572 research outputs found
Regioselective deacetylation based on teicoplanin-complexed Orf2*crystal structures
Lipoglycopeptide antibiotics are more effective than vancomycin against MRSA as they carry an extra aliphatic acyl side chain on glucosamine (Glm) at residue 4 (r4). The biosynthesis of the r4 N-acyl Glc moiety at teicoplanin (Tei) or A40926 has been elucidated, in which the primary amine nucleophile of Glm is freed from the r4 GlcNac pseudo-Tei precursor by Orf2* for the subsequent acylation reaction to occur. In this report, two Orf2* structures in complex with beta-D-octyl glucoside or Tei were solved. Of the complexed structures, the substrate binding site and a previously unknown hydrophobic cavity were revealed, wherein r4 GlcNac acts as the key signature for molecular recognition and the cavity allows substrates carrying longer acyl side chains in addition to the acetyl group. On the basis of the complexed structures, a triple-mutation mutant S98A/V121A/F193Y is able to regioselectively deacetylate r6 GlcNac pseudo-Tei instead of that at r4. Thereby, novel analogs can be made at the r6 sugar moiety
Identification of a Robust Methylation Classifier for Cutaneous Melanoma Diagnosis
Early diagnosis improves melanoma survival, yet the histopathological diagnosis of cutaneous primary melanoma can be challenging, even for expert dermatopathologists. Analysis of epigenetic alterations, such as DNA methylation, that occur in melanoma can aid in its early diagnosis. Using a genome-wide methylation screening, we assessed CpG methylation in a diverse set of 89 primary invasive melanomas, 73 nevi, and 41 melanocytic proliferations of uncertain malignant potential, classified based on interobserver review by dermatopathologists. Melanomas and nevi were split into training and validation sets. Predictive modeling in the training set using ElasticNet identified a 40-CpG classifier distinguishing 60 melanomas from 48 nevi. High diagnostic accuracy (area under the receiver operator characteristic curve = 0.996, sensitivity = 96.6%, and specificity = 100.0%)was independently confirmed in the validation set (29 melanomas, 25 nevi)and other published sample sets. The 40-CpG melanoma classifier included homeobox transcription factors and genes with roles in stem cell pluripotency or the nervous system. Application of the 40-CpG melanoma classifier to the diagnostically uncertain samples assigned melanoma or nevus status, potentially offering a diagnostic tool to assist dermatopathologists. In summary, the robust, accurate 40-CpG melanoma classifier offers a promising assay for improving primary melanoma diagnosis
MANAGING THE IMPACT OF DIFFERENCES IN NATIONAL CULTURE ON SOCIAL CAPITAL IN MULTINATIONAL IT PROJECT TEAMS – A GERMAN PERSPECTIVE
How can management handle relationship problems arising from cultural differences in multinational IT project teams? This paper uses a social capital lens to better understand the negative impact of cultural differences in IT project teams. In contrast to many previous works we do not consider cultural differences as a whole but explore the role of the different national culture dimensions. This allows for a more detailed view on cultural differences in a team context and thus contributes to a better understanding about which dimensions of national culture drive relationship problems and which management measures can help to dampen the negative effects. Based on several exploratory cases (6 multinational IT projects in 4 companies, headquartered in Germany), the authors identify three patterns showing typical problems in team social relationships which arise from differences in particular dimensions of national culture. Pattern-specific as well as general management measures, employed to address the culture-driven negative effects, are identified as well
Retrofit of existing railway bridges of short to medium spans for high-speed traffic using viscoelastic dampers
This paper presents a study on the energy-absorbing capacities of viscoelastic dampers (VEDs) for reducing the resonant vibrations of simply supported high-speed railway bridges of short to medium span. The proposed solution is based on retrofitting the bridge with a set of discrete VEDs connected to the slab and to an auxiliary structure, placed underneath the bridge deck and resting on the abutments. In this investigation attention is focused on mitigating flexural vibrations; therefore, both the bridge and the auxiliary structure are modelled as simply supported beams with Bernoulli-Euler (B-E) behavior, whereas a discrete fractional derivative model simulates the behavior of the damping material. Firstly, a parametric study of this planar model is carried out, which has led to a dimensioning procedure of the dissipative system. The technical feasibility of this particular retrofit design is numerically evaluated by applying it to a numerical model of a simply supported railway bridge with inadmissible vertical accelerations. Numerical results show that the dynamic response of the structure can be significantly reduced in resonance with the proposed damping system. © 2012 Elsevier Ltd.The authors wish to express their gratitude to the Spanish Ministry of Public Works for the financial support received in the framework of Research Project number 80021/A04.Moliner Cabedo, E.; Museros Romero, P.; Martínez Rodrigo, MDLD. (2012). Retrofit of existing railway bridges of short to medium spans for high-speed traffic using viscoelastic dampers. Engineering Structures. 40:519-528. doi:10.1016/j.engstruct.2012.03.016S5195284
Pion, kaon, proton and anti-proton transverse momentum distributions from p+p and d+Au collisions at GeV
Identified mid-rapidity particle spectra of , , and
from 200 GeV p+p and d+Au collisions are reported. A
time-of-flight detector based on multi-gap resistive plate chamber technology
is used for particle identification. The particle-species dependence of the
Cronin effect is observed to be significantly smaller than that at lower
energies. The ratio of the nuclear modification factor () between
protons and charged hadrons () in the transverse momentum
range GeV/c is measured to be
(stat)(syst) in minimum-bias collisions and shows little
centrality dependence. The yield ratio of in minimum-bias d+Au
collisions is found to be a factor of 2 lower than that in Au+Au collisions,
indicating that the Cronin effect alone is not enough to account for the
relative baryon enhancement observed in heavy ion collisions at RHIC.Comment: 6 pages, 4 figures, 1 table. We extended the pion spectra from
transverse momentum 1.8 GeV/c to 3. GeV/
Search for Higgs bosons decaying to tautau pairs in ppbar collisions at sqrt(s) = 1.96 TeV
We present a search for the production of neutral Higgs bosons decaying into
tautau pairs in ppbar collisions at a center-of-mass energy of 1.96 TeV. The
data, corresponding to an integrated luminosity of 5.4 fb-1, were collected by
the D0 experiment at the Fermilab Tevatron Collider. We set upper limits at the
95% C.L. on the product of production cross section and branching ratio for a
scalar resonance decaying into tautau pairs, and we then interpret these limits
as limits on the production of Higgs bosons in the minimal supersymmetric
standard model (MSSM) and as constraints in the MSSM parameter space.Comment: 7 pages, 5 figures, submitted to PL
Measurement of the photon-jet production differential cross section in collisions at \sqrt{s}=1.96~\TeV
We present measurements of the differential cross section dsigma/dpT_gamma
for the inclusive production of a photon in association with a b-quark jet for
photons with rapidities |y_gamma|< 1.0 and 30<pT_gamma <300 GeV, as well as for
photons with 1.5<|y_gamma|< 2.5 and 30< pT_gamma <200 GeV, where pT_gamma is
the photon transverse momentum. The b-quark jets are required to have pT>15 GeV
and rapidity |y_jet| < 1.5. The results are based on data corresponding to an
integrated luminosity of 8.7 fb^-1, recorded with the D0 detector at the
Fermilab Tevatron Collider at sqrt(s)=1.96 TeV. The measured cross
sections are compared with next-to-leading order perturbative QCD calculations
using different sets of parton distribution functions as well as to predictions
based on the kT-factorization QCD approach, and those from the Sherpa and
Pythia Monte Carlo event generators.Comment: 10 pages, 9 figures, submitted to Phys. Lett.
Limits on anomalous trilinear gauge boson couplings from WW, WZ and Wgamma production in pp-bar collisions at sqrt{s}=1.96 TeV
We present final searches of the anomalous gammaWW and ZWW trilinear gauge
boson couplings from WW and WZ production using lepton plus dijet final states
and a combination with results from Wgamma, WW, and WZ production with leptonic
final states. The analyzed data correspond to up to 8.6/fb of integrated
luminosity collected by the D0 detector in pp-bar collisions at sqrt{s}=1.96
TeV. We set the most stringent limits at a hadron collider to date assuming two
different relations between the anomalous coupling parameters
Delta\kappa_\gamma, lambda, and Delta g_1^Z for a cutoff energy scale Lambda=2
TeV. The combined 68% C.L. limits are -0.057<Delta\kappa_\gamma<0.154,
-0.015<lambda<0.028, and -0.008<Delta g_1^Z<0.054 for the LEP parameterization,
and -0.007<Delta\kappa<0.081 and -0.017<lambda<0.028 for the equal couplings
parameterization. We also present the most stringent limits of the W boson
magnetic dipole and electric quadrupole moments.Comment: 10 pages, 5 figures, submitted to PL
Measurement of three-jet differential cross sections d sigma-3jet / d M-3jet in p anti-p collisions at sqrt(s)=1.96 TeV
We present the first measurement of the inclusive three-jet differential
cross section as a function of the invariant mass of the three jets with the
largest transverse momenta in an event in p anti-p collisions at sqrt(s) = 1.96
TeV. The measurement is made in different rapidity regions and for different
jet transverse momentum requirements and is based on a data set corresponding
to an integrated luminosity of 0.7 fb^{-1} collected with the D0 detector at
the Fermilab Tevatron Collider. The results are used to test the three-jet
matrix elements in perturbative QCD calculations at next-to-leading order in
the strong coupling constant. The data allow discrimination between
parametrizations of the parton distribution functions of the proton.Comment: 10 pages, 4 figures, 2 tables, submitted to Phys. Lett. B, corrected
chi2 values for NNPD
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