7,831 research outputs found
Simultaneous Kummer congruences and -orientations of KO and tmf
Building on results of M. Ando, M.J. Hopkins and C. Rezk, we show the
existence of uncountably many -String orientations of real
K-theory KO and of topological modular forms tmf, generalizing the -
(resp. the Witten) genus. Furthermore, the obstruction to lifting an
-String orientations from KO to tmf is identified with a
classical Iwasawa-theoretic condition. The common key to all these results is a
precise understanding of the classical Kummer congruences, imposed for all
primes simultaneously. This result is of independent arithmetic interest.Comment: final versio
Bim and Bmf synergize to induce apoptosis in Neisseria gonorrhoeae infection
Abstract: Bcl-2 family proteins including the pro-apoptotic BH3-only proteins are central regulators of apoptotic cell death. Here we show by a focused siRNA miniscreen that the synergistic action of the BH3-only proteins Bim and Bmf is required for apoptosis induced by infection with Neisseria gonorrhoeae (Ngo). While Bim and Bmf were associated with the cytoskeleton of healthy cells, they both were released upon Ngo infection. Loss of Bim and Bmf from the cytoskeleton fraction required the activation of Jun-N-terminal kinase-1 (JNK-1), which in turn depended on Rac-1. Depletion and inhibition of Rac-1, JNK-1, Bim, or Bmf prevented the activation of Bak and Bax and the subsequent activation of caspases. Apoptosis could be reconstituted in Bim-depleted and Bmf-depleted cells by additional silencing of antiapoptotic Mcl-1 and Bcl-XL, respectively. Our data indicate a synergistic role for both cytoskeletal-associated BH3-only proteins, Bim, and Bmf, in an apoptotic pathway leading to the clearance of Ngo-infected cells. Author Summary: A variety of physiological death signals, as well as pathological insults, trigger apoptosis, a genetically programmed form of cell death. Pathogens often induce host cell apoptosis to establish a successful infection. Neisseria gonorrhoeae (Ngo), the etiological agent of the sexually transmitted disease gonorrhoea, is a highly adapted obligate human-specific pathogen and has been shown to induce apoptosis in infected cells. Here we unveil the molecular mechanisms leading to apoptosis of infected cells. We show that Ngo-mediated apoptosis requires a special subset of proapoptotic proteins from the group of BH3-only proteins. BH3-only proteins act as stress sensors to translate toxic environmental signals to the initiation of apoptosis. In a siRNA-based miniscreen, we found Bim and Bmf, BH3-only proteins associated with the cytoskeleton, necessary to induce host cell apoptosis upon infection. Bim and Bmf inactivated different inhibitors of apoptosis and thereby induced cell death in response to infection. Our data unveil a novel pathway of infection-induced apoptosis that enhances our understanding of the mechanism by which BH3-only proteins control apoptotic cell death
Single \pi^- production in np collisions for excess energies up to 90 MeV
The quasifree reaction np\to pp\pim was studied in a kinematically complete
experiment by bombarding a liquid hydrogen target with a deuteron beam of
momentum 1.85 GeV/c and analyzing the data along the lines of the spectator
model. In addition to the three charged ejectiles the spectator proton was also
detected in the large-acceptance time-of-flight spectrometer COSY-TOF. It was
identified by its momentum and flight direction thus yielding access to the
Fermi motion of the bound neutron and to the effective neutron 4-momentum
vector which differed from event to event. A range of almost 90
MeV excess energy above threshold was covered. Energy dependent angular
distributions, invariant mass spectra as well as fully covered Dalitz plots
were deduced. Sizeable FSI effects were found as were contributions of
and partial waves. The behavior of the elementary cross section
close to threshold is discussed in view of new cross section
data. In comparison with existing literature data the results provide a
sensitive test of the spectator model.Comment: 21 pages, 9 figures, 4 tables, submitted to EPJ
Single-Pion Production in pp Collisions at 0.95 GeV/c (II)
The single-pion production reactions , and
were measured at a beam momentum of 0.95 GeV/c (
400 MeV) using the short version of the COSY-TOF spectrometer. The central
calorimeter provided particle identification, energy determination and neutron
detection in addition to time-of-flight and angle measurements from other
detector parts. Thus all pion production channels were recorded with 1-4
overconstraints. Main emphasis is put on the presentation and discussion of the
channel, since the results on the other channels have already been
published previously. The total and differential cross sections obtained are
compared to theoretical calculations. In contrast to the channel we
find in the channel a strong influence of the excitation
already at this energy close to threshold. In particular we find a dependence in the pion angular distribution, typical for a
pure s-channel excitation and identical to that observed in the
channel. Since the latter is understood by a s-channel resonance in
the partial wave, we discuss an analogous scenario for the
channel
Measurement of pH. Definition, Standards, and Procedures
The definition of a “primary method of measurement” [1] has permitted
a full consideration of the definition of primary standards for pH, determined by a
primary method (cell without transference, Harned cell), of the definition of secondary
standards by secondary methods, and of the question whether pH, as a conventional
quantity, can be incorporated within the internationally accepted system
of measurement, the International System of Units (SI, Système International
d’Unités). This approach has enabled resolution of the previous compromise
IUPAC 1985 Recommendations [2]. Furthermore, incorporation of the uncertainties
for the primary method, and for all subsequent measurements, permits the
uncertainties for all procedures to be linked to the primary standards by an unbroken
chain of comparisons. Thus, a rational choice can be made by the analyst of
the appropriate procedure to achieve the target uncertainty of sample pH.
Accordingly, this document explains IUPAC recommended definitions, procedures,
and terminology relating to pH measurements in dilute aqueous solutions in
the temperature range 5–50 °C. Details are given of the primary and secondary
methods for measuring pH and the rationale for the assignment of pH values with
appropriate uncertainties to selected primary and secondary substances
Splenomegaly, elevated alkaline phosphatase and mutations in the SRSF2/ASXL1/RUNX1 gene panel are strong adverse prognostic markers in patients with systemic mastocytosis
We evaluated the impact of clinical and molecular characteristics on overall survival (OS) in 108 patients with indolent (n=41) and advanced SM (advSM, n=67). Organomegaly was measured by magnetic resonance imaging (MRI)-based volumetry of liver and spleen. In multivariate analysis of all patients, an increased spleen volume greater than or equal to450?ml (hazard ratio [HR], 5.2; 95% confidence interval [CI], [2.1–13.0]; P=0.003) and an elevated alkaline phosphatase (AP; HR 5.0 [1.1–22.2]; P=0.02) were associated with adverse OS. The 3-year OS was 100, 77, and 39%, respectively (P<0.0001), for patients with 0 (low-risk, n=37), 1 (intermediate-risk, n=32) or 2 (high-risk, n=39) parameters. For advSM patients with fully available clinical and molecular data (n=60), univariate analysis identified splenomegaly greater than or equal to1200?ml, elevated AP and mutations in the SRSF2/ASXL1/RUNX1 (S/A/R) gene panel as significant prognostic markers. In multivariate analysis, mutations in S/A/R (HR, 3.2 [1.1–9.6]; P=0.01) and elevated AP (HR 2.6 [1.0–7.1]; P=0.03) remained predictive adverse prognostic markers for OS. The 3-year OS was 76% and 38%, respectively (P=0.0003), for patients with 0-1 (intermediate-risk, n=28) or 2 (high-risk, n=32) parameters. We conclude that splenomegaly, elevated AP and mutations in the S/A/R gene panel are independent of the WHO classification and provide the most relevant prognostic information in SM patient
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