30 research outputs found

    A Parallel Processing Development System to Perform Automatic Correlation of Subsurface Petrophysical Logs. (Volumes I and II).

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    A parallel processing framework for the investigation of three dimensional subsurface geological problems is developed. The Floating Point Systems T-20 hypercube parallel computer system is used in the automatic correlation of petrophysical well logs. Parallel processing issues such as processor management, interprocessor communications management, memory management and algorithm development are discussed. Techniques are discussed to use spontaneous potential petrophysical logs to segregate subsurface strata into sand and shale segments. These segments are then used to generate sand/shale ratio logs for use in an automatic subsurface stratigraphic analysis system on a parallel machine. Phase one prepares petrophysical logs for stratigraphic analysis. The petrophysical logs are filtered and cleaned to remove any as salinity effects and improper tool responses. The spontaneous potential log is used to segregate each log into individual sand and shale beds and use these beds to create sand and shale databases which are used to create sand/shale ratio logs for later analysis. Phase two creates and solves a two dimensional matching probability matrix. The theoretical foundation is developed and several implementation issues are discussed. These issues include: (1) how to select data points, (2) how to compare data values from two petrophysical logs, (3) how to view the data, and (4) how to find the optimal set of strata observing several constraints imposed by the nature of the subsurface. Phase three developments parallel processing techniques to handle a multi-dimensional matching probability matrix. Each petrophysical log is treated as an axis of a multi-dimensional matrix with all points from one log being compared with all points from all other logs. A theoretical foundation is developed followed by implementation details. The data storage space required for this study was in excess of 10\sp{56} bytes

    The state of the Martian climate

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    60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

    SV2 Mediates Entry of Tetanus Neurotoxin into Central Neurons

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    Tetanus neurotoxin causes the disease tetanus, which is characterized by rigid paralysis. The toxin acts by inhibiting the release of neurotransmitters from inhibitory neurons in the spinal cord that innervate motor neurons and is unique among the clostridial neurotoxins due to its ability to shuttle from the periphery to the central nervous system. Tetanus neurotoxin is thought to interact with a high affinity receptor complex that is composed of lipid and protein components; however, the identity of the protein receptor remains elusive. In the current study, we demonstrate that toxin binding, to dissociated hippocampal and spinal cord neurons, is greatly enhanced by driving synaptic vesicle exocytosis. Moreover, tetanus neurotoxin entry and subsequent cleavage of synaptobrevin II, the substrate for this toxin, was also dependent on synaptic vesicle recycling. Next, we identified the potential synaptic vesicle binding protein for the toxin and found that it corresponded to SV2; tetanus neurotoxin was unable to cleave synaptobrevin II in SV2 knockout neurons. Toxin entry into knockout neurons was rescued by infecting with viruses that express SV2A or SV2B. Tetanus toxin elicited the hyper excitability in dissociated spinal cord neurons - due to preferential loss of inhibitory transmission - that is characteristic of the disease. Surprisingly, in dissociated cortical cultures, low concentrations of the toxin preferentially acted on excitatory neurons. Further examination of the distribution of SV2A and SV2B in both spinal cord and cortical neurons revealed that SV2B is to a large extent localized to excitatory terminals, while SV2A is localized to inhibitory terminals. Therefore, the distinct effects of tetanus toxin on cortical and spinal cord neurons are not due to differential expression of SV2 isoforms. In summary, the findings reported here indicate that SV2A and SV2B mediate binding and entry of tetanus neurotoxin into central neurons

    Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

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    Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes

    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

    Some accreted volcanic rocks of Alaska and their elemental abundances

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    This chapter describes and gives elemental abundances of many of the accreted volcanic rocks and of a few hypabyssal rocks of Alaska. These rocks range from early Paleozoic (or perhaps late Precambrian) to Eocene age. All formed prior to accretion of the terrane containing them and thus were generated either as primary features in the ancestral Pacific Ocean or on terranes or superterranes carried by plates underlying that ocean. These accreted volcanic rocks are important in terms of continental growth by accretion of oceanic rocks. Various workers have asserted that such growth is by accretion of intraoceanic island arcs. This assertion, however, must be appreciably modified for the ca. 400,000-km^2 region of southern and central Alaska that is underlain by accreted rocks. Though these rocks are not known in sufficient detail to yield a precise figure, I estimate that no more than 70 to 75 percent of this newly formed crust consists of former island arcs and arc-derived epiclastic sedimentary rocks. Most of the tectonostratigraphic (lithotectonic) terranes of Alaska have minor exposures of volcanic rocks. Accounts of local and regional geology of the state contain cursory to extensive descriptions of such rocks. However, a catalog of such occurrences is not considered appropriate for this volume, and we discuss here only rocks studied by modern methods. The particular terranes containing these rocks are shown on Plate 13 (Barker and others, this volume), whereas all tectonostratigraphic terranes of Alaska are shown on Plate 3 (Silberling and others, this volume)
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