Miracle-dz/UniFAR-FTUs huggingface dataset:
Protease Inhibitors Block Multiple Functions of the NS3/4A Protease-Helicase during the Hepatitis C Virus Life Cycle

ABSTRACT Hepatitis C virus (HCV) NS3 is a multifunctional protein composed of a protease domain and a helicase domain linked by a flexible linker. Protease activity is required to generate viral nonstructural (NS) proteins involved in RNA replication. Helicase activity is required for RNA replication, and genetic evidence implicates the helicase domain in virus assembly. Binding of protease inhibitors (PIs) to the protease active site blocks NS3-dependent polyprotein processing but might impact other steps of the virus life cycle. Kinetic analyses of antiviral suppression of cell culture-infectious genotype 1a strain H77S.3 were performed using assays that measure different readouts of the viral life cycle. In addition to the active-site PI telaprevir, we examined an allosteric protease-helicase inhibitor (APHI) that binds a site in the interdomain interface. By measuring nucleotide incorporation into HCV genomes, we found that telaprevir inhibits RNA synthesis as early as 12 h at high but clinically relevant concentrations. Immunoblot analyses showed that NS5B abundance was not reduced until after 12 h, suggesting that telaprevir exerts a direct effect on RNA synthesis. In contrast, the APHI could partially inhibit RNA synthesis, suggesting that the allosteric site is not always available during RNA synthesis. The APHI and active-site PI were both able to block virus assembly soon (<12 h) after drug treatment, suggesting that they rapidly engage with and block a pool of NS3 involved in assembly. In conclusion, PIs and APHIs can block NS3 functions in RNA synthesis and virus assembly, in addition to inhibiting polyprotein processing. IMPORTANCE The NS3/4A protease of hepatitis C virus (HCV) is an important antiviral target. Currently, three PIs have been approved for therapy of chronic hepatitis C, and several others are in development. NS3-dependent cleavage of the HCV polyprotein is required to generate the mature nonstructural proteins that form the viral replicase. Inhibition of protease activity can block RNA replication by preventing expression of mature replicase components. Like many viral proteins, NS3 is multifunctional, but how PIs affect stages of the HCV life cycle beyond polyprotein processing has not been well studied. Using cell-based assays, we show here that PIs can directly inhibit viral RNA synthesis and also block a late stage in virus assembly/maturation at clinically relevant concentrations.
Recasting readmissions by placing the hospital role in community context.

HOSPITAL READMISSIONS ARE UNDER SCRUTINY BY policy makers but are hardly a new problem. For more than 30 years, researchers have studied factors associated with readmission and tested care models to address these admissions, yet rates of readmissions have not declined appreciably during this time. The renewed focus on readmissions has been stimulated by several converging forces rather than by a strong evidence base for how improvements can be reliably achieved. US federal financial penalties for high rates of readmissions focus on hospitals as the locus of accountability for the problem, but such penalties are a weak incentive since the investment required to improve may exceed the potential loss of inpatient revenue. In this Viewpoint, we suggest that it may be more advantageous to view readmissions within a broader systems and community context that effectively engages all stakeholders to cooperatively improve outcomes.
Hospital restructuring and the epidemiology of hospital utilization: recent experience in Ontario.

