373 research outputs found
An integral turbulent kinetic energy analysis of free shear flows
Mixing of coaxial streams is analyzed by application of integral techniques. An integrated turbulent kinetic energy (TKE) equation is solved simultaneously with the integral equations for the mean flow. Normalized TKE profile shapes are obtained from incompressible jet and shear layer experiments and are assumed to be applicable to all free turbulent flows. The shear stress at the midpoint of the mixing zone is assumed to be directly proportional to the local TKE, and dissipation is treated with a generalization of the model developed for isotropic turbulence. Although the analysis was developed for ducted flows, constant-pressure flows were approximated with the duct much larger than the jet. The axisymmetric flows under consideration were predicted with reasonable accuracy. Fairly good results were also obtained for the fully developed two-dimensional shear layers, which were computed as thin layers at the boundary of a large circular jet
Large perturbation flow field analysis and simulation for supersonic inlets
An analysis technique for simulation of supersonic mixed compression inlets with large flow field perturbations is presented. The approach is based upon a quasi-one-dimensional inviscid unsteady formulation which includes engineering models of unstart/restart, bleed, bypass, and geometry effects. Numerical solution of the governing time dependent equations of motion is accomplished through a shock capturing finite difference algorithm, of which five separate approaches are evaluated. Comparison with experimental supersonic wind tunnel data is presented to verify the present approach for a wide range of transient inlet flow conditions
The Production of Antibody by Invading B Cells Is Required for the Clearance of Rabies Virus from the Central Nervous System
Every year over 50,000 people die from rabies worldwide, primarily due to the poor availability of rabies vaccine in developing countries. However, even when vaccines are available, human deaths from rabies occur if exposure to the causative virus is not recognized and vaccination is not sought in time. This is because rabies virus immunity induced by the natural infection or current vaccines is generally not effective at removing disease-causing rabies virus from brain tissues. Our studies provide insight into why this is the case and how vaccination can be changed so that the immune response can clear the virus from brain tissues. We show that the type of immune response induced by a live-attenuated rabies virus vaccine may be the key. In animal models, live-attenuated rabies virus vaccines are effective at delivering the immune cells capable of clearing the virus into CNS tissues and promote recovery from a rabies virus infection that has spread to the brain while conventional vaccines based on killed rabies virus do not. The production of rabies-specific antibody by B cells that invade the CNS tissues is important for complete elimination of the virus. We hypothesize that similar mechanisms may promote rabies virus clearance from individuals who are diagnosed after the virus has reached, but not extensively spread, through the CNS
Characterization of invasive and colonizing isolates of Streptococcus agalactiae in East African adults
Ninety-five colonizing isolates and 74 invasive isolates of Streptococcus agalactiae from Kenyan adults were characterized by using capsular serotyping and multilocus sequence typing. Twenty-two sequence types clustering into five clonal complexes were found. Data support the view that S. agalactiae isolates belonging to a limited number of clonal complexes are invasive in adults worldwide
Visualizing Graphene Based Sheets by Fluorescence Quenching Microscopy
Graphene based sheets have stimulated great interest due to their superior
mechanical, electrical and thermal properties. A general visualization method
that allows quick observation of these single atomic layers would be highly
desirable as it can greatly facilitate sample evaluation and manipulation, and
provide immediate feedback to improve synthesis and processing strategies. Here
we report that graphene based sheets can be made highly visible under a
fluorescence microscope by quenching the emission from a dye coating, which can
be conveniently removed afterwards by rinsing without disrupting the sheets.
Current imaging techniques for graphene based sheets rely on the use of special
substrates. In contrast, the fluorescence quenching mechanism is no longer
limited by the types of substrates. Graphene, reduced graphene oxide, or even
graphene oxide sheets deposited on arbitrary substrates can now be readily
visualized by eye with good contrast for layer counting. Direct observation of
suspended sheets in solution was also demonstrated. The fluorescence quenching
microscopy offers unprecedented imaging flexibility and could become a general
tool for characterizing graphene based materials.Comment: J. Am. Chem. Soc., Article ASA
Viral delivery of a peptide-based immunomodulator enhances T cell priming during vaccination
Modern, subunit-based vaccines have so far failed to induce significant T cell responses, contributing to ineffective vaccination against many pathogens. Importantly, while today’s adjuvants are designed to trigger innate and non-specific immune responses, they fail to directly stimulate the adaptive immune compartment. Programmed cell death 1 (PD-1) partly regulates naïve-to-antigen-specific effector T cell transition and differentiation by suppressing the magnitude of activation. Indeed, we previously reported on a microbial-derived, peptide-based PD-1 checkpoint inhibitor, LD01, which showed potent T cell-stimulating activity when combined with a vaccine. Here we sought to improve the potency of LD01 by designing and testing new LD01 derivatives. Accordingly, we found that a modified version of an 18-amino acid metabolite of LD01, LD10da, improved T cell activation capability in a malaria vaccine model. Specifically, LD10da demonstrates improved antigen-specific CD8+ T cell expansion when combined prophylactically with an adenovirus-based malaria vaccine. A single dose of LD10da at the time of vaccination is sufficient to increase antigen-specific CD8+ T cell expansion in wild-type mice. Further, we show that LD10 can be encoded and delivered by a Modified Vaccinia Ankara viral vector and can enhance antigen-specific CD8+ T cell expansion comparable to that of synthetic peptide administration. Therefore, LD10da represents a promising biologic-based immunomodulator that can be genetically encoded and delivered, along with the antigen, by viral or other nucleic acid vectors to improve the efficacy and delivery of vaccines for ineradicable and emerging infectious diseases
Computational Bacterial Genome-Wide Analysis of Phylogenetic Profiles Reveals Potential Virulence Genes of Streptococcus agalactiae
The phylogenetic profile of a gene is a reflection of its evolutionary history
and can be defined as the differential presence or absence of a gene in a set of
reference genomes. It has been employed to facilitate the prediction of gene
functions. However, the hypothesis that the application of this concept can also
facilitate the discovery of bacterial virulence factors has not been fully
examined. In this paper, we test this hypothesis and report a computational
pipeline designed to identify previously unknown bacterial virulence genes using
group B streptococcus (GBS) as an example. Phylogenetic profiles of all GBS
genes across 467 bacterial reference genomes were determined by
candidate-against-all BLAST searches,which were then used to identify candidate
virulence genes by machine learning models. Evaluation experiments with known
GBS virulence genes suggested good functional and model consistency in
cross-validation analyses (areas under ROC curve, 0.80 and 0.98 respectively).
Inspection of the top-10 genes in each of the 15 virulence functional groups
revealed at least 15 (of 119) homologous genes implicated in virulence in other
human pathogens but previously unrecognized as potential virulence genes in GBS.
Among these highly-ranked genes, many encode hypothetical proteins with possible
roles in GBS virulence. Thus, our approach has led to the identification of a
set of genes potentially affecting the virulence potential of GBS, which are
potential candidates for further in vitro and in
vivo investigations. This computational pipeline can also be
extended to in silico analysis of virulence determinants of
other bacterial pathogens
Understanding the sex difference in vulnerability to adolescent depression: an examination of child and parent characteristics
This study examined sex differences in risk factors associated with adolescent depression in a large sample of boys and girls. Moderation and mediation explanatory models of the sex difference in likelihood of depression were examined. Findings indicate that the factors associated with depression in adolescent boys and girls are quite similar. All of the variables considered were associated with depression, but sex did not moderate the impact of vulnerability factors on likelihood of depression diagnosis. However, negative self-perceptions in the domains of achievement, global self-worth, and physical appearance partially mediated the relationship between sex and depression. Further, girls had higher levels of positive self-perceptions in interpersonal domains that acted as suppressors and reduced the likelihood of depression in girls. These findings suggest that girls' higher incidence of depression is due in part to their higher levels of negative self-perceptions, whereas positive interpersonal factors serve to protect them from depressive episodes
Smoking during pregnancy and risk of abnormal glucose tolerance: a prospective cohort study
Background: Disturbances in glucose metabolism during pregnancy are associated with negative sequalae for both mother and infant. The association between smoking and abnormal glucose tolerance (AGT) remains controversial. Therefore, the aim of this study was to examine the relationship between smoking prior to and during pregnancy and risk of AGT. Methods: We utilized data from a prospective cohort of 1,006 Hispanic (predominantly Puerto Rican) prenatal care patients in Western Massachusetts. Women reported pre- and early pregnancy smoking at recruitment (mean = 15 weeks) and mid pregnancy smoking at a second interview (mean = 28 weeks). AGT was defined as \u3e 135 mg/dL on the routine 1-hour glucose tolerance test (1-hr OGTT). We used multivariable regression to assess the effect of pre, early, and mid-pregnancy smoking on risk of AGT and screening plasma glucose value from the 1-hr OGTT. Results: In age-adjusted models, women who smoked \u3e 0-9 cigarettes/day in pre-pregnancy had an increased risk of AGT (OR = 1.90; 95% CI 1.02-3.55) compared to non-smokers; this was attenuated in multivariable models. Smoking in early (OR = 0.48; 95% CI 0.21-1.10) and mid pregnancy (OR = 0.38; 95% CI 0.13-1.11) were not associated with AGT in multivariable models. Smoking during early and mid pregnancy were independently associated with lower glucose screening values, while smoking in pre-pregnancy was not. Conclusions: In this prospective cohort of Hispanic women, we did not observe an association between smoking prior to or during pregnancy and risk of AGT. Findings from this study, although based on small numbers of cases, extend prior research to the Hispanic population
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