High energy emission from microquasars

The microquasar phenomenon is associated with the production of jets by X-ray binaries and, as such, may be associated with the majority of such systems. In this chapter we briefly outline the associations, definite, probable, possible, and speculative, between such jets and X-ray, gamma-ray and particle emission.Comment: Contributing chapter to the book Cosmic Gamma-Ray Sources, K.S. Cheng and G.E. Romero (eds.), to be published by Kluwer Academic Publishers, Dordrecht, 2004. (19 pages

Increased CD8+ T cell responses to apoptotic T cell-associated antigens in multiple sclerosis.

BACKGROUND: Here, we evaluated the hypothesis that CD8(+) T cell responses to caspase-cleaved antigens derived from effector T cells undergoing apoptosis, may contribute to multiple sclerosis (MS) immunopathology. METHODS: The percentage of autoreactive CD8(+) T effector cells specific for various apoptotic T cell-associated self-epitopes (apoptotic epitopes) were detected in the peripheral blood and cerebrospinal fluid (CSF) by both enzyme-linked immunospot and dextramers of class I molecules complexed with relevant apoptotic epitopes. Moreover, the capacity of dextramer(+) CD8(+) T cells to produce interferon (IFN)-γ and/or interleukin (IL)-17 in response to the relevant apoptotic epitopes was evaluated by the intracellular cytokine staining. Cross-presentation assay of apoptotic T cells by dendritic cells was also evaluated ex vivo. RESULTS: We found that polyfunctional (IFN-γ and/or IL-17 producing) autoreactive CD8(+) T cells specific for apoptotic epitopes were represented in MS patients with frequencies significantly higher than in healthy donors. These autoreactive CD8(+) T cells with a strong potential to produce IFN-γ or IL-17 in response to the relevant apoptotic epitopes were significantly accumulated in the CSF from the same patients. In addition, the frequencies of these autoreactive CD8(+) T cells correlated with the disease disability. Cross-presentation assay revealed that caspase-cleaved cellular proteins are required to activate apoptotic epitope-specific CD8(+) T cells ex vivo. CONCLUSION: Taken together, these data indicate that apoptotic epitope-specific CD8(+) T cells with strong inflammatory potential are recruited at the level of the inflammatory site, where they may be involved in MS immunopathology through the production of high levels of inflammatory cytokines

Peripheral blood T-cell signatures from high-resolution immune phenotyping of γδ and αβ T-cells in younger and older subjects in the Berlin Aging Study II

Background Aging and latent infection with Cytomegalovirus (CMV) are thought to be major factors driving the immune system towards immunosenescence, primarily characterized by reduced amounts of naïve T-cells and increased memory T-cells, potentially associated with higher morbidity and mortality. The composition of both major compartments, γδ as well as αβ T-cells, is altered by age and CMV, but detailed knowledge of changes to the γδ subset is currently limited. Results Here, we have surveyed a population of 73 younger (23–35 years) and 144 older (62–85 years) individuals drawn from the Berlin Aging Study II, investigating the distribution of detailed differentiation phenotypes of both γδ and αβ T-cells. Correlation of frequencies and absolute counts of the identified phenotypes with age and the presence of CMV revealed a lower abundance of Vδ2-positive and a higher amount of Vδ1-positive cells. We found higher frequencies of late-differentiated and lower frequencies of early-differentiated cells in the Vδ1+ and Vδ1-Vδ2-, but not in the Vδ2+ populations in elderly CMV-seropositive individuals confirming the association of these Vδ2-negative cells with CMV-immunosurveillance. We identified the highest Vδ1:Vδ2 ratios in the CMV-seropositive elderly. The observed increased CD4:CD8 ratios in the elderly were significantly lower in CMV-seropositive individuals, who also possessed a lower naïve and a larger late-differentiated compartment of CD8+ αβ T-cells, reflecting the consensus in the literature. Conclusions Our findings illustrate in detail the strong influence of CMV on the abundance and differentiation pattern of γδ T-cells as well as αβ T-cells in older and younger people. Mechanisms responsible for the phenotypic alterations in the γδ T-cell compartment, associated both with the presence of CMV and with age require further clarification