OBJECTIVES The author highlights changes in hospital utilization that have occurred in association with restructuring of Ontario hospitals. The basic features of the epidemiology of hospital utilization described link the analysis of the organizational and structural components of hospitals with a more comprehensive evaluation of the impacts of their restructuring and have implications for international comparative studies. METHODS Data from the Canadian Institute for Health Information and the Canadian census were analyzed to provide a population-based description of hospital utilization and care. These hospital data provided information on changes in the patterns of care that occurred during restructuring, based on hospital separations for the fiscal years 1991-1992 through 1995-1996. RESULTS Analysis of hospital utilization patterns revealed a 30% decrease in the days of care provided per 1,000 population during the period, the result of declines in both the age-adjusted inpatient separation rates and average length of hospital stay. The shift of surgical treatment to outpatient settings contributed to the reduction in inpatient days of care. The decline in utilization was experienced unevenly across age groups, with the elderly experiencing less of the decline than did younger age groups. Individuals living in the poorest areas used more inpatient care than did those living in the richest areas, although the gap in utilization narrowed over the period. CONCLUSIONS International comparisons of the epidemiology of hospital utilization and the impact of hospital restructuring will require the use of multiple data sources and the development of shared evaluative frameworks. Health data systems in Canada support the assessment of the broader impacts of hospital restructuring and offer a framework for developing research projects that can provide useful information on these important changes in health-care policy.
A Practical of Memory-based Approach for Improving Accuracy of MT

Rule-Based Machine Translation (RBMT) [1] approach is a major approach in MT research. It needs linguistic knowledge to create appropriate rules of translation. However, we cannot completely add all linguistic rules to the system because adding new rules may cause a conflict with the old ones. So, we propose a memory based approach to improve the translation quality without modifying the existing linguistic rules. This paper analyses the translation problems and shows how this approach works.
A Vacuolar Arsenite Transporter Necessary for Arsenic Tolerance in the Arsenic Hyperaccumulating Fern Pteris vittata Is Missing in Flowering Plants[W][OA]

Gametophytes of the fern Pteris vittata can accumulate and tolerate more than 1% of their dry weight as arsenic. The authors provide evidence that the ACR3 arsenic transporter protein plays an important role in tolerance to high levels of arsenic by transporting arsenic into the vacuole. The fern Pteris vittata tolerates and hyperaccumulates exceptionally high levels of the toxic metalloid arsenic, and this trait appears unique to the Pteridaceae. Once taken up by the root, arsenate is reduced to arsenite as it is transported to the lamina of the frond, where it is stored in cells as free arsenite. Here, we describe the isolation and characterization of two P. vittata genes, ACR3 and ACR3;1, which encode proteins similar to the ACR3 arsenite effluxer of yeast. Pv ACR3 is able to rescue the arsenic-sensitive phenotypes of yeast deficient for ACR3. ACR3 transcripts are upregulated by arsenic in sporophyte roots and gametophytes, tissues that directly contact soil, whereas ACR3;1 expression is unaffected by arsenic. Knocking down the expression of ACR3, but not ACR3;1, in the gametophyte results in an arsenite-sensitive phenotype, indicating that ACR3 plays a necessary role in arsenic tolerance in the gametophyte. We show that ACR3 localizes to the vacuolar membrane in gametophytes, indicating that it likely effluxes arsenite into the vacuole for sequestration. Whereas single-copy ACR3 genes are present in moss, lycophytes, other ferns, and gymnosperms, none are present in angiosperms. The duplication of ACR3 in P. vittata and the loss of ACR3 in angiosperms may explain arsenic tolerance in this unusual group of ferns while precluding the same trait in angiosperms.
A mixed double negative feedback loop between the sRNA MicF and the global regulator Lrp

Roughly 10% of all genes in Escherichia coli are controlled by the global transcription factor Lrp, which responds to nutrient availability. Bioinformatically, we identified lrp as one of several putative targets for the sRNA MicF, which is transcriptionally downregulated by Lrp. Deleting micF results in higher Lrp levels, while overexpression of MicF inhibits Lrp synthesis. This effect is by antisense; mutations in the predicted interaction region relieve MicF‐dependent repression of Lrp synthesis, and regulation is restored by compensatory mutations. In vitro, MicF sterically interferes with initiation complex formation and inhibits lrp mRNA translation. In vivo, MicF indirectly activates genes in the Lrp regulon by repressing Lrp, and causes severely impaired growth in minimal medium, a phenotype characteristic of lrp deletion strains. The double negative feedback between MicF and Lrp may promote a switch for adequate Lrp‐dependent adaptation to nutrient availability. Lrp adds to the growing list of transcription factors that are targeted by sRNAs, thus indicating that perhaps the majority of all bacterial genes may be directly or indirectly controlled by sRNAs.
Digital Angle Sensor Self-Calibration: Two Approaches to Accuracy Increasing

