The Crystal Structure of PPIL1 Bound to Cyclosporine A Suggests a Binding Mode for a Linear Epitope of the SKIP Protein

BACKGROUND: The removal of introns from pre-mRNA is carried out by a large macromolecular machine called the spliceosome. The peptidyl-prolyl cis/trans isomerase PPIL1 is a component of the human spliceosome and binds to the spliceosomal SKIP protein via a binding site distinct from its active site. PRINCIPAL FINDINGS: Here, we have studied the PPIL1 protein and its interaction with SKIP biochemically and by X-ray crystallography. A minimal linear binding epitope derived from the SKIP protein could be determined using a peptide array. A 36-residue region of SKIP centred on an eight-residue epitope suffices to bind PPIL1 in pull-down experiments. The crystal structure of PPIL1 in complex with the inhibitor cyclosporine A (CsA) was obtained at a resolution of 1.15 A and exhibited two bound Cd(2+) ions that enabled SAD phasing. PPIL1 residues that have previously been implicated in binding of SKIP are involved in the coordination of Cd(2+) ions in the present crystal structure. Employing the present crystal structure, the determined minimal binding epitope and previously published NMR data, a molecular docking study was performed. In the docked model of the PPIL1.SKIP interaction, a proline residue of SKIP is buried in a hydrophobic pocket of PPIL1. This hydrophobic contact is encircled by several hydrogen bonds between the SKIP peptide and PPIL1. CONCLUSION: We characterized a short, linear epitope of SKIP that is sufficient to bind the PPIL1 protein. Our data indicate that this SKIP peptide could function in recruiting PPIL1 into the core of the spliceosome. We present a molecular model for the binding mode of SKIP to PPIL1 which emphasizes the versatility of cyclophilin-type PPIases to engage in additional interactions with other proteins apart from active site contacts despite their limited surface area

Multiplicity dependence of jet-like two-particle correlations in p-Pb collisions at sNN\sqrt{s_{NN}} = 5.02 TeV

Two-particle angular correlations between unidentified charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV. The transverse-momentum range 0.7 $< p_{\rm{T}, assoc} < p_{\rm{T}, trig} <$ 5.0 GeV/$c$ is examined, to include correlations induced by jets originating from low momen\-tum-transfer scatterings (minijets). The correlations expressed as associated yield per trigger particle are obtained in the pseudorapidity range $|\eta|<0.9$. The near-side long-range pseudorapidity correlations observed in high-multiplicity p-Pb collisions are subtracted from both near-side short-range and away-side correlations in order to remove the non-jet-like components. The yields in the jet-like peaks are found to be invariant with event multiplicity with the exception of events with low multiplicity. This invariance is consistent with the particles being produced via the incoherent fragmentation of multiple parton--parton scatterings, while the yield related to the previously observed ridge structures is not jet-related. The number of uncorrelated sources of particle production is found to increase linearly with multiplicity, suggesting no saturation of the number of multi-parton interactions even in the highest multiplicity p-Pb collisions. Further, the number scales in the intermediate multiplicity region with the number of binary nucleon-nucleon collisions estimated with a Glauber Monte-Carlo simulation.Comment: 23 pages, 6 captioned figures, 1 table, authors from page 17, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/161

Multi-particle azimuthal correlations in p-Pb and Pb-Pb collisions at the CERN Large Hadron Collider

Measurements of multi-particle azimuthal correlations (cumulants) for charged particles in p-Pb and Pb-Pb collisions are presented. They help address the question of whether there is evidence for global, flow-like, azimuthal correlations in the p-Pb system. Comparisons are made to measurements from the larger Pb-Pb system, where such evidence is established. In particular, the second harmonic two-particle cumulants are found to decrease with multiplicity, characteristic of a dominance of few-particle correlations in p-Pb collisions. However, when a $|\Delta \eta|$ gap is placed to suppress such correlations, the two-particle cumulants begin to rise at high-multiplicity, indicating the presence of global azimuthal correlations. The Pb-Pb values are higher than the p-Pb values at similar multiplicities. In both systems, the second harmonic four-particle cumulants exhibit a transition from positive to negative values when the multiplicity increases. The negative values allow for a measurement of $v_{2}\{4\}$ to be made, which is found to be higher in Pb-Pb collisions at similar multiplicities. The second harmonic six-particle cumulants are also found to be higher in Pb-Pb collisions. In Pb-Pb collisions, we generally find $v_{2}\{4\} \simeq v_{2}\{6\}\neq 0$ which is indicative of a Bessel-Gaussian function for the $v_{2}$ distribution. For very high-multiplicity Pb-Pb collisions, we observe that the four- and six-particle cumulants become consistent with 0. Finally, third harmonic two-particle cumulants in p-Pb and Pb-Pb are measured. These are found to be similar for overlapping multiplicities, when a $|\Delta\eta| > 1.4$ gap is placed.Comment: 25 pages, 11 captioned figures, 3 tables, authors from page 20, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/87

Neuropsychological Sequelae of Carotid Angioplasty with Stent Placement: Correlation with Ischemic Lesions in Diffusion Weighted Imaging

BACKGROUND AND PURPOSE: Few studies investigated the neuropsychological outcome after carotid angioplasty with stent placement (CAS), yielding partially inconsistent results. The present investigation evaluated the effect of CAS in patients with high-grade stenosis and assessed the predictive value of ischemic lesion number for postinterventional cognitive deterioration. METHODS: 22 patients were tested neuropsychologically before and six weeks after CAS. Cerebral ischemic changes were assessed with diffusion weighted imaging (DWI) prior to and after angioplasty. RESULTS: Pre- to postinterventional cognitive performance improved significantly in terms of verbal memory (t = -2.30; p<0.05), whereas significant deterioration was noted regarding verbal memory span (t = 2.31; p<0.05). 8 (36%) persons conformed to the criteria of cognitive improvement. 6 patients (27%) were postinterventionally classified as having deficits. Analysis yielded no statistically significant correlations between lesion quantity and cognitive change. CONCLUSION: Both improvement and deterioration of cognitive functioning was observed in our collective of patients, leaving the neuropsychological outcome after percutaneous transluminal angioplasty unpredictable in individual cases. The presence of acute ischemic lesions on DWI was found to be not tightly associated with cognitive dysfunction after CAS

EUDAQ - A data acquisition software framework for common beam telescopes

EUDAQ is a generic data acquisition software developed for use in conjunction with common beam telescopes at charged particle beam lines. Providing high-precision reference tracks for performance studies of new sensors, beam telescopes are essential for the research and development towards future detectors for high-energy physics. As beam time is a highly limited resource, EUDAQ has been designed with reliability and ease-of-use in mind. It enables flexible integration of different independent devices under test via their specific data acquisition systems into a top-level framework. EUDAQ controls all components globally, handles the data flow centrally and synchronises and records the data streams. Over the past decade, EUDAQ has been deployed as part of a wide range of successful test beam campaigns and detector development applications

Enhanced production of multi-strange hadrons in high-multiplicity proton-proton collisions

At sufficiently high temperature and energy density, nuclear matter undergoes a transition to a phase in which quarks and gluons are not confined: the quark-gluon plasma (QGP)(1). Such an exotic state of strongly interacting quantum chromodynamics matter is produced in the laboratory in heavy nuclei high-energy collisions, where an enhanced production of strange hadrons is observed(2-6). Strangeness enhancement, originally proposed as a signature of QGP formation in nuclear collisions(7), is more pronounced for multi-strange baryons. Several effects typical of heavy-ion phenomenology have been observed in high-multiplicity proton-proton (pp) collisions(8,9), but the enhanced production of multi-strange particles has not been reported so far. Here we present the first observation of strangeness enhancement in high-multiplicity proton-proton collisions. We find that the integrated yields of strange and multi-strange particles, relative to pions, increases significantly with the event charged-particle multiplicity. The measurements are in remarkable agreement with the p-Pb collision results(10,11), indicating that the phenomenon is related to the final system created in the collision. In high-multiplicity events strangeness production reaches values similar to those observed in Pb-Pb collisions, where a QGP is formed.Peer reviewe

K0S and Λ production in Pb-Pb collisions at sNN−−−−√=2.76 TeV

The ALICE measurement of K0S and Λ production at midrapidity in Pb-Pb collisions at sNN−−−√=2.76  TeV is presented. The transverse momentum (pT) spectra are shown for several collision centrality intervals and in the pT range from 0.4  GeV/c (0.6  GeV/c for Λ) to 12  GeV/c. The pT dependence of the Λ/K0S ratios exhibits maxima in the vicinity of 3  GeV/c, and the positions of the maxima shift towards higher pT with increasing collision centrality. The magnitude of these maxima increases by almost a factor of three between most peripheral and most central Pb-Pb collisions. This baryon excess at intermediate pT is not observed in pp interactions at s√=0.9  TeV and at s√=7  TeV. Qualitatively, the baryon enhancement in heavy-ion collisions is expected from radial flow. However, the measured pT spectra above 2  GeV/c progressively decouple from hydrodynamical-model calculations. For higher values of pT, models that incorporate the influence of the medium on the fragmentation and hadronization processes describe qualitatively the pT dependence of the Λ/K0S ratio

Актуальні питання реалізації іпотечних зобов'язань в нотаріальному процесі

Стаття присвячена теоретичному дослідженню важливості використання існуючих механізмів превентивної юстиції та дієвості правозахисної функції нотаріату. Доведено, що нотаріус як гарант превентивності правовідносин реалізує свої правозахисні функції не лише на стадії реалізації іпотечних зобовязань, шляхом вчинення виконавчого напису на борговому документі, а і на стадії узгодження та викладення всіх істотних умов договору. Ключові слова: нотаріат; правозахисна функція нотаріату; виконання зобовязань; превентивна юстиція.Статья посвящена теоретическому исследованию необходимости использования существующих механизмов превентивной юстиции и действенности правозащитной функции нотариата. Доказывается, что нотариус как гарант превентивности правоотношений реализует свои правозащитные функции не только на стадии реализации ипотечных обязательств, в связи с совершением исполнительной надписи на долговом документе, а и на стадии согласования и изложения всех существенных условий договора. Ключевые слова: нотариат; правозащитная функция нотариату; исполнение обязательств; превентивная юстиция.This article is dedicated into theoretical research of importance in using special mechanism of prevention justitia and acting law defender functions of notoriety. It is argued that notaries as a guaranty of prevention law relation realizes his law defender functions not only on the stage of realization ipothek obligations, making performance inscription on the duty document, but on the stage of consenting and stating all existence conditions of contract. Key words: notoriety, law defender function of notaries, making obligations, prevention justitia

Constraints on jet quenching in p-Pb collisions at root s(NN)=5.02 TeV measured by the event-activity dependence of semi-inclusive hadron-jet distributions

CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFINEP - FINANCIADORA DE ESTUDOS E PROJETOSFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOThe ALICE Collaboration reports the measurement of semi-inclusive distributions of charged-particle jets recoiling from a high-transverse momentum trigger hadron in p-Pb collisions at root s(NN) = 5.02TeV. Jets are reconstructed from charged-particle tracks using the anti-k(T) algorithm with resolution parameter R = 0.2 and 0.4. A data-driven statistical approach is used to correct the uncorrelated background jet yield. Recoil jet distributions are reported for jet transverse momentum 15 < p(T,jet)(ch) < 50 GeV/c and are compared in various intervals of p-Pb event activity, based on charged-particle multiplicity and zero-degree neutral energy in the forward (Pb-going) direction. The semi-inclusive observable is self-normalized and such comparisons do not require the interpretation of p-Pb event activity in terms of collision geometry, in contrast to inclusive jet observables. These measurements provide new constraints on the magnitude of jet quenching in small systems at the LHC. In p-Pb collisions with high event activity, the average medium-induced out-of-cone energy transport for jets with R = 0.4 and 15 < p(T,jet)(ch) < 50 GeV/c is measured to be less than 0.4 GeV/c at 90% confidence, which is over an order of magnitude smaller than a similar measurement for central Pb-Pb collisions at root s(NN) = 2.76 TeV. Comparison is made to theoretical calculations of jet quenching in small systems, and to inclusive jet measurements in p-Pb collisions selected by event activity at the LHC and in d-Au collisions at RHIC.78395113CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFINEP - FINANCIADORA DE ESTUDOS E PROJETOSFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFINEP - FINANCIADORA DE ESTUDOS E PROJETOSFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOSem informaçãoSem informaçãoSem informaçãoAgências de fomento estrangeiras apoiaram essa pesquisa, mais informações acesse artig