Showing papers by "Université Paris-Saclay published in 2009"

Genome-wide scan reveals association of psoriasis with IL-23 and NF-κB pathways

Abstract: Psoriasis is a common immune-mediated disorder that affects the skin, nails and joints. To identify psoriasis susceptibility loci, we genotyped 438,670 SNPs in 1,409 psoriasis cases and 1,436 controls of European ancestry. We followed up 21 promising SNPs in 5,048 psoriasis cases and 5,041 controls. Our results provide strong support for the association of at least seven genetic loci and psoriasis (each with combined P < 5 x 10(-8)). Loci with confirmed association include HLA-C, three genes involved in IL-23 signaling (IL23A, IL23R, IL12B), two genes that act downstream of TNF-alpha and regulate NF-kappaB signaling (TNIP1, TNFAIP3) and two genes involved in the modulation of Th2 immune responses (IL4, IL13). Although the proteins encoded in these loci are known to interact biologically, we found no evidence for epistasis between associated SNPs. Our results expand the catalog of genetic loci implicated in psoriasis susceptibility and suggest priority targets for study in other auto-immune disorders.

Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution

Abstract: To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.

Randomized Phase II Trial of Denosumab in Patients With Bone Metastases From Prostate Cancer, Breast Cancer, or Other Neoplasms After Intravenous Bisphosphonates

Abstract: Purpose Patients with bone metastases and elevated urinary N-telopeptide (uNTx), representing excessive bone resorption, are at increased risk for skeletal-related events (SREs), cancer progression, and death. Osteoclast-mediated bone resorption is regulated by RANKL. We evaluated the effect of denosumab, a fully human monoclonal antibody against RANKL, in patients with bone metastases and elevated uNTx levels despite ongoing intravenous (IV) bisphosphonate (BP) therapy. Patients and Methods Eligible patients had histologically confirmed malignancy, ≥ 1 bone metastases, and uNTx levels higher than 50 nmol/L bone collagen equivalents (BCE)/mM creatinine despite IV BPs. They were stratified by tumor type and screening uNTx levels (50 to 100 or > 100 nmol/L BCE/mM creatinine), and randomly assigned to continue IV BPs every 4 weeks or receive subcutaneous denosumab 180 mg every 4 weeks or every 12 weeks. Results Among 111 patients accrued, the primary end point of uNTx levels lower than 50 nmol/L BCE/mM creat...

Pulmonary veno-occlusive disease

Abstract: Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension (PH) characterised by preferential remodelling of the pulmonary venules. In the current PH classification, PVOD and pulmonary capillary haemangiomatosis (PCH) are considered to be a common entity and represent varied expressions of the same disease. The recent discovery of biallelic mutations in the EIF2AK4 gene as the cause of heritable PVOD/PCH represents a major milestone in our understanding of the molecular pathogenesis of PVOD. Although PVOD and pulmonary arterial hypertension (PAH) share a similar clinical presentation, with features of severe precapillary PH, it is important to differentiate these two conditions as PVOD carries a worse prognosis and life-threatening pulmonary oedema may occur following the initiation of PAH therapy. An accurate diagnosis of PVOD based on noninvasive investigations is possible utilising oxygen parameters, low diffusing capacity for carbon monoxide and characteristic signs on high-resolution computed tomography of the chest. No evidence-based medical therapy exists for PVOD at present and lung transplantation remains the preferred definitive therapy for eligible patients.

Molecular Characterization of Breast Cancer with High-Resolution Oligonucleotide Comparative Genomic Hybridization Array

Abstract: Purpose: We used high-resolution oligonucleotide comparative genomic hybridization (CGH) arrays and matching gene expression array data to identify dysregulated genes and to classify breast cancers according to gene copy number anomalies. Experimental Design: DNA was extracted from 106 pretreatment fine needle aspirations of stage II-III breast cancers that received preoperative chemotherapy. CGH was done using Agilent Human 4 × 44K arrays. Gene expression data generated with Affymetrix U133A gene chips was also available on 103 patients. All P values were adjusted for multiple comparisons. Results: The average number of copy number abnormalities in individual tumors was 76 (range 1-318). Eleven and 37 distinct minimal common regions were gained or lost in >20% of samples, respectively. Several potential therapeutic targets were identified, including FGFR1 that showed high-level amplification in 10% of cases. Close correlation between DNA copy number and mRNA expression levels was detected. Nonnegative matrix factorization (NMF) clustering of DNA copy number aberrations revealed three distinct molecular classes in this data set. NMF class I was characterized by a high rate of triple-negative cancers (64%) and gains of 6p21. VEGFA, E2F3 , and NOTCH4 were also gained in 29% to 34% of triple-negative tumors. A gain of ERBB2 gene was observed in 52% of NMF class II and class III was characterized by a high rate of estrogen receptor–positive tumors (73%) and a low rate of pathologic complete response to preoperative chemotherapy (3%). Conclusion: The present study identified dysregulated genes that could classify breast cancer and may represent novel therapeutic targets for molecular subsets of cancers.

Distributed and Antagonistic Contributions of Ongoing Activity Fluctuations to Auditory Stimulus Detection

Abstract: Recent studies have shown that ongoing activity fluctuations influence trial-by-trial perception of identical stimuli. Some brain systems seem to bias toward better perceptual performance and others toward worse. We tested whether these observations generalize to another as of yet unassessed sensory modality, audition, and a nonspatial but memory-dependent paradigm. In a sparse event-related functional magnetic resonance imaging design, we investigated detection of auditory near-threshold stimuli as a function of prestimulus baseline activity in early auditory cortex as well as several distributed networks that were defined on the basis of resting state functional connectivity. In accord with previous studies, hits were associated with higher prestimulus activity in related early sensory cortex as well as in a system comprising anterior insula, anterior cingulate, and thalamus, which other studies have related to processing salience and maintaining task set. In contrast to previous studies, however, higher prestimulus activity in the so-called dorsal attention system of frontal and parietal cortex biased toward misses, whereas higher activity in the so-called default mode network that includes posterior cingulate and precuneus biased toward hits. These results contradict a simple dichotomic view on the function of these two latter brain systems where higher ongoing activity in the dorsal attention network would facilitate perceptual performance, and higher activity in the default mode network would deteriorate perceptual performance. Instead, we show that the way in which ongoing activity fluctuations impact on perception depends on the specific sensory (i.e., nonspatial) and cognitive (i.e., mnemonic) context that is relevant.

Observation of single top-quark production

Abstract: We report observation of the electroweak production of single top quarks in pp collisions at s=1.96 TeV based on 2.3 fb(-1) of data collected by the D0 detector at the Fermilab Tevatron Collider. Using events containing an isolated electron or muon and missing transverse energy, together with jets originating from the fragmentation of b quarks, we measure a cross section of sigma(pp -> tb+X,tqb+X)=3.94 +/- 0.88 pb. The probability to measure a cross section at this value or higher in the absence of signal is 2.5x10(-7), corresponding to a 5.0 standard deviation significance for the observation.

Measurement of the gamma gamma* --> pi0 transition form factor

Abstract: We study the reaction e+e- --> e+e-pi0 and measure the gamma gamma* --> pi0 transition form factor in the momentum transfer range from 4 to 40 GeV^2. The analysis is based on 442 fb^-1 of integrated luminosity collected at PEP-II with the BABAR detector at e+e- center-of-mass energies near 10.6 GeV.

Genomewide Association Study of an AIDS-Nonprogression Cohort Emphasizes the Role Played by HLA Genes (ANRS Genomewide Association Study 02)

Abstract: To elucidate the genetic factors predisposing to AIDS progression, we analyzed a unique cohort of 275 human immunodeficiency virus (HIV) type 1-seropositive nonprogressor patients in relation to a control group of 1352 seronegative individuals in a genomewide association study (GWAS). The strongest association was obtained for HCP5 rs2395029 (P = 6.79 × 10 −10 ; odds ratio, 3.47) andwaspossibly linkedto aneffect of sex. Interestingly, this single-nucleotide polymorphism (SNP) was in high linkage disequilibrium with HLA-B, MICB, TNF, and several other HLA locus SNPs and haplotypes. A meta-analysis of our genomic data combined with data from the previously conducted Euro-CHAVI (Center for HIV/AIDS Vaccine Immunology) GWAS confirmed the HCP5 signal (P = 3.02 × 10 −19 ) and identified several new associations, all of them involving HLA genes: MICB, TNF, RDBP, BAT1-5, PSORS1C1, and HLA-C. Finally, stratification by HCP5 rs2395029 genotypes emphasized an independent role for ZNRD1, also in the HLA locus, and this finding was confirmed by experimental data. The present study, the first GWAS of HIV-1 nonprogressors, underscores the potential for some HLA genes to control disease progression soon after infection.

Evidence for X(3872)→ψ(2S)γ in B±→X(3872) K± Decays and a Study of B→cc̄γK

Abstract: In a search for B --> ccbar gamma K decays with the BaBar detector, where ccbar includes J/psi and psi(2S), and K includes K+, Ks, and K*(892), we find evidence for X(3872) --> J/psi gamma and X(3872) --> psi(2S) gamma with 3.6 sigma and 3.5 sigma significance, respectively. We measure the product of branching fractions BR(B+ --> X(3872) K+) x BR(X(3872) --> J/psi gamma) = (2.8 +/- 0.8(stat.) +/- 0.2(syst.)) x 10^(-6) and BR(B+ --> X(3872) K+) x BR(X(3872) --> psi(2S) gamma) = (9.9 +/- 2.9(stat.) +/- 0.6(syst.)) x 10^(-6).

Premenstrual syndrome prevalence and fluctuation over time: results from a French population-based survey.

Abstract: Objectives: To explore the experience of reproductive-age women in the French population with premenstrual syndrome (PMS) by estimating perceived symptom prevalence, identifying risk factors, and quantifying the burden of symptoms. This study also assesses the stability of the PMS diagnosis over a 1-year period of follow-up. Methods: The prevalence of reported PMS was estimated from a population-based cohort of 2863 French women interviewed in 2003 and 2004. Multivariate logistic regressions were used to identify risk factors associated with PMS. PMS fluctuation was studied by comparing women's responses in 2003 and 2004. Results: Results show that 4.1% of women qualified for severe PMS (six symptoms) and 8.1% qualified for moderate PMS (one to five symptoms), resulting in 12.2% of women who reported PMS symptoms that impacted their daily lives. Risk factors for PMS fell into three categories: hormonal, psychosocial, and physiological, with life stressors and exogenous hormonal exposure exerting ...

Combination of tt̄ cross section measurements and constraints on the mass of the top quark and its decays into charged Higgs bosons

Abstract: We combine measurements of the top quark pair production cross section in p (p) over bar collisions in the l + jets, ll, and tau l final states ( where l is an electron or muon) at a center of mass energy of root s = 1.96 TeV in 1 fb(-1) of data collected with the D0 detector. For a top quark mass of 170 GeV/c(2), we obtain sigma(t (t) over bar) = 8.18(-0.87)(+0.98) pb in agreement with the theoretical prediction. Based on predictions from higher order quantum chromodynamics, we extract a mass for the top quark from the combined t (t) over bar cross section, consistent with the world average of the top quark mass. In addition, the ratios of t (t) over bar cross sections in different final states are used to set upper limits on the branching fractions B(t -> H(+)b -> tau(+) vb) and B(t -> H(+)b -> c (s) over barb) as a function of the charged Higgs boson mass.

Measurement of Dijet Angular Distributions at s=1.96TeV and Searches for Quark Compositeness and Extra Spatial Dimensions

Abstract: We present the first measurement of dijet angular distributions in ppbar collisions at sqrt{s}=1.96TeV at the Fermilab Tevatron Collider. The measurement is based on a dataset corresponding to an integrated luminosity of up to 0.7fb-1 collected with the D0 detector. Dijet angular distributions have been measured over a range of dijet masses, from 0.25TeV to above 1.1TeV. The data are in good agreement with the predictions of perturbative QCD and are used to constrain new physics models including quark compositeness, large extra dimensions, and TeV-1 scale extra dimensions. For all models we set the most stringent direct limits to date.

Angular distributions in the decay B -> K*l(+)l(-)

Abstract: We use a sample of 384 million BBbar events collected with the Babar detector at the PEP-II e+e- collider to study angular distributions in the rare decays B -> K* l+l-, where l+l- is either e+e- or mu+mu-. For low dilepton invariant masses, m(l+l-) 3.2$ GeV/c^2, we measure AFB=0.76 (+0.52,-0.32) +/- 0.07 FL=0.71 (+0.20,-0.22) +/- 0.04.

Follow-Up of Low-Risk Differentiated Thyroid Cancer Patients Who Underwent Radioiodine Ablation of Postsurgical Thyroid Remnants after Either Recombinant Human Thyrotropin or Thyroid Hormone Withdrawal

Abstract: Background: We previously demonstrated comparable thyroid remnant ablation rates in postoperative low-risk thyroid cancer patients prepared for administration of 3.7GBq 131I (100 mCi) after recombinant human (rh) TSH during T4 (L-T4) therapy vs. withholding L-T4 (euthyroid vs. hypothyroid groups). We now compared the outcomes of these patients 3.7 yr later. Patients and Methods: Fifty-one of the 63 original patients (28 euthyroid, 23 hypothyroid) participated. Forty-eight received rhTSH and serum thyroglobulin (Tg) sampling. A 131I whole-body scan was performed in 43 patients, and successful ablation was defined by criteria from the previous study. Based on the criterion of uptake less than 0.1% in thyroid bed, 100% (43 of 43) remained ablated. When no visible uptake instead was used, five patients (four euthyroid, one hypothyroid) had minimal visible activity. When the TSH-stimulated Tg criterion was used, only two of 45 (one euthyroid, one hypothyroid) had a stimulated Tg level greater than 2 ng/ml. Res...

