Miracle-dz/UniFAR-FTUs huggingface dataset:
Glial-derived adenosine modulates spinal motor networks in mice

The activation of purinergic receptors modulates central pattern generators controlling rhythmic motor behaviors, including respiration in rodents and swimming in frog tadpoles. The present study aimed to determine whether purinergic signaling also modulates the mammalian locomotor central pattern generator. This was investigated by using isolated spinal cord preparations obtained from neonatal mice in which locomotor-related activity can be induced pharmacologically. The application of either ATP or adenosine led to a reduction in the frequency of locomotor activity recorded from ventral roots. ATP had no effect when applied in the presence of both the adenosine receptor antagonist theophylline and the ectonucleotidase inhibitor ARL67156, demonstrating that the effects of ATP application result from the breakdown of ATP to adenosine and subsequent activation of adenosine receptors. The application of theophylline or the A1-specific antagonist cyclopentyl dipropylxanthine, but not the A2A-receptor antagonist SCH58261, caused an increase in locomotor burst frequency, demonstrating that endogenously derived adenosine activates A1 receptors during locomotor network activity. Furthermore, theophylline had no effect in the presence of the ectonucleotidase inhibitor ARL67156 or the glial toxins methionine sulfoximine or ethyl fluoracetate, suggesting that endogenous adenosine is derived from ATP, which is released from glia. Finally, adenosine had no effect on slow rhythmic activity recorded upon blockade of all inhibitory transmission, suggesting that adenosine may act via the modulation of inhibitory transmission. Together, these data highlight endogenous purinergic gliotransmission, involving activation of A1 receptors, as an important intrinsic modulatory system controlling the frequency of activity generated by spinal locomotor circuitry in mammals.
Mediators' Cognitive Role Schema

This study identifies the cognitive role schema of 189 practicing mediators. An initial analysis of the mediators' questionnaire responses revealed 13 facets in the mediators' schema, and a second analysis condensed this to four goals: agreement, improvement of the parties' relationship, benefit the parties as well as society, and improve the mediation process. Not only do these facets indicate how the mediators think, but they also provide predictions about the mediators' behavior (e.g., they will strive primarily for agreement).
Molecular mechanisms of intercellular communication in the hormonal and neural systems

This paper reviews our studies that have addressed the molecular mechanisms underlying the biosynthesis and reception of extracellular signaling molecules and integrative mechanisms of extracellular‐intracellular signaling transmission in biological systems. We introduced recombinant DNA technology into the neuroendocrine system and established the concept that a single peptide precursor encompasses multiple biologically active peptides and brings about coordinate functions in various biological systems. We then developed a novel functional cloning of membrane receptors and ion channels by combining an oocyte expression system with electrophysiology. We molecularly elucidated not only various peptide receptors, including the first demonstration of the molecular entity of a G protein‐coupled peptide receptor (GPCR), substance K receptor, and also diverse members of both G protein‐coupled metabotropic type and NMDA type of neurotransmitter glutamate receptors. We demonstrated many novel synaptic mechanisms involving distinct types of glutamate receptors in brain function and dysfunction. These include the mechanisms underlying segregation of light‐dark signals in visual transmission, discrimination and memory formation in olfactory transmission, and motor co‐ordination in the cerebellum, basal ganglia and the retinal network. iubmb Life, 58: 349‐357, 2006
Utilizing Displayless Space in Collocated Games

Digital games have often been viewed as anti-social. However, this view has been recently changing as social aspects of games are gaining more emphasis. We explore the usage of physical space to enable socially richer game experiences. In particular, we utilize the spatial relationship between portable gaming devices to show multiple views into a shared game world. Similar multi-display systems have been studied in desktop PC environments to address the usability problems caused by gaps and bezels between the displays. In this paper, we demonstrate that this source of problems in utility applications can be a design opportunity in games. We implemented and evaluated two games that are played by two players using touch-screen controlled portable devices on a table. Results of our qualitative study show that the displayless space between the devices can be used to increase challenge, create positive surprises, stimulate imagination, and provoke social interaction in games. We also identified some design pitfalls that may break the illusion of a coherent space.
Geometric Bounds for Eigenvalues of Markov Chains

We develop bounds for the second largest eigenvalue and spectral gap of a reversible Markov chain. The bounds depend on geometric quantities such as the maximum degree, diameter and covering number of associated graphs. The bounds compare well with exact answers for a variety of simple chains and seem better than bounds derived tbrough Cheeger-like inequalities. They offer improved rates of convergence for the random walk associated to approximate computation of the permanent.
ARC15105 Is a Potent Antagonist of Von Willebrand Factor Mediated Platelet Activation and Adhesion

Objective—We investigated the stability, pharmacokinetic, and pharmacodynamic profile of the 2nd generation anti-von Willeband factor aptamer ARC15105. Methods and Results—Platelet plug formation was measured by collagen/adenosine diphosphate-induced closure time with the platelet function analyzer-100 and platelet aggregation by multiple electrode aggregometry. Platelet adhesion was measured on denuded porcine aortas and in a flow chamber. Aptamer stability was assessed by incubation in nuclease rich human, monkey, and rat serum for up to 72 hours. Pharmacokinetic and pharmacodynamic profiles were tested in cynomolgus monkeys after IV and SC administration. The median IC100 and IC50 to prolong collagen/adenosine diphosphate-induced closure timewere 27 nmol/L and 12 nmol/L, respectively. ARC15105 (1.3 &mgr;mol/L) completely inhibited ristocetin-induced platelet aggregation in whole blood (P<0.001), but also diminished collagen, ADP, arachidonic acid, and thrombin receptor activating peptide-induced platelet aggregation to some extent (P<0.05). ARC15105 (40 nmol/L) decreased platelet adhesion by >90% on denuded porcine aortas (P<0.001), which was comparable to the degree of inhibition obtained with abciximab. ARC15105 (100 nmol/L) also inhibited platelet adhesion to collagen under arterial shear in a flow chamber by >90% (P<0.001). The IV and SC terminal half-lives in cynomolgus monkeys were 67 and 65 hours, respectively, and the SC bioavailability was ≈98%. Allometric scaling estimates the human T1/2 would be ≈217 hours. Pharmacodynamic analysis confirms that ARC15105 inhibits von Willeband factor activity >90% in blood samples taken 300 hours after a 20 mg/kg IV or SC dose in monkeys. Conclusion—The potency, pharmacokinetic profile, and SC bioavailability of ARC15105 support its clinical investigation for chronic inhibition of von Willeband factor -mediated platelet activation.
La vision stratégique du propriétaire-dirigeant de PME: étude de cartographie cognitive

Le concept de vision strategique suscite depuis quelques annees un interet grandissant, notamment dans les etudes portant sur la PME. Cependant, les techniques a la disposition des chercheurs et des consultants pour etudier empiriquement la vision strategique des dirigeants d’entreprise sont encore tres peu nombreuses. A cet egard, l’utilisation de la cartographie cognitive s’avere interessante etant donne qu’elle facilite l’exploration des idees enoncees et qu’elle en rend possible une analyse particuliere a l’aide, notamment, du logiciel COPE. C’est ce que cette recherche mettra en evidence a partir du cas d’un proprietaire-dirigeant d’une PME manufacturiere quebecoise. Certaines difficultes relatives a l’utilisation de la cartographie cognitive seront soulevees et quelques avenues de recherche seront envisagees.
Implementation and computational results for the hierarchical algorithm for making sparse matrices sparser

If A is the (sparse) coefficient matrix of linear-equality constraints, for what nonsingular T is A = TA as sparse as possible, and how can it be efficiently computed? An efficient algorithm for this Sparsity Problem (SP) would be a valuable preprocessor for linearly constrained optimization problems. In a companion paper we developed a two-pass approach to solve SP called the Hierarchical Algorithm. In this paper we report on how we implemented the Hierarchical Algorithm into a code called HASP, and our computational experience in testing HASP on the NETLIB linear-programming problems. We found that HASP substantially outperformed a previous code for SP and that it produced a net savings in optimization time on the NETLIB problems. The results allow us to give guidelines for its use in practice.
Role of Kras Status in Patients with Metastatic Colorectal Cancer Receiving First-Line Chemotherapy plus Bevacizumab: A TTD Group Cooperative Study

