1,877 research outputs found
Functional type 1 regulatory T cells develop regardless of FOXP3 mutations inpatients with IPEX syndrome.
Agammaglobulinaemia despite terminal B-cell differentiation in a patient with a novel LRBA mutation
Mutations in lipopolysaccharide-responsive vesicle trafficking, beach and anchor-containing protein (LRBA) cause immune deficiency and inflammation. Here, we are reporting a novel homozygous mutation in LRBA allele in 7-year-old Omani boy, born to consanguineous parents. He presented with type 1 diabetes, autoimmune haematological cytopenia, recurrent chest infections and lymphocytic interstitial lung disease. The patient was treated with CTLA4-Ig (abatacept) with good outcome every 2 weeks for a period of 3 months. He developed complete IgG deficiency, but remarkably, histological examination revealed germinal centres and plasma cells in lymphoid and inflamed lung tissue. Further charatecterisation showed these cells to express IgM but not IgG. This ex vivo analysis suggests that LRBA mutation confers a defect in class switching despite plasma cell formation
A quantitative comparison of different methods to detect cardiorespiratory coordination during night-time sleep
BACKGROUND: The univariate approaches used to analyze heart rate variability have recently been extended by several bivariate approaches with respect to cardiorespiratory coordination. Some approaches are explicitly based on mathematical models which investigate the synchronization between weakly coupled complex systems. Others use an heuristic approach, i.e. characteristic features of both time series, to develop appropriate bivariate methods. OBJECTIVE: In this study six different methods used to analyze cardiorespiratory coordination have been quantitatively compared with respect to their performance (no. of sequences with cardiorespiratory coordination, no. of heart beats coordinated with respiration). Five of these approaches have been suggested in the recent literature whereas one method originates from older studies. RESULTS: The methods were applied to the simultaneous recordings of an electrocardiogram and a respiratory trace of 20 healthy subjects during night-time sleep from 0:00 to 6:00. The best temporal resolution and the highest number of coordinated heart beats were obtained with the analysis of 'Phase Recurrences'. Apart from the oldest method, all methods showed similar qualitative results although the quantities varied between the different approaches. In contrast, the oldest method detected considerably fewer coordinated heart beats since it only used part of the maximum amount of information available in each recording. CONCLUSIONS: The method of 'Phase Recurrences' should be the method of choice for the detection of cardiorespiratory coordination since it offers the best temporal resolution and the highest number of coordinated sequences and heart beats. Excluding the oldest method, the results of the heuristic approaches may also be interpreted in terms of the mathematical models
Gravitational Waves from Gravitational Collapse
Gravitational wave emission from the gravitational collapse of massive stars
has been studied for more than three decades. Current state of the art
numerical investigations of collapse include those that use progenitors with
realistic angular momentum profiles, properly treat microphysics issues,
account for general relativity, and examine non--axisymmetric effects in three
dimensions. Such simulations predict that gravitational waves from various
phenomena associated with gravitational collapse could be detectable with
advanced ground--based and future space--based interferometric observatories.Comment: 68 pages including 13 figures; revised version accepted for
publication in Living Reviews in Relativity (http://www.livingreviews.org
Patient-centred screening for primary immunodeficiency, a multi-stage diagnostic protocol designed for non-immunologists: 2011 update.
Grb2 monomer-dimer equilibrium determines normal versus oncogenic function
The adaptor protein growth factor receptor-bound protein 2 (Grb2) is ubiquitously expressed in eukaryotic cells and involved in a multitude of intracellular protein interactions. Grb2 plays a pivotal role in tyrosine kinase-mediated signal transduction including linking receptor tyrosine kinases to the Ras/mitogen-activated protein (MAP) kinase pathway, which is implicated in oncogenic outcome. Grb2 exists in a constitutive equilibrium between monomeric and dimeric states. Here we show that only monomeric Grb2 is capable of binding to SOS and upregulating MAP kinase signalling and that the dimeric state is inhibitory to this process. Phosphorylation of tyrosine 160 (Y160) on Grb2, or binding of a tyrosylphosphate-containing ligand to the SH2 domain of Grb2, results in dimer dissociation. Phosphorylation of Y160 on Grb2 is readily detectable in the malignant forms of human prostate, colon and breast cancers. The self-association/dissociation of Grb2 represents a switch that regulates MAP kinase activity and hence controls cancer progression
Reactivity of Metal-Free and Metal-Associated Amyloid-?? with Glycosylated Polyphenols and Their Esterified Derivatives
Both amyloid-?? (A??) and transition metal ions are shown to be involved in the pathogenesis of Alzheimer???s disease (AD), though the importance of their interactions remains unclear. Multifunctional molecules, which can target metal-free and metal-bound A?? and modulate their reactivity (e.g., A?? aggregation), have been developed as chemical tools to investigate their function in AD pathology; however, these compounds generally lack specificity or have undesirable chemical and biological properties, reducing their functionality. We have evaluated whether multiple polyphenolic glycosides and their esterified derivatives can serve as specific, multifunctional probes to better understand AD. The ability of these compounds to interact with metal ions and metal-free/-associated A??, and further control both metal-free and metal-induced A?? aggregation was investigated through gel electrophoresis with Western blotting, transmission electron microscopy, UV-Vis spectroscopy, fluorescence spectroscopy, and NMR spectroscopy. We also examined the cytotoxicity of the compounds and their ability to mitigate the toxicity induced by both metal-free and metal-bound A??. Of the polyphenols investigated, the natural product (Verbascoside) and its esterified derivative (VPP) regulate the aggregation and cytotoxicity of metal-free and/or metal-associated A?? to different extents. Our studies indicate Verbascoside represents a promising structure for further multifunctional tool development against both metal-free A?? and metal-A??.open0
Search for a Technicolor omega_T Particle in Events with a Photon and a b-quark Jet at CDF
If the Technicolor omega_T particle exists, a likely decay mode is omega_T ->
gamma pi_T, followed by pi_T -> bb-bar, yielding the signature gamma bb-bar. We
have searched 85 pb^-1 of data collected by the CDF experiment at the Fermilab
Tevatron for events with a photon and two jets, where one of the jets must
contain a secondary vertex implying the presence of a b quark. We find no
excess of events above standard model expectations. We express the result of an
exclusion region in the M_omega_T - M_pi_T mass plane.Comment: 14 pages, 2 figures. Available from the CDF server (PS with figs):
http://www-cdf.fnal.gov/physics/pub98/cdf4674_omega_t_prl_4.ps
FERMILAB-PUB-98/321-
Top Quark Mass Measurement from Dilepton Events at CDF II with the Matrix-Element Method
We describe a measurement of the top quark mass using events with two charged
leptons collected by the CDF II detector from collisions with TeV at the Fermilab Tevatron. The likelihood in top mass is
calculated for each event by convoluting the leading order matrix element
describing
with detector resolution functions. The presence of background events in the
data sample is modeled using similar calculations involving the matrix elements
for major background processes. In a data sample with integrated luminosity of
340 pb, we observe 33 candidate events and measure This
measurement represents the first application of this method to events with two
charged leptons and is the most precise single measurement of the top quark
mass in this channel.Comment: 21 pages, 14 figure
Search for New Physics in Lepton + Photon + X Events with L=305 pb-1 of ppbar Collisions at roots=1.96 TeV
We present results of a search for anomalous production of events containing
a charged lepton (either electron or muon) and a photon, both with high
transverse momentum, accompanied by additional signatures, X, including missing
transverse energy (MET) and additional leptons and photons. We use the same
kinematic selection criteria as in a previous CDF search, but with a
substantially larger data set, 305 pb-1, a ppbar collision energy of 1.96 TeV,
and the upgraded CDF II detector. We find 42 Lepton+Photon+MET events versus a
standard model expectation of 37.3 +- 5.4 events. The level of excess observed
in Run I, 16 events with an expectation of 7.6 +- 0.7 events (corresponding to
a 2.7 sigma effect), is not supported by the new data. In the signature of
Multi-Lepton+Photon+X we observe 31 events versus an expectation of 23.0 +- 2.7
events. In this sample we find no events with an extra photon or MET and so
find no events like the one ee+gg+MET event observed in Run I.Comment: 7 pages, 3 figures, 1 table. Accepted to PR
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