Miracle-dz/UniFAR-FTUs huggingface dataset:
A Proline-Rich Region in the Coxsackievirus 3A Protein Is Required for the Protein To Inhibit Endoplasmic Reticulum-to-Golgi Transport

ABSTRACT The ability of the 3A protein of coxsackievirus B (CVB) to inhibit protein secretion was investigated for this study. Here we show that the ectopic expression of CVB 3A blocked the transport of both the glycoprotein of vesicular stomatitis virus, a membrane-bound secretory marker, and the alpha-1 protease inhibitor, a luminal secretory protein, at a step between the endoplasmic reticulum (ER) and the Golgi complex. CVB 3A contains a conserved proline-rich region in its N terminus. The importance of this proline-rich region was investigated by introducing Pro-to-Ala substitutions. The mutation of Pro19 completely abolished the ability of 3A to inhibit ER-to-Golgi transport. The mutation of Pro14, Pro17, or Pro20 also impaired this ability, but to a lesser extent. The mutation of Pro18 had no effect. We also investigated the possible importance of this proline-rich region for the function of 3A in viral RNA replication. To this end, we introduced the Pro-to-Ala mutations into an infectious cDNA clone of CVB3. The transfection of cells with in vitro-transcribed RNAs of these clones gave rise to mutant viruses that replicated with wild-type characteristics. We concluded that the proline-rich region in CVB 3A is required for its ability to inhibit ER-to-Golgi transport, but not for its function in viral RNA replication. The functional relevance of the proline-rich region is discussed in light of the proposed structural model of 3A.
Enhanced data integration for LabVIEW laboratory systems

Integrating data is a basic concern in many accredited laboratories that perform a large variety of measurements. However, the present working style in engineering faculties does not focus much on this aspect. To deal with this challenge, we developed an educational platform that allows characterization of acquisition ensembles, generation of Web pages for lessons, as well as transformation of measured data and storage in a common format. As generally we had to develop individual parsers for each instrument, we also added the possibility to integrate the LabVIEW workbench, often used for rapid development of applications in electrical engineering and automatic control. This paper describes how we configure the platform for specific equipment, i.e. how we model it, how we create the learning material and how we integrate the results in a central database. It also introduces a case study for collecting data from a thermocouple-based acquisition system based on LabVIEW, used by students for a laboratory of measurement technologies and transducers.
Metamouse: multiple mice for legacy applications

Single Display Groupware (SDG) solutions have been used to create software for disadvantaged children, particularly in the developing world. SDG allows for greater utilization of the limited infrastructure available to these kids. However, SDG faces challenges in working with legacy applications. Our technology, called metamouse, takes a step toward an integrated multi-user application by allowing users to collaborate within unmodified legacy educational software. We conducted a preliminary qualitative user study of our technology with educational software in schools around Bangalore, India. We found that Metamouse is easily learned, encourages collaborative discussion among students, and allows for the use of existing educational applications with no modification.
Influence of service characteristics on high priority performance indicators and standards in the BreastScreen Australia program.

BACKGROUND Data from BreastScreen Australia Screening and Assessment Services (SAS) for 2002-2010 were analysed to determine whether some SAS characteristics were more conducive that others to high screening performance, as indicated by high priority performance indicators and standards. MATERIALS AND METHODS Indicators investigated related to: numbers of benign open biopsies, screen-detected invasive cancers, and interval cancers, and wait times between screening and assessment. Multivariate Poisson regression was undertaken using as candidate predictors of performance, SAS size (screening volume), urban or rural location, year of screening, accreditation status, and percentages of clients from culturally and linguistically diverse backgrounds, rural and remote areas, and socio-economically disadvantaged areas. RESULTS Performance standards for benign biopsies and invasive cancer detection were uniformly met irrespective of SAS location and size. The interval cancer standard was also met, except in 2003 when the 95% confidence interval of the rate still incorporated the national standard. Performance indicators improved over time for: benign open biopsy for second or subsequent screening rounds; rates of invasive breast cancer detection for second or subsequent screening rounds; and rates of small cancer detection. No differences were found over time in interval cancer rates. Interval cancer rates did not differ between non-metropolitan and metropolitan SAS, although state-wide SAS had lower rates. The standard for wait time between screening and assessment (being assessed <28 days) was mostly unmet and this applied in particular to SAS with high percentages of culturally and linguistically diverse women in their screening populations. CONCLUSIONS Gains in performance were observed, and all performance standards were met irrespective of SAS characteristics, except wait times to assessment. Additional descriptive data should be collected on SAS characteristics, and their associations with favourable screening performance, as these may be important when deciding on SAS design.
Demonstration of enhanced connectivity in ASON/GMPLS network

Automatically switched optical network (ASON) is controlled with the help of generalized multi protocol label switch (GMPLS) protocol. It enables telecom operators automatic traffic provisioning for enhanced network protection, operation and maintenance, but the deployed ASON/GMPLS realizes only point-to-point connections. The emerging broadband services, such as IPTV and e-Science, would need point-to-multipoint and multipoint-to-multipoint connections in optical layer. This paper investigates and summarizes the enhanced connectivity in ASON/GMPLS network with demonstration in field trial of regional China centered at Shanghai based on 3TNET project.
Modified mariner Transposons for Random Inducible-Expression Insertions and Transcriptional Reporter Fusion Insertions in Bacillus subtilis

ABSTRACT Transposons are mobile genetic elements bounded by insertion sequences that are recognized by a specific mobilizing transposase enzyme. The transposase may mobilize not only the insertion sequences but also intervening DNA. mariner is a particularly efficient transposon for the random chromosomal integration of genes and insertional mutagenesis. Here, we modify an existing mariner transposon, TnYLB, such that it can easily be genetically manipulated and introduced into Bacillus subtilis. We generate a series of three new mariner derivatives that mobilize spectinomycin, chloramphenicol, and kanamycin antibiotic resistance cassettes. Furthermore, we generate a series of transposons with a strong, outward-oriented, optionally isopropyl-β-d-thiogalactopyranoside (IPTG)-inducible promoter for the random overexpression of neighboring genes and a series of transposons with a promoterless lacZ gene for the random generation of transcriptional reporter fusions. We note that the modification of the base transposon is not restricted to B. subtilis and should be applicable to any mariner-compatible host organism, provided that in vitro mutagenesis or an in vivo species-specific delivery vector is employed.
Promoting motions in enzyme catalysis probed by pressure studies of kinetic isotope effects

Use of the pressure dependence of kinetic isotope effects, coupled with a study of their temperature dependence, as a probe for promoting motions in enzymatic hydrogen-tunneling reactions is reported. Employing morphinone reductase as our model system and by using stopped-flow methods, we measured the hydride transfer rate (a tunneling reaction) as a function of hydrostatic pressure and temperature. Increasing the pressure from 1 bar (1 bar = 100 kPa) to 2 kbar accelerates the hydride transfer reaction when both protium (from 50 to 161 s−1 at 25°C) and deuterium (12 to 31 s−1 at 25°C) are transferred. We found that the observed primary kinetic isotope effect increases with pressure (from 4.0 to 5.2 at 25°C), an observation incompatible with the Bell correction model for hydrogen tunneling but consistent with a full tunneling model. By numerical modeling, we show that both the pressure and temperature dependencies of the reaction rates are consistent with the framework of the environmentally coupled tunneling model of Kuznetsov and Ulstrup [Kuznetsov AM, Ulstrup J (1999) Can J Chem 77:1085–1096], providing additional support for the role of a promoting motion in the hydride tunneling reaction in morphinone reductase. Our study demonstrates the utility of “barrier engineering” by using hydrostatic pressure as a probe for tunneling regimes in enzyme systems and provides added and independent support for the requirement of promoting motions in such tunneling reactions.
Comparative Study of Pressure- and Nutrient-Induced Germination of Bacillus subtilis Spores

ABSTRACT Germination experiments with specific germination mutants ofBacillus subtilis, including a newly isolated mutant affected in pressure-induced germination, suggest that a pressure of 100 MPa triggers the germination cascades that are induced by the nutrient germinant alanine (Ala) and by a mixture of asparagine, glucose, fructose, and potassium ions (AGFK), by activating the receptors for alanine and asparagine, GerA and GerB, respectively. As opposed to germination at 100 MPa, germination at 600 MPa apparently shortcuts at least part of the Ala- and AGFK-induced germination pathways. Inhibitors of nutrient-induced germination (HgCl2and Nα-P-tosyl-l-arginine methyl ester) also inhibit pressure-induced germination at 600 MPa, suggesting that germination at 600 MPa involves activation of a true physiological germination pathway and is therefore not merely a physico-chemical process in which water is forced into the spore protoplast.
High-frequency self-excited oscillations in a collapsible-channel flow

High-Reynolds-number asymptotics and numerical simulations are used to describe two-dimensional, unsteady, pressure-driven flow in a finite-length channel, one wall of which contains a section of membrane under longitudinal tension. Asymptotic predictions of stability boundaries for small-amplitude, high-frequency, self-excited oscillations are derived in the limit of large membrane tension. The oscillations are closely related to normal modes of the system, which have a frequency set by a balance between membrane tension and the inertia of the fluid in the entire channel. Oscillations can grow by extracting kinetic energy from the mean Poiseuille flow faster than it is lost to viscous dissipation. Direct numerical simulations, based on a fully coupled finite-element discretization of the equations of large-displacement elasticity and the Navier–Stokes equations, support the predicted stability boundaries, and are used to explore larger-amplitude oscillations at lower tensions. These are characterized by vigorous axial sloshing motions superimposed on the mean flow, with transient secondary instabilities being generated both upstream and downstream of the collapsible segment.
Oral fluid-based rapid HIV testing: issues, challenges and research directions

‘. it is hoped that detection of [HIV-infected] individuals with high-quality, rapid, accurate point-of-care oral HIV tests will enable provision of early, timely and highly effective ART or expedite triage to care and prevention. ’ Nitika Pant Pai McGill University Health Centre, Division of Infectious Diseases & Immunodeficiency Service, Montreal Chest Institute, 3650 St Urbain Street, Montreal, Quebec, H2X 2P4, Canada Tel. : +1 514 889 9604 nitika.pai@mail.mcgill. ca Expert Rev. Mol. Diagn. 7(4), 325–328 (2007)
Routine storage of red blood cell (RBC) units in additive solution‐3: a comprehensive investigation of the RBC metabolome

In most countries, red blood cells (RBCs) can be stored up to 42 days before transfusion. However, observational studies have suggested that storage duration might be associated with increased morbidity and mortality. While clinical trials are under way, impaired metabolism has been documented in RBCs stored in several additive solutions (ASs). Here we hypothesize that, despite reported beneficial effects, storage in AS‐3 results in metabolic impairment weeks before the end of the unit shelf life.
Conserved regional patterns of GABA-related transcript expression in the neocortex of subjects with schizophrenia.

OBJECTIVE Individuals with schizophrenia exhibit disturbances in a number of cognitive, affective, sensory, and motor functions that depend on the circuitry of different cortical areas. The cognitive deficits associated with dysfunction of the dorsolateral prefrontal cortex result, at least in part, from abnormalities in GABA neurotransmission, as reflected in a specific pattern of altered expression of GABA-related genes. Consequently, the authors sought to determine whether this pattern of altered gene expression is restricted to the dorsolateral prefrontal cortex or could also contribute to the dysfunction of other cortical areas in subjects with schizophrenia. METHOD Real-time quantitative polymerase chain reaction was used to assess the levels of eight GABA-related transcripts in four cortical areas (dorsolateral prefrontal cortex, anterior cingulate cortex, and primary motor and primary visual cortices) of subjects (N=12) with schizophrenia and matched normal comparison subjects. RESULTS Expression levels of seven transcripts were lower in subjects with schizophrenia, with the magnitude of reduction for each transcript comparable across the four areas. The largest reductions were detected for mRNA encoding somatostatin and parvalbumin, followed by moderate decreases in mRNA expression for the 67-kilodalton isoform of glutamic acid decarboxylase, the GABA membrane transporter GAT-1, and the alpha 1 and delta subunits of GABA(A) receptors. In contrast, the expression of calretinin mRNA did not differ between the subject groups in any of the four areas. CONCLUSIONS Because the areas examined represent the major functional domains (e.g., association, limbic, motor, and sensory) of the cerebral cortex, our findings suggest that a conserved set of molecular alterations affecting GABA neurotransmission contribute to the pathophysiology of different clinical features of schizophrenia.
CYTOTOXIC THYMUS-DERIVED LYMPHOCYTES IN CEREBROSPINAL FLUID OF MICE WITH LYMPHOCYTIC CHORIOMENINGITIS

The fatal neurological disease occurring in adul t mice injected intracerebral ly (IC) with lymphocyt ic choriomeningit is (LCM) virus is apparen t ly induced by massive invasion of leukocytes (1, 2) into the central nervous system (CNS). Dosing with an t i thymocyte serum or cyclophosphamide (2, 3) prevents cellular infi l trat ion: mice survive as asymptomat ic carriers. Adopt ive induction of this inf lammatory process, by inject ing immune spleen cells into immunosuppressed recipients, depends on presence of specific thymus-der ived lymphocytes (T cells) in the transferred cell populat ion (4). Such lymphocytes can now be assayed in vi tro by measuring release of rad ioac t iv i ty from 51Cr-labeled target cells infected with L C M virus (5, 6). The present paper gives evidence tha t these cytotoxic T cells are found in cerebrospinal fluid (CSF) of mice with clinical LCM. This is, to our knowledge, the first direct demonstra t ion of specifically sensitized lymphocytes in a virus-induced inf lammatory exudate.
Dynamic vs. Static Decision Strategies in Adversarial Reasoning

Adversarial decision making is aimed at determining optimal decision strategies to deal with an adversarial and adaptive opponent. One defense against this adversary is to make decisions that are intended to confuse him, although our rewards can be di- minished. It is assumed that making decisions in an uncertain envi- ronment is a hard task. However, this situation is of upmost interest in the case of adversarial reasoning as what we want is to force the presence of uncertainty in order to confuse the adversary in situa- tions of repeated conflicting encounters. Using simulations, the use of dynamic vs. static decision strategies is analyzed. The main con- clusions are: a) the use of the proposed dynamic strategies has sense, b) the presence of an adversary may produce a decrease of, at least, 45% with respect to the theoretical best payoff and c) the relation between this reduction and the way the uncertainty is forced should be further investigated.
Preventing Vaccine-Derived Poliovirus Emergence during the Polio Endgame

Reversion and spread of vaccine-derived poliovirus (VDPV) to cause outbreaks of poliomyelitis is a rare outcome resulting from immunisation with the live-attenuated oral poliovirus vaccines (OPVs). Global withdrawal of all three OPV serotypes is therefore a key objective of the polio endgame strategic plan, starting with serotype 2 (OPV2) in April 2016. Supplementary immunisation activities (SIAs) with trivalent OPV (tOPV) in advance of this date could mitigate the risks of OPV2 withdrawal by increasing serotype-2 immunity, but may also create new serotype-2 VDPV (VDPV2). Here, we examine the risk factors for VDPV2 emergence and implications for the strategy of tOPV SIAs prior to OPV2 withdrawal. We first developed mathematical models of VDPV2 emergence and spread. We found that in settings with low routine immunisation coverage, the implementation of a single SIA increases the risk of VDPV2 emergence. If routine coverage is 20%, at least 3 SIAs are needed to bring that risk close to zero, and if SIA coverage is low or there are persistently “missed” groups, the risk remains high despite the implementation of multiple SIAs. We then analysed data from Nigeria on the 29 VDPV2 emergences that occurred during 2004−2014. Districts reporting the first case of poliomyelitis associated with a VDPV2 emergence were compared to districts with no VDPV2 emergence in the same 6-month period using conditional logistic regression. In agreement with the model results, the odds of VDPV2 emergence decreased with higher routine immunisation coverage (odds ratio 0.67 for a 10% absolute increase in coverage [95% confidence interval 0.55−0.82]). We also found that the probability of a VDPV2 emergence resulting in poliomyelitis in >1 child was significantly higher in districts with low serotype-2 population immunity. Our results support a strategy of focused tOPV SIAs before OPV2 withdrawal in areas at risk of VDPV2 emergence and in sufficient number to raise population immunity above the threshold permitting VDPV2 circulation. A failure to implement this risk-based approach could mean these SIAs actually increase the risk of VDPV2 emergence and spread.
Interleukin 4 reverses T cell proliferative unresponsiveness and prevents the onset of diabetes in nonobese diabetic mice