Background In the MACRO study, patients with metastatic colorectal cancer (mCRC) were randomised to first-line treatment with 6 cycles of capecitabine and oxaliplatin (XELOX) plus bevacizumab followed by either single-agent bevacizumab or XELOX plus bevacizumab until disease progression. An additional retrospective analysis was performed to define the prognostic value of tumour KRAS status on progression-free survival (PFS), overall survival (OS) and response rates. Methodology/Principal Findings KRAS data (tumour KRAS status and type of mutation) were collected by questionnaire from participating centres that performed KRAS analyses. These data were then cross-referenced with efficacy data for relevant patients in the MACRO study database. KRAS status was analysed in 394 of the 480 patients (82.1%) in the MACRO study. Wild-type (WT) KRAS tumours were found in 219 patients (56%) and mutant (MT) KRAS in 175 patients (44%). Median PFS was 10.9 months for patients with WT KRAS and 9.4 months for patients with MT KRAS tumours (p = 0.0038; HR: 1.40; 95% CI:1.12–1.77). The difference in OS was also significant: 26.7 months versus 18.0 months for WT versus MT KRAS, respectively (p = 0.0002; HR: 1.55; 95% CI: 1.23–1.96). Univariate and multivariate analyses showed that KRAS was an independent variable for both PFS and OS. Responses were observed in 126 patients (57.5%) with WT KRAS tumours and 76 patients (43.4%) with MT KRAS tumours (p = 0.0054; OR: 1.77; 95% CI: 1.18–2.64). Conclusions/Significance This analysis of the MACRO study suggests a prognostic role for tumour KRAS status in patients with mCRC treated with XELOX plus bevacizumab. For both PFS and OS, KRAS status was an independent factor in univariate and multivariate analyses.
Direct Sequencing of SARS-Coronavirus S and N Genes from Clinical Specimens Shows Limited Variation

Abstract Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) emerged, in November 2002, as a novel agent causing severe respiratory illness. To study sequence variation in the SARS-CoV genome, we determined the nucleic acid sequence of the S and N genes directly from clinical specimens from 10 patients—1 specimen with no matched SARS-CoV isolate, from 2 patients; multiple specimens from 3 patients; and matched clinical-specimen/ cell-culture-isolate pairs from 6 patients. We identified 3 nucleotide substitutions that were most likely due to natural variation and 2 substitutions that arose after cell-culture passage of the virus. These data demonstrate the overall stability of the S and N genes of SARS-CoV over 3 months during which a minimum of 4 generations for transmission events occurred. These findings are a part of the expanding investigation of the evolution of how this virus adapts to a new host.
Improved Monte-Carlo Search

Monte-Carlo search has been successful in many non-deterministic games, and recently in deterministic games with high branching factor. One of the drawbacks of the current approaches is that even if the iterative process would last for a very long time, the selected move does not necessarily converge to a game-theoretic optimal one. In this paper we introduce a new algorithm, UCT, which extends a bandit algorithm for Monte-Carlo search. It is proven that the probability that the algorithm selects the correct move converges to 1. Moreover it is shown empirically that the algorithm converges rather fast even in comparison with alpha-beta search. Experiments in Amazons and Clobber indicate that the UCT algorithm outperforms considerably a plain Monte-Carlo version, and it is competitive against alpha-beta based game programs.
Sensitivity of neural networks which approximate the Neyman-Pearson detector to threshold variations

The application of adaptive systems trained in a supervised manner to approximate the Neyman-Pearson detector is considered. The general expression of the function approximated when using the LMSE criterion is calculated. To evaluate the sensitivity of the decision rule based on this function to threshold variations, a novel strategy is proposed based on the calculus of the partial derivative of the probabilities of detection and false alarm with respect to detection threshold. Results allow us to explain the dependence of the decision rule performance on design parameters such as the prior probabilities, the desired outputs and the signal to noise ratio selected for training (TSNR). In previous works based on a trial and error strategy, TSNR has appeared as a critical parameter, but until now, no effort had been made to explain it. As an example, the detection of gaussian signals in gaussian interference is considered.
The effect of temporal psychological distance on reliance on word-of-mouth for information about destination image attributes

