The CMS experiment at the CERN LHC

The Compact Muon Solenoid (CMS) detector is described. The detector operates at the Large Hadron Collider (LHC) at CERN. It was conceived to study proton-proton (and leadlead) collisions at a centre-of-mass energy of 14 TeV (5.5 TeV nucleon-nucleon) and at luminosities up to 1034 cm-2s-1 (1027 cm-2s-1). At the core of the CMS detector sits a high-magnetic field and large-bore superconducting solenoid surrounding an all-silicon pixel and strip tracker, a lead-tungstate scintillating-crystals electromagnetic calorimeter, and a brass-scintillator sampling hadron calorimeter. The iron yoke of the flux-return is instrumented with four stations of muon detectors covering most of the 4π solid angle. Forward sampling calorimeters extend the pseudorapidity coverage to high values (|η| ≤ 5) assuring very good hermeticity. The overall dimensions of the CMS detector are a length of 21.6 m, a diameter of 14.6 m and a total weight of 12500 t

Measurement of the t-Channel Single Top Quark Production Cross Section in pp̅ Collisions at √s= 7 TeV

Electroweak production of the top quark is measured for the first time in pp collisions at √s= 7 TeV, using a data set collected with the CMS detector at the LHC and corresponding to an integrated luminosity of 36 pb-1. With an event selection optimized for t-channel production, two complementary analyses are performed. The first one exploits the special angular properties of the signal, together with background estimates from the data. The second approach uses a multivariate analysis technique to probe the compatibility with signal topology expected from electroweak top-quark production. The combined measurement of the cross section is 83.6±29.8 (stat + syst) ± 3.3 (lumi) pb, consistent with the standard model expectation

Search for aVectorlike Quarkwith Charge 2/3 in t + Z Events from pp Collisions at √s = 7 TeV

A search for pair-produced heavy vectorlike charge-2/3 quarks, T, in pp collisions at a center-of-mass energy of 7 TeV, is performed with the CMS detector at the LHC. Events consistent with the flavorchanging- neutral-current decay of a T quark to a top quark and a Z boson are selected by requiring two leptons from the Z-boson decay, as well as an additional isolated charged lepton. In a data sample corresponding to an integrated luminosity of 1.14 fb-1, the number of observed events is found to be consistent with the standard model background prediction. Assuming a branching fraction of 100% for the decay T → tZ, a T quark with a mass less than 475 GeV/c2 is excluded at the 95% confidence level

Search for Three-Jet Resonances in pp Collisions at √s= 7 TeV

A search for three-jet hadronic resonance production in pp collisions at a center-of-mass energy of 7 TeV has been conducted by the CMS Collaboration at the LHC, using a data sample corresponding to an integrated luminosity of 35 pb-1. Events with high jet multiplicity and a large scalar sum of jet transverse momenta are analyzed using a signature-based approach. The number of expected standard model background events is found to be in good agreement with the observed events. Limits on the cross section times branching ratio are set in a model of gluino pair production with an R-parity-violating decay to three quarks, and the data rule out such particles within the mass range of 200 to 280 GeV/c2

Search for Supersymmetry at the LHC in Events with Jets and Missing Transverse Energy

A search for events with jets and missing transverse energy is performed in a data sample of pp collisions collected at √s = 7 TeV by the CMS experiment at the LHC. The analyzed data sample corresponds to an integrated luminosity of 1.14 fb-1. In this search, a kinematic variable αT is used as the main discriminator between events with genuine and misreconstructed missing transverse energy. No excess of events over the standard model expectation is found. Exclusion limits in the parameter space of the constrained minimal supersymmetric extension of the standard model are set. In this model, squark masses below 1.1 TeV are excluded at 95% C.L. Gluino masses below 1.1 TeV are also ruled out at 95% C.L. for values of the universal scalar mass parameter below 500 GeV

Transverse-Momentum and Pseudorapidity Distributions of Charged Hadrons in pp Collisions at √s=7 TeV

Charged-hadron transverse-momentum and pseudorapidity distributions in proton-proton collisions at √s=7 TeV are measured with the inner tracking system of the CMS detector at the LHC. The charged-hadron yield is obtained by counting the number of reconstructed hits, hit pairs, and fully reconstructed charged-particle tracks. The combination of the three methods gives a charged-particle multiplicity per unit of pseudorapidity dNch=dη ⃒|η|\u3c0.5= 5.78 ± 0.01(stat) ± 0.23(syst) for non-single-diffractive events, higher than predicted by commonly used models. The relative increase in charged-particle multiplicity from √s=0.9 to 7 TeV is [±66.1 ± 1.0(stat) ± 4.2(syst)]%. The mean transverse momentum is measured to be 0.545 ± 0.005(stat) ± 0.015(syst) GeV/c. The results are compared with similar measurements at lower energies

Transverse-Momentum and Pseudorapidity Distributions of Charged Hadrons in pp Collisions at √s=7 TeV

Charged-hadron transverse-momentum and pseudorapidity distributions in proton-proton collisions at √s=7 TeV are measured with the inner tracking system of the CMS detector at the LHC. The charged-hadron yield is obtained by counting the number of reconstructed hits, hit pairs, and fully reconstructed charged-particle tracks. The combination of the three methods gives a charged-particle multiplicity per unit of pseudorapidity dNch=dη ⃒|η|\u3c0.5= 5.78 ± 0.01(stat) ± 0.23(syst) for non-single-diffractive events, higher than predicted by commonly used models. The relative increase in charged-particle multiplicity from √s=0.9 to 7 TeV is [±66.1 ± 1.0(stat) ± 4.2(syst)]%. The mean transverse momentum is measured to be 0.545 ± 0.005(stat) ± 0.015(syst) GeV/c. The results are compared with similar measurements at lower energies

Influenza A (H1N1) in Victoria, Australia: A Community Case Series and Analysis of Household Transmission

We characterise the clinical features and household transmission of pandemic influenza A (pH1N1) in community cases from Victoria, Australia in 2009.Questionnaires were used to collect information on epidemiological characteristics, illness features and co-morbidities of cases identified in the 2009 Victorian Influenza Sentinel Surveillance program.The median age of 132 index cases was 21 years, of whom 54 (41%) were under 18 years old and 28 (21%) had medical co-morbidities. The median symptom duration was significantly shorter for children who received antivirals than in those who did not (p = 0.03). Assumed influenza transmission was observed in 63 (51%) households. Influenza-like illness (ILI) developed in 115 of 351 household contacts, a crude secondary attack rate of 33%. Increased ILI rates were seen in households with larger numbers of children but not larger numbers of adults. Multivariate analysis indicated contacts of cases with cough and diarrhoea, and contacts in quarantined households were significantly more likely to develop influenza-like symptoms.Most cases of pH1N1 in our study were mild with similar clinical characteristics to seasonal influenza. Illness and case features relating to virus excretion, age and household quarantine may have influenced secondary ILI rates within households

Two additive mechanisms impair the differentiation of 'substrate-selective' p38 inhibitors from classical p38 inhibitors in vitro

<p>Abstract</p> <p>Background</p> <p>The success of anti-TNF biologics for the treatment of rheumatoid arthritis has highlighted the importance of understanding the intracellular pathways that regulate TNF production in the quest for an orally-available small molecule inhibitor. p38 is known to strongly regulate TNF production via MK2. The failure of several p38 inhibitors in the clinic suggests the importance of other downstream pathways in normal cell function. Recent work has described a 'substrate-selective' p38 inhibitor that is able to preferentially block the activity of p38 against one substrate (MK2) versus another (ATF2). Using a combined experimental and computational approach, we have examined this mechanism in greater detail for two p38 substrates, MK2 and ATF2.</p> <p>Results</p> <p>We found that in a dual (MK2 and ATF2) substrate assay, MK2-p38 interaction reduced the activity of p38 against ATF2. We further constructed a detailed kinetic mechanistic model of p38 phosphorylation in the presence of multiple substrates and successfully predicted the performance of classical and so-called 'substrate-selective' p38 inhibitors in the dual substrate assay. Importantly, it was found that excess MK2 results in a stoichiometric effect in which the formation of p38-MK2-inhibitor complex prevents the phosphorylation of ATF2, despite the preference of the compound for the p38-MK2 complex over the p38-ATF2 complex. MK2 and p38 protein expression levels were quantified in U937, Thp-1 and PBMCs and found that [MK2] > [p38].</p> <p>Conclusion</p> <p>Our integrated mechanistic modeling and experimental validation provides an example of how systems biology approaches can be applied to drug discovery and provide a basis for decision-making with limited chemical matter. We find that, given our current understanding, it is unlikely that 'substrate-selective' inhibitors of p38 will work as originally intended when placed in the context of more complex cellular environments, largely due to a stoichiometric excess of MK2 relative to p38.</p