96 research outputs found
General Analysis of Antideuteron Searches for Dark Matter
Low energy cosmic ray antideuterons provide a unique low background channel
for indirect detection of dark matter. We compute the cosmic ray flux of
antideuterons from hadronic annihilations of dark matter for various Standard
Model final states and determine the mass reach of two future experiments
(AMS-02 and GAPS) designed to greatly increase the sensitivity of antideuteron
detection over current bounds. We consider generic models of scalar, fermion,
and massive vector bosons as thermal dark matter, describe their basic features
relevant to direct and indirect detection, and discuss the implications of
direct detection bounds on models of dark matter as a thermal relic. We also
consider specific dark matter candidates and assess their potential for
detection via antideuterons from their hadronic annihilation channels. Since
the dark matter mass reach of the GAPS experiment can be well above 100 GeV, we
find that antideuterons can be a good indirect detection channel for a variety
of thermal relic electroweak scale dark matter candidates, even when the rate
for direct detection is highly suppressed.Comment: 44 pages, 15 Figure
Cosmic Ray Anomalies from the MSSM?
The recent positron excess in cosmic rays (CR) observed by the PAMELA
satellite may be a signal for dark matter (DM) annihilation. When these
measurements are combined with those from FERMI on the total () flux
and from PAMELA itself on the ratio, these and other results are
difficult to reconcile with traditional models of DM, including the
conventional mSUGRA version of Supersymmetry even if boosts as large as
are allowed. In this paper, we combine the results of a previously
obtained scan over a more general 19-parameter subspace of the MSSM with a
corresponding scan over astrophysical parameters that describe the propagation
of CR. We then ascertain whether or not a good fit to this CR data can be
obtained with relatively small boost factors while simultaneously satisfying
the additional constraints arising from gamma ray data. We find that a specific
subclass of MSSM models where the LSP is mostly pure bino and annihilates
almost exclusively into pairs comes very close to satisfying these
requirements. The lightest in this set of models is found to be
relatively close in mass to the LSP and is in some cases the nLSP. These models
lead to a significant improvement in the overall fit to the data by an amount
dof in comparison to the best fit without Supersymmetry
while employing boosts . The implications of these models for future
experiments are discussed.Comment: 57 pages, 31 figures, references adde
A phase II trial of lomeguatrib and temozolomide in metastatic colorectal cancer
To evaluate the tumour response to lomeguatrib and temozolomide (TMZ) administered for 5 consecutive days every 4 weeks in patients with metastatic colorectal carcinoma. Patients with stage IV metastatic colorectal carcinoma received lomeguatrib (40 mg) and TMZ (50–200 mg m−2) orally for 5 consecutive days every 4 weeks. Response was determined every two cycles. Pharmacokinetics of lomeguatrib and TMZ as well as their pharmacodynamic effects in peripheral blood mononuclear cells (PBMC) were determined. Nineteen patients received 49 cycles of treatments. Despite consistent depletion of O6-methylguanine-DNA methyltransferase in PBMC, none of the patients responded to treatment. Three patients had stable disease, one for the duration of the study, and no fall in carcinoembryonic antigen was observed in any patient. Median time to progression was 50 days. The commonest adverse effects were gastrointestinal and haematological and these were comparable to those of TMZ when given alone. This combination of lomeguatrib and TMZ is not efficacious in metastatic colorectal cancer. If further studies are to be performed, emerging data suggest that higher daily doses of lomeguatrib and a dosing period beyond that of TMZ should be evaluated
Modified Needle-Tip PcrV Proteins Reveal Distinct Phenotypes Relevant to the Control of Type III Secretion and Intoxication by Pseudomonas aeruginosa
The type III secretion system (T3SS) is employed to deliver effector proteins to the cytosol of eukaryotic hosts by multiple species of Gram-negative bacteria, including Pseudomonas aeruginosa. Translocation of effectors is dependent on the proteins encoded by the pcrGVHpopBD operon. These proteins form a T3S translocator complex, composed of a needle-tip complex (PcrV), translocons (PopB and PopD), and chaperones (PcrG and PcrH). PcrV mediates the folding and insertion of PopB/PopD in host plasmic membranes, where assembled translocons form a translocation channel. Assembly of this complex and delivery of effectors through this machinery is tightly controlled by PcrV, yet the multifunctional aspects of this molecule have not been defined. In addition, PcrV is a protective antigen for P. aeruginosa infection as is the ortholog, LcrV, for Yersinia. We constructed PcrV derivatives containing in-frame linker insertions and site-specific mutations. The expression of these derivatives was regulated by a T3S-specific promoter in a pcrV-null mutant of PA103. Nine derivatives disrupted the regulation of effector secretion and constitutively released an effector protein into growth medium. Three of these regulatory mutants, in which the linker was inserted in the N-terminal globular domain, were competent for the translocation of a cytotoxin, ExoU, into eukaryotic host cells. We also isolated strains expressing a delayed-toxicity phenotype, which secrete translocators slowly despite the normal level of effector secretion. Most of the cytotoxic translocation-competent strains retained the protective epitope of PcrV derivatives, and Mab166 was able to protect erythrocytes during infection with these strains. The use of defined PcrV derivatives possessing distinct phenotypes may lead to a better understanding of the functional aspects of T3 needle-tip proteins and the development of therapeutic agents or vaccines targeting T3SS-mediated intoxication
Anaemia in the Premature Infant and Red Blood Cell Transfusion: New Approaches to an Age-Old Problem
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