136 research outputs found
Neutralino dark matter in mSUGRA/CMSSM with a 125 GeV light Higgs scalar
The minimal supergravity (mSUGRA or CMSSM) model is an oft-used framework for
exhibiting the properties of neutralino (WIMP) cold dark matter (CDM). However,
the recent evidence from Atlas and CMS on a light Higgs scalar with mass
m_h\simeq 125 GeV highly constrains the superparticle mass spectrum, which in
turn constrains the neutralino annihilation mechanisms in the early universe.
We find that stau and stop co-annihilation mechanisms -- already highly
stressed by the latest Atlas/CMS results on SUSY searches -- are nearly
eliminated if indeed the light Higgs scalar has mass m_h\simeq 125 GeV.
Furthermore, neutralino annihilation via the A-resonance is essentially ruled
out in mSUGRA so that it is exceedingly difficult to generate
thermally-produced neutralino-only dark matter at the measured abundance. The
remaining possibility lies in the focus-point region which now moves out to
m_0\sim 10-20 TeV range due to the required large trilinear soft SUSY breaking
term A_0. The remaining HB/FP region is more fine-tuned than before owing to
the typically large top squark masses. We present updated direct and indirect
detection rates for neutralino dark matter, and show that ton scale noble
liquid detectors will either discover mixed higgsino CDM or essentially rule
out thermally-produced neutralino-only CDM in the mSUGRA model.Comment: 17 pages including 9 .eps figure
Reducing decision errors in the paired comparison of the diagnostic accuracy of screening tests with Gaussian outcomes
The rph1 Gene Is a Common Contributor to the Evolution of Phosphine Resistance in Independent Field Isolates of Rhyzopertha Dominica
Phosphine is the only economically viable fumigant for routine control of insect pests of stored food products, but its continued use is now threatened by the world-wide emergence of high-level resistance in key pest species. Phosphine has a unique mode of action relative to well-characterised contact pesticides. Similarly, the selective pressures that lead to resistance against field sprays differ dramatically from those encountered during fumigation. The consequences of these differences have not been investigated adequately. We determine the genetic basis of phosphine resistance in Rhyzopertha dominica strains collected from New South Wales and South Australia and compare this with resistance in a previously characterised strain from Queensland. The resistance levels range from 225 and 100 times the baseline response of a sensitive reference strain. Moreover, molecular and phenotypic data indicate that high-level resistance was derived independently in each of the three widely separated geographical regions. Despite the independent origins, resistance was due to two interacting genes in each instance. Furthermore, complementation analysis reveals that all three strains contain an incompletely recessive resistance allele of the autosomal rph1 resistance gene. This is particularly noteworthy as a resistance allele at rph1 was previously proposed to be a necessary first step in the evolution of high-level resistance. Despite the capacity of phosphine to disrupt a wide range of enzymes and biological processes, it is remarkable that the initial step in the selection of resistance is so similar in isolated outbreaks
Complement in glomerular injury
In recent years, research into the role of complement in the immunopathogenesis of renal disease has broadened our understanding of the fragile balance between the protective and harmful functions of the complement system. Interventions into the complement system in various models of immune-mediated renal disease have resulted in both favourable and unfavourable effects and will allow us to precisely define the level of the complement cascade at which a therapeutic intervention will result in an optimal effect. The discovery of mutations of complement regulatory molecules has established a role of complement in the haemolytic uremic syndrome and membranoproliferative glomerulonephritis, and genotyping for mutations of the complement system are already leaving the research laboratory and have entered clinical practice. These clinical discoveries have resulted in the creation of relevant animal models which may provide crucial information for the development of highly specific therapeutic agents. Research into the role of complement in proteinuria has helped to understand pathways of inflammation which ultimately lead to renal failure irrespective of the underlying renal disease and is of major importance for the majority of renal patients. Complement science is a highly exciting area of translational research and hopefully will result in meaningful therapeutic advances in the near future
Dilaton dominance relaxes LHC and cosmological constraints in supersymmetric models
It has been pointed out recently that the presence of dilaton field in the
early Universe can dilute the neutralino dark matter (DM) abundance, if
Universe is not radiation dominated at DM decoupling, due to its
dissipative-like coupling to DM. In this scenario two basic mechanisms compete,
the modified Hubble expansion rate tending to increase the relic density and a
dissipative force that tends to decrease it. The net effect can lead to an
overall dramatic decrease of the predicted relic abundance, sometimes by
amounts of the order of O(10^2) or so. This feature is rather generic,
independent of any particular assumption on the underlying string dynamics,
provided dilaton dominates at early eras after the end of inflation but before
Big Bang Nucleosynthesis (BBN). The latter ensures that BBN is not upset by the
presence of the dilaton. In this paper, within the context of such a scenario,
we study the phenomenology of the constrained minimal supersymmetric model
(CMSSM) by taking into account all recent experimental constraints, including
those from the LHC searches. We find that the allowed parameter space is
greatly enlarged and includes regions that are beyond the reach of LHC. The
allowed regions are compatible with Direct Dark Matter searches since the small
neutralino annihilation rates, that are now in accord with the cosmological
data on the relic density, imply small neutralino-nucleon cross sections below
the sensitivities of the Direct Dark Matter experiments. It is also important
that the new cosmologically accepted regions are compatible with Higgs boson
masses larger than 120 GeV, as it is indicated from the LHC experimental data.
The smaller annihilation cross sections needed to explain WMAP data require
that the detector performances of current and planned indirect DM search
experiments through gamma rays should be greatly improved in order to probe the
CMSSM regions.Comment: 20 pages, 10 eps figures. Revised and extended version to appear in
JHEP; a section on gamma rays adde
Macrophage signaling in HIV-1 infection
The human immunodeficiency virus-1 (HIV-1) is a member of the lentivirus genus. The virus does not rely exclusively on the host cell machinery, but also on viral proteins that act as molecular switches during the viral life cycle which play significant functions in viral pathogenesis, notably by modulating cell signaling. The role of HIV-1 proteins (Nef, Tat, Vpr, and gp120) in modulating macrophage signaling has been recently unveiled. Accessory, regulatory, and structural HIV-1 proteins interact with signaling pathways in infected macrophages. In addition, exogenous Nef, Tat, Vpr, and gp120 proteins have been detected in the serum of HIV-1 infected patients. Possibly, these proteins are released by infected/apoptotic cells. Exogenous accessory regulatory HIV-1 proteins are able to enter macrophages and modulate cellular machineries including those that affect viral transcription. Furthermore HIV-1 proteins, e.g., gp120, may exert their effects by interacting with cell surface membrane receptors, especially chemokine co-receptors. By activating the signaling pathways such as NF-kappaB, MAP kinase (MAPK) and JAK/STAT, HIV-1 proteins promote viral replication by stimulating transcription from the long terminal repeat (LTR) in infected macrophages; they are also involved in macrophage-mediated bystander T cell apoptosis. The role of HIV-1 proteins in the modulation of macrophage signaling will be discussed in regard to the formation of viral reservoirs and macrophage-mediated T cell apoptosis during HIV-1 infection
Twelve-month observational study of children with cancer in 41 countries during the COVID-19 pandemic
Introduction Childhood cancer is a leading cause of death. It is unclear whether the COVID-19 pandemic has impacted childhood cancer mortality. In this study, we aimed to establish all-cause mortality rates for childhood cancers during the COVID-19 pandemic and determine the factors associated with mortality. Methods Prospective cohort study in 109 institutions in 41 countries. Inclusion criteria: children <18 years who were newly diagnosed with or undergoing active treatment for acute lymphoblastic leukaemia, non-Hodgkin's lymphoma, Hodgkin lymphoma, retinoblastoma, Wilms tumour, glioma, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, medulloblastoma and neuroblastoma. Of 2327 cases, 2118 patients were included in the study. The primary outcome measure was all-cause mortality at 30 days, 90 days and 12 months. Results All-cause mortality was 3.4% (n=71/2084) at 30-day follow-up, 5.7% (n=113/1969) at 90-day follow-up and 13.0% (n=206/1581) at 12-month follow-up. The median time from diagnosis to multidisciplinary team (MDT) plan was longest in low-income countries (7 days, IQR 3-11). Multivariable analysis revealed several factors associated with 12-month mortality, including low-income (OR 6.99 (95% CI 2.49 to 19.68); p<0.001), lower middle income (OR 3.32 (95% CI 1.96 to 5.61); p<0.001) and upper middle income (OR 3.49 (95% CI 2.02 to 6.03); p<0.001) country status and chemotherapy (OR 0.55 (95% CI 0.36 to 0.86); p=0.008) and immunotherapy (OR 0.27 (95% CI 0.08 to 0.91); p=0.035) within 30 days from MDT plan. Multivariable analysis revealed laboratory-confirmed SARS-CoV-2 infection (OR 5.33 (95% CI 1.19 to 23.84); p=0.029) was associated with 30-day mortality. Conclusions Children with cancer are more likely to die within 30 days if infected with SARS-CoV-2. However, timely treatment reduced odds of death. This report provides crucial information to balance the benefits of providing anticancer therapy against the risks of SARS-CoV-2 infection in children with cancer
Age-dependent molecular alterations in the autophagy pathway in HIVE patients and in a gp120 tg mouse model: reversal with beclin-1 gene transfer
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