ABSTRACT This study examines the effect of temporal psychological distance on travellers’ reliance on three types of word-of-mouth (WOM): traditional WOM (tWOM), social media WOM (SNS-WOM), and online review WOM (OR-WOM) in the search for information related to the relaxation, excitement, cost level, and safety destination image attributes. High and low temporal distance was manipulated using distances of 12 months and 2 months, respectively. A series of t-tests of 283 valid responses (155 and 128 for the 12-month and 2-month scenarios, respectively) shows a significant difference in reliance on tWOM when respondents sought safety attribute information, for SNS-WOM when respondents sought relaxation and safety attribute information, and for OR-WOM when respondents sought relaxation attribute information. Thus, this study shows that in terms of temporal distance, WOM is not a homogeneous block. They have sufficiently different characteristics (e.g. level of tie strength and synchronous/asynchronous modes), which, when they interact with the nature of the destination attributes, results in differing reliance on the three types of WOM under various temporal distances. This study thus contributes to construal level theory research and provides a better understanding of the different characteristics of the three types of WOM.
Cost-effectiveness of insulin detemir versus insulin glargine for Thai type 2 diabetes from a payer’s perspective

Abstract Aims: An economic evidence is a vital tool that can inform the decision to use costly insulin analogs. This study aimed to evaluate long-term cost-effectiveness of insulin detemir (IDet) compared with insulin glargine (IGlar) in type 2 diabetes (T2DM) from the Thai payer’s perspective. Methods: Long-term costs and outcomes were projected using a validated IMS CORE Diabetes Model, version 8.5. Cohort characteristics, baseline risk factors, and costs of diabetes complications were derived from Thai data sources. Relative risk was derived from a systematic review and meta-analysis study. Costs and outcomes were discounted at 3% per annum. Incremental cost-effectiveness ratio (ICER) was presented in 2015 US Dollars (USD). A series of one-way and probabilistic sensitivity analyses were performed. Results: IDet yielded slightly greater quality-adjusted life years (QALYs) (8.921 vs 8.908), but incurred higher costs than IGlar (90,417.63 USD vs 66,674.03 USD), resulting in an ICER of ∼1.7 million USD per QALY. The findings were very sensitive to the cost of IDet. With a 34% reduction in the IDet cost, treatment with IDet would become cost-effective according to the Thai threshold of 4,434.59 USD per QALY. Conclusions: Treatment with IDet in patients with T2DM who had uncontrolled blood glucose with oral anti-diabetic agents was not a cost-effective strategy compared with IGlar treatment in the Thai context. These findings could be generalized to other countries with a similar socioeconomics level and healthcare systems.
Dynamic Instrumentation of C + + Applications on IA-64

Dynamic instrumentation is the process of modifying a program’s binary instructions on the fly while the program executes. This technique is used in a wide variety of tools for performance analysis, profiling, coverage analysis, correctness checking, and testing. Instrumenting applications generated from C++ sources reveals new complications, mainly caused by the C++ exception handling mechanism. This paper presents problems, solutions and experiences specific to dynamic instrumentation of multi-threaded C++ applications for HP-UX running on IA-64 processors.
An Approach to Function Annotation for Proteins of Unknown Function (PUFs) in the Transcriptome of Indian Mulberry

