p53 mutations in urinary bladder cancer

We have screened for mutations in exons 5–8 of the p53 gene in a series consisting of 189 patients with urinary bladder neoplasms. 82 (44%) neoplasms were lowly malignant (Ta, G1–G2a) and 106 (56%) were highly malignant (G2b–G4 or ≥T1). Only one mutation was in a lowly malignant urinary bladder neoplasm, in total we found p53 mutations in 26 (14%) of the 189 patients. 30% of the samples had loss of heterozygosity (LOH) for one or both of the p53 exogenic (CA)n repeat and the p53 intragenic (AAAAT)n repeat markers. 31 samples (21%) showed LOH but were not mutated, suggesting other mechanisms inactivating p53 than mutations. 4 mutations were found at codon 280 and 2 mutations were found at codon 285, 2 previously reported hot spots for urinary bladder cancer. The study indicate a boundary between G2a and G2b tumours concerning the occurrence of genetic events affecting p53 function; moderately differentiated (G2) urinary bladder neoplasms probably are genetically heterogeneous which supports the suggestion that they should not be grouped together but instead, for example, be categorized as either lowly or highly malignant. © 2001 Cancer Research Campaign http://www.bjcancer.co

The genetic contribution of the NO system at the glutamatergic post-synapse to schizophrenia : further evidence and meta-analysis

NO is a pleiotropic signaling molecule and has an important role in cognition and emotion. In the brain, NO is produced by neuronal nitric oxide synthase (NOS-I, encoded by NOS1) coupled to the NMDA receptor via PDZ. interactions; this protein-protein interaction is disrupted upon binding of NOS1 adapter protein (encoded by NOS1AP) to NOS-I. As both NOS1 and NOS1AP were associated with schizophrenia, we here investigated these genes in greater detail by genotyping new samples and conducting a meta-analysis of our own and published data. In doing so, we confirmed association of both genes with schizophrenia and found evidence for their interaction in increasing risk towards disease. Our strongest finding was the NOS1 promoter SNP rs41279104, yielding an odds ratio of 1.29 in the meta-analysis. As findings from heterologous cell systems have suggested that the risk allele decreases gene expression, we studied the effect of the variant on NOS1 expression in human post-mortem brain samples and found that the risk allele significantly decreases expression of NOS1 in the prefrontal cortex. Bioinformatic analyses suggest that this might be due the replacement of six transcription factor binding sites by two new binding sites as a consequence of proxy SNPs. Taken together, our data argue that genetic variance in NOS1 resulting in lower prefrontal brain expression of this gene contributes to schizophrenia liability, and that NOS1 interacts with NOS1AP in doing so. The NOS1-NOS1AP PDZ interface may thus well constitute a novel target for small molecules in at least some forms of schizophrenia. PostprintPeer reviewe

Maximal L p -regularity for the Laplacian on Lipschitz domains

We consider the Laplacian with Dirichlet or Neumann boundary conditions on bounded Lipschitz domains ?, both with the following two domains of definition:D1(?) = {u ? W1,p(?) : ?u ? Lp(?), Bu = 0}, orD2(?) = {u ? W2,p(?) : Bu = 0}, where B is the boundary operator.We prove that, under certain restrictions on the range of p, these operators generate positive analytic contraction semigroups on Lp(?) which implies maximal regularity for the corresponding Cauchy problems. In particular, if ? is bounded and convex and 1 < p ? 2, the Laplacian with domain D2(?) has the maximal regularity property, as in the case of smooth domains. In the last part,we construct an example that proves that, in general, the Dirichlet–Laplacian with domain D1(?) is not even a closed operator

Measurement of the production of charm jets tagged with D0^{0} mesons in pp collisions at s\sqrt{s}= 7 TeV

The production of charm jets in proton-proton collisions at a center-of-mass energy of $\sqrt{s}=7$ TeV was measured with the ALICE detector at the CERN Large Hadron Collider. The measurement is based on a data sample corresponding to a total integrated luminosity of $6.23$ ${\rm nb}^{-1}$, collected using a minimum-bias trigger. Charm jets are identified by the presence of a D$^0$ meson among their constituents. The D$^0$ mesons are reconstructed from their hadronic decay D$^0\rightarrow$K$^{-}\pi^{+}$. The D$^0$-meson tagged jets are reconstructed using tracks of charged particles (track-based jets) with the anti-$k_{\mathrm{T}}$ algorithm in the jet transverse momentum range $5<p_{\rm{T,jet}}^{\mathrm{ch}}<30$ ${\rm GeV/}c$ and pseudorapidity $|\eta_{\rm jet}|<0.5$. The fraction of charged jets containing a D$^0$-meson increases with $p_{\rm{T,jet}}^{\rm{ch}}$ from $0.042 \pm 0.004\, \mathrm{(stat)} \pm 0.006\, \mathrm{(syst)}$ to $0.080 \pm 0.009\, \rm{(stat)} \pm 0.008\, \rm{(syst)}$. The distribution of D$^0$-meson tagged jets as a function of the jet momentum fraction carried by the D$^0$ meson in the direction of the jet axis ($z_{||}^{\mathrm{ch}}$) is reported for two ranges of jet transverse momenta, $5<p_{\rm{T,jet}}^{\rm{ch}}<15$ ${\rm GeV/}c$ and $15<p_{\rm{T,jet}}^{\rm{ch}}<30$ ${\rm GeV/}c$ in the intervals $0.2<z_{||}^{\rm{ch}}<1.0$ and $0.4<z_{||}^{\rm{ch}}<1.0$, respectively. The data are compared with results from Monte Carlo event generators (PYTHIA 6, PYTHIA 8 and Herwig 7) and with a Next-to-Leading-Order perturbative Quantum Chromodynamics calculation, obtained with the POWHEG method and interfaced with PYTHIA 6 for the generation of the parton shower, fragmentation, hadronisation and underlying event.Comment: 29 pages, 8 captioned figures, 3 tables, authors from page 24, published version, figures at http://alice-publications.web.cern.ch/node/525

The influence of age, delay of repair, and tendon involvement in acute rotator cuff tears: Structural and clinical outcomes after repair of 42 shoulders

Background and purpose Few authors have considered the outcome after acute traumatic rotator cuff tears in previously asymptomatic patients. We investigated whether delay of surgery, age at repair, and the number of cuff tendons involved affect the structural and clinical outcome. Patients and methods 42 patients with pseudoparalysis after trauma and no previous history of shoulder symptoms were included. A full-thickness tear in at least 1 of the rotator cuff tendons was diagnosed in all patients. Mean time to surgery was 38 (6-91) days. Follow-up at a mean of 39 (12-108) months after surgery included ultrasound, plain radiographs, Constant-Murley score, DASH score, and western Ontario rotator cuff (WORC) score. Results At follow-up, 4 patients had a full-thickness tear and 9 had a partial-thickness tear in the repaired shoulder. No correlation between the structural or clinical outcome and the time to repair within 3 months was found. The patients with a tendon defect at follow-up had a statistically significantly lower Constant-Murley score and WORC index in the injured shoulder and were significantly older than those with intact tendons. The outcomes were similar irrespective of the number of tendons repaired. Interpretation A delay of 3 months to repair had no effect on outcome. The patients with cuff defects at follow-up were older and they had a worse clinical outcome. Multi-tendon injury did not generate worse outcomes than single-tendon tears at follow-up

First measurement of Ξc0\Xi_{\rm c}^0 production in pp collisions at s\mathbf{\sqrt{s}} = 7 TeV

The production of the charm-strange baryon $\Xi_{\rm c}^0$ is measured for the first time at the LHC via its semileptonic decay into e$^+\Xi^-\nu_{\rm e}$ in pp collisions at $\sqrt{s}=7$ TeV with the ALICE detector. The transverse momentum ($p_{\rm T}$) differential cross section multiplied by the branching ratio is presented in the interval 1 $<$ $p_{\rm T}$ $<$ 8 GeV/$c$ at mid-rapidity, $|y|$ $<$ 0.5. The transverse momentum dependence of the $\Xi_{\rm c}^0$ baryon production relative to the D$^0$ meson production is compared to predictions of event generators with various tunes of the hadronisation mechanism, which are found to underestimate the measured cross-section ratio.Comment: 22 pages, 6 captioned figures, 1 table, authors from page 17, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/412

Constraining the magnitude of the Chiral Magnetic Effect with Event Shape Engineering in Pb-Pb collisions at sNN\sqrt{s_{\rm NN}} = 2.76$ TeV

In ultrarelativistic heavy-ion collisions, the event-by-event variation of the elliptic flow $v_2$ reflects fluctuations in the shape of the initial state of the system. This allows to select events with the same centrality but different initial geometry. This selection technique, Event Shape Engineering, has been used in the analysis of charge-dependent two- and three-particle correlations in Pb-Pb collisions at $\sqrt{s_{_{\rm NN}}} =2.76$ TeV. The two-particle correlator $\langle \cos(\varphi_\alpha - \varphi_\beta) \rangle$, calculated for different combinations of charges $\alpha$ and $\beta$, is almost independent of $v_2$ (for a given centrality), while the three-particle correlator $\langle \cos(\varphi_\alpha + \varphi_\beta - 2\Psi_2) \rangle$ scales almost linearly both with the event $v_2$ and charged-particle pseudorapidity density. The charge dependence of the three-particle correlator is often interpreted as evidence for the Chiral Magnetic Effect (CME), a parity violating effect of the strong interaction. However, its measured dependence on $v_2$ points to a large non-CME contribution to the correlator. Comparing the results with Monte Carlo calculations including a magnetic field due to the spectators, the upper limit of the CME signal contribution to the three-particle correlator in the 10-50% centrality interval is found to be 26-33% at 95% confidence level.Comment: 20 pages, 6 captioned figures, 1 tables, authors from page 15, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/382

Energy dependence of exclusive J/ψJ/\psi photoproduction off protons in ultra-peripheral p-Pb collisions at sNN\sqrt{s_{\rm{NN}}} = 5.02 TeV

The ALICE Collaboration has measured the energy dependence of exclusive photoproduction of $J/\psi$ vector mesons off proton targets in ultra-peripheral p-Pb collisions at a centre-of-mass energy per nucleon pair $\sqrt{s_{\rm NN}} = 5.02$ TeV. The e$^+$e$^-$ and $\mu^+\mu^-$ decay channels are used to measure the cross section as a function of the rapidity of the $J/\psi$ in the range $-2.5 < y < 2.7$, corresponding to an energy in the $\gamma$p centre-of-mass in the interval $40 < W_{\gamma\mathrm{p}}<550$ GeV. The measurements, which are consistent with a power law dependence of the exclusive $J/\psi$ photoproduction cross section, are compared to previous results from HERA and the LHC and to several theoretical models. They are found to be compatible with previous measurements.Comment: 25 pages, 3 captioned figures, 3 tables, authors from page 19, published version, figures at http://alice-publications.web.cern.ch/node/455

Inclusive J/ψ production at mid-rapidity in pp collisions at √s = 5.02 TeV

Inclusive J/ψ production is studied in minimum-bias proton-proton collisions at a centre-of-mass energy of s = 5.02 TeV by ALICE at the CERN LHC. The measurement is performed at mid-rapidity (|y| &lt; 0.9) in the dielectron decay channel down to zero transverse momentum pT, using a data sample corresponding to an integrated luminosity of Lint = 19.4 ± 0.4 nb−1. The measured pT-integrated inclusive J/ψ production cross sec- tion is dσ/dy = 5.64 ± 0.22(stat.) ± 0.33(syst.) ± 0.12(lumi.) μb. The pT-differential cross section d2σ/dpTdy is measured in the pT range 0–10 GeV/c and compared with state-of- the-art QCD calculations. The J/ψ 〈pT〉 and 〈pT2〉 are extracted and compared with results obtained at other collision energies. [Figure not available: see fulltext.]

Measurement of Λ (1520) production in pp collisions at √s=7TeV and p–Pb collisions at √sNN=5.02TeV

The production of the Λ (1520) baryonic resonance has been measured at midrapidity in inelastic pp collisions at s=7TeV and in p–Pb collisions at sNN=5.02TeV for non-single diffractive events and in multiplicity classes. The resonance is reconstructed through its hadronic decay channel Λ (1520) → pK - and the charge conjugate with the ALICE detector. The integrated yields and mean transverse momenta are calculated from the measured transverse momentum distributions in pp and p–Pb collisions. The mean transverse momenta follow mass ordering as previously observed for other hyperons in the same collision systems. A Blast-Wave function constrained by other light hadrons (π, K, KS0, p, Λ) describes the shape of the Λ (1520) transverse momentum distribution up to 3.5GeV/c in p–Pb collisions. In the framework of this model, this observation suggests that the Λ (1520) resonance participates in the same collective radial flow as other light hadrons. The ratio of the yield of Λ (1520) to the yield of the ground state particle Λ remains constant as a function of charged-particle multiplicity, suggesting that there is no net effect of the hadronic phase in p–Pb collisions on the Λ (1520) yield