage, as happens when bacteria invade the mammalian host.
Understanding Drawings by Compositional Analogy

We describe an analogical method for constructing a structuralmodel froman unlabelled 2D line drawing. The source case is represented as a schema that contains its 2D line drawing, the lines and intersections in the drawing, the shapes in drawing, and the structural model of the device depicted in the drawing. Given a target drawing and a relevant source case, our method first constructs a graphical representation of the lines and the intersections in the target drawing, then uses the mappings at the level of line intersections to transfer the shape representations from the source case to the target, next uses the mappings at the level of shapes to transfer the structural model of the device from the source to the target. The Archytas system implements and evaluates this method of compositional analogy.
Energy Efficiency in MIMO Underlay and Overlay Device-to-Device Communications and Cognitive Radio Systems

This paper addresses the problem of resource allocation for systems in which a primary and a secondary link share the available spectrum by an underlay or overlay approach. After observing that such a scenario models both cognitive radio and D2D communications, we formulate the problem as the maximization of the secondary energy efficiency subject to a minimum rate requirement for the primary user. This leads to challenging nonconvex, fractional problems. In the underlay scenario, we obtain the global solution by means of a suitable reformulation. In the overlay scenario, two algorithms are proposed. The first one yields a resource allocation fulfilling the first-order optimality conditions of the resource allocation problem, by solving a sequence of easier fractional programs. The second one enjoys a weaker optimality claim, but an even lower computational complexity. Numerical results demonstrate the merits of the proposed algorithms both in terms of energy-efficient performance and complexity, also showing that the two proposed algorithms for the overlay scenario perform very similarly, despite the different complexity.
Effect of Exenatide, Sitagliptin, or Glimepiride on β-Cell Secretory Capacity in Early Type 2 Diabetes

OBJECTIVE Agents that augment GLP-1 effects enhance glucose-dependent β-cell insulin production and secretion and thus are hoped to prevent progressive impairment in insulin secretion characteristic of type 2 diabetes (T2D). The purpose of this study was to evaluate GLP-1 effects on β-cell secretory capacity, an in vivo measure of functional β-cell mass, early in the course of T2D. RESEARCH DESIGN AND METHODS We conducted a randomized controlled trial in 40 subjects with early T2D who received the GLP-1 analog exenatide (n = 14), the dipeptidyl peptidase IV inhibitor sitagliptin (n = 12), or the sulfonylurea glimepiride (n = 14) as an active comparator insulin secretagogue for 6 months. Acute insulin responses to arginine (AIRarg) were measured at baseline and after 6 months of treatment with 5 days of drug washout under fasting, 230 mg/dL (glucose potentiation of arginine-induced insulin release [AIRpot]), and 340 mg/dL (maximum arginine-induced insulin release [AIRmax]) hyperglycemic clamp conditions, in which AIRmax provides the β-cell secretory capacity. RESULTS The change in AIRpot was significantly greater with glimepiride versus exenatide treatment (P < 0.05), and a similar trend was notable for the change in AIRmax (P = 0.1). Within each group, the primary outcome measure, AIRmax, was unchanged after 6 months of treatment with exenatide or sitagliptin compared with baseline but was increased with glimepiride (P < 0.05). α-Cell glucagon secretion (AGRmin) was also increased with glimepiride treatment (P < 0.05), and the change in AGRmin trended higher with glimepiride than with exenatide (P = 0.06). CONCLUSIONS After 6 months of treatment, exenatide or sitagliptin had no significant effect on functional β-cell mass as measured by β-cell secretory capacity, whereas glimepiride appeared to enhance β- and α-cell secretion.
Superbubbles and energetic particles in the Galaxy. I. Collective effects of particle acceleration

Observations indicate that most massive stars in the Galaxy appear in groups, called OB associations, where their strong wind activity generates large structures known as superbubbles, inside which the subsequent supernovae (SNe) explode, with a tight space and time correlation. We investigate four main questions: 1) does the clustering of massive stars and SN explosions influence the particle acceleration process usually associated with SNe, and induce collective effects which would not manifest around isolated supernova remnants? ; 2) does it make a difference for the general phenomenology of Galactic Cosmic Rays (GCRs), notably for their energy spectrum and composition? ; 3) Can this help alleviate some of the problems encountered within the standard GCR source model? ; and 4) Is the link between superbubbles and energetic particles supported by observational data, and can it be further tested and constrained? We argue for a positive answer to all these questions. Theoretical, phenomenological and observational aspects are treated in separate papers. Here, we discuss the interaction of massive stellar winds and SN shocks inside superbubbles and indicate how this leads to specific acceleration effects. We also show that due to the high SN explosion rate and low diffusion coefficient, low-energy particles experience repeated shock acceleration inside superbubbles.
Distributed stopping for average consensus in directed graphs via a randomized event-triggered strategy

We consider how an iterative strategy for asymptotic average consensus in a directed graph (digraph) can be adapted so that the nodes can determine, in a distributed manner, a stopping criterion that allows them to terminate the execution of the iteration when approximate average consensus has been reached. The nodes are said to have reached approximate average consensus when each of them has a value that is close to the desirable average (in a way that we precisely define). The algorithm we propose can be used in practical settings to cap the number of transmissions that are required in order to reach (approximate) average consensus.
Freed-Witten anomaly in general flux compactification

