Selective transport of neurotransmitters and modulators by distinct volume-regulated LRRC8 anion channels

In response to swelling, mammalian cells release chloride and organic osmolytes through VRAC volume-regulated anion channels. VRACs are heteromers of LRRC8A and other LRRC8 isoforms (B-E) which are co-expressed in HEK293 and most other cells. The spectrum of VRAC substrates and its dependence on particular LRRC8 isoforms remains largely unknown. We show that besides the osmolytes taurine and myo-inositol, LRRC8 channels transport the neurotransmitters glutamate, aspartate and GABA and the co-activator D-serine. HEK293 cells engineered to express defined subsets of LRRC8 isoforms were used to elucidate the subunit-dependence of transport. Whereas LRRC8D was crucial for the translocation of overall neutral compounds like myo-inositol, taurine and GABA and sustained the transport of positively charged lysine, flux of negatively charged aspartate was equally well supported by LRRC8E. Disruption of LRRC8B or LRRC8C failed to decrease transport rates of all investigated substrates, but their inclusion into LRRC8 heteromers influenced VRAC's substrate preference. This suggested that individual VRACs can contain three or more different LRRC8 subunits, a conclusion confirmed by sequential co-immunoprecipitations. Our work suggests a composition-dependent role of VRACs in extracellular signal transduction

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

Study of CP violation in Dalitz-plot analyses of B0 --> K+K-KS, B+ --> K+K-K+, and B+ --> KSKSK+

We perform amplitude analyses of the decays $B^0 \to K^+K^-K^0_S$, $B^+ \rightarrow K^+K^-K^+$, and $B^+ \to K^0_S K^0_S K^+$, and measure CP-violating parameters and partial branching fractions. The results are based on a data sample of approximately $470\times 10^6$ $B\bar{B}$ decays, collected with the BABAR detector at the PEP-II asymmetric-energy $B$ factory at the SLAC National Accelerator Laboratory. For $B^+ \to K^+K^-K^+$, we find a direct CP asymmetry in $B^+ \to \phi(1020)K^+$ of $A_{CP}= (12.8\pm 4.4 \pm 1.3)$, which differs from zero by $2.8 \sigma$. For $B^0 \to K^+K^-K^0_S$, we measure the CP-violating phase $\beta_{\rm eff} (\phi(1020)K^0_S) = (21\pm 6 \pm 2)^\circ$. For $B^+ \to K^0_S K^0_S K^+$, we measure an overall direct CP asymmetry of $A_{CP} = (4 ^{+4}_{-5} \pm 2)$. We also perform an angular-moment analysis of the three channels, and determine that the $f_X(1500)$ state can be described well by the sum of the resonances $f_0(1500)$, $f_2^{\prime}(1525)$, and $f_0(1710)$.Comment: 35 pages, 68 postscript figures. v3 - minor modifications to agree with published versio

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

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

Search for charged Higgs bosons in decays of top quarks in p-pbar collisions at sqrt(s) = 1.96 TeV

7 pages, 2 figuresWe report the recent charged Higgs search in top quark decays in 2.2/fb CDF data. This is the first attempt to search for charged Higgs using fully reconstructed mass assuming H->c-sbar in small tan beta region. No evidence of a charged Higgs is observed in the CDF data, hence 95% upper limits are placed at B(t->H+b)We report on the first direct search for charged Higgs bosons decaying into cs̅ in tt̅ events produced by pp̅ collisions at √s=1.96  TeV. The search uses a data sample corresponding to an integrated luminosity of 2.2  fb-1 collected by the CDF II detector at Fermilab and looks for a resonance in the invariant mass distribution of two jets in the lepton+jets sample of tt̅ candidates. We observe no evidence of charged Higgs bosons in top quark decays. Hence, 95% upper limits on the top quark decay branching ratio are placed at B(t→H+b)< 0.1 to 0.3 for charged Higgs boson masses of 60 to 150  GeV/c2 assuming B(H+→cs̅ )=1.0. The upper limits on B(t→H+b) are also used as model-independent limits on the decay branching ratio of top quarks to generic scalar charged bosons beyond the standard model.Peer reviewe

W boson polarization measurement in the ttbar dilepton channel using the CDF II Detector

We present a measurement of $W$ boson polarization in top-quark decays in $t\bar{t}$ events with decays to dilepton final states using $5.1 {\rm fb^{-1}}$ of integrated luminosity in $p\bar{p}$ collisions collected by the CDF II detector at the Tevatron. A simultaneous measurement of the fractions of longitudinal ($f_0$) and right-handed ($f_+$) $W$ bosons yields the results $f_0 = 0.71 ^{+0.18}_{-0.17} {\rm (stat)} \pm 0.06 {\rm (syst)}$ and $f_+ = -0.07 \pm 0.09 {\rm (stat)} \pm 0.03 {\rm (syst)}$. Combining this measurement with our previous result based on single lepton final states, we obtain $f_0 = 0.84 \pm 0.09 {\rm (stat)} \pm 0.05 {\rm (syst)}$ and $f_{+} = -0.16 \pm 0.05 {\rm (stat)} \pm 0.04 {\rm (syst)}$. The results are consistent with standard model expectation.Comment: Published in Phys. Lett.

Observation of the Y(4140)Y(4140) structure in the J/ψ ϕJ/\psi\,\phi Mass Spectrum in B±→J/ψ ϕKB^\pm\to J/\psi\,\phi K cays

The observation of the $Y(4140)$ structure in $B^\pm\rightarrow J/\psi\,\phi K^\pm$ decays produced in $\bar{p} p$ collisions at \sqrt{s}=1.96~\TeV is reported with a statistical significance greater than 5 standard deviations. A fit to the $J/\psi\,\phi$ mass spectrum is performed assuming the presence of a Breit-Wigner resonance. The fit yields a signal of $19^{+6}_{-5}$ resonance events, and resonance mass and width of 4143.4^{+2.9}_{-3.0}(\mathrm{stat})\pm0.6(\mathrm{syst})~\MeVcc and 15.3^{+10.4}_{-6.1}(\mathrm{stat})\pm2.5(\mathrm{syst})~\MeVcc respectively. The parameters of this resonance-like structure are consistent with values reported from an earlier CDF analysis.Comment: 7 pages, 2 figures, submited to Phys. Rev. Let