The Significance of the ProtDeform Score for Structure Prediction and Alignment

Background: When a researcher uses a program to align two proteins and gets a score, one of her main concerns is how often the program gives a similar score to pairs that are or are not in the same fold. This issue was analysed in detail recently for the program TM-align with its associated TM-score. It was shown that because the TM-score is length independent, it allows a P-value and a hit probability to be defined depending only on the score. Also, it was found that the TM-scores of gapless alignments closely follow an Extreme Value Distribution (EVD). The program ProtDeform for structural protein alignment was developed recently and is characterised by the ability to propose different transformations of different protein regions. Our goal is to analyse its associated score to allow a researcher to have objective reasons to prefer one aligner over another, and carry out a better interpretation of the output. Results: The study on the ProtDeform score reveals that it is length independent in a wider score range than TM-scores and that PD-scores of gapless (random) alignments also approximately follow an EVD. On the CASP8 predictions, PD-scores and TM-scores, with respect to native structures, are highly correlated (0.95), and show that around a fifth of the predictions have a quality as low as 99.5 % of the random scores. Using the Gold Standard benchmark, ProtDeform has lower probabilities of error than TM-align both at a similar speed. The analysis is extended to homology discrimination showing that, again, ProtDeform offers higher hit probabilities than TM-align. Finally, we suggest using three different P-value

The α2β1 integrin mediates the malignant phenotype on type I collagen in pancreatic cancer cell lines

Pancreatic cancer is characterised by a hallmark desmoplastic response that includes upregulated expression of the extracellular matrix, and type I collagen in particular. Recent studies indicate that pancreatic cancer cells stimulate type I collagen synthesis in adjacent stellate cells, and that this upregulated type I collagen expression promotes the malignant phenotype in tumour cells as defined by increased proliferation, resistance to chemically induced apoptosis, and increased tumorigenesis. The integrin specificity of this interaction between type I collagen and tumour cells was not identified, however. In the present study, we examined eight pancreatic cancer cell lines for adhesion, proliferation, and migration, on types I and IV collagen, fibronectin, laminin, and vitronectin, as well as integrin expression. Our results indicate, for the overwhelming majority of cell lines, that type I collagen promotes the strongest adhesion, proliferation, and migration relative to the other substrates tested. Utilising function-blocking monoclonal antibodies directed against particular integrin subunits in cell adhesion and migration inhibition assays, we demonstrate further that the malignant phenotype on type I collagen is mediated specifically by the α2β1 integrin. These results identify α2β1 integrin-mediated adhesion to type I collagen as a potential therapeutic target in the treatment of pancreatic cancer

Py-GC/MS applied to the analysis of synthetic organic pigments: characterization and identification in paint samples

A collection of 76 synthetic organic pigments was analysed using pyrolysis–gas chromatography/mass spectrometry (Py-GC/MS). The purpose of this work was to expand the knowledge on synthetic pigments and to assess characteristic pyrolysis products that could help in the identification of these pigments in paint samples. We analysed several classes of synthetic pigments not previously reported as being analysed by this technique: some metal complexes, β-naphthol pigment lakes, BONA pigment lakes, disazopyrazolone, triarylcarbonium, dioxazine, anthraquinone, indanthrone, isoindoline and thioindigo classes. We also report for the first time the Py-GC/MS analysis of a number of naphthol AS, benzimidazolone, phthalocyanine and perylene pigments and other miscellaneous pigments including pigments with unpublished chemical structure. We successfully used the Py-GC/MS technique for the analysis of paints by artists Clyfford Still and Jackson Pollock to identify the synthetic organic pigments and the binding media

Measurement of the branching fraction and CP content for the decay B(0) -> D(*+)D(*-)

This is the pre-print version of the Article. The official published version can be accessed from the links below. Copyright @ 2002 APS.We report a measurement of the branching fraction of the decay B0→D*+D*- and of the CP-odd component of its final state using the BABAR detector. With data corresponding to an integrated luminosity of 20.4  fb-1 collected at the Υ(4S) resonance during 1999–2000, we have reconstructed 38 candidate signal events in the mode B0→D*+D*- with an estimated background of 6.2±0.5 events. From these events, we determine the branching fraction to be B(B0→D*+D*-)=[8.3±1.6(stat)±1.2(syst)]×10-4. The measured CP-odd fraction of the final state is 0.22±0.18(stat)±0.03(syst).This work is supported by DOE and NSF (USA), NSERC (Canada), IHEP (China), CEA and CNRS-IN2P3 (France), BMBF (Germany), INFN (Italy), NFR (Norway), MIST (Russia), and PPARC (United Kingdom). Individuals have received support from the A.P. Sloan Foundation, Research Corporation, and Alexander von Humboldt Foundation

A Mathematical Framework for Protein Structure Comparison

Comparison of protein structures is important for revealing the evolutionary relationship among proteins, predicting protein functions and predicting protein structures. Many methods have been developed in the past to align two or multiple protein structures. Despite the importance of this problem, rigorous mathematical or statistical frameworks have seldom been pursued for general protein structure comparison. One notable issue in this field is that with many different distances used to measure the similarity between protein structures, none of them are proper distances when protein structures of different sequences are compared. Statistical approaches based on those non-proper distances or similarity scores as random variables are thus not mathematically rigorous. In this work, we develop a mathematical framework for protein structure comparison by treating protein structures as three-dimensional curves. Using an elastic Riemannian metric on spaces of curves, geodesic distance, a proper distance on spaces of curves, can be computed for any two protein structures. In this framework, protein structures can be treated as random variables on the shape manifold, and means and covariance can be computed for populations of protein structures. Furthermore, these moments can be used to build Gaussian-type probability distributions of protein structures for use in hypothesis testing. The covariance of a population of protein structures can reveal the population-specific variations and be helpful in improving structure classification. With curves representing protein structures, the matching is performed using elastic shape analysis of curves, which can effectively model conformational changes and insertions/deletions. We show that our method performs comparably with commonly used methods in protein structure classification on a large manually annotated data set

Measurement of D-s(+) and D-s(*+) production in B meson decays and from continuum e(+)e(-) annihilation at √s=10.6 GeV

This is the pre-print version of the Article. The official published version can be accessed from the links below. Copyright @ 2002 APSNew measurements of Ds+ and Ds*+ meson production rates from B decays and from qq̅ continuum events near the Υ(4S) resonance are presented. Using 20.8 fb-1 of data on the Υ(4S) resonance and 2.6 fb-1 off-resonance, we find the inclusive branching fractions B(B⃗Ds+X)=(10.93±0.19±0.58±2.73)% and B(B⃗Ds*+X)=(7.9±0.8±0.7±2.0)%, where the first error is statistical, the second is systematic, and the third is due to the Ds+→φπ+ branching fraction uncertainty. The production cross sections σ(e+e-→Ds+X)×B(Ds+→φπ+)=7.55±0.20±0.34pb and σ(e+e-→Ds*±X)×B(Ds+→φπ+)=5.8±0.7±0.5pb are measured at center-of-mass energies about 40 MeV below the Υ(4S) mass. The branching fractions ΣB(B⃗Ds(*)+D(*))=(5.07±0.14±0.30±1.27)% and ΣB(B⃗Ds*+D(*))=(4.1±0.2±0.4±1.0)% are determined from the Ds(*)+ momentum spectra. The mass difference m(Ds+)-m(D+)=98.4±0.1±0.3MeV/c2 is also measured.This work was supported by DOE and NSF (USA), NSERC (Canada), IHEP (China), CEA and CNRS-IN2P3 (France), BMBF (Germany), INFN (Italy), NFR (Norway), MIST (Russia), and PPARC (United Kingdom). Individuals have received support from the Swiss NSF, A. P. Sloan Foundation, Research Corporation, and Alexander von Humboldt Foundation

HPLC-DAD and HPLC-ESI-Q-ToF characterisation of early 20th century lake and organic pigments from Lefranc archives

The characterisation of atelier materials and of the historical commercial formulation of paint materials has recently gained new interest in the field of conservation science applied to modern and contemporary art, since modern paint materials are subjected to peculiar and often unpredictable degradation and fading processes. Assessing the composition of the original materials purchased by artists can guide not only their identification in works of art, but also their restoration and conservation. Advances in characterisation methods and models for data interpretation are particularly important in studying organic coloring materials in the transition period corresponding to the late 19th-early 20th century, when many such variants or combinations were hypothetically possible in their formulations. There is thus a need for reliable databases of materials introduced in that period and for gaining chemical knowledge at a molecular level related to modern organic pigments, by state-of-the-art protocols. This paper reports on the results of a study on 44 samples of historical colorants in powder and paint tubes, containing both lake pigments and synthetic organic pigments dating from 1890 to 1926. The samples were collected at the Lefranc Archive in Le Mans (France) as a part of Project Futurahma "From Futurism to Classicism (1910-1922). Research, Art History and Material Analysis", (FIRB2012, Italian Ministry of University and Research), and were investigated using an analytical approach based on chromatographic and mass spectrometric techniques. The focus of the chemical analyses was to reveal the composition of the historical organic lake pigments including minor components, to discriminate between different recipes for the extraction of chromophore-containing molecules from the raw materials, and ultimately to distinguish between different formulations and recipes. High performance liquid chromatography (HPLC) with diode array detector (DAD) or electrospray-Quadrupole-Time of Flight tandem mass spectrometry detector (ESI-Q-ToF) were chosen given their considerable capacity to identify such complex and widespread organic materials. Although the inorganic components of the pigments were not taken into account in this survey, the specific molecular profiles provided invaluable information on the extraction procedures or synthetic strategy followed by the different producers, at different times. For instance, the use of Kopp's purpurin and garancine was highlighted, and synthetic by-products were identified. The results provided evidence that the addition of synthetic organic pigments to paint mixtures started from 1910 onwards, but they also suggest that in the formulation of high quality (surfin) colorants, natural products were still preferred. Moreover, in one of the samples the use of murexide as the colouring material was confirmed. This paper presents the first systematic and comprehensive survey on organic lakes and pigments belonging to an historical archive, by both HPLC-DAD and HPLC-ESI-Q-ToF. Specific by-products of synthetic production of pigments, which can act as specific molecular markers for dating or locating a work of art, were also identified for the first time

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT