bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monoclonal Antibodies Neutralize Bacillus cereus Nhe Enterotoxin by Inhibiting Ordered Binding of Its Three Exoprotein Components
Authors: Didier Andrea , Dietrich Richard , Gruber Stephanie , Bock Stefanie , Moravek Maximilian , Nakamura Tadashi , Lindbäck Toril , Granum Per Einar , Märtlbauer Erwin 
Published: November 2011

ABSTRACT

The Nhe enterotoxin from
Bacillus cereus
is known to induce cytotoxicity on Vero and CaCo-2 cells by ordered binding of its single components NheA, NheB, and NheC. This study aimed to elucidate functional sites on NheB by identifying the epitopes of the neutralizing monoclonal antibodies 1E11 and 2B11. The binding regions of both antibodies were determined by using recombinant NheB fragments and synthetic peptides. The antigenic site of antibody 1E11 was located within the amino acids 321 to 341 of NheB, whereas reactivity of antibody 2B11 was dependent on the presence of amino acids 122 to 150 and on conformation. Both antibodies were able to bind simultaneously to NheB and did not interfere with target cell binding as shown by immunofluorescence microscopy. A set of neutralization assays revealed that antibody 2B11 most likely interfered with the interaction between NheB and NheC both on the epithelium cell surface and in solution. In contrast, antibody 1E11 inhibited association between NheA and cell-bound NheB in a competitive manner, and effectively neutralized Nhe cytotoxicity on a variety of human cell lines. This distinct mechanism further supports that NheA is the key component during the Nhe mode of action and the C-terminal epitope recognized by antibody 1E11 points to an important functional region of NheB.
Toxoplasma gondii Triggers Release of Human and Mouse Neutrophil Extracellular Traps
Authors: Abi Abdallah Delbert S. , Lin Changyou , Ball Carissa J. , King Michael R. , Duhamel Gerald E. , Denkers Eric Y. 
Published: November 2011

ABSTRACTNeutrophils have recently been shown to release DNA-based extracellular traps that contribute to microbicidal killing and have also been implicated in autoimmunity. The role of neutrophil extracellular trap (NET) formation in the host response to nonbacterial pathogens has received much less attention. Here, we show that the protozoan pathogenToxoplasma gondiielicits the production of NETs from human and mouse neutrophils. Tachyzoites of each of the three major parasite strain types were efficiently entrapped within NETs, resulting in decreased parasite viability. We also show thatToxoplasmaactivates a MEK-extracellular signal-regulated kinase (ERK) pathway in neutrophils and that the inhibition of this pathway leads to decreased NET formation. To determine ifToxoplasmainduced NET formationin vivo, we employed a mouse intranasal infection model. We found that the administration of tachyzoites by this route induced a rapid tissue recruitment of neutrophils with evidence of extracellular DNA release. Taken together, these data indicate a role for NETs in the host innate response to protozoan infection. We propose that NET formation limits infection by direct microbicidal effects onToxoplasmaas well as by interfering with the ability of the parasite to invade target host cells.
Anthrax Edema Toxin Impairs Clearance in Mice
Authors: Sastalla Inka , Tang Shixing , Crown Devorah , Liu Shihui , Eckhaus Michael A. , Hewlett Indira K. , Leppla Stephen H. , Moayeri Mahtab 
Published: November 2011

