ProLuCID: An improved SEQUEST-like algorithm with enhanced sensitivity and specificity

AbstractProLuCID, a new algorithm for peptide identification using tandem mass spectrometry and protein sequence databases has been developed. This algorithm uses a three tier scoring scheme. First, a binomial probability is used as a preliminary scoring scheme to select candidate peptides. The binomial probability scores generated by ProLuCID minimize molecular weight bias and are independent of database size. A modified cross-correlation score is calculated for each candidate peptide identified by the binomial probability. This cross-correlation scoring function models the isotopic distributions of fragment ions of candidate peptides which ultimately results in higher sensitivity and specificity than that obtained with the SEQUEST XCorr. Finally, ProLuCID uses the distribution of XCorr values for all of the selected candidate peptides to compute a Z score for the peptide hit with the highest XCorr. The ProLuCID Z score combines the discriminative power of XCorr and DeltaCN, the standard parameters for assessing the quality of the peptide identification using SEQUEST, and displays significant improvement in specificity over ProLuCID XCorr alone. ProLuCID is also able to take advantage of high resolution MS/MS spectra leading to further improvements in specificity when compared to low resolution tandem MS data. A comparison of filtered data searched with SEQUEST and ProLuCID using the same false discovery rate as estimated by a target-decoy database strategy, shows that ProLuCID was able to identify as many as 25% more proteins than SEQUEST. ProLuCID is implemented in Java and can be easily installed on a single computer or a computer cluster.This article is part of a Special Issue entitled: Computational Proteomics

Stress corrosion cracking in Al-Zn-Mg-Cu aluminum alloys in saline environments

Copyright 2013 ASM International. This paper was published in Metallurgical and Materials Transactions A, 44A(3), 1230 - 1253, and is made available as an electronic reprint with the permission of ASM International. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplications of any material in this paper for a fee or for commercial purposes, or modification of the content of this paper are prohibited.Stress corrosion cracking of Al-Zn-Mg-Cu (AA7xxx) aluminum alloys exposed to saline environments at temperatures ranging from 293 K to 353 K (20 °C to 80 °C) has been reviewed with particular attention to the influences of alloy composition and temper, and bulk and local environmental conditions. Stress corrosion crack (SCC) growth rates at room temperature for peak- and over-aged tempers in saline environments are minimized for Al-Zn-Mg-Cu alloys containing less than ~8 wt pct Zn when Zn/Mg ratios are ranging from 2 to 3, excess magnesium levels are less than 1 wt pct, and copper content is either less than ~0.2 wt pct or ranging from 1.3 to 2 wt pct. A minimum chloride ion concentration of ~0.01 M is required for crack growth rates to exceed those in distilled water, which insures that the local solution pH in crack-tip regions can be maintained at less than 4. Crack growth rates in saline solution without other additions gradually increase with bulk chloride ion concentrations up to around 0.6 M NaCl, whereas in solutions with sufficiently low dichromate (or chromate), inhibitor additions are insensitive to the bulk chloride concentration and are typically at least double those observed without the additions. DCB specimens, fatigue pre-cracked in air before immersion in a saline environment, show an initial period with no detectible crack growth, followed by crack growth at the distilled water rate, and then transition to a higher crack growth rate typical of region 2 crack growth in the saline environment. Time spent in each stage depends on the type of pre-crack (“pop-in” vs fatigue), applied stress intensity factor, alloy chemistry, bulk environment, and, if applied, the external polarization. Apparent activation energies (E a) for SCC growth in Al-Zn-Mg-Cu alloys exposed to 0.6 M NaCl over the temperatures ranging from 293 K to 353 K (20 °C to 80 °C) for under-, peak-, and over-aged low-copper-containing alloys (~0.8 wt pct), they are typically ranging from 20 to 40 kJ/mol for under- and peak-aged alloys, and based on limited data, around 85 kJ/mol for over-aged tempers. This means that crack propagation in saline environments is most likely to occur by a hydrogen-related process for low-copper-containing Al-Zn-Mg-Cu alloys in under-, peak- and over-aged tempers, and for high-copper alloys in under- and peak-aged tempers. For over-aged high-copper-containing alloys, cracking is most probably under anodic dissolution control. Future stress corrosion studies should focus on understanding the factors that control crack initiation, and insuring that the next generation of higher performance Al-Zn-Mg-Cu alloys has similar longer crack initiation times and crack propagation rates to those of the incumbent alloys in an over-aged condition where crack rates are less than 1 mm/month at a high stress intensity factor

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02

The delivery of personalised, precision medicines via synthetic proteins

Introduction: The design of advanced drug delivery systems based on synthetic and su-pramolecular chemistry has been very successful. Liposomal doxorubicin (Caelyx®), and liposomal daunorubicin (DaunoXome®), estradiol topical emulsion (EstrasorbTM) as well as soluble or erodible polymer systems such as pegaspargase (Oncaspar®) or goserelin acetate (Zoladex®) represent considerable achievements. The Problem: As deliverables have evolved from low molecular weight drugs to biologics (currently representing approximately 30% of the market), so too have the demands made of advanced drug delivery technology. In parallel, the field of membrane trafficking (and endocytosis) has also matured. The trafficking of specific receptors i.e. material to be recycled or destroyed, as well as the trafficking of protein toxins has been well characterized. This, in conjunction with an ability to engineer synthetic, recombinant proteins provides several possibilities. The Solution: The first is using recombinant proteins as drugs i.e. denileukin diftitox (Ontak®) or agalsidase beta (Fabrazyme®). The second is the opportunity to use protein toxin architecture to reach targets that are not normally accessible. This may be achieved by grafting regulatory domains from multiple species to form synthetic proteins, engineered to do multiple jobs. Examples include access to the nucleocytosolic compartment. Herein the use of synthetic proteins for drug delivery has been reviewed

Extent and Causes of Chesapeake Bay Warming

Coastal environments such as the Chesapeake Bay have long been impacted by eutrophication stressors resulting from human activities, and these impacts are now being compounded by global warming trends. However, there are few studies documenting long-term estuarine temperature change and the relative contributions of rivers, the atmosphere, and the ocean. In this study, Chesapeake Bay warming, since 1985, is quantified using a combination of cruise observations and model outputs, and the relative contributions to that warming are estimated via numerical sensitivity experiments with a watershed–estuarine modeling system. Throughout the Bay’s main stem, similar warming rates are found at the surface and bottom between the late 1980s and late 2010s (0.02 +/- 0.02C/year, mean +/- 1 standard error), with elevated summer rates (0.04 +/- 0.01C/year) and lower rates of winter warming (0.01 +/- 0.01C/year). Most (~85%) of this estuarine warming is driven by atmospheric effects. The secondary influence of ocean warming increases with proximity to the Bay mouth, where it accounts for more than half of summer warming in bottom waters. Sea level rise has slightly reduced summer warming, and the influence of riverine warming has been limited to the heads of tidal tributaries. Future rates of warming in Chesapeake Bay will depend not only on global atmospheric trends, but also on regional circulation patterns in mid-Atlantic waters, which are currently warming faster than the atmosphere. Supporting model data available at: https://doi.org/10.25773/c774-a36

Projected WIMP sensitivity of the LUX-ZEPLIN dark matter experiment

LUX-ZEPLIN (LZ) is a next-generation dark matter direct detection experiment that will operate 4850 feet underground at the Sanford Underground Research Facility (SURF) in Lead, South Dakota, USA. Using a two-phase xenon detector with an active mass of 7 tonnes, LZ will search primarily for low-energy interactions with weakly interacting massive particles (WIMPs), which are hypothesized to make up the dark matter in our galactic halo. In this paper, the projected WIMP sensitivity of LZ is presented based on the latest background estimates and simulations of the detector. For a 1000 live day run using a 5.6-tonne fiducial mass, LZ is projected to exclude at 90% confidence level spin-independent WIMP-nucleon cross sections above 1.4 × 10-48cm2 for a 40 GeV/c2 mass WIMP. Additionally, a 5σ discovery potential is projected, reaching cross sections below the exclusion limits of recent experiments. For spin-dependent WIMP-neutron(-proton) scattering, a sensitivity of 2.3 × 10−43 cm2 (7.1 × 10−42 cm2) for a 40 GeV/c2 mass WIMP is expected. With underground installation well underway, LZ is on track for commissioning at SURF in 2020

Galaxy Clusters Associated with Short GRBs. II. Predictions for the Rate of Short GRBs in Field and Cluster Early-Type Galaxies

We determine the relative rates of short GRBs in cluster and field early-type galaxies as a function of the age probability distribution of their progenitors, P(\tau) \propto \tau^n. This analysis takes advantage of the difference in the growth of stellar mass in clusters and in the field, which arises from the combined effects of the galaxy stellar mass function, the early-type fraction, and the dependence of star formation history on mass and environment. This approach complements the use of the early- to late-type host galaxy ratio, with the added benefit that the star formation histories of early-type galaxies are simpler than those of late-type galaxies, and any systematic differences between progenitors in early- and late-type galaxies are removed. We find that the ratio varies from R(cluster)/R(field) ~ 0.5 for n = -2 to ~ 3 for n = 2. Current observations indicate a ratio of about 2, corresponding to n ~ 0 - 1. This is similar to the value inferred from the ratio of short GRBs in early- and late-type hosts, but it differs from the value of n ~ -1 for NS binaries in the Milky Way. We stress that this general approach can be easily modified with improved knowledge of the effects of environment and mass on the build-up of stellar mass, as well as the effect of globular clusters on the short GRB rate. It can also be used to assess the age distribution of Type Ia supernova progenitors.Comment: ApJ accepted versio

Measurement of the branching ratio Γ(Λb⁰ → ψ(2S)Λ0)/Γ(Λb⁰ → J/ψΛ0) with the ATLAS detector

An observation of the $\Lambda_b^0 \rightarrow \psi(2S) \Lambda^0$ decay and a comparison of its branching fraction with that of the $\Lambda_b^0 \rightarrow J/\psi \Lambda^0$ decay has been made with the ATLAS detector in proton--proton collisions at $\sqrt{s}=8\,$TeV at the LHC using an integrated luminosity of $20.6\,$fb$^{-1}$. The $J/\psi$ and $\psi(2S)$ mesons are reconstructed in their decays to a muon pair, while the $\Lambda^0\rightarrow p\pi^-$ decay is exploited for the $\Lambda^0$ baryon reconstruction. The $\Lambda_b^0$ baryons are reconstructed with transverse momentum $p_{\rm T}>10\,$GeV and pseudorapidity $|\eta|<2.1$. The measured branching ratio of the $\Lambda_b^0 \rightarrow \psi(2S) \Lambda^0$ and $\Lambda_b^0 \rightarrow J/\psi \Lambda^0$ decays is $\Gamma(\Lambda_b^0 \rightarrow \psi(2S)\Lambda^0)/\Gamma(\Lambda_b^0 \rightarrow J/\psi\Lambda^0) = 0.501\pm 0.033 ({\rm stat})\pm 0.019({\rm syst})$, lower than the expectation from the covariant quark model.Comment: 12 pages plus author list (28 pages total), 5 figures, 1 table, published on Physics Letters B 751 (2015) 63-80. All figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/BPHY-2013-08

Search for strong gravity in multijet final states produced in pp collisions at √s=13 TeV using the ATLAS detector at the LHC

A search is conducted for new physics in multijet final states using 3.6 inverse femtobarns of data from proton-proton collisions at √s = 13TeV taken at the CERN Large Hadron Collider with the ATLAS detector. Events are selected containing at least three jets with scalar sum of jet transverse momenta (HT) greater than 1TeV. No excess is seen at large HT and limits are presented on new physics: models which produce final states containing at least three jets and having cross sections larger than 1.6 fb with HT > 5.8 TeV are excluded. Limits are also given in terms of new physics models of strong gravity that hypothesize additional space-time dimensions