Turning on a Neveu-Schwarz\char21{}Neveu-Schwarz (NS-NS) three-form flux in a compact space drives some D-branes to be either Freed-Witten anomalous or unstable to decay into fluxes by the appearance of instantonic branes. By applying $T$-duality on a toroidal compactification, the NS flux is transformed into metric fluxes. We propose a $T$-dual version of the Atiyah-Hirzebruch Spectral Sequence upon which we describe the Freed-Witten anomaly and the brane-flux transition driven by NS and metric fluxes in a twisted torus. The required conditions to cancel the anomaly and the appearance of new instantonic branes are also described. In addition, we give an example in which all D6-branes wrapping Freed-Witten anomaly-free three-cycles in ${\stackrel{\texttildelow{}}{T}}^{6}/{\mathbb{Z}}_{2}\ifmmode\times\else\texttimes\fi{}{\mathbb{Z}}_{2}$ are nevertheless unstable to decay into fluxes. Even more we find a topological transformation between Ramond-Ramond, NS-NS, and metric fluxes driven by a chain of instantonic branes.
Sampling of pulse streams: Achieving the rate of innovation

We consider the problem of sampling signals which are comprised of pulse streams. This model belongs to the recently introduced framework of signals with finite rate of innovation. The minimal sampling rate for such signals is the number of degrees of freedom per unit of time, referred to as the rate of innovation. Although sampling of pulse streams was treated in various works, either the rate of innovation was not achieved, or the pulse shape was limited to diracs. In this work we propose multichannel schemes for arbitrary pulse streams, operating at the rate of innovation. The proposed approach is based on modulating the input signal in each channel with a properly chosen waveform, followed by an integrator. We show that the pulses delays and amplitudes can be recovered from the samples using standard spectral estimation tools. The resulting scheme is flexible and exhibits better noise robustness than previous approaches.
On the Expressiveness of Information Extraction Patterns

Many recently reported machine learning approaches to the a cquisition of information extraction (IE) patterns have us ed dependency trees as the basis for their pattern representat ions (Yangarber et al., 2000a; Yangarber, 2003; Sudo et al., 2003; Stevenson and Greenwood, 2005). While varying result s have been reported for the resulting IE systems little has been reported about the ability of dependency trees, or patt erns extracted from them, to represent relationships neede d to perform IE. In this paper we evaluate the ability of a number o f pattern representations, derived from dependency trees, to represent the relationships being extracted by an IE syst em. The paper concludes by suggesting the use of the “linked chains” model which represents around 94% of the possible re lations in text but without generating an unwieldy number of candidate extraction patterns.
Extracellular pH Dynamically Controls Cell Surface Delivery of Functional TRPV5 Channels

ABSTRACT Extracellular pH has long been known to affect the rate and magnitude of ion transport processes among others via regulation of ion channel activity. The Ca2+-selective transient receptor potential vanilloid 5 (TRPV5) channel constitutes the apical entry gate in Ca2+-transporting cells, contributing significantly to the overall Ca2+ balance. Here, we demonstrate that extracellular pH determines the cell surface expression of TRPV5 via a unique mechanism. By a comprehensive approach using total internal reflection fluorescence microscopy, cell surface protein labeling, electrophysiology, 45Ca2+ uptake assays, and functional channel recovery after chemobleaching, this study shows that upon extracellular alkalinization, a pool of TRPV5-containing vesicles is rapidly recruited to the cell surface without collapsing into the plasma membrane. These vesicles contain functional TRPV5 channels since extracellular alkalinization is accompanied by increased TRPV5 activity. Conversely, upon subsequent extracellular acidification, vesicles are retrieved from the plasma membrane, simultaneously resulting in decreased TRPV5 activity. Thus, TRPV5 accesses the extracellular compartment via transient openings of vesicles, suggesting that rapid responses of constitutive active TRP channels to physiological stimuli rely on vesicular “kiss and linger” interactions with the plasma membrane.
ON MORTGAGE PREPAYMENT AND DEFAULT: A HISTORICAL DISTRIBUTION ANALYSIS APPROACH

We present evidence on mortgage default and prepayment distributions based on a subset of PMI Mortgage Insurance Co. data. We show that marginal claim distributions for specific asset classes are varied and skewed in nature, and may be joined through an estimated covariance matrix and Monte-Carlo simulation. Ignoring correlation effects underestimates tail portfolio claim probabilities, which is illustrated through a set of examples. A ranking of asset classes defined by product type, Loan-to-Value-ratio (LTV), credit quality, and seasoning is presented based on unexpected claims and select measures of persistency. The impact of geographical diversification is examined to show that increasing diversification raises the expected claim rate, but lowers the unexpected claim rate.
Automatic traceability acquisition framework

In this paper we will describe an automatic traceability acquisition framework for existing web applications and how to take advantage of acquired provenance information about user actions on the Internet, namely resource uploading. We will show how traceability information provided by common websites can be stored in available Linked Open Data repositories, thus enhancing cross-domain trust upon resources published on the World Wide Web. A framework such as this is also submitted to evaluation on the popular Word-Press web application, demonstrating how easily it can be deployed to existing web applications.