Miracle-dz/UniFAR-FTUs huggingface dataset:
Catalytic mechanism of α-phosphate attack in dUTPase is revealed by X-ray crystallographic snapshots of distinct intermediates, 31P-NMR spectroscopy and reaction path modelling

Enzymatic synthesis and hydrolysis of nucleoside phosphate compounds play a key role in various biological pathways, like signal transduction, DNA synthesis and metabolism. Although these processes have been studied extensively, numerous key issues regarding the chemical pathway and atomic movements remain open for many enzymatic reactions. Here, using the Mason–Pfizer monkey retrovirus dUTPase, we study the dUTPase-catalyzed hydrolysis of dUTP, an incorrect DNA building block, to elaborate the mechanistic details at high resolution. Combining mass spectrometry analysis of the dUTPase-catalyzed reaction carried out in and quantum mechanics/molecular mechanics (QM/MM) simulation, we show that the nucleophilic attack occurs at the α-phosphate site. Phosphorus-31 NMR spectroscopy (31P-NMR) analysis confirms the site of attack and shows the capability of dUTPase to cleave the dUTP analogue α,β-imido-dUTP, containing the imido linkage usually regarded to be non-hydrolyzable. We present numerous X-ray crystal structures of distinct dUTPase and nucleoside phosphate complexes, which report on the progress of the chemical reaction along the reaction coordinate. The presently used combination of diverse structural methods reveals details of the nucleophilic attack and identifies a novel enzyme–product complex structure.
Skin regeneration stimulation: the role of PCL‐platelet gel nanofibrous scaffold

Skin is the largest organ of the human body. Thus far, tissue engineering of skin has developed rapidly and has used many types of growth factors and nanofibrous scaffolds. In this study, we differentiated neonate keratinocytes for epithelialization on the polycaprolactone‐Platelet gel (PCL‐PG) scaffold. Fabricated PCL nanofibers prepared by electrospinning technology and coated by platelet gel. Subsequently, the structure of the scaffold was evaluated by SEM, FTIR‐ATR, contact angle and tensile test assays. After seeding the neonate keratinocytes on neat PCL and PCL‐PG scaffolds, the epidermal maturation was tested by detecting cytokeratin 10 and loricrin determinants by immunocytochemistry; moreover, keratinocyte genes such as keratin 14, keratin 10, and Involucrin were investigated by real‐time PCR. The results of MTT assay indicated an increase in cell viability and cell proliferation of neonate keratinocytes on PCL‐PG nanofiber scaffolds compared with PCL. RT‐PCR and immunocytochemical analysis showed better cell differentiation on the PCL‐PG scaffolds than neat PCL. Furthermore, SEM microscopy images demonstrated that neo‐keratinocytes enhance adhesion and proliferation on PCL‐PG nanofiber scaffolds. We found that PG increases biocompatibility and wettability of scaffold, cell adhesion, and expression of keratinocyte markers. Overall, this procedure is recommended to be employed in skin tissue engineering and wounds healing.
Prognostic and clinicopathological significance of ubiquitin-specific protease 22 overexpression in cancers: evidence from a meta-analysis

Purpose This meta-analysis study aimed to reveal the prognostic relevance of ubiquitin-specific protease 22 (USP22) expression in patients with cancers. Methods PubMed, Embase, and the Cochrane Library electronic databases were searched for relevant studies published up to April 2017. The prognostic value of USP22 expression was evaluated by hazard ratio with 95% confidence intervals (CIs). Relative risk (RR) with 95% CIs assessed the effects of USP22 expression on clinicopathological parameters. A total of 16 studies of 2,233 Chinese patients were included in the final meta-analysis. Results A significant association was found between USP22 overexpression and survival in patients with cancers. The pooled RR indicated that USP22 overexpression was related to histological grade, advanced tumor–node–metastasis stage, positive lymph node metastasis, and distant metastasis. Conclusion This meta-analysis demonstrated that USP22 could be a novel biomarker for predicting prognosis in patients with cancers in the Chinese population.
The Jikes Research Virtual Machine project: Building an open-source research community

