CD4 memory T cells divide poorly in response to antigen because of their cytokine profile

Immunological memory is a hallmark of adaptive immunity, and understanding T cell memory will be central to the development of effective cell-mediated vaccines. The characteristics and functions of CD4 memory cells have not been well defined. Here we demonstrate that the increased size of the secondary response is solely a consequence of the increased antigen-specific precursor frequency within the memory pool. Memory cells proliferated less than primary responding cells, even within the same host. By analyzing the entry of primary and memory cells into the cell cycle, we found that the two populations proliferated similarly until day 5; after this time, fewer of the reactivated memory cells proliferated. At this time, fewer of the reactivated memory cells made IL-2 than primary responding cells, but more made IFNγ. Both these factors affected the low proliferation of the memory cells, because either exogenous IL-2 or inhibition of IFNγ increased the proliferation of the memory cells

Factors Impacting Habitable Volume Requirements: Results from the 2011 Habitable Volume Workshop

This report documents the results of the Habitable Volume Workshop held April 18-21, 2011 in Houston, TX at the Center for Advanced Space Studies-Universities Space Research Association. The workshop was convened by NASA to examine the factors that feed into understanding minimum habitable volume requirements for long duration space missions. While there have been confinement studies and analogs that have provided the basis for the guidance found in current habitability standards, determining the adequacy of the volume for future long duration exploration missions is a more complicated endeavor. It was determined that an improved understanding of the relationship between behavioral and psychosocial stressors, available habitable and net habitable volume, and interior layouts was needed to judge the adequacy of long duration habitat designs. The workshop brought together a multi-disciplinary group of experts from the medical and behavioral sciences, spaceflight, human habitability disciplines and design professionals. These subject matter experts identified the most salient design-related stressors anticipated for a long duration exploration mission. The selected stressors were based on scientific evidence, as well as personal experiences from spaceflight and analogs. They were organized into eight major categories: allocation of space; workspace; general and individual control of environment; sensory deprivation; social monotony; crew composition; physical and medical issues; and contingency readiness. Mitigation strategies for the identified stressors and their subsequent impact to habitat design were identified. Recommendations for future research to address the stressors and mitigating design impacts are presented

A Tale of Two Toxins: Helicobacter Pylori CagA and VacA Modulate Host Pathways that Impact Disease

Helicobacter pylori is a pathogenic bacterium that colonizes more than 50% of the world's population, which leads to a tremendous medical burden. H. pylori infection is associated with such varied diseases as gastritis, peptic ulcers, and two forms of gastric cancer: gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma. This association represents a novel paradigm for cancer development; H. pylori is currently the only bacterium to be recognized as a carcinogen. Therefore, a significant amount of research has been conducted to identify the bacterial factors and the deregulated host cell pathways that are responsible for the progression to more severe disease states. Two of the virulence factors that have been implicated in this process are cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA), which are cytotoxins that are injected and secreted by H. pylori, respectively. Both of these virulence factors are polymorphic and affect a multitude of host cellular pathways. These combined facts could easily contribute to differences in disease severity across the population as various CagA and VacA alleles differentially target some pathways. Herein we highlight the diverse types of cellular pathways and processes targeted by these important toxins

Building a Shared Definitional Model of Long Duration Human Spaceflight

In 1956, on the eve of human space travel Strughold first proposed a simple classification of the present and future stages of manned flight that identified key factors, risks and developmental stages for the evolutionary journey ahead. As we look to optimize the potential of the ISS as a gateway to new destinations, we need a current shared working definitional model of long duration human space flight to help guide our path. Initial search of formal and grey literature augmented by liaison with subject matter experts. Search strategy focused on both the use of term long duration mission and long duration spaceflight, and also broader related current and historical definitions and classification models of spaceflight. The related sea and air travel literature was also subsequently explored with a view to identifying analogous models or classification systems. There are multiple different definitions and classification systems for spaceflight including phase and type of mission, craft and payload and related risk management models. However the frequently used concepts of long duration mission and long duration spaceflight are infrequently operationally defined by authors, and no commonly referenced classical or gold standard definition or model of these terms emerged from the search. The categorization (Cat) system for sailing was found to be of potential analogous utility, with its focus on understanding the need for crew and craft autonomy at various levels of potential adversity and inability to gain outside support or return to a safe location, due to factors of time, distance and location

Marked changes in electron transport through the blue copper protein azurin in the solid state upon deuteration