ABSTRACT

The anthrax edema toxin (ET) of
Bacillus anthracis
is composed of the receptor-binding component protective antigen (PA) and of the adenylyl cyclase catalytic moiety, edema factor (EF). Uptake of ET into cells raises intracellular concentrations of the secondary messenger cyclic AMP, thereby impairing or activating host cell functions. We report here on a new consequence of ET action
in vivo
. We show that in mouse models of toxemia and infection, serum PA concentrations were significantly higher in the presence of enzymatically active EF. These higher concentrations were not caused by ET-induced inhibition of PA endocytosis; on the contrary, ET induced increased PA binding and uptake of the PA oligomer
in vitro
and
in vivo
through upregulation of the PA receptors TEM8 and CMG2 in both myeloid and nonmyeloid cells. ET effects on protein clearance from circulation appeared to be global and were not limited to PA. ET also impaired the clearance of ovalbumin, green fluorescent protein, and EF itself, as well as the small molecule biotin when these molecules were coinjected with the toxin. Effects on injected protein levels were not a result of general increase in protein concentrations due to fluid loss. Functional markers for liver and kidney were altered in response to ET. Concomitantly, ET caused phosphorylation and activation of the aquaporin-2 water channel present in the principal cells of the collecting ducts of the kidneys that are responsible for fluid homeostasis. Our data suggest that
in vivo
, ET alters circulatory protein and small molecule pharmacokinetics by an as-yet-undefined mechanism, thereby potentially allowing a prolonged circulation of anthrax virulence factors such as EF during infection.
Interim analyses from a randomised controlled trial to improve visual processing speed in older adults: the Iowa Healthy and Active Minds Study
Authors: Wolinsky Fredric D , Vander Weg Mark W , Howren M Bryant , Jones Michael P , Martin Rene , Luger Tana M , Duff Kevin , Dotson Megan M 
Published: November 2011

ObjectivesThe Iowa Healthy and Active Minds Study is a four-arm randomised controlled trial of a visual processing speed training programme (Road Tour). This article presents the preplanned interim results immediately after training (6–8 weeks post-randomisation) for the primary outcome.DesignWithin two age strata (50–64 vs ≥65), 681 men and women attending general internal and family medicine clinics were randomised to four training groups: (1) supervised, on-site standard (10 h) dose of Road Tour training; (2) supervised, on-site standard dose of Road Tour training with 4 h of subsequent booster training scheduled to occur at 11 months post-randomisation (ie, no booster training had occurred at the time of this interim analysis); (3) supervised, on-site standard dose of attention control (crossword puzzles) training and (4) self-administered, at-home standard dose of Road Tour training. The primary outcome was the Useful Field of View (UFOV) test. Three intent-to-treat interim analyses were conducted, including (1) multiple linear regression models of composite UFOV scores using Blom rank transformations, (2) general linear mixed effects models and (3) multiple logistic regression models among the 620 participants (91%) with complete data.ResultsIn the linear regression analyses of both age strata, random assignment to any Road Tour training group versus the attention control group was significant (p<0.001), with an effect size of −0.558 (adjusted for the Blom rank transformed UFOV score at randomisation). Similar results were obtained for each Road Tour group and within each age stratum and from the general linear and logistic regression models.ConclusionsAssignment to a standard dose of Road Tour training yielded medium-sized post-training improvements in visual processing speed. Road Tour was equally effective whether administered under laboratory supervision or self-administered in the patient's home and for participants in both age strata (50–64 vs ≥65).Clinical trial registration numberNCT01165463.
The future role of rectal and vaginal microbicides to prevent HIV infection in heterosexual populations: implications for product development and prevention
Authors: Boily Marie-Claude , Dimitrov Dobromir , Abdool Karim Salim S , Mâsse Benoît 
Published: November 2011