Transient integral boundary layer method to calculate the translesional pressure drop and the fractional flow reserve in myocardial bridges

BACKGROUND: The pressure drop – flow relations in myocardial bridges and the assessment of vascular heart disease via fractional flow reserve (FFR) have motivated many researchers the last decades. The aim of this study is to simulate several clinical conditions present in myocardial bridges to determine the flow reserve and consequently the clinical relevance of the disease. From a fluid mechanical point of view the pathophysiological situation in myocardial bridges involves fluid flow in a time dependent flow geometry, caused by contracting cardiac muscles overlying an intramural segment of the coronary artery. These flows mostly involve flow separation and secondary motions, which are difficult to calculate and analyse. METHODS: Because a three dimensional simulation of the haemodynamic conditions in myocardial bridges in a network of coronary arteries is time-consuming, we present a boundary layer model for the calculation of the pressure drop and flow separation. The approach is based on the assumption that the flow can be sufficiently well described by the interaction of an inviscid core and a viscous boundary layer. Under the assumption that the idealised flow through a constriction is given by near-equilibrium velocity profiles of the Falkner-Skan-Cooke (FSC) family, the evolution of the boundary layer is obtained by the simultaneous solution of the Falkner-Skan equation and the transient von-Kármán integral momentum equation. RESULTS: The model was used to investigate the relative importance of several physical parameters present in myocardial bridges. Results have been obtained for steady and unsteady flow through vessels with 0 – 85% diameter stenosis. We compare two clinical relevant cases of a myocardial bridge in the middle segment of the left anterior descending coronary artery (LAD). The pressure derived FFR of fixed and dynamic lesions has shown that the flow is less affected in the dynamic case, because the distal pressure partially recovers during re-opening of the vessel in diastole. We have further calculated the wall shear stress (WSS) distributions in addition to the location and length of the flow reversal zones in dependence on the severity of the disease. CONCLUSION: The described boundary layer method can be used to simulate frictional forces and wall shear stresses in the entrance region of vessels. Earlier models are supplemented by the viscous effects in a quasi three-dimensional vessel geometry with a prescribed wall motion. The results indicate that the translesional pressure drop and the mean FFR compares favourably to clinical findings in the literature. We have further shown that the mean FFR under the assumption of Hagen-Poiseuille flow is overestimated in developing flow conditions

The maternal and early embryonic transcriptome of the milkweed bug Oncopeltus fasciatus

<p>Abstract</p> <p>Background</p> <p>Most evolutionary developmental biology ("evo-devo") studies of emerging model organisms focus on small numbers of candidate genes cloned individually using degenerate PCR. However, newly available sequencing technologies such as 454 pyrosequencing have recently begun to allow for massive gene discovery in animals without sequenced genomes. Within insects, although large volumes of sequence data are available for holometabolous insects, developmental studies of basally branching hemimetabolous insects typically suffer from low rates of gene discovery.</p> <p>Results</p> <p>We used 454 pyrosequencing to sequence over 500 million bases of cDNA from the ovaries and embryos of the milkweed bug <it>Oncopeltus fasciatus</it>, which lacks a sequenced genome. This indirectly developing insect occupies an important phylogenetic position, branching basal to Diptera (including fruit flies) and Hymenoptera (including honeybees), and is an experimentally tractable model for short-germ development. 2,087,410 reads from both normalized and non-normalized cDNA assembled into 21,097 sequences (isotigs) and 112,531 singletons. The assembled sequences fell into 16,617 unique gene models, and included predictions of splicing isoforms, which we examined experimentally. Discovery of new genes plateaued after assembly of ~1.5 million reads, suggesting that we have sequenced nearly all transcripts present in the cDNA sampled. Many transcripts have been assembled at close to full length, and there is a net gain of sequence data for over half of the pre-existing <it>O. fasciatus </it>accessions for developmental genes in GenBank. We identified 10,775 unique genes, including members of all major conserved metazoan signaling pathways and genes involved in several major categories of early developmental processes. We also specifically address the effects of cDNA normalization on gene discovery in <it>de novo </it>transcriptome analyses.</p> <p>Conclusions</p> <p>Our sequencing, assembly and annotation framework provide a simple and effective way to achieve high-throughput gene discovery for organisms lacking a sequenced genome. These data will have applications to the study of the evolution of arthropod genes and genetic pathways, and to the wider evolution, development and genomics communities working with emerging model organisms.</p> <p>[The sequence data from this study have been submitted to GenBank under study accession number SRP002610 (<url>http://www.ncbi.nlm.nih.gov/sra?term=SRP002610</url>). Custom scripts generated are available at <url>http://www.extavourlab.com/protocols/index.html</url>. Seven Additional files are available.]</p

