A Persistent Simulation Environment for Autonomous Systems

The age of Autonomous Unmanned Aircraft Systems (AUAS) is creating new challenges for the accreditation and certification requiring new standards, policies and procedures that sanction whether a UAS is safe to fly. Establishing a basis for certification of autonomous systems via research into trust and trustworthiness is the focus of Autonomy Teaming and TRAjectories for Complex Trusted Operational Reliability (ATTRACTOR), a new NASA Convergent Aeronautics Solution (CAS) project. Simulation Environments to test and evaluate AUAS decision making may be a low-cost solution to help certify that various AUAS systems are trustworthy enough to be allowed to fly in current general and commercial aviation airspace. NASA is working to build a peer-to-peer persistent simulation (P3 Sim) environment. The P3 Sim will be a Massively Multiplayer Online (MMO) environment were AUAS avatars can interact with a complex dynamic environment and each other. The focus of the effort is to provide AUAS researchers a low-cost intuitive testing environment that will aid training for and assessment of decisions made by autonomous systems such as AUAS. This presentation focuses on the design approach and challenges faced in development of the P3 Sim Environment is support of investigating trustworthiness of autonomous systems

Bacterial Toxicity of Potassium Tellurite: Unveiling an Ancient Enigma

Biochemical, genetic, enzymatic and molecular approaches were used to demonstrate, for the first time, that tellurite (TeO(3) (2−)) toxicity in E. coli involves superoxide formation. This radical is derived, at least in part, from enzymatic TeO(3) (2−) reduction. This conclusion is supported by the following observations made in K(2)TeO(3)-treated E. coli BW25113: i) induction of the ibpA gene encoding for the small heat shock protein IbpA, which has been associated with resistance to superoxide, ii) increase of cytoplasmic reactive oxygen species (ROS) as determined with ROS-specific probe 2′7′-dichlorodihydrofluorescein diacetate (H(2)DCFDA), iii) increase of carbonyl content in cellular proteins, iv) increase in the generation of thiobarbituric acid-reactive substances (TBARs), v) inactivation of oxidative stress-sensitive [Fe-S] enzymes such as aconitase, vi) increase of superoxide dismutase (SOD) activity, vii) increase of sodA, sodB and soxS mRNA transcription, and viii) generation of superoxide radical during in vitro enzymatic reduction of potassium tellurite

A reexamination of information theory-based methods for DNA-binding site identification

<p>Abstract</p> <p>Background</p> <p>Searching for transcription factor binding sites in genome sequences is still an open problem in bioinformatics. Despite substantial progress, search methods based on information theory remain a standard in the field, even though the full validity of their underlying assumptions has only been tested in artificial settings. Here we use newly available data on transcription factors from different bacterial genomes to make a more thorough assessment of information theory-based search methods.</p> <p>Results</p> <p>Our results reveal that conventional benchmarking against artificial sequence data leads frequently to overestimation of search efficiency. In addition, we find that sequence information by itself is often inadequate and therefore must be complemented by other cues, such as curvature, in real genomes. Furthermore, results on skewed genomes show that methods integrating skew information, such as <it>Relative Entropy</it>, are not effective because their assumptions may not hold in real genomes. The evidence suggests that binding sites tend to evolve towards genomic skew, rather than against it, and to maintain their information content through increased conservation. Based on these results, we identify several misconceptions on information theory as applied to binding sites, such as negative entropy, and we propose a revised paradigm to explain the observed results.</p> <p>Conclusion</p> <p>We conclude that, among information theory-based methods, the most unassuming search methods perform, on average, better than any other alternatives, since heuristic corrections to these methods are prone to fail when working on real data. A reexamination of information content in binding sites reveals that information content is a compound measure of search and binding affinity requirements, a fact that has important repercussions for our understanding of binding site evolution.</p

Cellular processes of v-Src transformation revealed by gene profiling of primary cells - Implications for human cancer

