Requesting Distant Robotic Action: An Ontology for Naming and Action Identification for Planning on the Mars Exploration Rover Mission.

This paper focuses on the development of a naming convention and the use of abbreviated names and a related ontology for science work and distant robotic action that comprise requests for a robotic rover during the NASA Mars Exploration Rover (MER) mission, run by the Jet Propulsion Laboratory (JPL). We demonstrate how abbreviated names and an associated ontology support sharing and identifying information among teams and software tools. An ontology of distant action must take into account a dynamic environment, changing in response to physical events and intentional actions, and reflect the influence of context on the meaning of action. The nascent domain of Martian tele-robotic science, in which specialists request work from a rover moving through a distant landscape, as well as the need to consider the interdisciplinary teams involved in completing that work, required an empirical approach. The formulation of this ontology used ethnographic methods and grounded theory to study human behavior and work practice with software tools

Cannabinoid receptor interacting protein suppresses agonist-driven CB1 receptor internalization and regulates receptor replenishment in an agonist-biased manner

Cannabinoid receptor interacting protein 1a (CRIP1a) is a CB1 receptor (CB1R) distal C-terminus-associated protein that modulates CB1R signaling via G proteins, and CB1R down-regulation but not desensitization (Blume et al. [2015] Cell Signal., 27, 716-726; Smith et al. [2015] Mol. Pharmacol., 87, 747-765). In this study, we determined the involvement of CRIP1a in CB1R plasma membrane trafficking. To follow the effects of agonists and antagonists on cell surface CB(1)Rs, we utilized the genetically homogeneous cloned neuronal cell line N18TG2, which endogenously expresses both CB1R and CRIP1a, and exhibits a well-characterized endocannabinoid signaling system. We developed stable CRIP1a-over-expressing and CRIP1a-siRNA-silenced knockdown clones to investigate gene dose effects of CRIP1a on CB1R plasma membrane expression. Results indicate that CP55940 or WIN55212-2 (10 nM, 5 min) reduced cell surface CB1R by a dynamin-and clathrin-dependent process, and this was attenuated by CRIP1a over-expression. CP55940-mediated cell surface CB1R loss was followed by a cycloheximide-sensitive recovery of surface receptors (30120 min), suggesting the requirement for new protein synthesis. In contrast, WIN55212-2-mediated cell surface CB(1)Rs recovered only in CRIP1a knockdown cells. Changes in CRIP1a expression levels did not affect a transient rimonabant (10 nM)mediated increase in cell surface CB(1)Rs, which is postulated to be as a result of rimonabant effects on \u27non-agonist-driven\u27 internalization. These studies demonstrate a novel role for CRIP1a in agonist-driven CB1R cell surface regulation postulated to occur by two mechanisms: 1) attenuating internalization that is agonist-mediated, but not that in the absence of exogenous agonists, and 2) biased agonist-dependent trafficking of de novo synthesized receptor to the cell surface

Surface properties of Mars' polar layered deposits and polar landing sites

On December 3, 1999, the Mars Polar Lander and Mars Microprobes will land on the planet's south polar layered deposits near (76°S, 195°W) and conduct the first in situ studies of the planet's polar regions. The scientific goals of these missions address several poorly understood and globally significant issues, such as polar meteorology, the composition and volatile content of the layered deposits, the erosional state and mass balance of their surface, their possible relationship to climate cycles, and the nature of bright and dark aeolian material. Derived thermal inertias of the southern layered deposits are very low (50–100 J m^(−2) s^(−1/2) K^(−1)), suggesting that the surface down to a depth of a few centimeters is generally fine grained or porous and free of an appreciable amount of rock or ice. The landing site region is smoother than typical cratered terrain on ∼1 km pixel^(−1) Viking Orbiter images but contains low-relief texture on ∼5 to 100 m pixel^(−1) Mariner 9 and Mars Global Surveyor images. The surface of the southern deposits is older than that of the northern deposits and appears to be modified by aeolian erosion or ablation of ground ice

Planning Considerations for a Mars Sample Receiving Facility: Summary and Interpretation of Three Design Studies

It has been widely understood for many years that an essential component of a Mars Sample Return mission is a Sample Receiving Facility (SRF). The purpose of such a facility would be to take delivery of the flight hardware that lands on Earth, open the spacecraft and extract the sample container and samples, and conduct an agreed-upon test protocol, while ensuring strict containment and contamination control of the samples while in the SRF. Any samples that are found to be non-hazardous (or are rendered non-hazardous by sterilization) would then be transferred to long-term curation. Although the general concept of an SRF is relatively straightforward, there has been considerable discussion about implementation planning. The Mars Exploration Program carried out an analysis of the attributes of an SRF to establish its scope, including minimum size and functionality, budgetary requirements (capital cost, operating costs, cost profile), and development schedule. The approach was to arrange for three independent design studies, each led by an architectural design firm, and compare the results. While there were many design elements in common identified by each study team, there were significant differences in the way human operators were to interact with the systems. In aggregate, the design studies provided insight into the attributes of a future SRF and the complex factors to consider for future programmatic planning

Using automated pharmacy records to assess the management of tuberculosis.

