Use of Data Denial Experiments to Evaluate ESA Forecast Sensitivity Patterns

The overall goal of this multi-phased research project known as WindSENSE is to develop an observation system deployment strategy that would improve wind power generation forecasts. The objective of the deployment strategy is to produce the maximum benefit for 1- to 6-hour ahead forecasts of wind speed at hub-height ({approx}80 m). In this phase of the project the focus is on the Mid-Columbia Basin region which encompasses the Bonneville Power Administration (BPA) wind generation area shown in Figure 1 that includes Klondike, Stateline, and Hopkins Ridge wind plants. The Ensemble Sensitivity Analysis (ESA) approach uses data generated by a set (ensemble) of perturbed numerical weather prediction (NWP) simulations for a sample time period to statistically diagnose the sensitivity of a specified forecast variable (metric) for a target location to parameters at other locations and prior times referred to as the initial condition (IC) or state variables. The ESA approach was tested on the large-scale atmospheric prediction problem by Ancell and Hakim 2007 and Torn and Hakim 2008. ESA was adapted and applied at the mesoscale by Zack et al. (2010a, b, and c) to the Tehachapi Pass, CA (warm and cools seasons) and Mid-Colombia Basin (warm season only) wind generation regions. In order to apply the ESA approach at the resolution needed at the mesoscale, Zack et al. (2010a, b, and c) developed the Multiple Observation Optimization Algorithm (MOOA). MOOA uses a multivariate regression on a few select IC parameters at one location to determine the incremental improvement of measuring multiple variables (representative of the IC parameters) at various locations. MOOA also determines how much information from each IC parameter contributes to the change in the metric variable at the target location. The Zack et al. studies (2010a, b, and c), demonstrated that forecast sensitivity can be characterized by well-defined, localized patterns for a number of IC variables such as 80-m wind speed and vertical temperature difference. Ideally, the data assimilation scheme used in the experiments would have been based upon an ensemble Kalman filter (EnKF) that was similar to the ESA method used to diagnose the Mid-Colombia Basin sensitivity patterns in the previous studies. However, the use of an EnKF system at high resolution is impractical because of the very high computational cost. Thus, it was decided to use the three-dimensional variational analysis data assimilation that is less computationally intensive and more economically practical for generating operational forecasts. There are two tasks in the current project effort designed to validate the ESA observational system deployment approach in order to move closer to the overall goal: (1) Perform an Observing System Experiment (OSE) using a data denial approach which is the focus of this task and report; and (2) Conduct a set of Observing System Simulation Experiments (OSSE) for the Mid-Colombia basin region. The results of this task are presented in a separate report. The objective of the OSE task involves validating the ESA-MOOA results from the previous sensitivity studies for the Mid-Columbia Basin by testing the impact of existing meteorological tower measurements on the 0- to 6-hour ahead 80-m wind forecasts at the target locations. The testing of the ESA-MOOA method used a combination of data assimilation techniques and data denial experiments to accomplish the task objective

TIGIT can inhibit T cell activation via ligation-induced nanoclusters, independent of CD226 co-stimulation

TIGIT is an inhibitory receptor expressed on lymphocytes and can inhibit T cells by preventing CD226 co-stimulation through interactions in cis or through competition of shared ligands. Whether TIGIT directly delivers cell-intrinsic inhibitory signals in T cells remains unclear. Here we show, by analysing lymphocytes from matched human tumour and peripheral blood samples, that TIGIT and CD226 co-expression is rare on tumour-infiltrating lymphocytes. Using super-resolution microscopy and other techniques, we demonstrate that ligation with CD155 causes TIGIT to reorganise into dense nanoclusters, which coalesce with T cell receptor (TCR)-rich clusters at immune synapses. Functionally, this reduces cytokine secretion in a manner dependent on TIGIT’s intracellular ITT-like signalling motif. Thus, we provide evidence that TIGIT directly inhibits lymphocyte activation, acting independently of CD226, requiring intracellular signalling that is proximal to the TCR. Within the subset of tumours where TIGIT-expressing cells do not commonly co-express CD226, this will likely be the dominant mechanism of action

Pneumococcal carriage following PCV13 delivered as one primary and one booster dose (1 + 1) compared to two primary doses and a booster (2 + 1) in UK infants

In January 2020 the UK changed from a 2 + 1 schedule for 13-valent pneumococcal conjugate vaccine (PCV13) to a 1 + 1 schedule (doses at 3 and 12 months) based on a randomized immunogenicity trial comparing the two schedules. Carriage prevalence measured at the time of booster and 6 months later in 191 of the 213 study infants was 57 % (109/191) and 60 % (114/190) respectively. There were eight episodes of vaccine-type (VT) or vaccine-related 6C carriage in the 2 + 1 and six in the 1 + 1 group; ≥4-fold rises in serotype-specific IgG in 71 children with paired post-booster and follow up blood samples at 21–33 months of age were found in 20 % (7/35) of the 2 + 1 and 15 % (6/41) of the 1 + 1 group. VTs identified in carriage and inferred from serology were similar comprising 3, 19A and 19F. Dropping a priming dose from the 2 + 1 PCV 13 schedule did not increase VT carriage in the study cohort. Ongoing population level carriage studies will be important to confirm this

The convective storm initiation project

Copyright @ 2007 AMSThe Convective Storm Initiation Project (CSIP) is an international project to understand precisely where, when, and how convective clouds form and develop into showers in the mainly maritime environment of southern England. A major aim of CSIP is to compare the results of the very high resolution Met Office weather forecasting model with detailed observations of the early stages of convective clouds and to use the newly gained understanding to improve the predictions of the model. A large array of ground-based instruments plus two instrumented aircraft, from the U.K. National Centre for Atmospheric Science (NCAS) and the German Institute for Meteorology and Climate Research (IMK), Karlsruhe, were deployed in southern England, over an area centered on the meteorological radars at Chilbolton, during the summers of 2004 and 2005. In addition to a variety of ground-based remote-sensing instruments, numerous rawin-sondes were released at one- to two-hourly intervals from six closely spaced sites. The Met Office weather radar network and Meteosat satellite imagery were used to provide context for the observations made by the instruments deployed during CSIP. This article presents an overview of the CSIP field campaign and examples from CSIP of the types of convective initiation phenomena that are typical in the United Kingdom. It shows the way in which certain kinds of observational data are able to reveal these phenomena and gives an explanation of how the analyses of data from the field campaign will be used in the development of an improved very high resolution NWP model for operational use.This work is funded by the National Environment Research Council following an initial award from the HEFCE Joint Infrastructure Fund

Neutrophils in cancer: neutral no more

Neutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view. The traditionally held belief that neutrophils are inert bystanders is being challenged by the recent literature. Emerging evidence indicates that tumours manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumour behaviour. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets

Safety and immunogenicity of AS03B adjuvanted split virion versus non-adjuvanted whole virion H1N1 influenza vaccine in UK children aged 6 months-12 years: open label, randomised, parallel group, multicentre study

Objectives To compare the safety, reactogenicity, and immunogenicity of an adjuvanted split virion H1N1 vaccine and a non-adjuvanted whole virion vaccine used in the pandemic immunisation programme in the United Kingdom

Problems in obtaining precise and accurate Sr isotope analysis from geological materials using laser ablation MC-ICPMS

This paper reviews the problems encountered in eleven studies of Sr isotope analysis using laser ablation multicollector inductively coupled plasma mass spectrometry (LA-MC-ICPMS) in the period 1995–2006. This technique has been shown to have great potential, but the accuracy and precision are limited by: (1) large instrumental mass discrimination, (2) laser-induced isotopic and elemental fractionations and (3) molecular interferences. The most important isobaric interferences are Kr and Rb, whereas Ca dimer/argides and doubly charged rare earth elements (REE) are limited to sample materials which contain substantial amounts of these elements. With modern laser (193 nm) and MC-ICPMS equipment, minerals with >500 ppm Sr content can be analysed with a precision of better than 100 ppm and a spatial resolution (spot size) of approximately 100 μm. The LA MC-ICPMS analysis of 87Sr/86Sr of both carbonate material and plagioclase is successful in all reported studies, although the higher 84Sr/86Sr ratios do suggest in some cases an influence of Ca dimer and/or argides. High Rb/Sr (>0.01) materials have been successfully analysed by carefully measuring the 85Rb/87Rb in standard material and by applying the standard-sample bracketing method for accurate Rb corrections. However, published LA-MC-ICPMS data on clinopyroxene, apatite and sphene records differences when compared with 87Sr/86Sr measured by thermal ionisation mass spectrometry (TIMS) and solution MC-ICPMS. This suggests that further studies are required to ensure that the most optimal correction methods are applied for all isobaric interferences

Maintenance of Large Subpopulations of Differentiated CD8 T-Cells Two Years after Cytomegalovirus Infection in Gambian Infants

BACKGROUND: In a previously published study, we found that large differentiated subpopulations of CD8 T-cells emerged rapidly after CMV infection in young infants and persisted throughout the following year. Here we describe a follow-up study conducted on the same infants to establish whether the differentiated subpopulations continued through the second year post-infection. METHODOLOGY / PRINCIPAL FINDINGS: CMV-specific cells identified using tetramers remained more activated and differentiated than the overall CD8 population. The large subpopulation of differentiated cytotoxic (CD28(-)CD62L(-)Bcl-2(low)CD95(+)perforin(+)) cells that emerged rapidly after infection remained stable after two years. No similar subpopulation was found in CMV-uninfected infants indicating that two years after infection, CMV remained a major factor in driving CD8 T-cell differentiation. Although markers of activation (CD45R0 and HLA-D) declined throughout the first year, HLA-D expression continued to decline during the second year and CD45R0 expression increased slightly. The age-related increase in IFNgamma response observed during the first year continued but was non-significant during the second year, indicating that the rate of functional improvement had slowed substantially. CONCLUSIONS / SIGNIFICANCE: The large differentiated subpopulations of CD8 T-cells that had emerged immediately after CMV infection persisted through the second year post-infection, while levels of activation and functional capacity remained fairly constant.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Outbreaks of foot-and-mouth disease in Libya and Saudi Arabia during 2013 due to an exotic O/ME-SA/Ind-2001 lineage virus

Foot-and-mouth disease viruses are often restricted to specific geographical regions and spread to new areas may lead to significant epidemics. Phylogenetic analysis of sequences of the VP1 genome region of recent outbreak viruses from Libya and Saudi Arabia has revealed a lineage, O-Ind-2001, normally found in the Indian subcontinent. This paper describes the characterization of field viruses collected from these cases and provides information about a new real-time RT-PCR assay that can be used to detect viruses from this lineage and discriminate them from other endemic FMD viruses that are co-circulating in North Africa and western Eurasia.N.J. Knowles, K. Bachanek-Bankowska, J. Wadsworth, V. Mioulet, B. Valdazo-González, I.M. Eldaghayes, A.S. Dayhum, A.M. Kammon, M.A. Sharif, S. Waight, A.M. Shamia, S. Tenzin, U. Wernery, S. Grazioli, E. Brocchi, S. Subramaniam, B. Pattnaik, and D.P. Kin