ARE THERE GENDER-SPECIFIC DIFFERENCES IN ELEMENTARY MOTOR SPEED ABILITY?

The purpose of this study was to analyse gender-specific differences in elementary motor speed ability. The reliability of 7 tests with 15 items was investigated using intra-classcoefficients. Gender-specific differences of performance were analysed using independent samples t-tests. There were no differences between men and women in elementary motor speed. The structure of the elementary motor speed ability (reaction time, tapping, reactive speed and arbitrarily initiated speed) was investigated with confirmatory factor analysis. Here, we identified gender-specific differences in the structure using structural equation models. The models are characterized with a good model fit. Based on the present findings, conclusions for a gender-specific training of elementary motor speed abilities are derived

An Adjuvanted Polyprotein HIV-1 Vaccine Induces Polyfunctional Cross-Reactive CD4+ T Cell Responses in Seronegative Volunteers

A novel AS01-adjuvanted HIV-1 vaccine candidate consisting of a recombinant fusion protein (F4) containing 4 HIV-1 clade B antigens (Gag p24, Pol reverse transcriptase [RT], Nef and Gag p17) induced long-lasting, polyfunctional cross-reactive CD4+ T-cell responses in HIV-seronegative volunteers

Genic regions of a large salamander genome contain long introns and novel genes

BACKGROUND: The basis of genome size variation remains an outstanding question because DNA sequence data are lacking for organisms with large genomes. Sixteen BAC clones from the Mexican axolotl (Ambystoma mexicanum: c-value = 32 x 10(9) bp) were isolated and sequenced to characterize the structure of genic regions. RESULTS: Annotation of genes within BACs showed that axolotl introns are on average 10x longer than orthologous vertebrate introns and they are predicted to contain more functional elements, including miRNAs and snoRNAs. Loci were discovered within BACs for two novel EST transcripts that are differentially expressed during spinal cord regeneration and skin metamorphosis. Unexpectedly, a third novel gene was also discovered while manually annotating BACs. Analysis of human-axolotl protein-coding sequences suggests there are 2% more lineage specific genes in the axolotl genome than the human genome, but the great majority (86%) of genes between axolotl and human are predicted to be 1:1 orthologs. Considering that axolotl genes are on average 5x larger than human genes, the genic component of the salamander genome is estimated to be incredibly large, approximately 2.8 gigabases! CONCLUSION: This study shows that a large salamander genome has a correspondingly large genic component, primarily because genes have incredibly long introns. These intronic sequences may harbor novel coding and non-coding sequences that regulate biological processes that are unique to salamanders

A mathematical model for breath gas analysis of volatile organic compounds with special emphasis on acetone

Recommended standardized procedures for determining exhaled lower respiratory nitric oxide and nasal nitric oxide have been developed by task forces of the European Respiratory Society and the American Thoracic Society. These recommendations have paved the way for the measurement of nitric oxide to become a diagnostic tool for specific clinical applications. It would be desirable to develop similar guidelines for the sampling of other trace gases in exhaled breath, especially volatile organic compounds (VOCs) which reflect ongoing metabolism. The concentrations of water-soluble, blood-borne substances in exhaled breath are influenced by: (i) breathing patterns affecting gas exchange in the conducting airways; (ii) the concentrations in the tracheo-bronchial lining fluid; (iii) the alveolar and systemic concentrations of the compound. The classical Farhi equation takes only the alveolar concentrations into account. Real-time measurements of acetone in end-tidal breath under an ergometer challenge show characteristics which cannot be explained within the Farhi setting. Here we develop a compartment model that reliably captures these profiles and is capable of relating breath to the systemic concentrations of acetone. By comparison with experimental data it is inferred that the major part of variability in breath acetone concentrations (e.g., in response to moderate exercise or altered breathing patterns) can be attributed to airway gas exchange, with minimal changes of the underlying blood and tissue concentrations. Moreover, it is deduced that measured end-tidal breath concentrations of acetone determined during resting conditions and free breathing will be rather poor indicators for endogenous levels. Particularly, the current formulation includes the classical Farhi and the Scheid series inhomogeneity model as special limiting cases.Comment: 38 page