Digital angle sensors built on multipole resolvers and angle-to-digital converters have found a wide application in mission-critical systems operating in severe environment and determine their accuracy and efficiency to a significant extent. A method for self-calibration of digital angle sensors based on integration of two conversion channels with the errors of different spectrums is suggested. Two approaches specially intended to increase the accuracy of self-calibration for the case of high initial errors of the channels are discussed. The results of the simulation and experiment are presented
Assessing Mindfulness on a Sample of Catalan-Speaking Spanish Adolescents: Validation of the Catalan Version of the Child and Adolescent Mindfulness Measure

Abstract Background: Interest in mindfulness has increased over the last decade, resulting in several mindfulness-based interventions being developed and their efficacy empirically demonstrated. The practice of mindfulness has been associated with low levels of anxiety or depression and improved quality of life or personal well-being. The aim of this study is to translate the Child and Adolescent Mindfulness Measure (CAMM) and adapt it to Catalan so as to analyze its internal consistency and construct and convergent validity. Method: The CAMM was administered to a sample of secondary school students ranging in age from 11 to 16 years old. Results: The Catalan version of the CAMM shows a good fit with the unidimensional model and internal consistency similar to the original version (α = .80). Furthermore, CAMM scores correlated positively with subjective well-being, temperamental dimensions of effortful control and self-esteem. Conclusions: The Catalan Version of CAMM is a valid and reliable measure of mindfulness skills.
Parallélisme et équilibrage de charges dans le traitement de la jointure sur des architectures distribuées. (Parallelism and load balancing in the treatment of the join on distributed architectures)

L'emergence des applications de bases de donnees dans les domaines tels que le data warehousing, le data mining et l'aide a la decision qui font generalement appel a de tres grands volumes de donnees rend la parallelisation des algorithmes des jointures necessaire pour avoir un temps de reponse acceptable. Une acceleration lineaire est l'objectif principal des algorithmes paralleles, cependant dans les applications reelles, elle est difficilement atteignable : ceci est du generalement d'une part aux couts de communications inherents aux systemes multi-processeur et d'autre part au desequilibre des charges des differents processeurs. En plus, dans un environnement heterogene multi-utilisateur, la charge des differents processeurs peut varier de maniere dynamique et imprevisible. Dans le cadre de cette these, nous nous interessons au traitement de la jointure et de la multi-jointure sur les architectures distribuees heterogenes, les grilles de calcul et les systemes de fichiers distribues. Nous avons propose une variete d'algorithmes, bases sur l'utilisation des histogrammes distribues, pour traiter de maniere efficace le desequilibre des donnees, tout en garantissant un equilibrage presque parfait de la charge des differents processeurs meme dans un environnement heterogene et multi-utilisateur. Ces algorithmes sont bases sur une approche dynamique de redistribution des donnees permettant de reduire les couts de communication a un minimum tout en traitant de maniere tres efficace le probleme de desequilibre des valeurs de l'attribut de jointure. L'analyse de complexite de nos algorithmes et les resultats experimentaux obtenus montrent que ces algorithmes possedent une acceleration presque lineaire.
UML based Security Function Policy Verification Method for Requirements Specification

One key to success for high quality systems developments is to verify not only functional requirements but also the security requirements at the early stage of developments. However, it is difficult for general developers who have only less security knowledge to define verifiable requirements specification without leakages and errors. To reduce these some leakages or errors, this paper proposes a UML-based security requirements verification method using the security knowledge of Common Criteria.
Claudin-2–deficient mice are defective in the leaky and cation-selective paracellular permeability properties of renal proximal tubules

Claudin-2 is highly expressed in tight junctions of mouse renal proximal tubules, which possess a leaky epithelium whose unique permeability properties underlie their high rate of NaCl reabsorption. To investigate the role of claudin-2 in paracellular NaCl transport in this nephron segment, we generated knockout mice lacking claudin-2 (Cldn2−/−). The Cldn2−/− mice displayed normal appearance, activity, growth, and behavior. Light microscopy revealed no gross histological abnormalities in the Cldn2−/− kidney. Ultrathin section and freeze-fracture replica electron microscopy revealed that, similar to those of wild types, the proximal tubules of Cldn2−/− mice were characterized by poorly developed tight junctions with one or two continuous tight junction strands. In contrast, studies in isolated, perfused S2 segments of proximal tubules showed that net transepithelial reabsorption of Na+, Cl–, and water was significantly decreased in Cldn2−/− mice and that there was an increase in paracellular shunt resistance without affecting the apical or basolateral membrane resistances. Moreover, deletion of claudin-2 caused a loss of cation (Na+) selectivity and therefore relative anion (Cl–) selectivity in the proximal tubule paracellular pathway. With free access to water and food, fractional Na+ and Cl– excretions in Cldn2−/− mice were similar to those in wild types, but both were greater in Cldn2−/− mice after i.v. administration of 2% NaCl. We conclude that claudin-2 constitutes leaky and cation (Na+)–selective paracellular channels within tight junctions of mouse proximal tubules.
An analysis of a layered system architecture for autonomous construction vehicles

It has been suggested in the literature to organize software in autonomous vehicles as hierarchical layers where each layer makes its own decisions based on its own world model. This paper presents two alternative designs for autonomous construction vehicles based on the layered framework 4D/RCS. As a first step, the typical use cases for these vehicles were defined. Then one use case for a hauler was traversed through the two alternatives to see how they supported safety, flexibility and the use of a product platform. We found that the coordination between bucket control and motion control must be done at a low level in the hierarchy and that the relationship between the vehicle actuators and the built-in autonomous system is important for how the software is organized.
Impact of a community-based diabetes self-management program on key metabolic parameters

Objective: Characterize the impact of a pharmacist-led diabetes self-management program on three key metabolic parameters: glycosylated hemoglobin (HbA1c), low-density lipoprotein cholesterol (LDL-C), and mean arterial blood pressure (MAP) among employee health program participants. Methods: A self-insured company in the Kansas City metropolitan area began offering a pharmacist-led diabetes self-management program to eligible company employees and their dependents in 2008. A retrospective pre-post analysis was conducted to determine if the program affected key metabolic parameters in participants by determining mean change after one year of participation. Results: Among 183 program participants, 65 participants met inclusion criteria. All three key metabolic parameters were significantly reduced from baseline to one year of program participation: HbA1c decreased from 8.1 % to 7.3% (p=0.007); LDL-C decreased from 108.3 mg/dL to 96.4 mg/dL (p=0.009); and MAP decreased from 96.1 to 92.3 mm Hg (p=0.005). Conclusions: The pharmacist-led diabetes self-management program demonstrated significant reductions in HbA1c, LDL-C, and MAP from baseline to one year of program participation. Improvements were statistically significant and clinically relevant for each parameter. Previous studies indicate these reductions may cause reduced overall healthcare costs.
Prehistoric Figurine Styles as Fashion: a Case from Formative Central Mexico

Small, ceramic figurines used in household settings in Central Mexico during the first millennium bc were emphatically stylistic. Attributes cooperated to direct the viewer's attention to the style of the figurine, to how the figurine was made, and to the choices of makers and users from a range of alternative ways of making. This article draws on studies of modern fashion to develop a social interpretation of these patterns based on two collections of figurines, one from the Basin of Mexico and the other from Tlaxcala. The history of Formative figurine fashions is considered at multiple scales.
Optogenetic control of chemokine receptor signal and T-cell migration

Significance Precise regulation of chemokine signal is critical for directional migration of cells. In the study of complex cell behavior, it remains difficult to manipulate chemokine activity at precise times and places within living animals, and it is not possible to study different chemokine effects on defined cell types over a range of timescales. Furthermore, a given chemokine can activate multiple chemokine receptors and vice versa. Here we developed a photoactivatable chemokine receptor that can induce highly specific chemokine signals and guide cell migration toward the light stimulation. This work will advance our understanding of the cell migration process with a number of previously unidentified findings. Clinically, our photoactivatable chemokine receptor approach may have broad applications for adoptive cell transfer therapy. Adoptive cell transfer of ex vivo-generated immune-promoting or tolerogenic T cells to either enhance immunity or promote tolerance in patients has been used with some success. However, effective trafficking of the transferred cells to the target tissue sites is the main barrier to achieving successful clinical outcomes. Here we developed a strategy for optically controlling T-cell trafficking using a photoactivatable (PA) chemokine receptor. Photoactivatable-chemokine C-X-C motif receptor 4 (PA-CXCR4) transmitted intracellular CXCR4 signals in response to 505-nm light. Localized activation of PA-CXCR4 induced T-cell polarization and directional migration (phototaxis) both in vitro and in vivo. Directing light onto the melanoma was sufficient to recruit PA-CXCR4–expressing tumor-targeting cytotoxic T cells and improved the efficacy of adoptive T-cell transfer immunotherapy, with a significant reduction in tumor growth in mice. These findings suggest that the use of photoactivatable chemokine receptors allows remotely controlled leukocyte trafficking with outstanding spatial resolution in tissues and may be feasible in other cell transfer therapies.
Management and Organisational Factors in New Product Development (NPD) Success

The desire to improve the performance of their new product development activities and process is firmly established within companies. This paper describes an attempt to produce an evaluation taxonomy and framework to enable comparisons to assess their NPD performance and the factors leading to success. This framework is based on a product's complexities (structural and functional) and related factors and commercial constraints. In particular, it looks at the management and organisational factors involved in NPD and how these may be enhanced to increase NPD success rates. These factors were investigated during a three-year Engineering and Physi cal Sciences Research Council (EPSRC) funded research programme. The outcome of this research programme is the Assessment Tool and Methodology (ATM) which evaluates a company's NPD activities and process performance. The various ways in which the ATM may be used are explained. Significant findings relating to success in product development are shown from the initial results comparing successful product devel opments from a variety of companies. Also described are the results of a survey of company based NPD performance improvement ap proaches and the related NPD performance measurement systems and metrics being used. The results from the use of the ATM with Japanese companies within Japan are also included as a comparison.
Analysis of electrical and thermal stress effects on PCBM:P3HT solar cells by photocurrent and impedance spectroscopy modeling

We investigated the effects of electrical stress and thermal storage by means of photocurrent, Impedance Spectroscopy and Open Circuit Voltage Decay models. The electrical stress damages only the active layer, by reducing the generation rate, the polaron separation probability and the carrier lifetime. The thermal stress also degrades the anode interface. This reflects on the appearance of an inflection in the I-V photocurrent shape close to the operative region.
Pedestrian detection with an ensemble of localized features

In this paper, a new human detection approach from still image is proposed. Two vector features are extracted from the image. Histogram of oriented Gradient feature represents the gradient information of human. Histogram of modified local binary pattern is extracted from images convolved with Gabor filter, as a feature vector to represent texture information. It can be seen as a supplement of gradient information. Different support vector machine classifiers are trained by each type of vectors. Finally, two classifiers are combined together for the final result by using the proposed integration method. Because two features contain different information, they have low error dependency and can get high detection rate. Experiment is performed in a large dataset and it shows that this method outperforms state-of-the-art approaches and other combinations of features.