Inorganic nitrate supplementation improves muscle oxygenation, O2 uptake kinetics and exercise tolerance at high but not low pedal rates

Copyright © 2014, Journal of Applied PhysiologyWe tested the hypothesis that inorganic nitrate (NO3-) supplementation would improve muscle oxygenation, pulmonary O2 uptake (VO2) kinetics and exercise tolerance (Tlim) to a greater extent when cycling at high compared low pedal rates. In a randomized, placebo-controlled, cross-over study, seven subjects (mean ± SD, age 21 ± 2 yr, body mass 86 ± 10 kg) completed severe-intensity step cycle tests at pedal cadences of 35 rpm and 115 rpm during separate 9 day supplementation periods with NO3--rich beetroot juice (BR; providing 8.4 mmol NO3-∙day-1) and placebo (PLA). Compared to PLA, plasma nitrite concentration increased 178% with BR (P0.05). However, when cycling at 115 rpm, muscle [O2Hb] was higher at baseline and throughout exercise, phase II VO2 kinetics was faster (47 ± 16 s vs. 61 ± 25 s; P<0.05) and Tlim was greater (362 ± 137 s vs. 297 ± 79 s; P<0.05) with BR compared to PLA. These results suggest that short-term BR supplementation can increase muscle oxygenation, expedite the adjustment of oxidative metabolism and enhance exercise tolerance when cycling at a high, but not a low, pedal cadence in healthy recreationally-active subjects. These findings support recent observations that NO3- supplementation may be particularly effective at improving physiological and functional responses in type II muscle fibers

Synergism/complementarity of recombinant adenoviral vectors and other vaccination platforms during induction of protective immunity against malaria

The lack of immunogenicity of most malaria antigens and the complex immune responses required for achieving protective immunity against this infectious disease have traditionally hampered the development of an efficient human malaria vaccine. The current boom in development of recombinant viral vectors and their use in prime-boost protocols that result in enhanced immune outcomes have increased the number of malaria vaccine candidates that access pre-clinical and clinical trials. In the frontline, adenoviruses and poxviruses seem to be giving the best immunization results in experimental animals and their mutual combination, or their combination with recombinant proteins (formulated in adjuvants and given in sequence or being given as protein/virus admixtures), has been shown to reach unprecedented levels of anti-malaria immunity that predictably will be somehow reproduced in the human setting. However, all this optimism was previously seen in the malaria vaccine development field without many real applicable results to date. We describe here the current state-of-the-art in the field of recombinant adenovirus research for malaria vaccine development, in particular referring to their use in combination with other immunogens in heterologous prime-boost protocols, while trying to simultaneously show our contributions and point of view on this subject

Generating and repairing genetically programmed DNA breaks during immunoglobulin class switch recombination

Adaptive immune responses require the generation of a diverse repertoire of immunoglobulins (Igs) that can recognize and neutralize a seemingly infinite number of antigens. V(D)J recombination creates the primary Ig repertoire, which subsequently is modified by somatic hypermutation (SHM) and class switch recombination (CSR). SHM promotes Ig affinity maturation whereas CSR alters the effector function of the Ig. Both SHM and CSR require activation-induced cytidine deaminase (AID) to produce dU:dG mismatches in the Ig locus that are transformed into untemplated mutations in variable coding segments during SHM or DNA double-strand breaks (DSBs) in switch regions during CSR. Within the Ig locus, DNA repair pathways are diverted from their canonical role in maintaining genomic integrity to permit AID-directed mutation and deletion of gene coding segments. Recently identified proteins, genes, and regulatory networks have provided new insights into the temporally and spatially coordinated molecular interactions that control the formation and repair of DSBs within the Ig locus. Unravelling the genetic program that allows B cells to selectively alter the Ig coding regions while protecting non-Ig genes from DNA damage advances our understanding of the molecular processes that maintain genomic integrity as well as humoral immunity

Examining Local Post-School Outcomes and IEP Components in Transition: A Descriptive Inquiry

