44 research outputs found

    Radiometric performance of AVIRIS: Assessment for an arid region geologic target

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    Data from several AVIRIS flight lines were examined to assess instrument stability and response. Both scene and in-flight calibration data were analyzed statistically. The data clearly indicates that, although the instrument output was noisy and unstable at the time of the data acquisition, valuable spectral signatures can still be extracted and analyzed. Some first order calibration corrections can be performed by forcing internal consistency within the data. AVIRIS data are delivered in band-interleaved-by-line format, but high efficiency routines were developed which access the data as either image or spectral planes and enable effective statistical and visual examination of both AVIRIS scenes and ancillary files. Two methods were used to extract spectral information from segment 4 of the Kelso Dunes flight. Both successfully identified at least three distinct spectral signatures, but neither has positively identified a specific material

    Overview of Spirit Microscopic Imager Results

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    This paper provides an overview of Mars Exploration Rover Spirit Microscopic Imager (MI) operations and the calibration, processing, and analysis of MI data. The focus of this overview is on the last five Earth years (2005-2010) of Spirit's mission in Gusev crater, supplementing the previous overview of the first 450 sols of the Spirit MI investigation. Updates to radiometric calibration using in-flight data and improvements in high-level processing are summarized. Released data products are described, and a table of MI observations, including target/feature names and associated data sets, is appended. The MI observed natural and disturbed exposures of rocks and soils as well as magnets and other rover hardware. These hand-lens-scale observations have provided key constraints on interpretations of the formation and geologic history of features, rocks, and soils examined by Spirit. MI images complement observations by other Spirit instruments, and together show that impact and volcanic processes have dominated the origin and evolution of the rocks in Gusev crater, with aqueous activity indicated by the presence of silica-rich rocks and sulfate-rich soils. The textures of some of the silica-rich rocks are similar to terrestrial hot spring deposits, and observations of subsurface cemented layers indicate recent aqueous mobilization of sulfates in places. Wind action has recently modified soils and abraded many of the rocks imaged by the MI, as observed at other Mars landing sites. Plain Language Summary The Microscopic Imager (MI) on NASA's Spirit rover returned the highest-resolution images of the Martian surface available at the time of the 2004-2010 mission. Designed to survive 90 Mars days (sols) and search for evidence of water in the past, Spirit returned data for 2210 sols, far exceeding all expectations. This paper summarizes the scientific insights gleaned from the thousands of MI images acquired during the last 5years of the mission, supplementing the summary of the first 450 sols of the Spirit MI investigation published previously (Herkenhoff et al., ). Along with data from the other instruments on Spirit, MI images guided the scientific interpretation of the geologic history of the rocks and soils observed in Gusev crater on Mars. We conclude that the geologic history of the area explored by Spirit has been dominated by impacts and volcanism, and that water, perhaps very hot water, was involved in the evolution of some of the rocks and soils. More recently, winds have moved soil particles and abraded rocks, as observed elsewhere on Mars. These results have improved our understanding of Mars' history and informed planning of future missions to Mars.National Aeronautics and Space AdministrationPublic domain articleThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

    Mutation in utp15 Disrupts Vascular Patterning in a p53-Dependent Manner in Zebrafish Embryos

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    Angiogenesis is the process by which the highly branched and functional vasculature arises from the major vessels, providing developing tissues with nutrients, oxygen, and removing metabolic waste. During embryogenesis, vascular patterning is dependent on a tightly regulated balance between pro- and anti-angiogenic signals, and failure of angiogenesis leads to embryonic lethality. Using the zebrafish as a model organism, we sought to identify genes that influence normal vascular patterning.In a forward genetic screen, we identified mutant LA1908, which manifests massive apoptosis during early embryogenesis, abnormal expression of several markers of arterial-venous specification, delayed angiogenic sprouting of the intersegmental vessels (ISV), and malformation of the caudal vein plexus (CVP), indicating a critical role for LA1908 in cell survival and angiogenesis. Genetic mapping and sequencing identified a G to A transition in the splice site preceding exon 11 of utp15 in LA1908 mutant embryos. Overexpression of wild type utp15 mRNA suppresses all observed mutant phenotypes, demonstrating a causative relationship between utp15 and LA1908. Furthermore, we found that injecting morpholino oligonucleotides inhibiting p53 translation prevents cell death and rescues the vascular abnormalities, indicating that p53 is downstream of Utp15 deficiency in mediating the LA1908 phenotypes.Taken together, our data demonstrate an early embryonic effect of Utp15 deficiency on cell survival and the normal patterning of the vasculature and highlight an anti-angiogenic role of p53 in developing embryos

    Genomewide Association Study for Determinants of HIV-1 Acquisition and Viral Set Point in HIV-1 Serodiscordant Couples with Quantified Virus Exposure

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    Host genetic factors may be important determinants of HIV-1 sexual acquisition. We performed a genome-wide association study (GWAS) for host genetic variants modifying HIV-1 acquisition and viral control in the context of a cohort of African HIV-1 serodiscordant heterosexual couples. To minimize misclassification of HIV-1 risk, we quantified HIV-1 exposure, using data including plasma HIV-1 concentrations, gender, and condom use.We matched couples without HIV-1 seroconversion to those with seroconversion by quantified HIV-1 exposure risk. Logistic regression of single nucleotide polymorphisms (SNPs) for 798 samples from 496 HIV-1 infected and 302 HIV-1 exposed, uninfected individuals was performed to identify factors associated with HIV-1 acquisition. In addition, a linear regression analysis was performed using SNP data from a subset (n = 403) of HIV-1 infected individuals to identify factors predicting plasma HIV-1 concentrations.After correcting for multiple comparisons, no SNPs were significantly associated with HIV-1 infection status or plasma HIV-1 concentrations.This GWAS controlling for HIV-1 exposure did not identify common host genotypes influencing HIV-1 acquisition. Alternative strategies, such as large-scale sequencing to identify low frequency variation, should be considered for identifying novel host genetic predictors of HIV-1 acquisition

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

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    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

    Is HIV-1 evolving to a less virulent form in humans?

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    Patient and stakeholder engagement learnings: PREP-IT as a case study

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    Correction to: Cluster identification, selection, and description in Cluster randomized crossover trials: the PREP-IT trials

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    An amendment to this paper has been published and can be accessed via the original article

    31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

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    Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival
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