Review of Issues Associated with Safe Operation and Management of the Space Shuttle Program

At the request of the President of the United States through the Office of Science and Technology Policy (OSTP), the NASA Administrator tasked the Aerospace Safety Advisory Panel with the responsibility to identify and review issues associated with the safe operation and management of the Space Shuttle program arising from ongoing efforts to improve and streamline operations. These efforts include the consolidation of operations under a single Space Flight Operations Contract (SFOC), downsizing the Space Shuttle workforce and reducing costs of operations and management. The Panel formed five teams to address the potentially significant safety impacts of the seven specific topic areas listed in the study Terms of Reference. These areas were (in the order in which they are presented in this report): Maintenance of independent safety oversight; implementation plan for the transition of Shuttle program management to the Lead Center; communications among NASA Centers and Headquarters; transition plan for downsizing to anticipated workforce levels; implementation of a phased transition to a prime contractor for operations; Shuttle flight rate for Space Station assembly; and planned safety and performance upgrades for Space Station assembly. The study teams collected information through briefings, interviews, telephone conversations and from reviewing applicable documentation. These inputs were distilled by each team into observations and recommendations which were then reviewed by the entire Panel

Designing a Study to Investigate Older Novice Drivers

DTNH2217D00031/693JJ920F000207Drivers 15 to 20 years old\u2014many of whom were novice drivers\u2014represented 8.5 percent of drivers involved in fatal crashes but only 5.1 percent of all licensed drivers in 2020. Graduated driver licensing (GDL) laws are the most effective behavioral countermeasure for young drivers. However, although an increasing proportion of young people are delaying licensure until 18 or older, few States currently apply the full GDL program to 18- to 20-year-old novice drivers, and little is known about the safety and driving habits of this group. In this project the research team developed a hypothetical naturalistic driving study to investigate research questions about the safety and driving exposure of younger (15.5 to 16.5 years old) and older (18 to 20 years old) novice drivers in the first year of unsupervised (independent) driving

Extinction Risk and Diversification Are Linked in a Plant Biodiversity Hotspot

Plant extinction risks in the Cape, South Africa differ from those for vertebrates worldwide, with young and fast-evolving plant lineages marching towards extinction at the fastest rate, but independently of human effects

Stochastic Species Turnover and Stable Coexistence in a Species-Rich, Fire-Prone Plant Community

Understanding the mechanisms that maintain diversity is important for managing ecosystems for species persistence. Here we used a long-term data set to understand mechanisms of coexistence at the local and regional scales in the Cape Floristic Region, a global hotspot of plant diversity. We used a dataset comprising 81 monitoring sites, sampled in 1966 and again in 1996, and containing 422 species for which growth form, regeneration mode, dispersal distance and abundances at both the local (site) and meta-community scales are known. We found that species presence and abundance were stable at the meta-community scale over the 30 year period but highly unstable at the local scale, and were not influenced by species' biological attributes. Moreover, rare species were no more likely to go extinct at the local scale than common species, and that alpha diversity in local communities was strongly influenced by habitat. We conclude that stochastic environmental fluctuations associated with recurrent fire buffer populations from extinction, thereby ensuring stable coexistence at the meta-community scale by creating a “neutral-like” pattern maintained by niche-differentiation

Trait Variation in Yeast Is Defined by Population History

A fundamental goal in biology is to achieve a mechanistic understanding of how and to what extent ecological variation imposes selection for distinct traits and favors the fixation of specific genetic variants. Key to such an understanding is the detailed mapping of the natural genomic and phenomic space and a bridging of the gap that separates these worlds. Here we chart a high-resolution map of natural trait variation in one of the most important genetic model organisms, the budding yeast Saccharomyces cerevisiae, and its closest wild relatives and trace the genetic basis and timing of major phenotype changing events in its recent history. We show that natural trait variation in S. cerevisiae exceeds that of its relatives, despite limited genetic variation, and follows the population history rather than the source environment. In particular, the West African population is phenotypically unique, with an extreme abundance of low-performance alleles, notably a premature translational termination signal in GAL3 that cause inability to utilize galactose. Our observations suggest that many S. cerevisiae traits may be the consequence of genetic drift rather than selection, in line with the assumption that natural yeast lineages are remnants of recent population bottlenecks. Disconcertingly, the universal type strain S288C was found to be highly atypical, highlighting the danger of extrapolating gene-trait connections obtained in mosaic, lab-domesticated lineages to the species as a whole. Overall, this study represents a step towards an in-depth understanding of the causal relationship between co-variation in ecology, selection pressure, natural traits, molecular mechanism, and alleles in a key model organism

A Variable Region within the Genome of Streptococcus pneumoniae Contributes to Strain-Strain Variation in Virulence

The bacterial factors responsible for the variation in invasive potential between different clones and serotypes of Streptococcus pneumoniae are largely unknown. Therefore, the isolation of rare serotype 1 carriage strains in Indigenous Australian communities provided a unique opportunity to compare the genomes of non-invasive and invasive isolates of the same serotype in order to identify such factors. The human virulence status of non-invasive, intermediately virulent and highly virulent serotype 1 isolates was reflected in mice and showed that whilst both human non-invasive and highly virulent isolates were able to colonize the murine nasopharynx equally, only the human highly virulent isolates were able to invade and survive in the murine lungs and blood. Genomic sequencing comparisons between these isolates identified 8 regions >1 kb in size that were specific to only the highly virulent isolates, and included a version of the pneumococcal pathogenicity island 1 variable region (PPI-1v), phage-associated adherence factors, transporters and metabolic enzymes. In particular, a phage-associated endolysin, a putative iron/lead permease and an operon within PPI-1v exhibited niche-specific changes in expression that suggest important roles for these genes in the lungs and blood. Moreover, in vivo competition between pneumococci carrying PPI-1v derivatives representing the two identified versions of the region showed that the version of PPI-1v in the highly virulent isolates was more competitive than the version from the less virulent isolates in the nasopharyngeal tissue, blood and lungs. This study is the first to perform genomic comparisons between serotype 1 isolates with distinct virulence profiles that correlate between mice and humans, and has highlighted the important role that hypervariable genomic loci, such as PPI-1v, play in pneumococcal disease. The findings of this study have important implications for understanding the processes that drive progression from colonization to invasive disease and will help direct the development of novel therapeutic strategies

Multi-Platform Next-Generation Sequencing of the Domestic Turkey (Meleagris gallopavo): Genome Assembly and Analysis

The combined application of next-generation sequencing platforms has provided an economical approach to unlocking the potential of the turkey genome

Functional, Non-Clonal IgMa-Restricted B Cell Receptor Interactions with the HIV-1 Envelope gp41 Membrane Proximal External Region

The membrane proximal external region (MPER) of HIV-1 gp41 has several features that make it an attractive antibody-based vaccine target, but eliciting an effective gp41 MPER-specific protective antibody response remains elusive. One fundamental issue is whether the failure to make gp41 MPER-specific broadly neutralizing antibodies like 2F5 and 4E10 is due to structural constraints with the gp41 MPER, or alternatively, if gp41 MPER epitope-specific B cells are lost to immunological tolerance. An equally important question is how B cells interact with, and respond to, the gp41 MPER epitope, including whether they engage this epitope in a non-canonical manner i.e., by non-paratopic recognition via B cell receptors (BCR). To begin understanding how B cells engage the gp41 MPER, we characterized B cell-gp41 MPER interactions in BALB/c and C57BL/6 mice. Surprisingly, we found that a significant (∼7%) fraction of splenic B cells from BALB/c, but not C57BL/6 mice, bound the gp41 MPER via their BCRs. This strain-specific binding was concentrated in IgMhi subsets, including marginal zone and peritoneal B1 B cells, and correlated with enriched fractions (∼15%) of gp41 MPER-specific IgM secreted by in vitro-activated splenic B cells. Analysis of Igha (BALB/c) and Ighb (C57BL/6) congenic mice demonstrated that gp41 MPER binding was controlled by determinants of the Igha locus. Mapping of MPER gp41 interactions with IgMa identified MPER residues distinct from those to which mAb 2F5 binds and demonstrated the requirement of Fc CH regions. Importantly, gp41 MPER ligation produced detectable BCR-proximal signaling events, suggesting that interactions between gp41 MPER and IgMa determinants may elicit partial B cell activation. These data suggest that low avidity, non-paratopic interactions between the gp41 MPER and membrane Ig on naïve B cells may interfere with or divert bnAb responses