The modern sequencing technologies are generating large volumes of information at the transcriptome and genome level. Translation of this information into a biological meaning is far behind the race due to which a significant portion of proteins discovered remain as proteins of unknown function (PUFs). Attempts to uncover the functional significance of PUFs are limited due to lack of easy and high throughput functional annotation tools. Here, we report an approach to assign putative functions to PUFs, identified in the transcriptome of mulberry, a perennial tree commonly cultivated as host of silkworm. We utilized the mulberry PUFs generated from leaf tissues exposed to drought stress at whole plant level. A sequence and structure based computational analysis predicted the probable function of the PUFs. For rapid and easy annotation of PUFs, we developed an automated pipeline by integrating diverse bioinformatics tools, designated as PUFs Annotation Server (PUFAS), which also provides a web service API (Application Programming Interface) for a large-scale analysis up to a genome. The expression analysis of three selected PUFs annotated by the pipeline revealed abiotic stress responsiveness of the genes, and hence their potential role in stress acclimation pathways. The automated pipeline developed here could be extended to assign functions to PUFs from any organism in general. PUFAS web server is available at http://caps.ncbs. res.in/pufas/ and the web service is accessible at http://capservices.ncbs. res.in/help/pufas.
On the cell probe complexity of membership and perfect hashing

We study two fundamental static data structure problems, membership and perfect hashing, in Yao's cell probe model. The first space and bit probe optimal worst case upper bound is given for the membership problem. We also give a new efficient membership scheme where the query algorithm makes just one adaptive choice, and probes a total of three words. A lower bound shows that two word probes generally do not suffice. For minimal perfect hashing we show a tight bit probe lower bound, and give a simple scheme achieving this performance, making just one adaptive choice. Linear range perfect hashing is shown to be implementable with the same number of bit probes, of which just one is adaptive. In contrast, we establish that for sufficiently sparse sets, non-adaptive perfect hashing needs exponentially more bit probes. This is the first such separation of adaptivity and non-adaptivity.
CD4+ T Cells and CD40 Participate in Selection and Homeostasis of Peripheral B Cells

Control of peripheral B cell development and homeostasis depends critically on coordinate signals received through the BAFFRs and BCRs. The extent to which other signals contribute to this process, however, remains undefined. We present data indicating that CD4+ T cells directly influence naive B cell development via CD40 signaling. Loss of CD4+ T cells or CD40–CD40L interaction leads to reduced B cell homeostatic proliferation and hindered B cell reconstitution posttransplantation. Furthermore, we demonstrate that in the absence of CD40 signals, these events are modulated by BCR self-reactivity. Strikingly, murine models lacking CD40 reveal a broadly altered BCR specificity and limited diversity by both single-cell cloning and high-throughput sequencing techniques. Collectively, our results imply that any setting of T cell lymphopenia or reduced CD40 function, including B cell recovery following transplantation, will impact the naive B cell repertoire.
Early aggressive nutrition in the neonate.

1. Patti J. Thureen, MD* 1. 2. *Associate Professor, Department of Pediatrics, University of Colorado Health Sciences Center, Denver, CO. After completing this article, readers should be able to: 1. Describe the possible long-term effects of suboptimal nutrition in preterm infants and critically ill term neonates. 2. Explain why the current standard for postnatal nutrition in preterm infants may not be adequate for postnatal growth. 3. List the the lower limit at which to start intravenous protein delivery in very low-birthweight infants. 4. Characterize the commonly used definition for minimal enteral nutrition. 5. List the advantages of minimal enteral nutrition compared with exclusive total parenteral nutrition for the neonate. Nutritional practices vary dramatically among neonatal intensive care units (NICUs) in the United States. In many institutions, nutrition is introduced only gradually over the first weeks of life because of concerns of nutrient intolerance by the very preterm or ill infant who is fed intravenously and the risk of necrotizing enterocolitis (NEC) in preterm infants who are fed enterally. Often this period of nutritional deficiency is accepted as inevitable in this population. However, such a strategy of cautious nutrition might lead to a period of early malnutrition from which the neonate has a prolonged recovery and may have long-term adverse consequences. In many neonates this period of early nutritional deprivation need not be inescapable. Many neonatologists will consider the early feeding strategies for the NICU population suggested in this article to be somewhat aggressive. The premise for these recommendations for extremely low-birthweight (ELBW) infants is that avoiding early malnutrition has both short- and long-term benefits for the neonate. This strategy involves initiating total parenteral nutrition (TPN) in the first hours after birth and administering it in conjunction with initially small, and then advancing, enteral feedings beginning on the first or second day of life. Use of TPN is a means to achieve rapid, maximal nutrition, and early enteral feedings are designed to prime the gut and …