The Peptide MS/MS-Fragmentome: A Set of Predictable Fragment Ions with Highly Redundant Sequence Information

Upon low energy collision induced dissociation (CID), multiply protonated peptides generate a set of interdependent fragment ions detectable by MS/MS, the \u27[peptide]n+-fragmentome\u27. In particular dynamic fragmentation of [peptide]n+ ions in a collision cell generates information-rich MS/MS spectra. Currently, database-supported annotations of peptide MS/MS spectra are mainly based on a combination of peptide molecular weight and y type fragment ions, leaving a considerable number of good-quality peptide MS/MS spectra in proteomics studies unannotated. This situation may be improved by a more complete use of the structural information present in the [peptide]n+-fragmentome. The presentation provides an overview on the fragment ions of multiply protonated peptides and their connectivity, comprising a ions, b ions, y ions, and neutral loss reactions from the N-, and C-terminus, and internal b ions. In the low-mass region, the unique set of 19 y1 ions and of the 190 b2 ions carries a particular message, since these ions define the N-or C-terminal amino acid(s). Further, the b1 ions of the basic residues K, H, W, and R carry a specific N-terminal information, which is redundant to that contained in the corresponding b2 ions and in the N-terminal neutral loss peaks. Redundant information is also found in b and y ion series and in complementary b/y ion pairs. The latter are particularly abundant when generated by proline- or aspartate-induced backbone cleavages. From complementary b/y ion pairs the molecular weight of the precursor ion can be reconstructed to confirm or determine its molecular weight. This procedure is helpful in case a mixture of precursor ions is isolated or in case a precursor ion of very low abundance is isolated. Information about the precursor ion charge state is also delivered by precursor ion reconstruction using MS/MS data. In the analysis of covalently modified peptides, reporter ions are of particular importance. These ions can be used for mining of MS/MS data sets for the occurrence of selected modifications. Examples are presented for selected modifications, such as acetylation and phosphorylation. In phosphorylation analysis neutral loss reactions are highly important, and may also carry redundant information, when observed both from the molecular ion and from fragment ions. Search tools, which fully incorporate the current knowledge about the [peptide]n+-fragmentome will increase the scores of peptide/protein identifications by MS/MS and thus will increase the fraction of automatically assigned MS/MS spectra in proteomics studies

Accurate quantification of selenoproteins in human plasma/serum by isotope dilution ICP-MS : focus on selenoprotein P

Acknowledgements The research leading to these results was funded by the EMRP Joint Research Project “Metrology for metalloproteins” (HLT-05 2012). The EMRP is jointly funded by the EMRP participating countries within EURAMET and the European Union.Peer reviewedPostprin

Spin qubits with electrically gated polyoxometalate molecules

Spin qubits offer one of the most promising routes to the implementation of quantum computers. Very recent results in semiconductor quantum dots show that electrically-controlled gating schemes are particularly well-suited for the realization of a universal set of quantum logical gates. Scalability to a larger number of qubits, however, remains an issue for such semiconductor quantum dots. In contrast, a chemical bottom-up approach allows one to produce identical units in which localized spins represent the qubits. Molecular magnetism has produced a wide range of systems with tailored properties, but molecules permitting electrical gating have been lacking. Here we propose to use the polyoxometalate [PMo12O40(VO)2]q-, where two localized spins-1/2 can be coupled through the electrons of the central core. Via electrical manipulation of the molecular redox potential, the charge of the core can be changed. With this setup, two-qubit gates and qubit readout can be implemented.Comment: 9 pages, 6 figures, to appear in Nature Nanotechnolog

Parallel computation of 3-D soil-structure interaction in time domain with a coupled FEM/SBFEM approach

The final publication is available at Springer via http://dx.doi.org/10.1007/s10915-011-9551-xThis paper introduces a parallel algorithm for the scaled boundary finite element method (SBFEM). The application code is designed to run on clusters of computers, and it enables the analysis of large-scale soil-structure-interaction problems, where an unbounded domain has to fulfill the radiation condition for wave propagation to infinity. The main focus of the paper is on the mathematical description and numerical implementation of the SBFEM. In particular, we describe in detail the algorithm to compute the acceleration unit impulse response matrices used in the SBFEM as well as the solvers for the Riccati and Lyapunov equations. Finally, two test cases validate the new code, illustrating the numerical accuracy of the results and the parallel performances. © Springer Science+Business Media, LLC 2011.Jose E. Roman and Enrique S. Quintana-Orti were partially supported by the Spanish Ministerio de Ciencia e Innovacion under grants TIN2009-07519, and TIN2008-06570-C04-01, respectively.Schauer, M.; Román Moltó, JE.; Quintana Orti, ES.; Langer, S. (2012). Parallel computation of 3-D soil-structure interaction in time domain with a coupled FEM/SBFEM approach. Journal of Scientific Computing. 52(2):446-467. doi:10.1007/s10915-011-9551-xS446467522Anderson, E., Bai, Z., Bischof, C., Demmel, J., Dongarra, J., Croz, J.D., Greenbaum, A., Hammarling, S., McKenney, A., Sorensen, D.: LAPACK User’s Guide. Society for Industrial and Applied Mathematics, Philadelphia (1992)Antes, H., Spyrakos, C.: Soil-structure interaction. In: Beskos, D., Anagnotopoulos, S. (eds.) Computer Analysis and Design of Earthquake Resistant Structures, p. 271. Computational Mechanics Publications, Southampton (1997)Appelö, D., Colonius, T.: A high-order super-grid-scale absorbing layer and its application to linear hyperbolic systems. J. Comput. Phys. 228(11), 4200–4217 (2009)Astley, R.J.: Infinite elements for wave problems: a review of current formulations and a assessment of accuracy. Int. J. Numer. Methods Eng. 49(7), 951–976 (2000)Balay, S., Buschelman, K., Eijkhout, V., Gropp, W.D., Kaushik, D., Knepley, M., McInnes, L.C., Smith, B.F., Zhang, H.: PETSc users manual. Tech. Rep. ANL-95/11 - Revision 3.1, Argonne National Laboratory (2010)Benner, P.: Contributions to the numerical solution of algebraic Riccati equations and related eigenvalue problems. Dissertation, Fak. f. Mathematik, TU Chemnitz–Zwickau, Chemnitz, FRG (1997)Benner, P.: Numerical solution of special algebraic Riccati equations via an exact line search method. In: Proc. European Control Conf. ECC 97, Paper 786, BELWARE Information Technology, Waterloo (B) (1997)Benner, P., Quintana-Ortí, E.: Solving stable generalized Lyapunov equations with the matrix sign function. Numer. Algorithms 20(1), 75–100 (1999)Benner, P., Byers, R., Quintana-Ortí, E., Quintana-Ortí, G.: Solving algebraic Riccati equations on parallel computers using Newton’s method with exact line search. Parallel Comput. 26(10), 1345–1368 (2000)Benner, P., Quintana-Ortí, E.S., Quintana-Ortí, G.: Solving linear-quadratic optimal control problems on parallel computers. Optim. Methods Softw. 23(6), 879–909 (2008)Bettess, P.: Infinite Elements. Penshaw Press, Sunderland (1992)Blackford, L.S., Choi, J., Cleary, A., D’Azevedo, E., Demmel, J., Dhillon, I., Dongarra, J., Hammarling, S., Henry, G., Petitet, A., Stanley, K., Walker, D., Whaley, R.C.: ScaLAPACK Users’ Guide. Society for Industrial and Applied Mathematics, Philadelphia (1997)Borsutzky, R.: Braunschweiger Schriften zur Mechanik - Seismic Risk Analysis of Buried Lifelines, vol. 63. Mechanik-Zentrum Technische Universität. Braunschweig (2008)Dongarra, J.J., Whaley, R.C.: LAPACK working note 94: A user’s guide to the BLACS v1.1. Tech. Rep. 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Toward Comprehensive Analysis of the Galectin Network in Chicken: Unique Diversity of Galectin-3 and Comparison of its Localization Profile in Organs of Adult Animals to the Other Four Members of this Lectin Family

18 pags, 11 figs, 2 tabs. -- Additional Supporting Information may be found in the online version of this articleCharacterization of all members of a gene family established by gene divergence is essential to delineate distinct or overlapping expression profiles and functionalities. Their activity as potent modulators of diverse physiological processes directs interest to galectins (endogenous lectins with β-sandwich fold binding β-galactosides and peptide motifs), warranting their study with the long-term aim of a comprehensive analysis. The comparatively low level of complexity of the galectin network in chicken with five members explains the choice of this organism as model. Previously, the three proto-type chicken galectins CG-1A, CG-1B, and CG-2 as well as the tandem-repeat-type CG-8 had been analyzed. Our study fills the remaining gap to determine gene structure, protein characteristics and expression profile of the fifth protein, that is, chimera-type chicken galectin-3 (CG-3). Its gene has a unique potential to generate variants: mRNA production stems from two promoters, alternative splicing of the form from the second transcription start point (tsp) can generate three mRNAs. The protein with functional phosphorylation sites in the N-terminus generated by transcription from the first tsp (tsp1CG-3) is the predominant CG-3 type present in adult tissues. Binding assays with neoglycoproteins and cultured cells disclose marked similarity to properties of human galectin-3. The expression and localization profiles as well as proximal promoter regions have characteristic features distinct from the other four CGs. This information on CG-3 completes the description of the panel of CGs, hereby setting the stage for detailed comparative analysis of the entire CG family, e.g., in embryogenesis. © 2011 Wiley-Liss, Inc.Spanish Ministry of Science and Innovation Grant number: BFU2009-10052; Grant sponsor: CIBER of Respiratory Diseases (CIBERES) (ISCII

Division of labor by dual feedback regulators controls JAK2/STAT5 signaling over broad ligand range

