76 research outputs found
Characterization of Major Surface Protease Homologues of Trypanosoma congolense
Trypanosomes encode a family of proteins known as Major Surface Metalloproteases (MSPs). We have identified six putative MSPs encoded within the partially sequenced T. congolense genome. Phylogenic analysis indicates that T. congolense MSPs belong to five subfamilies that are conserved among African trypanosome species. Molecular modeling, based on the known structure of Leishmania Major GP63, reveals subfamily-specific structural variations around the putative active site despite conservation of overall structure, suggesting that each MSP subfamily has evolved to recognize distinct substrates. We have cloned and purified a protein encoding the amino-terminal domain of the T. congolense homologue TcoMSP-D (most closely related to Leishmania GP63). We detect TcoMSP-D in the serum of T. congolense-infected mice. Mice immunized with the amino-terminal domain of TcoMSP-D generate a persisting IgG1 antibody response. Surprisingly, a low-dose challenge of immunized mice with T. congolense significantly increases susceptibility to infection, indicating that immunity to TcoMSP-D is a factor affecting virulence
Specific Receptor Usage in Plasmodium falciparum Cytoadherence Is Associated with Disease Outcome
Our understanding of the basis of severe disease in malaria is incomplete. It is clear that pathology is in part related to the pro-inflammatory nature of the host response but a number of other factors are also thought to be involved, including the interaction between infected erythrocytes and endothelium. This is a complex system involving several host receptors and a major parasite-derived variant antigen (PfEMP1) expressed on the surface of the infected erythrocyte membrane. Previous studies have suggested a role for ICAM-1 in the pathology of cerebral malaria, although these have been inconclusive. In this study we have examined the cytoadherence patterns of 101 patient isolates from varying clinical syndromes to CD36 and ICAM-1, and have used variant ICAM-1 proteins to further characterise this adhesive phenotype. Our results show that increased binding to CD36 is associated with uncomplicated malaria while ICAM-1 adhesion is raised in parasites from cerebral malaria cases
What does an interferometer really measure? Including instrument and data characteristics in the reconstruction of the 21cm power spectrum
Combining the visibilities measured by an interferometer to form a
cosmological power spectrum is a complicated process in which the window
functions play a crucial role. In a delay-based analysis, the mapping between
instrumental space, made of per-baseline delay spectra, and cosmological space
is not a one-to-one relation. Instead, neighbouring modes contribute to the
power measured at one point, with their respective contributions encoded in the
window functions. To better understand the power spectrum measured by an
interferometer, we assess the impact of instrument characteristics and analysis
choices on the estimator by deriving its exact window functions, outside of the
delay approximation. Focusing on HERA as a case study, we find that
observations made with long baselines tend to correspond to enhanced low-k
tails of the window functions, which facilitate foreground leakage outside the
wedge, whilst the choice of bandwidth and frequency taper can help narrow them
down. With the help of simple test cases and more realistic visibility
simulations, we show that, apart from tracing mode mixing, the window functions
can accurately reconstruct the power spectrum estimator of simulated
visibilities. We note that the window functions depend strongly on the
chromaticity of the beam, and less on its spatial structure - a Gaussian
approximation, ignoring side lobes, is sufficient. Finally, we investigate the
potential of asymmetric window functions, down-weighting the contribution of
low-k power to avoid foreground leakage. The window functions presented in this
work correspond to the latest HERA upper limits for the full Phase I data. They
allow an accurate reconstruction of the power spectrum measured by the
instrument and can be used in future analyses to confront theoretical models
and data directly in cylindrical space.Comment: 18 pages, 18 figures, submitted to MNRAS. Comments welcome
Characterization Of Inpaint Residuals In Interferometric Measurements of the Epoch Of Reionization
Radio Frequency Interference (RFI) is one of the systematic challenges
preventing 21cm interferometric instruments from detecting the Epoch of
Reionization. To mitigate the effects of RFI on data analysis pipelines,
numerous inpaint techniques have been developed to restore RFI corrupted data.
We examine the qualitative and quantitative errors introduced into the
visibilities and power spectrum due to inpainting. We perform our analysis on
simulated data as well as real data from the Hydrogen Epoch of Reionization
Array (HERA) Phase 1 upper limits. We also introduce a convolutional neural
network that capable of inpainting RFI corrupted data in interferometric
instruments. We train our network on simulated data and show that our network
is capable at inpainting real data without requiring to be retrained. We find
that techniques that incorporate high wavenumbers in delay space in their
modeling are best suited for inpainting over narrowband RFI. We also show that
with our fiducial parameters Discrete Prolate Spheroidal Sequences (DPSS) and
CLEAN provide the best performance for intermittent ``narrowband'' RFI while
Gaussian Progress Regression (GPR) and Least Squares Spectral Analysis (LSSA)
provide the best performance for larger RFI gaps. However we caution that these
qualitative conclusions are sensitive to the chosen hyperparameters of each
inpainting technique. We find these results to be consistent in both simulated
and real visibilities. We show that all inpainting techniques reliably
reproduce foreground dominated modes in the power spectrum. Since the
inpainting techniques should not be capable of reproducing noise realizations,
we find that the largest errors occur in the noise dominated delay modes. We
show that in the future, as the noise level of the data comes down, CLEAN and
DPSS are most capable of reproducing the fine frequency structure in the
visibilities of HERA data.Comment: 26 pages, 18 figure
Direct Optimal Mapping Image Power Spectrum and its Window Functions
The key to detecting neutral hydrogen during the epoch of reionization (EoR)
is to separate the cosmological signal from the dominating foreground
radiation. We developed direct optimal mapping (Xu et al. 2022) to map
interferometric visibilities; it contains only linear operations, with full
knowledge of point spread functions from visibilities to images. Here we
present an FFT-based image power spectrum and its window functions based on
direct optimal mapping. We use noiseless simulation, based on the Hydrogen
Epoch of Reionization Array (HERA) Phase I configuration, to study the image
power spectrum properties. The window functions show power leakage
from the foreground-dominated region into the EoR window; the 2D and 1D power
spectra also verify the separation between the foregrounds and the EoR.
Furthermore, we simulated visibilities from a -complete array and
calculated its image power spectrum. The result shows that the foreground--EoR
leakage is further suppressed below , dominated by the tapering
function sidelobes; the 2D power spectrum does not show signs of the horizon
wedge. The -complete result provides a reference case for future 21cm
cosmology array designs.Comment: Submitted to Ap
Direct Optimal Mapping for 21cm Cosmology: A Demonstration with the Hydrogen Epoch of Reionization Array
Motivated by the desire for wide-field images with well-defined statistical
properties for 21cm cosmology, we implement an optimal mapping pipeline that
computes a maximum likelihood estimator for the sky using the interferometric
measurement equation. We demonstrate this direct optimal mapping with data from
the Hydrogen Epoch of Reionization (HERA) Phase I observations. After
validating the pipeline with simulated data, we develop a maximum likelihood
figure-of-merit for comparing four sky models at 166MHz with a bandwidth of
100kHz. The HERA data agree with the GLEAM catalogs to <10%. After subtracting
the GLEAM point sources, the HERA data discriminate between the different
continuum sky models, providing most support for the model of Byrne et al.
2021. We report the computation cost for mapping the HERA Phase I data and
project the computation for the HERA 320-antenna data; both are feasible with a
modern server. The algorithm is broadly applicable to other interferometers and
is valid for wide-field and non-coplanar arrays.Comment: 16 pages, 10 figures, 2 tables, published on Ap
Search for the Epoch of Reionisation with HERA: Upper Limits on the Closure Phase Delay Power Spectrum
Radio interferometers aiming to measure the power spectrum of the redshifted
21 cm line during the Epoch of Reionisation (EoR) need to achieve an
unprecedented dynamic range to separate the weak signal from overwhelming
foreground emissions. Calibration inaccuracies can compromise the sensitivity
of these measurements to the effect that a detection of the EoR is precluded.
An alternative to standard analysis techniques makes use of the closure phase,
which allows one to bypass antenna-based direction-independent calibration.
Similarly to standard approaches, we use a delay spectrum technique to search
for the EoR signal. Using 94 nights of data observed with Phase I of the
Hydrogen Epoch of Reionization Array (HERA), we place approximate constraints
on the 21 cm power spectrum at . We find at 95% confidence that the 21
cm EoR brightness temperature is (372) "pseudo" mK at 1.14
"pseudo" Mpc, where the "pseudo" emphasises that these limits are to
be interpreted as approximations to the actual distance scales and brightness
temperatures. Using a fiducial EoR model, we demonstrate the feasibility of
detecting the EoR with the full array. Compared to standard methods, the
closure phase processing is relatively simple, thereby providing an important
independent check on results derived using visibility intensities, or related.Comment: 16 pages, 14 figures, accepted for publication by MNRA
New genetic loci link adipose and insulin biology to body fat distribution.
Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms
Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world
Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic.
Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality.
Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States.
Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis.
Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection
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