Ion mobility-mass spectrometry for structural characterization and applied \u27omics: A study in neurodegenerative diseases

Huntington\u27s disease is neurodegenerative disease caused by an expanded polyglutamine-coding CAG repeat in exon 1 of the huntingtin gene. Huntingtin exon 1 forms the primary toxic amyloid structure in Huntington\u27s disease; disease severity is directly correlated with polyglutamine length. Recent works have shown that fully formed amyloid plaques may not represent the most toxic species in Huntington\u27s disease; the most neurotoxic species may be small, diffuse oligomer (4 - 20 monomer units) that are precursors to amyloid plaques. While the polyglutamine region is undisputed as the primary constituent of amyloid structure, aggregation kinetics and morphology are regulated by the presence of flanking sequences that are N- and C-terminal to theamyloid forming tract. The first seventeen residues of huntingtin exon 1 (Nt17) can form an amphipathic &agr;-helix depending upon solution conditions and the presence of a binding partner, and in most cases, mediates oligomer formation. C-terminal to the polyglutamine tract is a proline-rich region, or in the case of a model peptide a polyproline region (polyP), that can form a polyproline-type II (PPII) helix, which may regulate Nt17 in huntingtin protein with short polyglutamine regions. Much is unknown regarding residue-specific Nt17-Nt17 and Nt17-polyP interactions. The work described here utilized state-of-the-art deuterium exchange mass spectrometry techniques to identify critical hydrophilic residues in early stages of oligomer formation. Monomeric and multimeric conformations of Nt17, idependent og the polyglutamine domain, were then studied using ion mobility-mass spectrometry and molecular dynamics to gain insight into the earliest stages of Nt17-Nt17 association, and thus, aggregation. Monomeric and multimeric Nt17 could form extended helices in the gas phase. Key hydrophilic residues were chemically modified, which resulted in a sharp decline in multimer formation. Finally, Nt17-polyP interactions were probed using gas-phase deuterium exchange mass spectrometry, supplemented with molecular dynamics and an exchange kinetics model. The obtained gas-phase structures showed a reduction in Nt17 extended &agr;-helix, when compared to a monomeric and extended homodimeric conformation. Thus, it is hypothesized that polyP regulates Nt17 by not allowing transition to the amphipathic &agr;-helix. The results of this study examine the structural heterogeneity of a sequence thought to drive a potentially toxic aggregate morphology, pinpoint key residues in early oligomer formation, and provide strategies for regulation of oligomer formation

Search for anomalous couplings in boosted WW/WZ -> l nu q(q)over-bar production in proton-proton collisions at root s=8TeV

Peer reviewe

Search for high-mass Zγ\mathrm{ Z }\gamma resonances in proton-proton collisions at s=\sqrt{s}= 8 and 13 TeV using jet substructure techniques

A search for massive resonances decaying to a Z boson and a photon is performed in events with a hadronically decaying Z boson candidate, separately in light-quark and b quark decay modes, identified using jet substructure and advanced b tagging techniques. Results are based on samples of proton-proton collisions collected with the CMS detector at the LHC at center-of-mass energies of 8 and 13 TeV, corresponding to integrated luminosities of 19.7 and 2.7 inverse femtobarns, respectively. The results of the search are combined with those of a similar search in the leptonic decay modes of the Z boson, based on the same data sets. Spin-0 resonances with various widths and with masses in a range between 0.2 and 3.0 TeV are considered. No significant excess is observed either in the individual analyses or the combination. The results are presented in terms of upper limits on the production cross section of such resonances and constitute the most stringent limits to date for a wide range of masses

Lesson 6

The spectra of charged particles produced within the pseudorapidity window $| \eta |$ 20 GeV, ${R_{\mathrm{ p }\mathrm{A}}}$ exhibits weak momentum dependence and shows a moderate enhancement above unity.The spectra of charged particles produced within the pseudorapidity window abs(eta) 20 GeV, R[pA] exhibits weak momentum dependence and shows a moderate enhancement above unity.The spectra of charged particles produced within the pseudorapidity window |η| 20 GeV, R$_{pA}$ exhibits weak momentum dependence and shows a moderate enhancement above unity

Search for single production of vector-like quarks decaying to a Z boson and a top or a bottom quark in proton-proton collisions at s=13 \sqrt{s}=13 TeV

A search for single production of vector-like quarks, T and B, decaying into a Z boson and a top or a bottom quark, respectively, is presented. The search is performed using data collected by the CMS experiment at the LHC in proton-proton collisions at $\sqrt{s}=13$ TeV, corresponding to an integrated luminosity of 2.3fb$^{−1}$. An exotic T quark production mode through the decay of a heavy Z′ resonance is also considered. The search is performed in events with a Z boson decaying leptonically, accompanied by a bottom or a top quark decaying hadronically. No excess of events is observed over the standard model background expectation. Products of production cross section and branching fraction for T and B quarks from 1.26 and 0.13 pb are excluded at 95% confidence level for the range of resonance mass considered, which is between 0.7 and 1.7 TeV. Limits on the product of the Z′ boson production cross section and branching fraction, with the Z′ boson decaying to the Tt final state, are set between 0.31 and 0.13 pb, for Z′ boson masses in the range from 1.5 to 2.5 TeV. This is the first search at 13 TeV for single production of vector-like quarks in events with a Z boson decaying leptonically accompanied by boosted jets

Measurement of prompt and nonprompt J/ψJ/\psi production in pp and pPb collisions at sNN=\sqrt{s_{NN}} = 5.02 TeV

This paper reports the measurement of $J/\psi$ meson production in proton-proton (pp) and proton-lead (pPb) collisions at a center-of-mass energy per nucleon pair of 5.02 TeV by the CMS experiment at the LHC. The data samples used in the analysis correspond to integrated luminosities of 28 pb$^{-1}$ and 35 nb$^{-1}$ for pp and pPb collisions, respectively. Prompt and nonprompt J/psi mesons, the latter issuing from the decay of B mesons, are measured in their dimuon decay channels. Differential cross sections are measured in the transverse momentum range of 2 < $p_t$ < 30 GeV/c, and center-of-mass rapidity ranges of |y$_{CM}$| < 2.4 (pp) and -2.87 < y$_{CM}$ < 1.93 (pPb). The nuclear modification factor, R$_{pPb}$, is measured as functions of $p_t$ and y$_{CM}$. Small modifications of the $J/\psi$ cross sections are observed in pPb relative to pp collisions. The ratio of $J/\psi$ production cross sections in p-going and Pb-going directions, R$_{FB}$, studied as functions of $p_t$ and y$_{CM}$, shows a significant decrease for increasing transverse energy deposited at large pseudorapidities. These results, which cover a wide kinematic range, provide new insight on the role of cold nuclear matter effects on prompt and nonprompt $J/\psi$ production

Search for CP violation in ttˉt\bar{t} production and decay in proton-proton collisions at s\sqrt{s} = 8 TeV

The results of a first search for CP violation in the production and decay of top quark-antiquark $(t\bar{t})$ pairs are presented. The search is based on asymmetries in T-odd, triple-product correlation observables, where T is the time-reversal operator. The analysis uses a sample of proton-proton collisions at $\sqrt{s}$ TeV collected by the CMS experiment, corresponding to an integrated luminosity of 19.7 inverse femtobarns.. Events are selected having one electron or muon and at least four jets. The T-odd observables are measured using four-momentum vectors associated with ttbar production and decay. The measured asymmetries exhibit no evidence for CP-violating effects, consistent with the expectation from the standard model