79 research outputs found
Plasmodium falciparum EPCR-binding PfEMP1 expression increases with malaria disease severity and is elevated in retinopathy negative cerebral malaria.
Background Expression of group A and the A-like subset of group B Plasmodium falciparumerythrocyte membrane protein 1 (PfEMP1) is associated with severe malaria (SM). The diversity of var sequences combined with the challenges of distinct classification of patient pathologies has made studying the role of distinct PfEMP1 variants on malaria disease severity challenging. The application of retinopathy in the recent years has provided a further method to clinically evaluate children with cerebral malaria (CM). The question of whether children with clinical CM but no retinopathy represent a completely different disease process or a subgroup within the spectrum of CM remains an important question in malaria. In the current study, we use newly designed primer sets with the best coverage to date in a large cohort of children with SM to determine the role of var genes in malaria disease severity and especially CM as discriminated by retinopathy. Methods We performed qRT-PCR targeting the different subsets of these var genes on samples from Ugandan children with CM (n = 98, of whom 50 had malarial retinopathy [RP] and 47 did not [RN]), severe malarial anemia (SMA, n = 47), and asymptomatic parasitemia (AP, n = 14). The primers used in this study were designed based on var sequences from 226 Illumina whole genome sequenced P. falciparum field isolates. Results Increasing severity of illness was associated with increasing levels of endothelial protein C receptor (EPCR)-binding PfEMP1. EPCR-binding PfEMP1 transcript levels were highest in children with combined CM and SMA and then decreased by level of disease severity: RP CM \u3e RN CM \u3e SMA \u3e AP. Conclusions The study findings indicate that PfEMP1 binding to EPCR is important in the pathogenesis of SM, including RN CM, and suggest that increased expression of EPCR-binding PfEMP1 is associated with progressively more severe disease. Agents that block EPCR-binding of PfEMP1 could provide novel interventions to prevent or decrease disease severity in malaria
Plasmodium falciparum Histidine-Rich Protein-2 Plasma Concentrations Are Higher in Retinopathy-Negative Cerebral Malaria Than in Severe Malarial Anemia
Background
Malaria retinopathy has been proposed as marker of “true” cerebral malaria (CM), ie, coma due to Plasmodium falciparum vs coma due to other causes, with incidental P falciparum parasitemia. Plasma P falciparum histidine-rich protein-2 (PfHRP2) concentrations distinguish retinopathy-positive (RP) from retinopathy-negative (RN) CM but have not been compared between RN CM and other forms of severe malaria or asymptomatic parasitemia (AP).
Methods
We compared plasma PfHRP2 concentrations in 260 children with CM (247 examined for retinopathy), 228 children with severe malarial anemia (SMA), and 30 community children with AP.
Results
Plasmodium falciparum HRP2 concentrations were higher in children with RP CM than RN CM (P = .006), with an area under the receiver operating characteristic curve of 0.61 (95% confidence interval, 0.53–0.68). Plasmodium falciparum HRP2 concentrations and sequestered parasite biomass were higher in RN CM than SMA (both P < .03) or AP (both P < .001).
Conclusions
Plasmodium falciparum HRP2 concentrations are higher in children with RN CM than in children with SMA or AP, suggesting that P falciparum is involved in disease pathogenesis in children with CM. Plasmodium falciparum HRP2 concentrations may provide a more feasible and consistent assessment of the contribution of P falciparum to severe disease than malaria retinopathy
Implementing a Registry Federation for Materials Science Data Discovery
As a result of a number of national initiatives, we are seeing rapid growth in the data important to materials science that are available over the web. Consequently, it is becoming increasingly difficult for researchers to learn what data are available and how to access them. To address this problem, the Research Data Alliance (RDA) Working Group for International Materials Science Registries (IMRR) was established to bring together materials science and information technology experts to develop an international federation of registries that can be used for global discovery of data resources for materials science. A resource registry collects high-level metadata descriptions of resources such as data repositories, archives, websites, and services that are useful for data-driven research. By making the collection searchable, it aids scientists in industry, universities, and government laboratories to discover data relevant to their research and work interests.
We present the results of our successful piloting of a registry federation for materials science data discovery. In particular, we out a blueprint for creating such a federation that is capable of amassing a global view of all available materials science data, and we enumerate the requirements for the standards that make the registries interoperable within the federation. These standards include a protocol for exchanging resource descriptions and a standard metadata schema for encoding those descriptions. We summarize how we leveraged an existing standard (OAI-PMH) for metadata exchange. Finally, we review the registry software developed to realize the federation and describe the user experience
Constraints on Supersymmetry from Relic Density compared with future Higgs Searches at the LHC
Among the theories beyond the Standard Model (SM) of particle physics
Supersymmetry (SUSY) provides an excellent dark matter (DM) candidate, the
neutralino. One clear prediction of cosmology is the annihilation cross section
of DM particles, assuming them to be a thermal relic from the early universe.
In most of the parameter space of Supersymmetry the annihilation cross section
is too small compared with the prediction of cosmology. However, for large
values of the tan beta parameter the annihilation through s-channel
pseudoscalar Higgs exchange yields the correct relic density in practically the
whole range of possible SUSY masses up to the few TeV range. The required
values of tan beta are typically around 50, i.e. of the order of top and bottom
mass ratio, which happens to be also the range allowing for Yukawa unification
in a Grand Unified Theory with gauge coupling unification. For such large
values of tan beta the associated production of the heavier Higgses, which is
enhanced by tan beta squared, becomes three orders of magnitude larger than the
production of a simlar SM-like Higgs and could be observable as one of the
first hints of new physics at the LHC.Comment: 12 pages, 5 figures, Published version in Phys. Lett. B with updated
references and minor correction
The Eruption of the Candidate Young Star ASASSN-15qi
Outbursts on young stars are usually interpreted as accretion bursts caused by instabilities in the disk or the star-disk connection. However, some protostellar outbursts may not fit into this framework. In this paper, we analyze optical and near-infrared spectra and photometry to characterize the 2015 outburst of the probable young star ASASSN-15qi. The mag brightening in the band was sudden, with an unresolved rise time of less than one day. The outburst decayed exponentially by 1 mag for 6 days and then gradually back to the pre-outburst level after 200 days. The outburst is dominated by emission from K gas. An explosive release of energy accelerated matter from the star in all directions, seen in a spectacular cool, spherical wind with a maximum velocity of 1000 km/s. The wind and hot gas both disappeared as the outburst faded and the source the source returned to its quiescent F-star spectrum. Nebulosity near the star brightened with a delay of 10-20 days. Fluorescent excitation of H is detected in emission from vibrational levels as high as , also with a possible time delay in flux increase. The mid-infrared spectral energy distribution does not indicate the presence of warm dust emission, although the optical photospheric absorption and CO overtone emission could be related to a gaseous disk. Archival photometry reveals a prior outburst in 1976. Although we speculate about possible causes for this outburst, none of the explanations are compelling
Advancing sepsis clinical research: harnessing transcriptomics for an omics-based strategy - a comprehensive scoping review
Sepsis continues to be recognized as a significant global health challenge across all ages and is characterized by a complex pathophysiology. In this scoping review, PRISMA-ScR guidelines were adhered to, and a transcriptomic methodology was adopted, with the protocol registered on the Open Science Framework. We hypothesized that gene expression analysis could provide a foundation for establishing a clinical research framework for sepsis. A comprehensive search of the PubMed database was conducted with a particular focus on original research and systematic reviews of transcriptomic sepsis studies published between 2012 and 2022. Both coding and non-coding gene expression studies have been included in this review. An effort was made to enhance the understanding of sepsis at the mRNA gene expression level by applying a systems biology approach through transcriptomic analysis. Seven crucial components related to sepsis research were addressed in this study: endotyping (n = 64), biomarker (n = 409), definition (n = 0), diagnosis (n = 1098), progression (n = 124), severity (n = 451), and benchmark (n = 62). These components were classified into two groups, with one focusing on Biomarkers and Endotypes and the other oriented towards clinical aspects. Our review of the selected studies revealed a compelling association between gene transcripts and clinical sepsis, reinforcing the proposed research framework. Nevertheless, challenges have arisen from the lack of consensus in the sepsis terminology employed in research studies and the absence of a comprehensive definition of sepsis. There is a gap in the alignment between the notion of sepsis as a clinical phenomenon and that of laboratory indicators. It is potentially responsible for the variable number of patients within each category. Ideally, future studies should incorporate a transcriptomic perspective. The integration of transcriptomic data with clinical endpoints holds significant potential for advancing sepsis research, facilitating a consensus-driven approach, and enabling the precision management of sepsis
Measurement of the W±Z boson pair-production cross section in pp collisions at √s=13TeV with the ATLAS detector
published_or_final_versio
Search for TeV-scale gravity signatures in high-mass final states with leptons and jets with the ATLAS detector at sqrt [ s ] = 13TeV
A search for physics beyond the Standard Model, in final states with at least one high transverse momentum charged lepton (electron or muon) and two additional high transverse momentum leptons or jets, is performed using 3.2 fb−1 of proton–proton collision data recorded by the ATLAS detector at the Large Hadron Collider in 2015 at √s = 13 TeV. The upper end of the distribution of the scalar sum of the transverse momenta of leptons and jets is sensitive to the production of high-mass objects. No excess of events beyond Standard Model predictions is observed. Exclusion limits are set for models of microscopic black holes with two to six extra dimensions
Charged-particle distributions at low transverse momentum in √s=13 13 TeV pp interactions measured with the ATLAS detector at the LHC
Measurements of distributions of charged particles produced in proton–proton collisions with a centre-of-mass energy of 13 TeV are presented. The data were recorded by the ATLAS detector at the LHC and correspond to an integrated luminosity of 151 μb −1 μb−1 . The particles are required to have a transverse momentum greater than 100 MeV and an absolute pseudorapidity less than 2.5. The charged-particle multiplicity, its dependence on transverse momentum and pseudorapidity and the dependence of the mean transverse momentum on multiplicity are measured in events containing at least two charged particles satisfying the above kinematic criteria. The results are corrected for detector effects and compared to the predictions from several Monte Carlo event generators
Measurement of the inelastic proton-proton cross section at √s=13 TeV with the ATLAS detector at the LHC
This Letter presents a measurement of the inelastic proton-proton cross section using 60 μb −1 of pp collisions at a center-of-mass energy √s of 13 TeV with the ATLAS detector at the LHC. Inelastic interactions are selected using rings of plastic scintillators in the forward region (2.0710 −6 , where M X is the larger invariant mass of the two hadronic systems separated by the largest rapidity gap in the event. In this ξ range the scintillators are highly efficient. For diffractive events this corresponds to cases where at least one proton dissociates to a system with M X >13 GeV . The measured cross section is compared with a range of theoretical predictions. When extrapolated to the full phase space, a cross section of 78.1±2.9 mb is measured, consistent with the inelastic cross section increasing with center-of-mass energy
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