Prevalence of non-communicable diseases in Brazilian children: follow-up at school age of two Brazilian birth cohorts of the 1990's

<p>Abstract</p> <p>Background</p> <p>Few cohort studies have been conducted in low and middle-income countries to investigate non-communicable diseases among school-aged children. This article aims to describe the methodology of two birth cohorts, started in 1994 in Ribeirão Preto (RP), a more developed city, and in 1997/98 in São Luís (SL), a less developed town.</p> <p>Methods</p> <p>Prevalences of some non-communicable diseases during the first follow-up of these cohorts were estimated and compared. Data on singleton live births were obtained at birth (2858 in RP and 2443 in SL). The follow-up at school age was conducted in RP in 2004/05, when the children were 9-11 years old and in SL in 2005/06, when the children were 7-9 years old. Follow-up rates were 68.7% in RP (790 included) and 72.7% in SL (673 participants). The groups of low (<2500 g) and high (≥ 4250 g) birthweight were oversampled and estimates were corrected by weighting.</p> <p>Results</p> <p>In the more developed city there was a higher percentage of non-nutritive sucking habits (69.1% vs 47.9%), lifetime bottle use (89.6% vs 68.3%), higher prevalence of primary headache in the last 15 days (27.9% vs 13.0%), higher positive skin tests for allergens (44.3% vs 25.3%) and higher prevalence of overweight (18.2% vs 3.6%), obesity (9.5% vs 1.8%) and hypertension (10.9% vs 4.6%). In the less developed city there was a larger percentage of children with below average cognitive function (28.9% vs 12.2%), mental health problems (47.4% vs 38.4%), depression (21.6% vs 6.0%) and underweight (5.8% vs 3.6%). There was no difference in the prevalence of bruxism, recurrent abdominal pain, asthma and bronchial hyperresponsiveness between cities.</p> <p>Conclusions</p> <p>Some non-communicable diseases were highly prevalent, especially in the more developed city. Some high rates suggest that the burden of non-communicable diseases will be high in the future, especially mental health problems.</p

Pompe disease diagnosis and management guideline

ACMG standards and guidelines are designed primarily as an educational resource for physicians and other health care providers to help them provide quality medical genetic services. Adherence to these standards and guidelines does not necessarily ensure a successful medical outcome. These standards and guidelines should not be considered inclusive of all proper procedures and tests or exclusive of other procedures and tests that are reasonably directed to obtaining the same results. in determining the propriety of any specific procedure or test, the geneticist should apply his or her own professional judgment to the specific clinical circumstances presented by the individual patient or specimen. It may be prudent, however, to document in the patient's record the rationale for any significant deviation from these standards and guidelines.Duke Univ, Med Ctr, Durham, NC 27706 USAOregon Hlth Sci Univ, Portland, OR 97201 USANYU, Sch Med, New York, NY USAUniv Florida, Coll Med, Powell Gene Therapy Ctr, Gainesville, FL 32611 USAIndiana Univ, Bloomington, in 47405 USAUniv Miami, Miller Sch Med, Coral Gables, FL 33124 USAHarvard Univ, Childrens Hosp, Sch Med, Cambridge, MA 02138 USAUniversidade Federal de São Paulo, São Paulo, BrazilColumbia Univ, New York, NY 10027 USANYU, Bellevue Hosp, Sch Med, New York, NY USAColumbia Univ, Med Ctr, New York, NY 10027 USAUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc