Observation of exclusive charmonium production and gamma+gamma to mu+mu- in p+pbar collisions at sqrt{s} = 1.96 TeV

We have observed the reactions p+pbar --> p+X+pbar, with X being a centrally produced J/psi, psi(2S) or chi_c0, and gamma+gamma --> mu+mu-, in proton- antiproton collisions at sqrt{s} = 1.96 TeV using the Run II Collider Detector at Fermilab. The event signature requires two oppositely charged muons, each with pseudorapidity |eta| mu+mu-. Events with a J/psi and an associated photon candidate are consistent with exclusive chi_c0 production through double pomeron exchange. The exclusive vector meson production is as expected for elastic photo- production, gamma+p --> J/psi(psi(2S)) + p, which is observed here for the first time in hadron-hadron collisions. The cross sections ds/dy(y=0) for p + pbar --> p + X + pbar with X = J/psi, psi(2S) orchi_c0 are 3.92+/-0.62 nb, 0.53+/-0.14 nb, and 75+/-14 nb respectively. The cross section for the continuum, with |eta(mu+/-)|

Data integration from two microarray platforms identifies bi-allelic genetic inactivation of RIC8A in a breast cancer cell line

Background: Using array comparative genomic hybridization (aCGH), a large number of deleted genomic regions have been identified in human cancers. However, subsequent efforts to identify target genes selected for inactivation in these regions have often been challenging. Methods: We integrated here genome-wide copy number data with gene expression data and non-sense mediated mRNA decay rates in breast cancer cell lines to prioritize gene candidates that are likely to be tumour suppressor genes inactivated by bi-allelic genetic events. The candidates were sequenced to identify potential mutations. Results: This integrated genomic approach led to the identification of RIC8A at 11p15 as a putative candidate target gene for the genomic deletion in the ZR-75-1 breast cancer cell line. We identified a truncating mutation in this cell line, leading to loss of expression and rapid decay of the transcript. We screened 127 breast cancers for RIC8A mutations, but did not find any pathogenic mutations. No promoter hypermethylation in these tumours was detected either. However, analysis of gene expression data from breast tumours identified a small group of aggressive tumours that displayed low levels of RIC8A transcripts. qRT-PCR analysis of 38 breast tumours showed a strong association between low RIC8A expression and the presence of TP53 mutations (P = 0.006). Conclusion: We demonstrate a data integration strategy leading to the identification of RIC8A as a gene undergoing a classical double-hit genetic inactivation in a breast cancer cell line, as well as in vivo evidence of loss of RIC8A expression in a subgroup of aggressive TP53 mutant breast cancers.

Measurement of the top quark mass in the dilepton channel using mT2 at CDF

We present measurements of the top quark mass using the \mT2, a variable related to the transverse mass in events with two missing particles. We use the template method applied to t\tbar dilepton events produced in p\pbar collisions at Fermilab's Tevatron and collected by the CDF detector. From a data sample corresponding to an integrated luminosity of 3.4 \invfb, we select 236 t\tbar candidate events. Using the \mT2 distribution, we measure the top quark mass to be M_{Top} = 168.0^{+4.8}_{-4.0} $\pm$ {2.9} GeV/c^{2}. By combining the \mT2 with the reconstructed top mass distributions based on a neutrino weighting method, we measure M_{top}=169.3 $\pm$ 2.7 $\pm$ 3.2 GeV/c^{2}. This is the first application of the \mT2 variable in a mass measurement at a hadron collider.

Integrative functional genomics analysis of sustained polyploidy phenotypes in breast cancer cells identifies an oncogenic profile for GINS2

Aneuploidy is among the most obvious differences between normal and cancer cells. However, mechanisms contributing to development and maintenance of aneuploid cell growth are diverse and incompletely understood. Functional genomics analyses have shown that aneuploidy in cancer cells is correlated with diffuse gene expression signatures and that aneuploidy can arise by a variety of mechanisms, including cytokinesis failures, DNA endoreplication and possibly through polyploid intermediate states. Here, we used a novel cell spot microarray technique to identify genes with a loss-of-function effect inducing polyploidy and/or allowing maintenance of polyploid cell growth of breast cancer cells. Integrative genomics profiling of candidate genes highlighted GINS2 as a potential oncogene frequently overexpressed in clinical breast cancers as well as in several other cancer types. Multivariate analysis indicated GINS2 to be an independent prognostic factor for breast cancer outcome (p = 0.001). Suppression of GINS2 expression effectively inhibited breast cancer cell growth and induced polyploidy. In addition, protein level detection of nuclear GINS2 accurately distinguished actively proliferating cancer cells suggesting potential use as an operational biomarker.

Detection,amplification and sequence homology of sodC in clinical isolates of Salmonella sp

Background & objectives: Periplasmic copper and zinc superoxide dismutase (Cu,Zn-SOD or SodC) is an important component of the antioxidant shield which protects bacteria from the phagocytic oxidative burst. Cu,Zn-SODs protect Gram-negative bacteria against oxygen damage which have also been shown to contribute to the pathogenicity of these bacterial species. We report the presence of SodC in drug resistant Salmonella sp. isolated from patients suffering from enteric fever. Further sodC was amplified, cloned into Escherichia coli and the nucleotide sequence and amino acid sequence homology were compared with the standard strain Salmonella Typhimurium 14028. Methods: Salmonella enterica serovar Typhi (S. Typhi) and Salmonellaenterica serovar Paratyphi (S. Paratyphi) were isolated and identified from blood samples of the patients. The isolates were screened for the presence of Cu, Zn-SOD by PAGE using KCN as inhibitor of Cu,Zn-SOD. The gene (sodC) was amplified by PCR, cloned and sequenced. The nucleotide and amino acid sequences of sodC were compared using CLUSTAL X.Results: SodC was detected in 35 per cent of the Salmonella isolates. Amplification of the genomic DNA of S. Typhi and S. Paratyphi with sodC specific primers resulted in 519 and 515 bp amplicons respectively. Single mutational difference at position 489 was observed between thesodC of S. Typhi and S. Paratyphi while they differed at 6 positions with the sodC of S. Typhimurium 14028. The SodC amino acid sequences of the two isolates were homologous but 3 amino acid difference was observed with that of standard strain S. Typhimurium 14028.Interpretation & conclusions: The presence of SodC in pathogenic bacteria could be a novel candidate as phylogenetic marker.

Measurement of the Single Top Quark Production Cross Section at CDF

We report a measurement of the single top quark production cross section in 2.2 ~fb-1 of p-pbar collision data collected by the Collider Detector at Fermilab at sqrt{s}=1.96 TeV. Candidate events are classified as signal-like by three parallel analyses which use likelihood, matrix element, and neural network discriminants. These results are combined in order to improve the sensitivity. We observe a signal consistent with the standard model prediction, but inconsistent with the background-only model by 3.7 standard deviations with a median expected sensitivity of 4.9 standard deviations. We measure a cross section of 2.2 +0.7 -0.6(stat+sys) pb, extract the CKM matrix element value |V_{tb}|=0.88 +0.13 -0.12 (stat+sys) +- 0.07(theory), and set the limit |V_{tb}|>0.66 at the 95% C.L.

Measurement of the top quark mass with dilepton events selected using neuroevolution at CDF

We report a measurement of the top quark mass $M_t$ in the dilepton decay channel $t\bar{t}\to b\ell'^{+}\nu'_\ell\bar{b}\ell^{-}\bar{\nu}_{\ell}$. Events are selected with a neural network which has been directly optimized for statistical precision in top quark mass using neuroevolution, a technique modeled on biological evolution. The top quark mass is extracted from per-event probability densities that are formed by the convolution of leading order matrix elements and detector resolution functions. The joint probability is the product of the probability densities from 344 candidate events in 2.0 fb$^{-1}$ of $p\bar{p}$ collisions collected with the CDF II detector, yielding a measurement of $M_t= 171.2\pm 2.7(\textrm{stat.})\pm 2.9(\textrm{syst.})\mathrm{GeV}/c^2$.