ObjectivesTo compare the potential impact of rectal (RMB), vaginal (VMB) and bi-compartment (RVMB) (applied vaginally and protective during vaginal and anal intercourse) microbicides to prevent HIV in various heterosexual populations. To understand when a RMB is as useful than a VMB for women practicing anal intercourse (AI).MethodsMathematical model was used to assess the population-level impact (cumulative fraction of new HIV infections prevented (CFP)) of the three different microbicides in various intervention scenarios and prevalence settings. We derived the break-even RMB efficacy required to reduce a female's cumulative risk of HIV infection by the same amount than a VMB.ResultsUnder optimistic coverage (fast roll-out, 100% uptake), a 50% efficacious VMB used in 75% of sex acts in population without AI may prevent ∼33% (27, 42%) new total (men and women combined) HIV infections over 25 years. The 25-year CFP reduces to ∼25% (20, 32%) and 17% (13, 23%) if uptake decreases to 75% and 50%, respectively. Similar loss of impact (by 25%–50%) is observed if the same VMB is introduced in populations with 5%–10% AI and for RRRAI=4–20. A RMB is as useful as a VMB (ie, break-even) in populations with 5% AI if RRRAI=20 and in populations with 15%–20% AI if RRRAI=4, independently of adherence as long as it is the same with both products. The 10-year CFP with a RVMB is twofold larger than for a VMB or RMB when AI=10% and RRRAI=10.ConclusionsEven low AI frequency can compromise the impact of VMB interventions. RMB and RVMB will be important prevention tools for heterosexual populations.
Matrix Metalloproteinase-10 Effectively Reduces Infarct Size in Experimental Stroke by Enhancing Fibrinolysis via a Thrombin-Activatable Fibrinolysis Inhibitor–Mediated Mechanism
Authors: Orbe J. , Barrenetxe J. , Rodriguez J.A. , Vivien D. , Orset C. , Parks W.C. , Birkland T.P. , Serrano R. , Purroy A. , Martinez de Lizarrondo S. , Angles-Cano E. , Páramo J.A. 
Published: November 2011

Background—
The fibrinolytic and matrix metalloproteinase (MMP) systems cooperate in thrombus dissolution and extracellular matrix proteolysis. The plasminogen/plasmin system activates MMPs, and some MMPs have been involved in the dissolution of fibrin by targeting fibrin(ogen) directly or by collaborating with plasmin. MMP-10 has been implicated in inflammatory/thrombotic processes and vascular integrity, but whether MMP-10 could have a profibrinolytic effect and represent a promising thrombolytic agent is unknown.

Methods and Results—

The effect of MMP-10 on fibrinolysis was studied in vitro and in vivo, in MMP-10–null mice (
Mmp10
−/−
), with the use of 2 different murine models of arterial thrombosis: laser-induced carotid injury and ischemic stroke. In vitro, we showed that MMP-10 was capable of enhancing tissue plasminogen activator–induced fibrinolysis via a thrombin-activatable fibrinolysis inhibitor inactivation–mediated mechanism. In vivo, delayed fibrinolysis observed after photochemical carotid injury in
Mmp10
−/−
mice was reversed by active recombinant human MMP-10. In a thrombin-induced stroke model, the reperfusion and the infarct size in sham or tissue plasminogen activator–treated animals were severely impaired in
Mmp10
−/−
mice. In this model, administration of active MMP-10 to wild-type animals significantly reduced blood reperfusion time and infarct size to the same extent as tissue plasminogen activator and was associated with shorter bleeding time and no intracranial hemorrhage. This effect was not observed in thrombin-activatable fibrinolysis inhibitor–deficient mice, suggesting thrombin-activatable fibrinolysis inhibitor inactivation as one of the mechanisms involved in the MMP-10 profibrinolytic effect.

Conclusions—
A novel profibrinolytic role for MMP-10 in experimental ischemic stroke is described, opening new pathways for innovative fibrinolytic strategies in arterial thrombosis.
Regression-Guided Clustering: A Semisupervised Method for Circulation-to-Environment Synoptic Classification
Authors: Cannon Alex J. 
Published: November 2011

AbstractRegression-guided clustering is introduced as a means of constructing circulation-to-environment synoptic climatological classifications. Rather than applying an unsupervised clustering algorithm to synoptic-scale atmospheric circulation data, one instead augments the atmospheric circulation dataset with predictions from a supervised regression model linking circulation to environment. The combined dataset is then entered into the clustering algorithm. The level of influence of the environmental dataset can be controlled by a simple weighting factor. The method is generic in that the choice of regression model and clustering algorithm is left to the user. Examples are given using standard multivariate linear regression models and the k-means clustering algorithm, both established methods in synoptic climatology. Results for southern British Columbia, Canada, indicate that model performance can be made to range between that of a fully unsupervised algorithm and a fully supervised algorithm.
Sensitivities of Orographic Precipitation to Terrain Geometry and Upstream Conditions in Idealized Simulations
Authors: Watson Campbell D. , Lane Todd P. 
Published: November 2011

Abstract
This study examines how variations in relatively simple terrain geometries influence orographic precipitation and its spatial patterns of sensitivity to small changes in upstream conditions. An idealized three-dimensional model is used to simulate a moist flow impinging upon three alpine-scale terrain shapes: a straight ridge, a concave ridge, and a convex ridge. A variety of simulations are conducted to investigate the sensitivity of precipitation patterns to ridge length and upstream thermodynamic and wind conditions for an impinging flow with a nondimensional mountain height of approximately unity. It is found that for the straight and convex ridges, the flow response is mostly linear for the conditions examined here and passes over the obstacles with little lateral deflection. The concave ridge, however, exhibits strengthened flow deceleration, wave breaking in the lee, and flow confluence between the ridge arms. The concave ridge also generates substantially more precipitation than the other two ridge geometries via an established precipitation-enhancing funneling mechanism near the ridge vertex. However, for some concave ridge configurations the results feature dual-precipitation maxima, which is an important difference from previous findings. Finally, results from a simple ensemble of simulations elucidate the sensitivity of precipitation patterns to small variations in upstream conditions and how these vary for the different terrain geometries.
Stochastic Simulation of Intermittent DSD Fields in Time
Authors: Schleiss Marc , Jaffrain Joel , Berne Alexis 
Published: November 2011

Abstract
A method for the stochastic simulation of (rain)drop size distributions (DSDs) in space and time using geostatistics is presented. At each pixel, the raindrop size distribution is described by a Gamma distribution with two or three stochastic parameters. The presence or absence of rainfall is modeled using an indicator field. Separable space–time variograms are used to estimate and reproduce the spatial and temporal structures of all these parameters. A simple and user-oriented procedure for the parameterization of the simulator is proposed. The only data required are DSD time series and radar rain-rate (or reflectivity) measurements. The proposed simulation method is illustrated for both frontal and convective precipitation using real data collected in the vicinity of Lausanne, Switzerland. The spatial and temporal structures of the simulated fields are evaluated and validated using DSD measurements from eight independent disdrometers.
Improving Medication Management Through the Redesign of the Hospital Code Cart Medication Drawer
Authors: Rousek Justin B. , Hallbeck M. Susan 
Published: November 2011

Objective: This study utilized usability testing and human factors engineering (HFE) principles to create efficient code cart medication drawer modifications to improve code blue medical emergency (code) medication management. Background: Effective access to medications during a code is a key component in delivering optimal care and has been found to be a major problem among health care organizations; however, little research has been conducted to improve the efficiency of medication management during a code. Method: A total of 26 health care professionals (13 pharmacists and 13 nurses) were asked to locate items within a code cart medication drawer during two independent simulated code scenarios alternately using either a baseline medication drawer (control; Drawer 1) or a prototype medication drawer (prototype; Drawer 2), which was developed using HFE principles and usability testing. Overall medication retrieval time, wasteful actions, and survey responses were recorded. Results: Drawer 2 had significantly faster trial completion times ( p = .005) and fewer wasteful actions ( p < .001) compared to Drawer 1. Participant survey results rated Drawer 2 (prototype) significantly higher (more favorable) for medication drawer visibility ( p < .001), usability ( p = .011), and organization ( p < .001) compared to Drawer 1 (baseline). Conclusion: The HFE redesign concepts incorporated into Drawer 2 (consisting of visibility, grouping, and organization) produced successful, low-cost, and generalizable modifications that can improve patient care. Application: The findings demonstrate that HFE and usability applied to code cart design are effective, are customizable, and can affect patient safety by saving valuable time and reducing wasted motions (including errors) during code situations.
Structural analysis for flexible components with freeform surfaces with the aid of a coordinate measuring machine
Authors: Ascione R , Polini W 
Published: November 2011