Transition beyond high school for students with disabilities was introduced in education over 50 years ago. Today, it has evolved to include data collection of ongoing mandated activities and post-school outcomes. The purpose of this study was to examine student transition planning components and how these related to the post-school outcome data collected by a local New Jersey high school district. The data utilized included the Individual Education Programs (IEPs) and results from the Post School Outcomes Study of student exiters who had graduated, dropped out, or aged out for the two cohort years of 2012-2013 and 2015-2016. Both cohort years shared parallel outcomes in that most students of all disability types, except Multiple Disabilities, participated in higher education after leaving high school, followed by students with disabilities who sought competitive employment. Students with Multiple Disabilities were more likely to seek competitive employment. A low number of students were not engaged one year after exiting high school as they had not been involved in education, employment, training, or any other option after exiting high school. Mandated transition components and strategies were mostly present in student IEPs, demonstrating mostly complete transition statements, plans, and activities. These components were also at the center of driving students towards positive post-school outcomes. Goals, activities, and strategies which address employment and continuing education were considered to positively impact student decision-making and ongoing activities, training, and/or education beyond high school

SRS supplemental safety system injection (gas pressurizer) test

An evaluation and validation of an existing version of the RELAP5 thermal hydraulics computer code was undertaken for the purpose of certification for use in the new production reactor - heavy water reactor (NPR-HWR) program. This version of the code was RELAP5/MOD3 Version 5q, designated for the purposes of the NPR-HWR program as RELAP5/NPR Version 0. As part of the evaluation and assessment, test data from theSRS Supplemental Safety System Injection (Gas Pressurizer) was used to verify and assess the ability of RELAP5/NPR Version 0 to perform thermal-hydraulic model analysis using the test data. Specifically, the assessment determines RELAP5/NPR Version 0 capability in modeling sudden depressurization phenomena. Two RELAP5/NPR Version 0 components (pipe and accumulator) were used to compare calculated pressure and temperature against test data. The code deficiencies are a temperature clamp in the accumulator component prevents the gas temperature from going below [minus]9[degrees]F, and RELAP5 accumulator and pipe components wall-to-fluid heat transfer correlation and interfacial vapor heat transfer correlation need substantial improvement. Only the code pipe component calculated pressures and temperatures within the specified 10 percent accuracy

RELAP5/MOD3 analysis of a heated channel in downflow

The onset of flow instability (OFI) is a significant phenomenon affecting the determination of a safe operating power limit in the Savannah River Site production reactors. Tests performed at Columbia University for a single tube with uniform axial and azimuthal heating have been analyzed with RELAP5/NPR, Version 0, a version of RELAP5/MOD3. The tests include water flow rates from 3.2 {times} l0{sup {minus}4} - 2.l {times} 10{sup {minus}3} m{sup 3}/s (5 - 33 gpm), Reynolds numbers from 30,000 - 400,000, and surface heat fluxes from 0 - 3.2 {times} l0{sup 6} w/m{sup 2} (0 - 1,000,000 Btu/hr- ft{sup 2}). Pressure drop versus flow rate curves were mapped for both fixed pressure boundary conditions and fixed flow boundary conditions. RELAP5/MOD3 results showed fair agreement with data for both types of boundary conditions, and good internal consistency between calculations using the two different types of boundary conditions. Under single-phase unheated conditions, the code overpredicted the pressure drop by 22 - 34%. Under single-phase heated conditions, the overprediction increased to as much as 55%. For those tests where two-phase conditions were observed at the channel exit, RELAP5 predicted lower flows than seen in the tests before voiding occurred

SPEEDUP simulation of liquid waste batch processing. Revision 1

The Savannah River Site (SRS) has accumulated radioactive hazardous waste for over 40 years during the time SRS made nuclear materials for the United States Department of Energy (DOE) and its predecessors. This waste is being stored as caustic slurry in a large number of 1 million gallon steel tanks, some of which were initially constructed in the early 1950`s. SRS and DOE intend to clean up the Site and convert this waste into stable forms which then can be safely stored. The liquid waste will be separated into a partially decontaminated low-level and radioactive high-level waste in one feed preparation operation, In-Tank Precipitation. The low-level waste will be used to make a concrete product called saltstone in the Saltstone Facility, a part of the Defense Waste Processing Facility (DWPF). The concrete will be poured into large vaults, where it will be permanently stored. The high-level waste will be added to glass-formers and waste slurry solids from another feed preparation operation, Extended Sludge Processing. The mixture will then be converted to a stable borosilicate glass by a vitrification process that is the other major part of the DWPF. This glass will be poured into stainless steel canisters and sent to a temporary storage facility prior to delivery to a permanent underground storage site