This paper describes the evolution of the JikesTM Research Virtual Machine project from an IBM internal research project, called Jalapeno, into an open-source project. After summarizing the original goals of the project, we discuss the motivation for releasing it as an open-source project and the activities performed to ensure the success of the project. Throughout, we highlight the unique challenges of developing and maintaining an open-source project designed specifically to support a research community.
Sketching as a solid modeling tool

This paper describes ‘Quick-sketch’, a 2d and 3d modeling tool for pen based computers. Users of this system define a model by simple pen strokes drawn directly on the screen of a pen-based PC. Lines, circles, arcs, or B-spline curves are automatically distinguished, and interpreted from these strokes. The system also automatically determines relations, such as right angles, tangencies, symmetry, and parallelism, from the sketch input, These relationships are then used to clean up the drawing by making the approximate relationships exact. Constraints are established to maintain the relationships in further editing. A constraint maintenance system, which is based on gestural manipulation and soft constraints, is employed in this system. Several techniques for sketch based definitions of solid objects are provided as well, including extrusion, surface of revolution, ruled surfaces and sweep. Feat ures can be sketched on the surfaces of 3d objects, using the same 2dand 3d techniques. This way, objects of medium complexity can be sketched in seconds. The system can be used as a front-end to more sophisticated modeling, rendering or animation environments, serving as a hand sketching tool in the preliminary design phase.
ENRICHING PRODUCT INFORMATION DURING THE PRODUCT LIFECYCLE

Abstract A manufactured product usually has a great amount of design knowledge and other product information associated with it in CAD drawings and other technical documentation. Today, such product information mainly enables preventive maintenance of products. By collecting usage, performance and maintenance information about the product, it could be possible to perform more predictive maintenance. The key issue is to document product information in a way that would enable analysing the relation between usage parameters and actual product failures. Semantic networks are here proposed as an intermediate knowledge representation format for combining such static and dynamic product information.
The ferric reducing ability of plasma (FRAP) as a measure of "antioxidant power": the FRAP assay.

A simple, automated test measuring the ferric reducing ability of plasma, the FRAP assay, is presented as a novel method for assessing "antioxidant power. " Ferric to ferrous ion reduction at low pH causes a colored ferrous-tripyridyltriazine complex to form. FRAP values are obtained by comparing the absorbance change at 593 nm in test reaction mixtures with those containing ferrous ions in known concentration. Absorbance changes are linear over a wide concentration range with antioxidant mixtures, including plasma, and with solutions containing one antioxidant in purified form. There is no apparent interaction between antioxidants. Measured stoichiometric factors of Trolox, alpha-tocopherol, ascorbic acid, and uric acid are all 2.0; that of bilirubin is 4.0. Activity of albumin is very low. Within- and between-run CVs are <1.0 and <3.0%, respectively, at 100-1000 micromol/liter. FRAP values of fresh plasma of healthy Chinese adults: 612-1634 micromol/liter (mean, 1017; SD, 206; n = 141). The FRAP assay is inexpensive, reagents are simple to prepare, results are highly reproducible, and the procedure is straightforward and speedy. The FRAP assay offers a putative index of antioxidant, or reducing, potential of biological fluids within the technological reach of every laboratory and researcher interested in oxidative stress and its effects.
Acetazolamide-induced cerebral and ocular vasodilation in humans is independent of nitric oxide.

Acetazolamide, a carbonic anhydrase inhibitor, is used orally in the treatment of primary and secondary open-angle glaucoma and induces ocular and cerebral vasodilation. Several in vitro studies have shown that carbonic anhydrase pharmacology and thel-arginine-nitric oxide (NO) pathway are closely related. We investigated the role of NO in acetazolamide-induced vasodilation on cerebral and ocular vessels in 12 healthy subjects in the presence or absence of N G-monomethyl-l-arginine (l-NMMA), a NO synthase inhibitor, and in the presence or absence ofl-arginine, the precursor of NO. Acetazolamide was administered after pretreatment with eitherl-NMMA or placebo and eitherl-arginine or placebo. Pulsatile choroidal blood flow was assessed with laser interferometric measurement of fundus pulsation. In addition, mean blood flow velocity (MFV) in the middle cerebral artery (MCA) and ophthalmic artery (OA) was measured with Doppler sonography. Acetazolamide increased ocular fundus pulsation amplitude (FPA; +27%, P < 0.001) and MFV in the MCA (+38%, P < 0.001) and in the OA (+19%, P = 0.003). Administration of l-NMMA alone reduced FPA (-21%, P < 0.001) and MFV in the MCA (-11%, P = 0.030) but did not change MFV in the OA. All hemodynamic effects ofl-NMMA were reversed byl-arginine. However, neitherl-NMMA norl-arginine altered acetazolamide-induced changes in cerebral or ocular hemodynamic parameters. The present data indicate that acetazolamide-induced hemodynamic changes are not mediated by NO. Which mediators other than NO are involved in the hemodynamic effects as induced by carbonic anhydrase inhibitors remains to be elucidated.
A Model of Evaluating Competitive Advantages Associated with ERP from SCM Perspective