Bridging the gap: evaluating high TB burden country data needs to support the potential introduction of TB vaccines for adolescents and adults: a workshop report

High tuberculosis (TB) burden countries (HBCs) need to prepare for TB vaccine implementation alongside licensure, to ensure rapid rollout. WHO policy/implementation frameworks have been created to support this effort. Using WHO frameworks, we convened a workshop to ask HBC experts about what epidemiological, impact, feasibility and acceptability data they anticipated they would need to guide TB vaccine introduction. For required data, we asked HBC and global experts which data were already available, data collection planned, or gaps. HBC experts expressed high demand for epidemiological, impact, feasibility and acceptability data, reported variable availability of existing epidemiological data, and low availability for impact, feasibility, and acceptability data. Global experts reported additional knowledge of existing data on impact, upcoming collection of infection prevalence, acceptability and feasibility data, and potential epidemiological data collection on adolescents, adults, people living with HIV, and underweight individuals. HBC and global experts made key recommendations for: a coordinated data collation, collection, analysis and sharing system; updating existing HBC health and economic impact estimates and extending impact analyses to other HBCs; demand/market forecasting; resource gap mapping; aligning delivery strategies; addressing manufacturing, procurement, delivery, and regulatory barriers; sharing potential vaccine licensure timing; incorporating TB vaccine introduction strategies into NSPs, immunization programs, and health services; collecting vaccine hesitancy, mistrust, and misinformation data; collecting adolescent/adult vaccine demand generation data, and identifying funding. Experts recommended expanding this analysis to other areas of the WHO frameworks, including more HBC stakeholders, and repeating this analysis after country and community advocacy and socialization around different vaccine candidates

B Cell Recognition of the Conserved HIV-1 Co-Receptor Binding Site Is Altered by Endogenous Primate CD4

The surface HIV-1 exterior envelope glycoprotein, gp120, binds to CD4 on the target cell surface to induce the co-receptor binding site on gp120 as the initial step in the entry process. The binding site is comprised of a highly conserved region on the gp120 core, as well as elements of the third variable region (V3). Antibodies against the co-receptor binding site are abundantly elicited during natural infection of humans, but the mechanism of elicitation has remained undefined. In this study, we investigate the requirements for elicitation of co-receptor binding site antibodies by inoculating rabbits, monkeys and human-CD4 transgenic (huCD4) rabbits with envelope glycoprotein (Env) trimers possessing high affinity for primate CD4. A cross-species comparison of the antibody responses showed that similar HIV-1 neutralization breadth was elicited by Env trimers in monkeys relative to wild-type (WT) rabbits. In contrast, antibodies against the co-receptor site on gp120 were elicited only in monkeys and huCD4 rabbits, but not in the WT rabbits. This was supported by the detection of high-titer co-receptor antibodies in all sera from a set derived from human volunteers inoculated with recombinant gp120. These findings strongly suggest that complexes between Env and (high-affinity) primate CD4 formed in vivo are responsible for the elicitation of the co-receptor-site-directed antibodies. They also imply that the naïve B cell receptor repertoire does not recognize the gp120 co-receptor site in the absence of CD4 and illustrate that conformational stabilization, imparted by primary receptor interaction, can alter the immunogenicity of a type 1 viral membrane protein

Structure-Based Stabilization of HIV-1 gp120 Enhances Humoral Immune Responses to the Induced Co-Receptor Binding Site