Direct Top-Quark Width Measurement at CDF

We present a measurement of the top-quark width using $t\bar{t}$ events produced in $p\bar{p}$ collisions at Fermilab's Tevatron collider and collected by the CDF II detector. In the mode where the top quark decays to a $W$ boson and a bottom quark, we select events in which one $W$ decays leptonically and the other hadronically~(lepton + jets channel) . From a data sample corresponding to 4.3~fb$^{-1}$ of integrated luminosity, we identify 756 candidate events. The top-quark mass and the mass of $W$ boson that decays hadronically are reconstructed for each event and compared with templates of different top-quark widths~($\Gamma_t$) and deviations from nominal jet energy scale~($\Delta_{JES}$) to perform a simultaneous fit for both parameters, where $\Delta_{JES}$ is used for the {\it in situ} calibration of the jet energy scale. By applying a Feldman-Cousins approach, we establish an upper limit at 95$\%$ confidence level~(CL) of $\Gamma_t $

Measurement of the top quark mass in the dilepton channel using mT2 at CDF

We present measurements of the top quark mass using the \mT2, a variable related to the transverse mass in events with two missing particles. We use the template method applied to t\tbar dilepton events produced in p\pbar collisions at Fermilab's Tevatron and collected by the CDF detector. From a data sample corresponding to an integrated luminosity of 3.4 \invfb, we select 236 t\tbar candidate events. Using the \mT2 distribution, we measure the top quark mass to be M_{Top} = 168.0^{+4.8}_{-4.0} $\pm$ {2.9} GeV/c^{2}. By combining the \mT2 with the reconstructed top mass distributions based on a neutrino weighting method, we measure M_{top}=169.3 $\pm$ 2.7 $\pm$ 3.2 GeV/c^{2}. This is the first application of the \mT2 variable in a mass measurement at a hadron collider.

Search for Pair Production of Supersymmetric Top Quarks in Dilepton Events from pp̅ Collisions at √s=1.96 TeV

We present the results of a search for pair production of the supersymmetric partner of the top quark (the stop quark $\tilde{t}_{1}$) decaying to a $b$-quark and a chargino $\chargino$ with a subsequent $\chargino$ decay into a neutralino $\neutralino$, lepton $\ell$, and neutrino $\nu$. Using a data sample corresponding to 2.7 fb$^{-1}$ of integrated luminosity of $p\bar{p}$ collisions at $\sqrt{s} = 1.96$ TeV collected by the CDF II detector, we reconstruct the mass of candidate stop events and fit the observed mass spectrum to a combination of standard model processes and stop quark signal. We find no evidence for $\pairstop$ production and set 95% C.L. limits on the masses of the stop quark and the neutralino for several values of the chargino mass and the branching ratio ${\cal B}(\chargino\to\neutralino\ell^{\pm}\nu)$.

Search for Supersymmetry with Gauge-Mediated Breaking in Diphoton Events with Missing Transverse Energy at CDF II

We present the results of a search for supersymmetry with gauge-mediated breaking and $\NONE\to\gamma\Gravitino$ in the $\gamma\gamma$+missing transverse energy final state. In 2.6$\pm$0.2 \invfb of $p{\bar p}$ collisions at $\sqrt{s}$$=$1.96 TeV recorded by the CDF II detector we observe no candidate events, consistent with a standard model background expectation of 1.4$\pm$0.4 events. We set limits on the cross section at the 95% C.L. and place the world's best limit of 149\gevc on the \none mass at $\tau_{\tilde{\chi}_1^0}$$

Observation of single top quark production and measurement of |Vtb| with CDF

We report the observation of electroweak single top quark production in 3.2  fb-1 of pp̅ collision data collected by the Collider Detector at Fermilab at √s=1.96  TeV. Candidate events in the W+jets topology with a leptonically decaying W boson are classified as signal-like by four parallel analyses based on likelihood functions, matrix elements, neural networks, and boosted decision trees. These results are combined using a super discriminant analysis based on genetically evolved neural networks in order to improve the sensitivity. This combined result is further combined with that of a search for a single top quark signal in an orthogonal sample of events with missing transverse energy plus jets and no charged lepton. We observe a signal consistent with the standard model prediction but inconsistent with the background-only model by 5.0 standard deviations, with a median expected sensitivity in excess of 5.9 standard deviations. We measure a production cross section of 2.3-0.5+0.6(stat+sys)  pb, extract the value of the Cabibbo-Kobayashi-Maskawa matrix element |Vtb|=0.91-0.11+0.11(stat+sys)±0.07  (theory), and set a lower limit |Vtb|>0.71 at the 95% C.L., assuming mt=175  GeV/c2.

Observation of single top quark production and measurement of |Vtb| with CDF

We report the observation of electroweak single top quark production in 3.2 fb-1 of ppbar collision data collected by the Collider Detector at Fermilab at sqrt{s}=1.96 TeV. Candidate events in the W+jets topology with a leptonically decaying W boson are classified as signal-like by four parallel analyses based on likelihood functions, matrix elements, neural networks, and boosted decision trees. These results are combined using a super discriminant analysis based on genetically evolved neural networks in order to improve the sensitivity. This combined result is further combined with that of a search for a single top quark signal in an orthogonal sample of events with missing transverse energy plus jets and no charged lepton. We observe a signal consistent with the standard model prediction but inconsistent with the background-only model by 5.0 standard deviations, with a median expected sensitivity in excess of 5.9 standard deviations. We measure a production cross section of 2.3+0.6-0.5(stat+sys) pb, extract the CKM matrix element value |Vtb|=0.91+0.11-0.11 (stat+sys)+-0.07(theory), and set a lower limit |Vtb|>0.71 at the 95% confidence level, assuming m_t=175 GeVc^2.

Measurement of the Single-Top-Quark Production Cross Section at CDF

We report a measurement of the single top quark production cross section in 2.2 ~fb-1 of p-pbar collision data collected by the Collider Detector at Fermilab at sqrt{s}=1.96 TeV. Candidate events are classified as signal-like by three parallel analyses which use likelihood, matrix element, and neural network discriminants. These results are combined in order to improve the sensitivity. We observe a signal consistent with the standard model prediction, but inconsistent with the background-only model by 3.7 standard deviations with a median expected sensitivity of 4.9 standard deviations. We measure a cross section of 2.2 +0.7 -0.6(stat+sys) pb, extract the CKM matrix element value |V_{tb}|=0.88 +0.13 -0.12 (stat+sys) +- 0.07(theory), and set the limit |V_{tb}|>0.66 at the 95% C.L.

Identification of genetic susceptibility loci for migraine

Migraine is the common cause of chronic episodic headache, affecting 12%-15% of the Caucasian population (41 million Europeans and some half a million Finns), and causes considerable loss of quality of life to its sufferers, as well as being linked to increased risk for a wide range of conditions, from depression to stroke. Migraine is the 19th most severe disease in terms of disability-adjusted life years, and 9th among women. It is characterized by attacks of headache accompanied by sensitivity to external stimuli lasting 4-72 hours, and in a third of cases by neurological aura symptoms, such as loss of vision, speech or muscle function. The underlying pathophysiology, including what triggers migraine attacks and why they occur in the first place, is largely unknown. The aim of this study was to identify genetic factors associated with the hereditary susceptibility to migraine, in order to gain a better understanding of migraine mechanisms. In this thesis, we report the results of genetic linkage and association analyses on a Finnish migraine patient collection as well as migraineurs from Australia, Denmark, Germany, Iceland and the Netherlands. Altogether we studied genetic information of nearly 7,000 migraine patients and over 50,000 population-matched controls. We also developed a new migraine analysis method called the trait component analysis, which is based on individual patient responses instead of the clinical diagnosis. Using this method, we detected a number of new genetic loci for migraine, including on chromosome 17p13 (HLOD 4.65) and 10q22-q23 (female-specific HLOD 7.68) with significant evidence of linkage, along with five other loci (2p12, 8q12, 4q28-q31, 18q12-q22, and Xp22) detected with suggestive evidence of linkage. The 10q22-q23 locus was the first genetic finding in migraine to show linkage to the same locus and markers in multiple populations, with consistent detection in six different scans. Traditionally, ion channels have been thought to play a role in migraine susceptibility, but we were able to exclude any significant role for common variants in a candidate gene study of 155 ion transport genes. This was followed up by the first genome-wide association study in migraine, conducted on 2,748 migraine patients and 10,747 matched controls followed by a replication in 3,209 patients and 40,062 controls. In this study, we found interesting results with genome-wide significance, providing targets for future genetic and functional studies. Overall, we found several promising genetic loci for migraine providing a promising base for future studies in migraine.