326 research outputs found
Recurrent plasmodium falciparum malaria infections in kenyan children diminish t-cell immunity to epstein barr virus lytic but not latent antigens
Plasmodium falciparum malaria (Pf-malaria) and Epstein Barr Virus (EBV) infections coexist in children at risk for endemic Burkitt's lymphoma (eBL); yet studies have only glimpsed the cumulative effect of Pf-malaria on EBV-specific immunity. Using pooled EBV lytic and latent CD8+ T-cell epitope-peptides, IFN-γ ELISPOT responses were surveyed three times among children (10 months to 15 years) in Kenya from 2002–2004. Prevalence ratios (PR) and 95% confidence intervals (CI) were estimated in association with Pf-malaria exposure, defined at the district-level (Kisumu: holoendemic; Nandi: hypoendemic) and the individual-level. We observed a 46% decrease in positive EBV lytic antigen IFN-γ responses among 5–9 year olds residing in Kisumu compared to Nandi (PR: 0.54; 95% CI: 0.30–0.99). Individual-level analysis in Kisumu revealed further impairment of EBV lytic antigen responses among 5–9 year olds consistently infected with Pf-malaria compared to those never infected. There were no observed district- or individual-level differences between Pf-malaria exposure and EBV latent antigen IFN-γ response. The gradual decrease of EBV lytic antigen but not latent antigen IFN-γ responses after primary infection suggests a specific loss in immunological control over the lytic cycle in children residing in malaria holoendemic areas, further refining our understanding of eBL etiology
Proteogenomic integration reveals therapeutic targets in breast cancer xenografts
Recent advances in mass spectrometry (MS) have enabled extensive analysis of cancer proteomes. Here, we employed quantitative proteomics to profile protein expression across 24 breast cancer patient-derived xenograft (PDX) models. Integrated proteogenomic analysis shows positive correlation between expression measurements from transcriptomic and proteomic analyses; further, gene expression-based intrinsic subtypes are largely re-capitulated using non-stromal protein markers. Proteogenomic analysis also validates a number of predicted genomic targets in multiple receptor tyrosine kinases. However, several protein/phosphoprotein events such as overexpression of AKT proteins and ARAF, BRAF, HSP90AB1 phosphosites are not readily explainable by genomic analysis, suggesting that druggable translational and/or post-translational regulatory events may be uniquely diagnosed by MS. Drug treatment experiments targeting HER2 and components of the PI3K pathway supported proteogenomic response predictions in seven xenograft models. Our study demonstrates that MS-based proteomics can identify therapeutic targets and highlights the potential of PDX drug response evaluation to annotate MS-based pathway activities
Shrinking a large dataset to identify variables associated with increased risk of Plasmodium falciparum infection in Western Kenya
Large datasets are often not amenable to analysis using traditional single-step approaches. Here, our general objective was to apply imputation techniques, principal component analysis (PCA), elastic net and generalized linear models to a large dataset in a systematic approach to extract the most meaningful predictors for a health outcome. We extracted predictors for Plasmodium falciparum infection, from a large covariate dataset while facing limited numbers of observations, using data from the People, Animals, and their Zoonoses (PAZ) project to demonstrate these techniques: data collected from 415 homesteads in western Kenya, contained over 1500 variables that describe the health, environment, and social factors of the humans, livestock, and the homesteads in which they reside. The wide, sparse dataset was simplified to 42 predictors of P. falciparum malaria infection and wealth rankings were produced for all homesteads. The 42 predictors make biological sense and are supported by previous studies. This systematic data-mining approach we used would make many large datasets more manageable and informative for decision-making processes and health policy prioritization
Global Search for New Physics with 2.0/fb at CDF
Data collected in Run II of the Fermilab Tevatron are searched for
indications of new electroweak-scale physics. Rather than focusing on
particular new physics scenarios, CDF data are analyzed for discrepancies with
the standard model prediction. A model-independent approach (Vista) considers
gross features of the data, and is sensitive to new large cross-section
physics. Further sensitivity to new physics is provided by two additional
algorithms: a Bump Hunter searches invariant mass distributions for "bumps"
that could indicate resonant production of new particles; and the Sleuth
procedure scans for data excesses at large summed transverse momentum. This
combined global search for new physics in 2.0/fb of ppbar collisions at
sqrt(s)=1.96 TeV reveals no indication of physics beyond the standard model.Comment: 8 pages, 7 figures. Final version which appeared in Physical Review D
Rapid Communication
Observation of Orbitally Excited B_s Mesons
We report the first observation of two narrow resonances consistent with
states of orbitally excited (L=1) B_s mesons using 1 fb^{-1} of ppbar
collisions at sqrt{s} = 1.96 TeV collected with the CDF II detector at the
Fermilab Tevatron. We use two-body decays into K^- and B^+ mesons reconstructed
as B^+ \to J/\psi K^+, J/\psi \to \mu^+ \mu^- or B^+ \to \bar{D}^0 \pi^+,
\bar{D}^0 \to K^+ \pi^-. We deduce the masses of the two states to be m(B_{s1})
= 5829.4 +- 0.7 MeV/c^2 and m(B_{s2}^*) = 5839.7 +- 0.7 MeV/c^2.Comment: Version accepted and published by Phys. Rev. Let
Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set
We report a measurement of the bottom-strange meson mixing phase \beta_s
using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays
in which the quark-flavor content of the bottom-strange meson is identified at
production. This measurement uses the full data set of proton-antiproton
collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment
at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity.
We report confidence regions in the two-dimensional space of \beta_s and the
B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2,
-1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in
agreement with the standard model expectation. Assuming the standard model
value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +-
0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +-
0.009 (syst) ps, which are consistent and competitive with determinations by
other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012
Design and construction of the MicroBooNE detector
This paper describes the design and construction of the MicroBooNE liquid
argon time projection chamber and associated systems. MicroBooNE is the first
phase of the Short Baseline Neutrino program, located at Fermilab, and will
utilize the capabilities of liquid argon detectors to examine a rich assortment
of physics topics. In this document details of design specifications, assembly
procedures, and acceptance tests are reported
Saethre-Chotzen syndrome : cranofacial anomalies caused by genetic changes in the TWIST gene
In this thesis, one of the most frequently occurring and most variable craniosynostosis
syndromes was investigated; Saethre-Chotzen syndrome. Craniosynostosis is the premature
obliteration of cranial sutures in the developing embryo. It can also occur in the first few
months of life. Saethre-Chotzen syndrome is, besides craniosynostosis, characterized by
specific facial and limb abnormalities, of which the most frequently reported are ptosis,
prominent crus helicis, cutaneous syndactyly of digit 2 and 3 on both hands and feet, and
broad halluces. Saethre-Chotzen syndrome has been linked to the TWIST gene on
chromosome 7p21.1. Mutations in and variably sized deletions of this gene can be found in
patients with clinical features of Saethre-Chotzen syndrome. The latter, TWIST deletions,
often also include part of the surrounding chromosome 7p and are reported to be associated
with mental retardation. In Saethre-Chotzen patients, in whom neither a mutation nor a
deletion of TWIST had been found, the FGFR3 P250R mutation was in some cases detected.
This mutation has specifically been linked to Muenke syndrome that is characterized by unior
bicoronal synostosis and slight facial dysmorphology. However, a Saethre-Chotzen like
phenotype can also result from this mutation.
Because of the possible overlap of Saethre-Chotzen with Muenke syndrome, these syndromes
were studied in order to provide clinical criteria that discriminate between the two (chapter 4).
Many phenotypic features occur in both syndromes. In addition, although unicoronal
synostosis occurs slightly more frequently in Muenke syndrome, unicoronal and bicoronal
synostosis are seen in both syndromes. The discrimination between Saethre-Chotzen and
Muenke is often not made easily and the associated genes, TWIST and FGFR3, respectively,
are simultaneously tested for pathogenic m
Measurement of the Bs Lifetime in Fully and Partially Reconstructed Bs -> Ds- (phi pi-)X Decays in pbar-p Collisions at sqrt(s) = 1.96 TeV
We present a measurement of the Bs lifetime in fully and partially
reconstructed Bs -> Ds(phi pi)X decays in 1.3 fb-1 of pbar-p collisions at
sqrt(s) = 1.96 TeV collected by the CDF II detector at the Fermilab Tevatron.
We measure tau(Bs) = 1.518 +/- 0.041 (stat.) +/- 0.027 (syst.) ps. The ratio of
this result and the world average B0 lifetime yields tau(Bs)/tau(B0) = 0.99
+/-0.03, which is in agreement with recent theoretical predictions.Comment: submitted to Phys. Rev. Let
W boson polarization measurement in the ttbar dilepton channel using the CDF II Detector
We present a measurement of boson polarization in top-quark decays in
events with decays to dilepton final states using of integrated luminosity in collisions collected by the
CDF II detector at the Tevatron. A simultaneous measurement of the fractions of
longitudinal () and right-handed () bosons yields the results
and . Combining this measurement
with our previous result based on single lepton final states, we obtain and . The results are consistent with standard
model expectation.Comment: Published in Phys. Lett.
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