<p>Abstract</p> <p>Background</p> <p>Cell transformation by the Src tyrosine kinase is characterized by extensive changes in gene expression. In this study, we took advantage of several strains of the Rous sarcoma virus (RSV) to characterize the patterns of v-Src-dependent gene expression in two different primary cell types, namely chicken embryo fibroblasts (CEF) and chicken neuroretinal (CNR) cells. We identified a common set of v-Src regulated genes and assessed if their expression is associated with disease-free survival using several independent human tumor data sets.</p> <p>Methods</p> <p>CEF and CNR cells were infected with transforming, non-transforming, and temperature sensitive mutants of RSV to identify the patterns of gene expression in response to v-Src-transformation. Microarray analysis was used to measure changes in gene expression and to define a common set of v-Src regulated genes (CSR genes) in CEF and CNR cells. A clustering enrichment regime using the CSR genes and two independent breast tumor data-sets was used to identify a 42-gene aggressive tumor gene signature. The aggressive gene signature was tested for its prognostic value by conducting survival analyses on six additional tumor data sets.</p> <p>Results</p> <p>The analysis of CEF and CNR cells revealed that cell transformation by v-Src alters the expression of 6% of the protein coding genes of the genome. A common set of 175 v-Src regulated genes (CSR genes) was regulated in both CEF and CNR cells. Within the CSR gene set, a group of 42 v-Src inducible genes was associated with reduced disease- and metastasis-free survival in several independent patient cohorts with breast or lung cancer. Gene classes represented within this group include DNA replication, cell cycle, the DNA damage and stress responses, and blood vessel morphogenesis.</p> <p>Conclusion</p> <p>By studying the v-Src-dependent changes in gene expression in two types of primary cells, we identified a set of 42 inducible genes associated with poor prognosis in breast and lung cancer. The identification of these genes provides a set of biomarkers of aggressive tumor behavior and a framework for the study of cancer cells characterized by elevated Src kinase activity.</p

Student Doctor Network: Fake News or Facts for Emergency Medicine Applicants?

Introduction: Residency applicants use multiple resources to guide their application process including the Student Doctor Network (SDN), a publicly available online forum for the discussion of various topics in medical education. In recent years, specialty-specific forums for residency applicants to self-report their own application information have become popular. These forums allow other applicants to review self-reported data from their peers to inform their own application process. The accuracy of this resource is unknown. To determine whether the SDN is an accurate source of information for emergency medicine (EM) applicants, we compared self-reported SDN data to objective data from the National Resident Matching Program (NRMP). Methods: We retrospectively reviewed self-reported SDN data by DO and MD candidates from EM forums for the 2014, 2016, and 2018 residency application cycles. These data were compared to the NRMP charting outcomes for each respective year. Results: A total of 360 EM applicants self-reported data on the SDN during the years reviewed. The majority of these applicants (79%) posted for the 2018 application cycle following transition to a Google Docs spreadsheet. For the first two years of analysis, mean United States Medical Licensing Examination (USMLE) scores were similar to SDN reports. For the most recent year studied, applicants who posted to SDN reported higher mean (USMLE) Step 1 (234, 95% confidence interval [CI], 233-236) and Step 2 scores (250, 95% CI, 248-251) when compared to NRMP data (231 and 241). Reported contiguous residency program ranks were similar to NRMP in all years, and the proportion indicating Alpha Omega Alpha Honor Medical Society membership was similar to NRMP only for the most recent year studied.&nbsp; Conclusion: Self-reporting on SDN showed a slight bias toward higher USMLE step scores in the most recent year when compared to objective NRMP data. Self-reporting on SDN has increased in recent years, but it is unknown whether this increase will lead to more accurate information for EM applicants. Given the self-reported nature of the SDN, applicants should use SDN forums with caution

Evidence for elongation of the helical pitch of the RecA filament upon ATP and ADP binding using small-angle neutron scattering

Structural changes of the RecA filament upon binding of cofactors have been investigated by small-angle neutron scattering. Both ATP and ADP increased the helical pitch of the RecA homopolymer, which is observed to be 7 nm in the absence of any cofactor. The binding of ATP altered the pitch to 9 nm, whereas the binding of ADP only produced a pitch of 8.2 nm. The pitch determined for the RecA complex with the ATP analog adenosine 5'-[gamma-thio]triphosphate was similar to that found with ATP. Thus, at least three, somewhat different, RecA helical filamentous structures may form in solution. The binding of DNA to RecA did not alter the pitch significantly, indicating that the cofactor binding is the determining factor for the size of the helical pitch of the RecA filament. We also found that elongation of the helical pitch is a necessary, but not a sufficient condition, for the coprotease activity of RecA. The presence of acetate or glutamate ions is also required. The pitch of the ADP . RecA filament is in agreement with that found in the crystal structure. This correlation indicates that this structure corresponds to that of the ADP . RecA filament in solution, although this is not the species active in recombination