Electron capture dissociation mass spectrometry of phosphopeptides: Arginine and phosphoserine

AbstractWe have previously shown that the presence of phosphorylation can inhibit detection of electron capture dissociation (ECD) fragments of doubly charged peptide ions. The presence of non-covalent interactions, in the form of salt-bridges or ionic hydrogen bonds, prevents the separation of fragments following backbone cleavage. Here, we show the electron capture dissociation mass spectrometry of a suite of model peptides designed to investigate the relationship between phosphoserine and arginine position, namely AApSAnRAmKA (n=0–6, m=6–0), the presence of lysine residues (AApSAAKAARAKA) and AAApSARAAAAKAAAK, and the presence of proline A(A/P)ApSARAAA(A/P)KAAAK. The latter are analogous to the peptides studied previously. The results show that the presence of phosphoserine and basic amino acid residues alone does not inhibit ECD fragmentation, even when the number of basic amino acid residues is greater than the precursor charge state. Neither did the presence of proline in the peptide sequence suppress ECD backbone cleavage. Nevertheless, the presence and relative position of the phosphorylated residue do alter the observed backbone fragmentation abundance. In addition, the presence of phosphorylation appears to inhibit cleavage within the arginine side-chain regardless of the relative position of the arginine residue. The results suggest that ECD fragmentation behaviour is dependent on the three-dimensional structure of a peptide rather than its sequence

Exploiting graphic processing units parallelism to improve intelligent data acquisition system performance in JET's correlation reflectometer

The performance of intelligent data acquisition systems relies heavily on their processing capabilities and local bus bandwidth, especially in applications with high sample rates or high number of channels. This is the case of the self adaptive sampling rate data acquisition system installed as a pilot experiment in KG8B correlation reflectometer at JET. The system, which is based on the ITMS platform, continuously adapts the sample rate during the acquisition depending on the signal bandwidth. In order to do so it must transfer acquired data to a memory buffer in the host processor and run heavy computational algorithms for each data block. The processing capabilities of the host CPU and the bandwidth of the PXI bus limit the maximum sample rate that can be achieved, therefore limiting the maximum bandwidth of the phenomena that can be studied. Graphic processing units (GPU) are becoming an alternative for speeding up compute intensive kernels of scientific, imaging and simulation applications. However, integrating this technology into data acquisition systems is not a straight forward step, not to mention exploiting their parallelism efficiently. This paper discusses the use of GPUs with new high speed data bus interfaces to improve the performance of the self adaptive sampling rate data acquisition system installed on JET. Integration issues are discussed and performance evaluations are presente

Assessment of exposure determinants and exposure levels by using stationary concentration measurements and a probabilistic near-field/far-field exposure model

Background: The Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) regulation requires the establishment of Conditions of Use (CoU) for all exposure scenarios to ensure good communication of safe working practices. Setting CoU requires the risk assessment of all relevant Contributing Scenarios (CSs) in the exposure scenario. A new CS has to be created whenever an Operational Condition (OC) is changed, resulting in an excessive number of exposure assessments. An efficient solution is to quantify OC concentrations and to identify reasonable worst-case scenarios with probabilistic exposure modeling. Methods: Here, we appoint CoU for powder pouring during the industrial manufacturing of a paint batch by quantifying OC exposure levels and exposure determinants. The quantification was performed by using stationary measurements and a probabilistic Near-Field/Far-Field (NF/FF) exposure model. Work shift and OC concentration levels were quantified for pouring TiO 2 from big bags and small bags, pouring Micro Mica from small bags, and cleaning. The impact of exposure determinants on NF concentration level was quantified by (1) assessing exposure determinants correlation with the NF exposure level and (2) by performing simulations with different OCs. Results: Emission rate, air mixing between NF and FF and local ventilation were the most relevant exposure determinants affecting NF concentrations. Potentially risky OCs were identified by performing Reasonable Worst Case (RWC) simulations and by comparing the exposure 95 th percentile distribution with 10% of the occupational exposure limit value (OELV). The CS was shown safe except in RWC scenario (ventilation rate from 0.4 to 1.6 1/h, 100 m 3 room, no local ventilation, and NF ventilation of 1.6 m 3/min). Conclusions: The CoU assessment was considered to comply with European Chemicals Agency (ECHA) legislation and EN 689 exposure assessment strategy for testing compliance with OEL values. One RWC scenario would require measurements since the exposure level was 12.5% of the OELV

Experimental study and calculation of the electron transfer coefficients on the dissolution behavior of chitosan in organic acids

Chitosan (CH) consists of water-insoluble N-acetylglucosamine and D-glucosamine molecules and has a higher solubility at a pH below six. This studyevaluated the solubility of chitosan in solutions of organic acids for the formation of films. HyperChemTMsoftware was used to perform the quantum analysis. In the experimental trials, the total soluble mass (TSM) and the viscosity of the solutions were measured by capillary viscometer. The chitosan filmswere made by the plate melting method, and the filmcharacteristics were evaluated. A quantum simulation suggested that lactic acid (LA) has a greater stability to react with chitosan. It was then verified experimentally that LA is a better solvent for chitosan due to the increase in its viscosity. The chemical interaction between CH and LA in solution favors the polymerization of films with better physical properties. We thereforeconclude that the uniformity in the formation of films of this polymer depends on the chemical interaction between the CH and the acid and not on the degree of solubility of the polymer

Matrix Model Description of Laughlin Hall States

We analyze Susskind's proposal of applying the non-commutative Chern-Simons theory to the quantum Hall effect. We study the corresponding regularized matrix Chern-Simons theory introduced by Polychronakos. We use holomorphic quantization and perform a change of matrix variables that solves the Gauss law constraint. The remaining physical degrees of freedom are the complex eigenvalues that can be interpreted as the coordinates of electrons in the lowest Landau level with Laughlin's wave function. At the same time, a statistical interaction is generated among the electrons that is necessary to stabilize the ground state. The stability conditions can be expressed as the highest-weight conditions for the representations of the W-infinity algebra in the matrix theory. This symmetry provides a coordinate-independent characterization of the incompressible quantum Hall states.Comment: 31 pages, large additions on the path integral and overlaps, and on the W-infinity symmetr

A database of microRNA expression patterns in Xenopus laevis

MicroRNAs (miRNAs) are short, non-coding RNAs around 22 nucleotides long. They inhibit gene expression either by translational repression or by causing the degradation of the mRNAs they bind to. Many are highly conserved amongst diverse organisms and have restricted spatio-temporal expression patterns during embryonic development where they are thought to be involved in generating accuracy of developmental timing and in supporting cell fate decisions and tissue identity. We determined the expression patterns of 180 miRNAs in Xenopus laevis embryos using LNA oligonucleotides. In addition we carried out small RNA-seq on different stages of early Xenopus development, identified 44 miRNAs belonging to 29 new families and characterized the expression of 5 of these. Our analyses identified miRNA expression in many organs of the developing embryo. In particular a large number were expressed in neural tissue and in the somites. Surprisingly none of the miRNAs we have looked at show expression in the heart. Our results have been made freely available as a resource in both XenMARK and Xenbase

The short term debt vs. long term debt puzzle: a model for the optimal mix

This paper argues that the existing finance literature is inadequate with respect to its coverage of capital structure of small and medium sized enterprises (SMEs). In particular it is argued that the cost of equity (being both conceptually ill defined and empirically non quantifiable) is not applicable to the capital structure decisions for a large proportion of SMEs and the optimal capital structure depends only on the mix of short and long term debt. The paper then presents a model, developed by practitioners for optimising the debt mix and demonstrates its practical application using an Italian firm's debt structure as a case study

Naturalness constraints on gauge-mediated supersymmetry breaking models

The question of naturalness is addressed in the context of gauge-mediated supersymmetry breaking models. Requiring that $M_Z$ arises naturally imposes upper limits on the right-handed selectron mass in these models that are stronger than in the Minimal Supersymmetric Standard Model and are interesting from the point of view of searches at the current and future colliders.Comment: Latex, 8 pages, 1 eps figure enclosed. Minor changes, version to be publishe

Kepler-68: Three Planets, One With a Density Between That of Earth and Ice Giants

NASA's Kepler Mission has revealed two transiting planets orbiting Kepler-68. Follow-up Doppler measurements have established the mass of the innermost planet and revealed a third jovian-mass planet orbiting beyond the two transiting planets. Kepler-68b, in a 5.4 day orbit has mass 8.3 +/- 2.3 Earth, radius 2.31 +/- 0.07 Earth radii, and a density of 3.32 +/- 0.92 (cgs), giving Kepler-68b a density intermediate between that of the ice giants and Earth. Kepler-68c is Earth-sized with a radius of 0.953 Earth and transits on a 9.6 day orbit; validation of Kepler-68c posed unique challenges. Kepler-68d has an orbital period of 580 +/- 15 days and minimum mass of Msin(i) = 0.947 Jupiter. Power spectra of the Kepler photometry at 1-minute cadence exhibit a rich and strong set of asteroseismic pulsation modes enabling detailed analysis of the stellar interior. Spectroscopy of the star coupled with asteroseismic modeling of the multiple pulsation modes yield precise measurements of stellar properties, notably Teff = 5793 +/- 74 K, M = 1.079 +/- 0.051 Msun, R = 1.243 +/- 0.019 Rsun, and density 0.7903 +/- 0.0054 (cgs), all measured with fractional uncertainties of only a few percent. Models of Kepler-68b suggest it is likely composed of rock and water, or has a H and He envelope to yield its density of about 3 (cgs).Comment: 32 pages, 13 figures, Accepted to Ap

THP-1 macrophage cholesterol efflux is impaired by palmitoleate through Akt activation.

Lipoprotein lipase (LPL) is upregulated in atherosclerotic lesions and it may promote the progression of atherosclerosis, but the mechanisms behind this process are not completely understood. We previously showed that the phosphorylation of Akt within THP-1 macrophages is increased in response to the lipid hydrolysis products generated by LPL from total lipoproteins. Notably, the free fatty acid (FFA) component was responsible for this effect. In the present study, we aimed to reveal more detail as to how the FFA component may affect Akt signalling. We show that the phosphorylation of Akt within THP-1 macrophages increases with total FFA concentration and that phosphorylation is elevated up to 18 hours. We further show that specifically the palmitoleate component of the total FFA affects Akt phosphorylation. This is tied with changes to the levels of select molecular species of phosphoinositides. We further show that the total FFA component, and specifically palmitoleate, reduces apolipoprotein A-I-mediated cholesterol efflux, and that the reduction can be reversed in the presence of the Akt inhibitor MK-2206. Overall, our data support a negative role for the FFA component of lipoprotein hydrolysis products generated by LPL, by impairing macrophage cholesterol efflux via Akt activation