The human immunodeficiency virus type 1 (HIV-1) exterior envelope glycoprotein, gp120, possesses conserved binding sites for interaction with the primary virus receptor, CD4, and also for the co-receptor, generally CCR5. Although gp120 is a major target for virus-specific neutralizing antibodies, the gp120 variable elements and its malleable nature contribute to evasion of effective host-neutralizing antibodies. To understand the conformational character and immunogenicity of the gp120 receptor binding sites as potential vaccine targets, we introduced structure-based modifications to stabilize gp120 core proteins (deleted of the gp120 major variable regions) into the conformation recognized by both receptors. Thermodynamic analysis of the re-engineered core with selected ligands revealed significant stabilization of the receptor-binding regions. Stabilization of the co-receptor-binding region was associated with a marked increase in on-rate of ligand binding to this site as determined by surface plasmon resonance. Rabbit immunization studies showed that the conformational stabilization of core proteins, along with increased ligand affinity, was associated with strikingly enhanced humoral immune responses against the co-receptor-binding site. These results demonstrate that structure-based approaches can be exploited to stabilize a conformational site in a large functional protein to enhance immunogenic responses specific for that region

Initial antibodies binding to HIV-1 gp41 in acutely infected subjects are polyreactive and highly mutated

Many HIV-1 envelope-reactive antibodies shortly after HIV-1 transmission may arise from crow-reactive memory B cells previously stimulated by non-HIV-1 host or microbial antigen

Recyclable transmission line (RTL) and linear transformer driver (LTD) development for Z-pinch inertial fusion energy (Z-IFE) and high yield.

Z-Pinch Inertial Fusion Energy (Z-IFE) complements and extends the single-shot z-pinch fusion program on Z to a repetitive, high-yield, power plant scenario that can be used for the production of electricity, transmutation of nuclear waste, and hydrogen production, all with no CO{sub 2} production and no long-lived radioactive nuclear waste. The Z-IFE concept uses a Linear Transformer Driver (LTD) accelerator, and a Recyclable Transmission Line (RTL) to connect the LTD driver to a high-yield fusion target inside a thick-liquid-wall power plant chamber. Results of RTL and LTD research are reported here, that include: (1) The key physics issues for RTLs involve the power flow at the high linear current densities that occur near the target (up to 5 MA/cm). These issues include surface heating, melting, ablation, plasma formation, electron flow, magnetic insulation, conductivity changes, magnetic field diffusion changes, possible ion flow, and RTL mass motion. These issues are studied theoretically, computationally (with the ALEGRA and LSP codes), and will work at 5 MA/cm or higher, with anode-cathode gaps as small as 2 mm. (2) An RTL misalignment sensitivity study has been performed using a 3D circuit model. Results show very small load current variations for significant RTL misalignments. (3) The key structural issues for RTLs involve optimizing the RTL strength (varying shape, ribs, etc.) while minimizing the RTL mass. Optimization studies show RTL mass reductions by factors of three or more. (4) Fabrication and pressure testing of Z-PoP (Proof-of-Principle) size RTLs are successfully reported here. (5) Modeling of the effect of initial RTL imperfections on the buckling pressure has been performed. Results show that the curved RTL offers a much greater buckling pressure as well as less sensitivity to imperfections than three other RTL designs. (6) Repetitive operation of a 0.5 MA, 100 kV, 100 ns, LTD cavity with gas purging between shots and automated operation is demonstrated at the SNL Z-IFE LTD laboratory with rep-rates up to 10.3 seconds between shots (this is essentially at the goal of 10 seconds for Z-IFE). (7) A single LTD switch at Tomsk was fired repetitively every 12 seconds for 36,000 shots with no failures. (8) Five 1.0 MA, 100 kV, 100 ns, LTD cavities have been combined into a voltage adder configuration with a test load to successfully study the system operation. (9) The combination of multiple LTD coaxial lines into a tri-plate transmission line is examined. The 3D Quicksilver code is used to study the electron flow losses produced near the magnetic nulls that occur where coax LTD lines are added together. (10) Circuit model codes are used to model the complete power flow circuit with an inductive isolator cavity. (11) LTD architectures are presented for drivers for Z-IFE and high yield. A 60 MA LTD driver and a 90 MA LTD driver are proposed. Present results from all of these power flow studies validate the whole LTD/RTL concept for single-shot ICF high yield, and for repetitive-shot IFE