Quantitative analysis of time-resolved data in primary erythroid progenitor cells reveals that a dual negative transcriptional feedback mechanism underlies the ability of STAT5 to respond to the broad spectrum of physiologically relevant Epo concentrations

The XMM-Newton Serendipitous Survey. VI. The X-ray Luminosity Function

We present the X-ray luminosity function of AGN in three energy bands (Soft: 0.5-2 keV, Hard: 2-10 keV and Ultrahard: 4.5-7.5 keV). We have used the XMS survey along with other highly complete flux-limited deeper and shallower surveys for a total of 1009, 435 and 119 sources in the Soft, Hard and Ultrahard bands, respectively. We have modeled the intrinsic absorption of the Hard and Ultrahard sources (NH function) and computed the intrinsic X-ray luminosity function in all bands using a Maximum Likelihood fit technique to an analytical model. We find that the X-ray luminosity function (XLF) is best described by a Luminosity-Dependent Density Evolution (LDDE) model. Our results show a good overall agreement with previous results in the Hard band, although with slightly weaker evolution. Our model in the Soft band present slight discrepancies with other works in this band, the shape of our present day XLF being significantly flatter. We find faster evolution in the AGN detected in the Ultrahard band than those in the Hard band. The fraction of absorbed AGN in the Hard and Ultrahard bands is dependent on the X-ray luminosity. We find evidence of evolution of this fraction with redshift in the Hard band but not in the Ultrahard band, possibly due to the low statistics. Our best-fit XLF shows that the high-luminosity AGN are fully formed earlier than the less luminous AGN. The latter sources account for the vast majority of the accretion rate and mass density of the Universe, according to an anti-hierarchical black hole growth scenario.Comment: 16 pages, 12 figures, accepted for publication in Astronomy and Astrophysic

A complementary neutron and anomalous x-ray diffraction study

Distinguishing the scattering contributions of isoelectronic atomic species by means of conventional x-ray- and/or electron diffraction techniques is a difficult task. Such a problem occurs when determining the crystal structure of compounds containing different types of atoms with equal number of electrons. We propose a new structural model of Cu(InxGa1−x)3Se5 which is valid for the entire compositional range of the CuIn3Se5–CuGa3Se5 solid solution. Our model is based on neutron and anomalous x-ray diffraction experiments. These complementary techniques allow the separation of scattering contributions of the isoelectronic species Cu+ and Ga3+, contributing nearly identically in monoenergetic x-ray diffraction experiments. We have found that CuIII3Se5 (III=In,Ga) in its room temperature near-equilibrium modification exhibits a modified stannite structure (space group I4¯2m). Different occupation factors of the species involved, Cu+, In3+, Ga3+, and vacancies have been found at three different cationic positions of the structure (Wyckoff sites 2a, 2b, and 4d) depending on the composition of the compound. Significantly, Cu+ does not occupy the 2b site for the In-free compound, but does for the In-containing case. Structural parameters, including lattice constants, tetragonal distortions, and occupation factors are given for samples covering the entire range of the CuIn3Se5–CuGa3Se5 solid solution. At the light of the result, the denotation of Cu-poor 1:3:5 compounds as chalcopyrite-related materials is only valid in reference to their composition

Measurement of Spin Correlation Parameters ANN_{NN}, ASS_{SS}, and A_SL{SL} at 2.1 GeV in Proton-Proton Elastic Scattering

At the Cooler Synchrotron COSY/J\"ulich spin correlation parameters in elastic proton-proton (pp) scattering have been measured with a 2.11 GeV polarized proton beam and a polarized hydrogen atomic beam target. We report results for A$_{NN}$, A$_{SS}$, and A_${SL}$ for c.m. scattering angles between 30$^o$ and 90$^o$. Our data on A$_{SS}$ -- the first measurement of this observable above 800 MeV -- clearly disagrees with predictions of available of pp scattering phase shift solutions while A$_{NN}$ and A_${SL}$ are reproduced reasonably well. We show that in the direct reconstruction of the scattering amplitudes from the body of available pp elastic scattering data at 2.1 GeV the number of possible solutions is considerably reduced.Comment: 4 pages, 4 figure

Human cooperation in groups: variation begets variation

Many experiments on human cooperation have revealed that individuals differ systematically in their tendency to cooperate with others. It has also been shown that individuals condition their behaviour on the overall cooperation level of their peers. Yet, little is known about how individuals respond to heterogeneity in cooperativeness in their neighbourhood. Here, we present an experimental study investigating whether and how people respond to heterogeneous behaviour in a public goods game. We find that a large majority of subjects does respond to heterogeneity in their group, but they respond in quite different ways. Most subjects contribute less to the public good when the contributions of their peers are more heterogeneous, but a substantial fraction of individuals consistently contributes more in this case. In addition, we find that individuals that respond positively to heterogeneity have a higher general cooperation tendency. The finding that social responsiveness occurs in different forms and is correlated with cooperativeness may have important implications for the outcome of cooperative interactions