Beginning at the time of insulitis (7 wk of age), CD4+ and CD8+ mature thymocytes from nonobese diabetic (NOD) mice exhibit a proliferative unresponsiveness in vitro after T cell receptor (TCR) crosslinking. This unresponsiveness does not result from either insulitis or thymic involution and is long lasting, i.e., persists until diabetes onset (24 wk of age). We previously proposed that it represents a form of thymic T cell anergy that predisposes to diabetes onset. This hypothesis was tested in the present study by further investigating the mechanism responsible for NOD thymic T cell proliferative unresponsiveness and determining whether reversal of this unresponsiveness protects NOD mice from diabetes. Interleukin 4 (IL-4) secretion by thymocytes from > 7-wk- old NOD mice was virtually undetectable after treatment with either anti-TCR alpha/beta, anti-CD3, or Concanavalin A (Con A) compared with those by thymocytes from age- and sex-matched control BALB/c mice stimulated under identical conditions. NOD thymocytes stimulated by anti-TCR alpha/beta or anti-CD3 secreted less IL-2 than did similarly activated BALB/c thymocytes. However, since equivalent levels of IL-3 were secreted by Con A-activated NOD and BALB/c thymocytes, the unresponsiveness of NOD thymic T cells does not appear to be dependent on reduced IL-2 secretion. The surface density and dissociation constant of the high affinity IL-2 receptor of Con A-activated thymocytes from both strains are also similar. The patterns of unresponsiveness and lymphokine secretion seen in anti-TCR/CD3- activated NOD thymic T cells were also observed in activated NOD peripheral spleen T cells. Exogenous recombinant (r)IL-2 only partially reverses NOD thymocyte proliferative unresponsiveness to anti-CD3, and this is mediated by the inability of IL-2 to stimulate a complete IL-4 secretion response. In contrast, exogenous IL-4 reverses the unresponsiveness of both NOD thymic and peripheral T cells completely, and this is associated with the complete restoration of an IL-2 secretion response. Furthermore, the in vivo administration of rIL-4 to prediabetic NOD mice protects them from diabetes. Thus, the ability of rIL-4 to reverse completely the NOD thymic and peripheral T cell proliferative defect in vitro and protect against diabetes in vivo provides further support for a causal relationship between this T cell proliferative unresponsiveness and susceptibility to diabetes in NOD mice.
The symbiotic system CH Cygni: An analysis of the shocked nebulae at different epochs

We analyse the line and continuum spectra of the symbiotic system CH Cygni. We adopt the colliding-wind model to explain the symbiotic system at different phases. Peculiar observed features such as flickering, radio variation, X-ray emission, as well as the distribution of the nebulae and shells throughout the system are investigated by modelling the spectra at different epochs. The models account consistently for shock and photoionization and are constrained by absolute fluxes. We find that the reverse shock between the stars leads to the broad lines observed during the active phases, as well as to radio and hard X-ray emission, while the expanding shock is invoked to explain the data particularly during the transition phases (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)
A Guide to Anticoagulant Therapy

The physician who undertakes anticoagulant therapy tampers with one of the most important homeostatic functions of the body. In so doing, he subjects the patient to the calculated hazard of possible hemorrhage balanced against the risks of the thrombosis or embolism that he seeks to prevent or treat. Agents currently employed are heparin and coumarin-type compounds. These two categories of anticoagulants act at different sites of the coagulation mechanism, are administered differently, are metabolized differently, are reversed by different antidotes, and their effects are measured by different tests. Certain facts about which the physician should be adequately informed have been presented regarding the hemostatic mechanism; the physiology and pharmacology of the anticoagulants, especially as they may explain the wide variation in individual response; certain aspects of methodology; and the various practical problems involved in therapeutic management. Emphasis has been placed on the importance of individualization of treatment, careful clinical observation, and frequent reliable laboratory tests as guides to proper therapy.