We used automated pharmacy dispensing data to characterize tuberculosis (TB) management for 45 health maintenance organization (HMO) members. Pharmacy records distinguished patients treated in HMOs from those treated elsewhere. For cases treated in HMOs, they provided useful information about appropriateness of prescribed regimens and adherence to therapy

Chromosomal microarray testing in adults with intellectual disability presenting with comorbid psychiatric disorders.

Chromosomal copy-number variations (CNVs) are a class of genetic variants highly implicated in the aetiology of neurodevelopmental disorders, including intellectual disabilities (ID), schizophrenia and autism spectrum disorders (ASD). Yet the majority of adults with idiopathic ID presenting to psychiatric services have not been tested for CNVs. We undertook genome-wide chromosomal microarray analysis (CMA) of 202 adults with idiopathic ID recruited from community and in-patient ID psychiatry services across England. CNV pathogenicity was assessed using standard clinical diagnostic methods and participants underwent comprehensive medical and psychiatric phenotyping. We found an 11% yield of likely pathogenic CNVs (22/202). CNVs at recurrent loci, including the 15q11-q13 and 16p11.2-p13.11 regions were most frequently observed. We observed an increased frequency of 16p11.2 duplications compared with those reported in single-disorder cohorts. CNVs were also identified in genes known to effect neurodevelopment, namely NRXN1 and GRIN2B. Furthermore deletions at 2q13, 12q21.2-21.31 and 19q13.32, and duplications at 4p16.3, 13q32.3-33.3 and Xq24-25 were observed. Routine CMA in ID psychiatry could uncover ~11% new genetic diagnoses with potential implications for patient management. We advocate greater consideration of CMA in the assessment of adults with idiopathic ID presenting to psychiatry services

Reference Ranges for the Clinical Laboratory Derived from a Rural Population in Kericho, Kenya

The conduct of Phase I/II HIV vaccine trials internationally necessitates the development of region-specific clinical reference ranges for trial enrolment and participant monitoring. A population based cohort of adults in Kericho, Kenya, a potential vaccine trial site, allowed development of clinical laboratory reference ranges. Lymphocyte immunophenotyping was performed on 1293 HIV seronegative study participants. Hematology and clinical chemistry were performed on up to 1541 cohort enrollees. The ratio of males to females was 1.9∶1. Means, medians and 95% reference ranges were calculated and compared with those from other nations. The median CD4+ T cell count for the group was 810 cells/µl. There were significant gender differences for both red and white blood cell parameters. Kenyan subjects had lower median hemoglobin concentrations (9.5 g/dL; range 6.7–11.1) and neutrophil counts (1850 cells/µl; range 914–4715) compared to North Americans. Kenyan clinical chemistry reference ranges were comparable to those from the USA, with the exception of the upper limits for bilirubin and blood urea nitrogen, which were 2.3-fold higher and 1.5-fold lower, respectively. This study is the first to assess clinical reference ranges for a highland community in Kenya and highlights the need to define clinical laboratory ranges from the national community not only for clinical research but also care and treatment

Profiling Critical Cancer Gene Mutations in Clinical Tumor Samples

BACKGROUND: Detection of critical cancer gene mutations in clinical tumor specimens may predict patient outcomes and inform treatment options; however, high-throughput mutation profiling remains underdeveloped as a diagnostic approach. We report the implementation of a genotyping and validation algorithm that enables robust tumor mutation profiling in the clinical setting. METHODOLOGY: We developed and implemented an optimized mutation profiling platform ("OncoMap") to interrogate approximately 400 mutations in 33 known oncogenes and tumor suppressors, many of which are known to predict response or resistance to targeted therapies. The performance of OncoMap was analyzed using DNA derived from both frozen and FFPE clinical material in a diverse set of cancer types. A subsequent in-depth analysis was conducted on histologically and clinically annotated pediatric gliomas. The sensitivity and specificity of OncoMap were 93.8% and 100% in fresh frozen tissue; and 89.3% and 99.4% in FFPE-derived DNA. We detected known mutations at the expected frequencies in common cancers, as well as novel mutations in adult and pediatric cancers that are likely to predict heightened response or resistance to existing or developmental cancer therapies. OncoMap profiles also support a new molecular stratification of pediatric low-grade gliomas based on BRAF mutations that may have immediate clinical impact. CONCLUSIONS: Our results demonstrate the clinical feasibility of high-throughput mutation profiling to query a large panel of "actionable" cancer gene mutations. In the future, this type of approach may be incorporated into both cancer epidemiologic studies and clinical decision making to specify the use of many targeted anticancer agents

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe