Graded inhibition of oncogenic Ras-signaling by multivalent Ras-binding domains

BACKGROUND: Ras is a membrane-associated small G-protein that funnels growth and differentiation signals into downstream signal transduction pathways by cycling between an inactive, GDP-bound and an active, GTP-bound state. Aberrant Ras activity as a result of oncogenic mutations causes de novo cell transformation and promotes tumor growth and progression. RESULTS: Here, we describe a novel strategy to block deregulated Ras activity by means of oligomerized cognate protein modules derived from the Ras-binding domain of c-Raf (RBD), which we named MSOR for multivalent scavengers of oncogenic Ras. The introduction of well-characterized mutations into RBD was used to adjust the affinity and hence the blocking potency of MSOR towards activated Ras. MSOR inhibited several oncogenic Ras-stimulated processes including downstream activation of Erk1/2, induction of matrix-degrading enzymes, cell motility and invasiveness in a graded fashion depending on the oligomerization grade and the nature of the individual RBD-modules. The amenability to accurate experimental regulation was further improved by engineering an inducible MSOR-expression system to render the reversal of oncogenic Ras effects controllable. CONCLUSION: MSOR represent a new tool for the experimental and possibly therapeutic selective blockade of oncogenic Ras signals

Accessible biometrics: a frustrated total internal reflection approach to imaging fingerprints

Fingerprints are widely used as a means of identifying persons of interest because of the highly individual nature of the spatial distribution and types of features (or minuta) found on the surface of a finger. This individuality has led to their wide application in the comparison of fingerprints found at crime scenes with those taken from known offenders and suspects in custody. However, despite recent advances in machine vision technology and image processing techniques, fingerprint evidence is still widely being collected using outdated practices involving ink and paper – a process that can be both time consuming and expensive. Reduction of forensic service budgets increasingly requires that evidence be gathered and processed more rapidly and efficiently. However, many of the existing digital fingerprint acquisition devices have proven too expensive to roll out on a large scale. As a result new, low-cost imaging technologies are required to increase the quality and throughput of the processing of fingerprint evidence. Here we describe an inexpensive approach to digital fingerprint acquisition that is based upon frustrated total internal reflection imaging. The quality and resolution of the images produced are shown to be as good as those currently acquired using ink and paper based methods. The same imaging technique is also shown to be capable of imaging powdered fingerprints that have been lifted from a crime scene using adhesive tape or gel lifters

Ökologische Milchviehzucht: Entwicklung und Bewertung züchterischer Ansätze unter Berücksichtigung der Genotyp x Umwelt-Interaktion und Schaffung eines Informationssystems für nachhaltige Zuchtstrategien

In dem Projekt wurden für verschiedene Merkmalskomplexe an zwei verschiedenen Datensätzen Genotyp x Umwelt-Interaktionen zwischen ökologischen und konventionellen Produktionssystemen geschätzt. Anhand Schweizer Daten wurden für Braunvieh und Fleckvieh für Milchleistungsmerkmale Korrelationen > 0.9 zwischen beiden Betriebsformen geschätzt, wohingegen die genetische Korrelationen für funktionale Merkmale (Rastzeit, Zellzahl) geringer (0.8 bis 0.9) waren. Diese Korrelationen konnten für die Rasse Holstein Friesian auf Grund einer Auswertung Deutscher Daten bestätigt werden. Generell liegt für Leistungsmerkmale keine und für funktionale Merkmale eine geringe Genotyp x Umwelt-Interaktion zwischen ökologischen und konventionellen Betrieben vor, wobei insbesondere für letztere die Informationsbasis begrenzt ist. Auswertungen der Betriebsdaten von > 450 ökologisch wirtschaftenden Milchviehbetrieben und Befragungen der Betriebsleiter haben ergeben, dass sich diese Betriebe in ihren züchterischen Zielen kaum und in ihrem züchterischen Handeln gar nicht von konventionellen Betrieben unterscheiden. Zuchtplanerische Rechnungen haben ergeben, dass unter den gefundenen genetischen Parametern weder ein geschlossenes noch ein offenes eigenes Zuchtprogramm im ökologischen Sektor wirtschaftlich gerechtfertigt ist. Vielmehr ist anzustreben, dass sich ökologisch wirtschaftende Milchviehbetriebe stärker aktiv an etablierten Zuchtprogrammen beteiligen, z.B. durch den stärkeren Einsatz von Testbullen. Es wird vorgeschlagen, aufgrund der bestehenden Teilzuchtwerte einen Ökologischen Gesamtzuchtwert zu entwickeln, in dem funktionale Merkmale stärker gewichtet werden. Ein im Projekt entwickeltes Internetportal und eine entsprechend angepasste Anpaarungssoftware kann die Umsetzung dieses Vorschlags unterstützen. Erforderlich ist allerdings eine vollständigere Erfassung der ökologischen Milchviehbetriebe als Voraussetzung für eine bessere Unterstützung der ökologischen Milchviehzucht

Measurement of the photon+b+b-jet production differential cross section in ppˉp\bar{p} 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 $p\bar{p}$ 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.

Measurements of single top quark production cross sections and |Vtb| in ppbar collisions at sqrt{s}=1.96 TeV

We present measurements of production cross sections of single top quarks in \ppbar collisions at $\sqrt{s}=1.96\;\rm TeV$ in a data sample corresponding to an integrated luminosity of $5.4\;\rm fb^{-1}$ collected by the D0 detector at the Fermilab Tevatron Collider. We select events with an isolated electron or muon, an imbalance in transverse energy, and two, three, or four jets, with one or two of them containing a bottom hadron. We obtain an inclusive cross section of \sigma({\ppbar}{\rargap}tb+X, tqb+X) = 3.43\pm^{0.73}_{0.74}\;\rm pb and use it to extract the CKM matrix element $0.79 < |V_{tb}| \leq 1$ at the 95% C.L. We also measure \sigma({\ppbar}{\rargap}tb+X) = 0.68\pm^{0.38}_{0.35}\;\rm pb and \sigma({\ppbar}{\rargap}tqb+X) = 2.86\pm^{0.69}_{0.63}\;\rm pb when assuming, respectively, $tqb$ and $tb$ production rates as predicted by the standard model.Comment: 11 pages, 8 figures, submitted to Phys. Rev.

Search for the Higgs boson in lepton, tau and jets final states

We present a search for the standard model Higgs boson in final states with an electron or muon and a hadronically decaying tau lepton in association with two or more jets using 9.7 fb^{-1} of Run II Fermilab Tevatron Collider data collected with the D0 detector. The analysis is sensitive to Higgs boson production via gluon fusion, associated vector boson production, and vector boson fusion, followed by the Higgs boson decay to tau lepton pairs or to W boson pairs. The ratios of 95% C.L. upper limits on the cross section times branching ratio to those predicted by the standard model are obtained for orthogonal subsamples that are enriched in either H -> tau tau decays or H -> WW decays, and for the combination of these subsample limits. The observed and expected limit ratios for the combined subsamples at a Higgs boson mass of 125 GeV are 11.3 and 9.0 respectively

Search for a Narrow ttbar Resonance in ppbar Collisions at sqrt{s}=1.96 TeV

We report a search for a narrow ttbar resonance that decays into a lepton+jets final state based on an integrated luminosity of 5.3/fb of proton-antiproton collisions at sqrt{s}=1.96 TeV collected by the D0 Collaboration at the Fermilab Tevatron Collider. We set upper limits on the production cross section of such a resonance multiplied by its branching fraction to ttbar which we compare to predictions for a leptophobic topcolor Z' boson. We exclude such a resonance at the 95% confidence level for masses below 835 GeV.Comment: 7 pages, 3 figures, submitted to Physical Review Letter