This study constructs a conceptual model to evaluate the performance and competitive advantages associated with ERP form SCM perspective. The resulting model can be used to assist an enterprise in evaluating the potential partnerships. The survey data was gathered from a trans-national textile firm in Taiwan. The training and learning model was based on the strategic thrust theory and used the Back-Propagation Network as an evaluation tool.
The Cytokine Response of U937-Derived Macrophages Infected through Antibody-Dependent Enhancement of Dengue Virus Disrupts Cell Apical-Junction Complexes and Increases Vascular Permeability

ABSTRACT Severe dengue (SD) is a life-threatening complication of dengue that includes vascular permeability syndrome (VPS) and respiratory distress. Secondary infections are considered a risk factor for developing SD, presumably through a mechanism called antibody-dependent enhancement (ADE). Despite extensive studies, the molecular bases of how ADE contributes to SD and VPS are largely unknown. This work compares the cytokine responses of differentiated U937 human monocytic cells infected directly with dengue virus (DENV) or in the presence of enhancing concentrations of a humanized monoclonal antibody recognizing protein E (ADE-DENV infection). Using a cytometric bead assay, ADE-DENV-infected cells were found to produce significantly higher levels of the proinflammatory cytokines interleukin 6 (IL-6), IL-12p70, and tumor necrosis factor alpha (TNF-α), as well as prostaglandin E2 (PGE2), than cells directly infected. The capacity of conditioned supernatants (conditioned medium [CM]) to disrupt tight junctions (TJs) in MDCK cell cultures was evaluated. Exposure of MDCK cell monolayers to CM collected from ADE-DENV-infected cells (ADE-CM) but not from cells infected directly led to a rapid loss of transepithelial electrical resistance (TER) and to delocalization and degradation of apical-junction complex proteins. Depletion of either TNF-α, IL-6, or IL-12p70 from CM from ADE-DENV-infected cells fully reverted the disrupting effect on TJs. Remarkably, mice injected intraperitoneally with ADE-CM showed increased vascular permeability in sera and lungs, as indicated by an Evans blue quantification assay. These results indicate that the cytokine response of U937-derived macrophages to ADE-DENV infection shows an increased capacity to disturb TJs, while results obtained with the mouse model suggest that such a response may be related to the vascular plasma leakage characteristic of SD.
Efficient dissemination of personalized information using content-based multicast

There has been a surge of interest in the delivery of personalized information to users (e.g., personalized stocks or travel information), particularly as mobile users with limited terminal device capabilities increasingly desire updated and targeted information in real time. When the number of information recipients is large and there is sufficient commonality in their interests, as is often the case, IP multicast is an efficient way of delivering the information. However, IP multicast services do not consider the structure and semantics of the information in the multicast process. We propose the use of Content-Based Multicast (CBM) where extra content filtering is performed at the interior nodes of the IP multicast tree; this will reduce network bandwidth usage and delivery delay, as well as the computation required at the sources and sinks. We evaluate the situations in which CBM is advantageous. The benefits of CBM depend critically upon how well filters are placed at interior nodes of the IP multicast tree and the costs depend upon those introduced by filters themselves. Further, we consider the benefits of allowing the filters to be mobile so as to respond to user mobility or changes in user interests and the corresponding costs of filter mobility. The criterion that we consider is the total network bandwidth utilization. For this criterion, we develop an optimal filter placement algorithm, as well as a heuristic that executes faster than the optimal algorithm. We evaluate the algorithms by means of simulation experiments. Our results indicate that filters can be effective in substantially reducing bandwidth. We also find filter mobility is worthwhile if there is marked large-scale user mobility. We conclude with suggestions for further work.
H_infinity robust controller design for a certain helicopter’s lateral motion using genetic algorithm

