195 research outputs found
Rapid diffusion of electrons in GaMnAs
We report ultrafast transient-grating measurements, above and below the Curie
temperature, of the dilute ferromagnetic semiconductor (Ga,Mn)As containing 6%
Mn. At 80 K (15 K), we observe that photoexcited electrons in the conduction
band have a lifetime of 8 ps (5 ps) and diffuse at about 70 cm2/s (60 cm2/s).
Such rapid diffusion requires either an electronic mobility exceeding 7,700
cm2/Vs or a conduction-band effective mass less than half the GaAs value. Our
data suggest that neither the scattering rate nor the effective mass of the
(Ga,Mn)As conduction band differs significantly from that of GaAs.Comment: 5 pages, 3 figures. Differs from the previous version in
incorporating additional data and changes made during the review process.
Differs from the published version in including section headings and in
omitting AIP copy-edits. No substantial differences in scientific conclusions
from either versio
Age-specific incidence of A/H1N1 2009 influenza infection in England from sequential antibody prevalence data using likelihood-based estimation.
Estimating the age-specific incidence of an emerging pathogen is essential for understanding its severity and transmission dynamics. This paper describes a statistical method that uses likelihoods to estimate incidence from sequential serological data. The method requires information on seroconversion intervals and allows integration of information on the temporal distribution of cases from clinical surveillance. Among a family of candidate incidences, a likelihood function is derived by reconstructing the change in seroprevalence from seroconversion following infection and comparing it with the observed sequence of positivity among the samples. This method is applied to derive the cumulative and weekly incidence of A/H1N1 pandemic influenza in England during the second wave using sera taken between September 2009 and February 2010 in four age groups (1-4, 5-14, 15-24, 25-44 years). The highest cumulative incidence was in 5-14 year olds (59%, 95% credible interval (CI): 52%, 68%) followed by 1-4 year olds (49%, 95% CI: 38%, 61%), rates 20 and 40 times higher respectively than estimated from clinical surveillance. The method provides a more accurate and continuous measure of incidence than achieved by comparing prevalence in samples grouped by time period
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
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
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
Multipolymer microsphere delivery of SARS-CoV-2 antigens
Effective antigen delivery facilitates antiviral vaccine success defined by effective immune protective re- sponses against viral exposures. To improve severe acute respiratory syndrome coronavirus-2 (SARS-CoV- 2) antigen delivery, a controlled biodegradable, stable, biocompatible, and nontoxic polymeric micro- sphere system was developed for chemically inactivated viral proteins. SARS-CoV-2 proteins encapsulated in polymeric microspheres induced robust antiviral immunity. The viral antigen-loaded microsphere sys- tem can preclude the need for repeat administrations, highlighting its potential as an effective vaccine
Multipolymer microsphere delivery of SARS-CoV-2 antigens
Effective antigen delivery facilitates antiviral vaccine success defined by effective immune protective responses against viral exposures. To improve severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antigen delivery, a controlled biodegradable, stable, biocompatible, and nontoxic polymeric microsphere system was developed for chemically inactivated viral proteins. SARS-CoV-2 proteins encapsulated in polymeric microspheres induced robust antiviral immunity. The viral antigen-loaded microsphere system can preclude the need for repeat administrations, highlighting its potential as an effective vaccine.
Statement of significance
Successful SARS-CoV-2 vaccines were developed and quickly approved by the US Food and Drug Administration (FDA). However, each of the vaccines requires boosting as new variants arise. We posit that injectable biodegradable polymers represent a means for the sustained release of emerging viral antigens. The approach offers a means to reduce immunization frequency by predicting viral genomic variability. This strategy could lead to longer-lasting antiviral protective immunity. The current proof-of-concept multipolymer study for SARS-CoV-2 achieve these metrics.
[PDF also includes a graphical abstract that can not be displayed here.
Generation time of the alpha and delta SARS-CoV-2 variants: an epidemiological analysis.
BACKGROUND: In May, 2021, the delta (B.1.617.2) SARS-CoV-2 variant became dominant in the UK, superseded by the omicron (B.1.1.529) variant in December, 2021. The delta variant is associated with increased transmissibility compared with the alpha variant, which was the dominant variant in the UK between December, 2020, and May, 2021. To understand transmission and the effectiveness of interventions, we aimed to investigate whether the delta variant generation time (the interval between infections in infector-infectee pairs) is shorter-ie, transmissions are happening more quickly-than that of the alpha variant. METHODS: In this epidemiological analysis, we analysed transmission data from an ongoing UK Health Security Agency (UKHSA) prospective household study. Households were recruited to the study after an index case had a positive PCR test and genomic sequencing was used to determine the variant responsible. By fitting a mathematical transmission model to the data, we estimated the intrinsic generation time (which assumes a constant supply of susceptible individuals throughout infection) and the household generation time (which reflects realised transmission in the study households, accounting for susceptible depletion) for the alpha and delta variants. FINDINGS: Between February and August, 2021, 227 households consisting of 559 participants were recruited to the UKHSA study. The alpha variant was detected or assumed to be responsible for infections in 131 households (243 infections in 334 participants) recruited in February-May, and the delta variant in 96 households (174 infections in 225 participants) in May-August. The mean intrinsic generation time was shorter for the delta variant (4·7 days, 95% credible interval [CI] 4·1-5·6) than the alpha variant (5·5 days, 4·7-6·5), with 92% posterior probability. The mean household generation time was 28% (95% CI 0-48%) shorter for the delta variant (3·2 days, 95% CI 2·5-4·2) than the alpha variant (4·5 days, 3·7-5·4), with 97·5% posterior probability. INTERPRETATION: The delta variant transmits more quickly in households than the alpha variant, which can be attributed to faster depletion of susceptible individuals in households and a possible decrease in the intrinsic generation time. Interventions such as contact tracing, testing, and isolation might be less effective if transmission of the virus occurs quickly. FUNDING: National Institute for Health Research, UK Health Security Agency, Engineering and Physical Sciences Research Council, and UK Research and Innovation
A large impact crater beneath Hiawatha Glacier in northwest Greenland.
We report the discovery of a large impact crater beneath Hiawatha Glacier in northwest Greenland. From airborne radar surveys, we identify a 31-kilometer-wide, circular bedrock depression beneath up to a kilometer of ice. This depression has an elevated rim that cross-cuts tributary subglacial channels and a subdued central uplift that appears to be actively eroding. From ground investigations of the deglaciated foreland, we identify overprinted structures within Precambrian bedrock along the ice margin that strike tangent to the subglacial rim. Glaciofluvial sediment from the largest river draining the crater contains shocked quartz and other impact-related grains. Geochemical analysis of this sediment indicates that the impactor was a fractionated iron asteroid, which must have been more than a kilometer wide to produce the identified crater. Radiostratigraphy of the ice in the crater shows that the Holocene ice is continuous and conformable, but all deeper and older ice appears to be debris rich or heavily disturbed. The age of this impact crater is presently unknown, but from our geological and geophysical evidence, we conclude that it is unlikely to predate the Pleistocene inception of the Greenland Ice Sheet
Impact melt rocks from the Late Paleocene Hiawatha impact structure, northwest Greenland
Impact melt rocks formed during hypervelocity impact events are ideal for studying impact structures. Here, we describe impact melt rock samples collected proximal to the 31 km wide 58 Ma Hiawatha impact structure, northwest Greenland, which is completely covered by the Greenland Ice Sheet. The melt rocks contain diagnostic shock indicators (e.g., planar deformation features [PDF] in quartz and shocked zircon) and form three groups based on melt textures and chemistry: (i) hypocrystalline, (ii) glassy, and (iii) carbonate-based melt rocks. The exposed foreland directly in front of the structure consists of metasedimentary successions and igneous plutons; however, the carbonate-based impactites indicate a mixed target sequence with a significant carbonate-rich component. Well-preserved organic material in some melt rocks indicates that North Greenland at the time of impact was host to abundant organic material, likely a dense high-latitude temperate forest. Geochemical signatures of platinum-group elements in selected samples indicate an extraterrestrial component and support previous identification of a highly fractionated iron impactor in glaciofluvial sand. Our results illustrate the possibility to study impact structures hidden beneath a thick ice sheet based on transported samples and this opens a new avenue for identifying other potential impact craters in Greenland and Antarctica
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