Measuring electron transport (ETp) across proteins in the solid-state offers a way to study electron transfer (ET) mechanism(s) that minimizes solvation effects on the process. Solid state ETp is sensitive to any static (conformational) or dynamic (vibrational) changes in the protein. Our macroscopic measurement technique extends the use of ETp meas-urements down to low temperatures and the concomitant lower current densities, because the larger area still yields measurable currents. Thus, we reported previously a surprising lack of temperature-dependence for ETp via the blue copper protein azurin (Az), from 80K till denaturation, while ETp via apo-(Cu-free) Az was found to be temperature de-pendent \geq 200K. H/D substitution (deuteration) can provide a potentially powerful means to unravel factors that affect the ETp mechanism at a molecular level. Therefore, we measured and report here the kinetic deuterium isotope effect (KIE) on ETp through holo-Az as a function of temperature (30-340K). We find that deuteration has a striking effect in that it changes ETp from temperature independent to temperature dependent above 180K. This change is expressed in KIE values between 1.8 at 340K and 9.1 at \leq 180K. These values are particularly remarkable in light of the previously reported inverse KIE on the ET in Az in solution. The high values that we obtain for the KIE on the ETp process across the protein monolayer are consistent with a transport mechanism that involves through-(H-containing)-bonds of the {\beta}-sheet structure of Az, likely those of am-ide groups.Comment: 15 pages, 3 figures, 2 Supplementary figure

Design and Testing of a Feed-Forward Control System for Deployable Vortex Generators Dependent on Angle of Attack

A vortex generator (VG hereafter) is a common feature of an aircraft wing that disturbs the flow on the leading edge of the wing, thus energizing the boundary layer and reducing flow separation. For an aircraft experiencing flow separation, VGs can increase the lift-to-drag ratio of the wing and prevent stall; however, if flow separation isn’t an issue, the unnecessary frontal area of the VGs has the potential to produce parasitic drag. This study seeks to determine whether the use of a deployment system can improve the performance of VG’s by raising or lowering them depending on the angle of attack of the wing. Using wind tunnel testing, a feed-forward control deployment system was developed which improved the lift to drag ratio for some angles of attack, and it was determined that further development could potentially produce a system with significant improvements in aircraft efficiency

Meal Replacement Mass Reduction Integration and Acceptability Study

The Orion Multi-Purpose Crew Vehicle (MPCV) and future exploration missions are mass constrained; therefore we are challenged to reduce the mass of the food system by 10% while maintaining safety, nutrition, and acceptability to support crew health and performance for exploration missions. Meal replacement with nutritionally balanced, 700-900 calorie bars was identified as a method to reduce mass. However, commercially available products do not meet the requirements for a meal replacement in the spaceflight food system. The purpose of this task was to develop a variety of nutritionally balanced, high quality, breakfast replacement bars, which enable a 10% food mass savings. To date, six nutrient-dense meal replacement bars have been developed, all of which meet spaceflight nutritional, microbiological, sensory, and shelf-life requirements. The four highest scoring bars were evaluated based on final product sensory acceptability, nutritional stability, qualitative stability of analytical measurements (i.e. color and texture), and microbiological compliance over a period of two years to predict long-term acceptability. All bars maintained overall acceptability throughout the first year of storage, despite minor changes in color and texture. However, added vitamins C, B1, and B9 degraded rapidly in fortified samples of Banana Nut bars, indicating the need for additional development. In addition to shelf-life testing, four bar varieties were evaluated in the Human Exploration Research Analog (HERA), campaign 3, to assess the frequency with which actual meal replacement options may be implemented, based on impact to satiety and psychosocial measurements. Crewmembers (n=16) were asked to consume meal replacement bars every day for the first fifteen days of the mission and every three days for the second half of the mission. Daily surveys assessed the crew's responses to bar acceptability, mood, food fatigue and perceived stress. Preliminary results indicate that the majority of crew members were noncompliant with daily meal replacement during the first half of the mission. Several crew members chose to forgo the meal, resulting in caloric deficits that were higher on skipped-bar days. Body mass loss was significant throughout the mission. Although there was no significant difference in body mass loss overall between the first half and second half of the mission, a higher number of individual crew members lost more body mass in the first half of the mission. Analysis is still ongoing, but current trends suggest that daily involuntary meal replacement can lead to greater individual impacts on body mass and psychological factors, while meal replacement on a more limited basis may be acceptable to most crew for missions up to 30 days. This data should be considered in Orion mass trades with health and human performance

Overview of NASA Behavioral Health and Performance Standard Measures

NASAs Human Research Program (HRP) is developing a set of Standard Measures for use in spaceflight and spaceflight analog environments to monitor the risks of long-duration missions on human health and performance, including behavioral health, individual and team performance, and social processes. Based on measures selected, developed, and tested under the NASA-funded Behavioral Core Measures project (PI: D.F. Dinges) as well as other projects from NASAs Human Factors & Behavioral Performance research portfolio, NASAs Behavioral Health & Performance (BHP) Laboratory is further evaluating the operational feasibility, acceptability, and validity of a multidisciplinary suite of objective, subjective, behavioral, and biological measures for monitoring monitor behavioral health, individual and team performance, and social processes over time. The inaugural generation of the NASA Behavioral Health & Performance (BHP) Standard Measures includes a neurocognitive test battery, actigraphy, physical proximity sensors, cardiovascular monitors, and subjective self-reports of mood, depression, and various team and social processes and performance outcomes