Measurement of bottom versus charm as a function of transverse momentum with electron-hadron correlations in p+p Collisions at s=200GeV

Abstract: The momentum distribution of electrons from semileptonic decays of charm and bottom quarks for midrapidity |y| e(+/-)K(-/+)X (K unidentified) reconstruction. It is found that the yield of electrons from bottom becomes significant above 4 GeV/c in p(T). A fixed-order-plus-next-to-leading-log perturbative quantum chromodynamics calculation agrees with the data within the theoretical and experimental uncertainties. The extracted total bottom production cross section at this energy is sigma(bb)=3.2(-1.1)(+1.2)(stat)(-1.3)(+1.4)(syst)mu b.

Inclusive cross section and double helicity asymmetry for π0 production in p+p collisions at s=62.4GeV

Abstract: The PHENIX experiment presents results from the RHIC 2006 run with polarized p + p collisions at root s = 62.4 GeV, for inclusive pi(0) production at midrapidity. Unpolarized cross section results are measured for transverse momenta p(T) = 0.5 to 7 GeV/c. Next-to-leading order perturbative quantum chromodynamics calculations are compared with the data, and while the calculations are consistent with the measurements, next-to-leading logarithmic corrections improve the agreement. Double helicity asymmetries A(LL) are presented for p(T) = 1 to 4 GeV/c and probe the higher range of Bjorken x of the gluon (x(g)) with better statistical precision than our previous measurements at root s = 200 GeV. These measurements are sensitive to the gluon polarization in the proton for 0.06 < x(g) < 0.4.

Search for Long-Lived Charged Massive Particles with the D0 Detector

Abstract: We search for long-lived charged massive particles using 1.1 fb(-1) of data collected by the D0 detector at the Fermilab Tevatron pp Collider. Time-of-flight information is used to search for pair produced long-lived tau sleptons, gauginolike charginos, and Higgsino-like charginos. We find no evidence of a signal and set 95% C.L. cross section upper limits for staus, which vary from 0.31 to 0.04 pb for stau masses between 60 and 300 GeV. We also set lower mass limits of 206 GeV (171 GeV) for pair produced charged gauginos (Higgsinos).

Prospects for polarized foreground removal

Abstract: In this report we discuss the impact of polarized foregrounds on a future CMBPol satellite mission. We review our current knowledge of Galactic polarized emission at microwave frequencies, including synchrotron and thermal dust emission. We use existing data and our understanding of the physical behavior of the sources of foreground emission to generate sky templates, and start to assess how well primordial gravitational wave signals can be separated from foreground contaminants for a CMBPol mission. At the estimated foreground minimum of ∼100 GHz, the polarized foregrounds are expected to be lower than a primordial polarization signal with tensor‐to‐scalar ratio r = 0.01, in a small patch (∼1%) of the sky known to have low Galactic emission. Over 75% of the sky we expect the foreground amplitude to exceed the primordial signal by about a factor of eight at the foreground minimum and on scales of two degrees. Only on the largest scales does the polarized foreground amplitude exceed the primordial signal by a larger factor of about 20. The prospects for detecting an r = 0.01 signal including degree‐scale measurements appear promising, with 5σ_r∼0.003 forecast from multiple methods. A mission that observes a range of scales offers better prospects from the foregrounds perspective than one targeting only the lowest few multipoles. We begin to explore how optimizing the composition of frequency channels in the focal plane can maximize our ability to perform component separation, with a range of typically 40 ≲ ν ≲ 300 GHz preferred for ten channels. Foreground cleaning methods are already in place to tackle a CMBPol mission data set, and further investigation of the optimization and detectability of the primordial signal will be useful for mission design.

Viral subversion of immunogenic cell death.

Abstract: While physiological cell death is non-immunogenic, pathogen induced cell death can be immunogenic and hence stimulate an immune response against antigens that derive from dying cells and are presented by dendritic cells (DCs). The obligate immunogenic “eat-me” signal generated by dying cells consists in the exposure of calreticulin (CRT) at the cell surface. This particular “eat-me” signal, which facilitates engulfment by DCs, can only be found on cells that succumb to immunogenic apoptosis, while it is not present on cells dying in an immunologically silent fashion. CRT normally resides in the lumen of the endoplasmic reticulum (ER), yet can translocate to the plasma membrane surface through a complex pathway that involves elements of the ER stress response (e.g., the eIF2α-phosphorylating kinase PERK), the apoptotic machinery (e.g., caspase-8 and its substrate BAP31, Bax, Bak), the anterograde transport from the ER to the Golgi apparatus, and SNARE-dependent exocytosis. A large panoply of viruses encode...

Evidence for the ηb(1S) Meson in Radiative Υ(2S) Decay

Abstract: We have performed a search for the eta_b(1S) meson in the radiative decay of the Upsilon(2S) resonance using a sample of 91.6 million Upsilon(2S) events recorded with the BABAR detector at the PEP-II B factory at the SLAC National Accelerator Laboratory. We observe a peak in the photon energy spectrum at E_gamma = 610.5 {+4.5} {-4.3} (stat) +/- 1.8 (syst) MeV, corresponding to an eta_b(1S) mass of 9392.9 {+4.6} {-4.8} (stat) +/- 1.9 (syst) MeV/c^2. The branching fraction for the decay Upsilon(2S) --> gamma eta_b(1S) is determined to be (4.2 {+1.1} {-1.0} (stat) +/- 0.9 (syst)) x 10^(-4). The ratio B(Upsilon(2S) --> gamma eta_b(1S))/B(Upsilon(3S) --> gamma eta_b(1S)) = 0.89 {+0.25} {-0.23} (stat) {+0.12}{-0.16} (syst) is consistent with the ratio expected for magnetic dipole transitions to the eta_b(1S) meson.

CXCR4 Expression in Early Breast Cancer and Risk of Distant Recurrence

Abstract: Background. Chemokine receptor 4 (CXCR4) has been demonstrated to have a critical role in the early metastatic process. The aim of this study was to eval

Precise measurement of the neutron magnetic form factor G(M)n in the few-GeV2 region

Abstract: The neutron elastic magnetic form factor was extracted from quasielastic electron scattering on deuterium over the range Q;{2}=1.0-4.8 GeV2 with the CLAS detector at Jefferson Lab. High precision was achieved with a ratio technique and a simultaneous in situ calibration of the neutron detection efficiency. Neutrons were detected with electromagnetic calorimeters and time-of-flight scintillators at two beam energies. The dipole parametrization gives a good description of the data.

Measurement of the lifetime of the Bc± meson in the semileptonic decay channel

Abstract: Using approximately 1.3 fb(-1) of data collected by the D0 detector between 2002 and 2006, we measure the lifetime of the B-c(+/-) meson in the B-c(+/-)-> J/psi mu(+/-)+X final state. A simultaneous unbinned likelihood fit to the J/psi+mu invariant mass and lifetime distributions yields a signal of 881 +/- 80(stat) candidates and a lifetime measurement of tau(B-c(+/-))=0.448(-0.036)(+0.038)(stat)+/- 0.032(syst) ps.

Time-dependent amplitude analysis of B0 -> KS0π+π-

Abstract: We perform a time-dependent amplitude analysis of B^0→K_S^0π^+π^- decays to extract the CP violation parameters of f_0(980)K_S^0 and ρ^0(770)K_S^0 and the direct CP asymmetry of K^(*+)(892)π^-. The results are obtained from a data sample of (383±3)×10^6 BB decays, collected with the BABAR detector at the PEP-II asymmetric–energy B factory at SLAC. We find two solutions, with an equivalent goodness-of-fit. Including systematic and Dalitz plot model uncertainties, the combined confidence interval for values of the CP parameter β_(eff) in B^0 decays to f_0(980)K_S^0 is 18°<β_(eff)<76° at 95% confidence level (C.L). CP conservation in B^0 decays to f_0(980)K_S^0 is excluded at 3.5 standard deviations including systematic uncertainties. For B^0 decays to ρ^0(770)K_S^0, the combined confidence interval is -9°<β_(eff)<57° at 95% C.L. In decays to K^(*+)(892)π^- we measure the direct CP asymmetry to be A_(CP)=-0.20±0.10±0.01±0.02. The measured phase difference (including B^0B ^0 mixing) between decay amplitudes of B^0→K^(*+)(892)π^- and B ^0→K^(*-)(892)π^+, excludes the interval -137°<ΔΦ(K^(*+)(892)π^-)<-5° at 95% C.L.