In order to deal with uncertainties existing in the models of helicopters more effectively, a novel GA-based H_infinity robust controller design method for a certain helicopterpsilas lateral motion is proposed. In this method, GA is used to optimize the parameters of weighting functions matrices with the knowledge of structure of weighting functions matrices. Meanwhile, related requirements of ADS-33D are viewed as constraints of GA intention to provide helicopters preferable handling qualities. The simulation results show that the designed lateral flight control system is of preferable robustness and handling qualities.
Quantitative and Qualitative Evaluation of Darpa Communicator Spoken Dialogue Systems

This paper describes the application of the PARADISE evaluation framework to the corpus of 662 human-computer dialogues collected in the June 2000 Darpa Communicator data collection. We describe results based on the standard logfile metrics as well as results based on additional qualitative metrics derived using the DATE dialogue act tagging scheme. We show that performance models derived via using the standard metrics can account for 37% of the variance in user satisfaction, and that the addition of DATE metrics improved the models by an absolute 5%.
Proactive Workload Forecasting Model with Dynamic Resource Allocation for Modern Internet Application

Modern Internet applications are subject to significant variations in workload demand and this may affect the applications performance. Such kind of applications are usually hosted on multi-tiered, cluster based web hosting environments. Dynamic resource allocation play a curial role in handling sudden events where servers are moved from another (quieter) pool to meet such demand. In this work two well-known dynamic switching policies -- the Proportional Switching Policy (PSP) and the Bottleneck Aware Switching Policy (BSP) -- alongside the proactive properties of a workload forecasting model -- Simple Moving Average (SMA) -- with several different interval times. The experiments have been conducted over a real-time Internet traces. The results show that changing the interval time alongside the workload forecasting model can be very effective when applied alongside dynamic resource allocation strategies. The improvement of the system performance can be up to 12.4% when the right combination are conducted between the proposed approaches.
A Suggestion for Constructing a Bayesian Network Model with Simple Correlation and an Appropriate Regression Analysis: A Real Medical Diagnosis Application

The major task of medical science is to prevent or diagnose disease. Medical diagnosis is usually made by using some blood metrics and in addition, to be able to reach better results, one can benefit from different scientific methods. In this paper a Bayesian network method is proposed. This method is a hybrid that uses simple correlation and according to dependent variable type either simple linear regression or logistic regression for constructing a Bayesian topology. The Bayesian network is a method for representing probabilistic relationships between variables associated with an outcome of interest. To develop a Bayesian network, a structure must first be constructed. To build the topology of the Bayesian network, some alternative method can be used. One is using domain experts who usually have a good grasp of the conditional dependencies in the domain to develop the structure of the Bayesian network. Another is using structure learning algorithms, such as genetic algorithms, to construct the network topology from training data. In this paper a different construction method is proposed by using correlation analysis and one of the simple linear regression or logistic regression analyses. First, correlations of the examined variables are found. Then according to the significant correlation coefficients, the degree and direction of the interactions between these variables are established by using either simple linear regression or logistic regression. Finally the Bayesian network model is constructed by using this information. For evaluating our model, another model which does not have any relation between the input variables is also constructed. And these two models are compared by using an original thyroid data set. It is concluded that our proposed model provides a high degree of performance and good explanatory power and it may prove useful for clinicians in the medical field.
Lack of association between receptor protein tyrosine phosphatase RPTP mu and cadherins

RPTP mu is a receptor-like protein tyrosine phosphatase that mediates homophilic cell-cell interactions. Surface expression of RPTP mu is restricted to cell-cell contacts and is upregulated with increasing cell density, suggesting a role for RPTP mu in contact-mediated signaling. It was recently reported (Brady-Kalnay, S.M., D.L. Rimm, and N.K. Tonks. 1995. J. Cell Biol. 130:977-986) that RPTP mu binds directly to cadherin/catenin complexes, and thus may regulate the tyrosine phosphorylation of such complexes. Here we report that this concept needs revision. Through reciprocal precipitations using a variety of antibodies against RPTP mu, cadherins, and catenins, we show that RPTP mu does not interact with cadherin/catenin complexes, even when assayed under very mild lysis conditions. We find that the anti- RPTP mu antiserum used by others precipitates cadherins in a nonspecific manner independent of RPTP mu. We conclude that, contrary to previous claims, RPTP mu does not interact with cadherin complexes and thus is unlikely to directly regulate cadherin/catenin function.
Self-Renewal of Multipotent Long-Term Repopulating Hematopoietic Stem Cells Is Negatively Regulated by FAS and Tumor Necrosis Factor Receptor Activation

Multipotent self-renewing hematopoietic stem cells (HSCs) are responsible for reconstitution of all blood cell lineages. Whereas growth stimulatory cytokines have been demonstrated to promote HSC self-renewal, the potential role of negative regulators remains elusive. Receptors for tumor necrosis factor (TNF) and Fas ligand have been implicated as regulators of steady-state hematopoiesis, and if overexpressed mediate bone marrow failure. However, it has been proposed that hematopoietic progenitors rather than stem cells might be targeted by Fas activation. Here, murine Lin−Sca1+c-kit+ stem cells revealed little or no constitutive expression of Fas and failed to respond to an agonistic anti-Fas antibody. However, if induced to undergo self-renewal in the presence of TNF-α, the entire short and long-term repopulating HSC pool acquired Fas expression at high levels and concomitant activation of Fas suppressed in vitro growth of Lin−Sca1+c-kit+ cells cultured at the single cell level. Moreover, Lin−Sca1+c-kit+ stem cells undergoing self-renewal divisions in vitro were severely and irreversibly compromised in their short- and long-term multilineage reconstituting ability if activated by TNF-α or through Fas, providing the first evidence for negative regulators of HSC self-renewal.
Dynamic Host Configuration Protocol (DHCP) Option for CableLabs Client Configuration

This document defines a Dynamic Host Configuration Protocol (DHCP) option that will be used to configure various devices deployed within CableLabs architectures. Specifically, the document describes DHCP option content that will be used to configure one class of CableLabs client device: a PacketCable Media Terminal Adapter (MTA). The option content defined within this document will be extended as future CableLabs client devices are developed.
Precipitation, circulation, and cloud variability over the past two decades

To better understand the variability of precipitation, circulation, and cloud, we examine the precipitation, vertical velocity, total cloud fraction, condensed water path, and ice water path from observations and 13 Coupled Model Intercomparison Project 5 (CMIP5) models over 1988–2008. All variables are averaged over wet areas and dry areas to investigate temporal variations of different variables over these regions. We found that all models demonstrate similar temporal variations of precipitation as the observational data from the Global Precipitation Climatology Project, with positive trend over wet areas (6.22 ± 3.75 mm/mon/decade) and negative trend over dry areas (−0.77 ± 0.54 mm/mon/decade). Positive trends of vertical velocity, total cloud fraction, condensed water path, and ice water path are also found in the observations and models over the wet areas. Observations also demonstrate decreasing trends of vertical velocity, total clouds, condensed water path, and ice water path over the dry areas, which can be simulated by most models with a few exceptions. The qualitatively consistent trends in these variables (i.e., vertical velocity, cloud, liquid, and ice water contents) as revealed from the observations and CMIPS models provide a clearer picture of the dynamics and physics behind the temporal variations of precipitation over different areas.
Electronic Dictionary Encoding: Customizing the TEI Guidelines

The Text Encoding Initiative (TEI) Guidelines propose an encoding scheme that is applicable to a large variety of dictionaries. This paper takes a widely-used and simple French dictionary (Petit Larousse Illustre) as an example to describe some of the problems that arise when using the TEI Document Type Definition (DTD), particularly from an editorial standpoint, where it is necessary to retain the presentational features of a text. It also discusses general issues in DTD customizing and compatibility.