A non-rigid part could be subjected to significant distortion after the removal of manufacturing forces. This condition, known as free state variation, is principally due to weight and flexibility of the part and the release of internal stresses resulting from fabrication. The present work deals with the inspection of freeform surfaces belonging to non-rigid parts with the objective of analysing the internal stress and relative strain due to assembly sequences. A manufactured aeronautic component, named Mid Cowling, is considered as a case study. An appropriate fixture equipment has been used in the inspection process to simulate the mating part interface and to locate the part in the coordinate measuring machine (CMM) working volume. In this way the assemblage in the final product has been reproduced. The results of the measurement process are used to evaluate the quality of the real surfaces in terms of deviation from the nominal one. Therefore, these deviations are used as input in a finite element model (FEM) analysis to estimate the stress and strain fields due to the constraint of the assembly.
Aerosolized adenovirus-vectored vaccine as an alternative vaccine delivery method
Authors: Roy Chad J , Ault Alida , Sivasubramani Satheesh K , Gorres J Patrick , Wei Chih-Jen , Andersen Hanne , Gall Jason , Roederer Mario , Rao Srinivas S 
Published: November 2011

AbstractConventional parenteral injection of vaccines is limited in its ability to induce locally-produced immune responses in the respiratory tract, and has logistical disadvantages in widespread vaccine administration. Recent studies suggest that intranasal delivery or vaccination in the respiratory tract with recombinant viral vectors can enhance immunogenicity and protection against respiratory diseases such as influenza and tuberculosis, and can offer more broad-based generalized protection by eliciting durable mucosal immune responses. Controlled aerosolization is a method to minimize vaccine particle size and ensure delivery to the lower respiratory tract. Here, we characterize the dynamics of aerosolization and show the effects of vaccine concentration on particle size, vector viability, and the actual delivered dose of an aerosolized adenoviral vector. In addition, we demonstrate that aerosol delivery of a recombinant adenoviral vaccine encoding H1N1 hemagglutinin is immunogenic and protects ferrets against homologous viral challenge. Overall, aerosol delivery offers comparable protection to intramuscular injection, and represents an attractive vaccine delivery method for broad-based immunization campaigns.
Complex trait subtypes identification using transcriptome profiling reveals an interaction between two QTL affecting adiposity in chicken
Authors: Blum Yuna , Le Mignon Guillaume , Causeur David , Filangi Olivier , Désert Colette , Demeure Olivier , Le Roy Pascale , Lagarrigue Sandrine 
Published: November 2011

Abstract

Background
Integrative genomics approaches that combine genotyping and transcriptome profiling in segregating populations have been developed to dissect complex traits. The most common approach is to identify genes whose eQTL colocalize with QTL of interest, providing new functional hypothesis about the causative mutation. Another approach includes defining subtypes for a complex trait using transcriptome profiles and then performing QTL mapping using some of these subtypes. This approach can refine some QTL and reveal new ones.
In this paper we introduce Factor Analysis for Multiple Testing (FAMT) to define subtypes more accurately and reveal interaction between QTL affecting the same trait. The data used concern hepatic transcriptome profiles for 45 half sib male chicken of a sire known to be heterozygous for a QTL affecting abdominal fatness (AF) on chromosome 5 distal region around 168 cM.

Results
Using this methodology which accounts for hidden dependence structure among phenotypes, we identified 688 genes that are significantly correlated to the AF trait and we distinguished 5 subtypes for AF trait, which are not observed with gene lists obtained by classical approaches. After exclusion of one of the two lean bird subtypes, linkage analysis revealed a previously undetected QTL on chromosome 5 around 100 cM. Interestingly, the animals of this subtype presented the same q paternal haplotype at the 168 cM QTL. This result strongly suggests that the two QTL are in interaction. In other words, the "q configuration" at the 168 cM QTL could hide the QTL existence in the proximal region at 100 cM. We further show that the proximal QTL interacts with the previous one detected on the chromosome 5 distal region.

Conclusion
Our results demonstrate that stratifying genetic population by molecular phenotypes followed by QTL analysis on various subtypes can lead to identification of novel and interacting QTL.