3,336 research outputs found
Dielectric and thermal relaxation in the energy landscape
We derive an energy landscape interpretation of dielectric relaxation times
in undercooled liquids, comparing it to the traditional Debye and
Gemant-DiMarzio-Bishop pictures. The interaction between different local
structural rearrangements in the energy landscape explains qualitatively the
recently observed splitting of the flow process into an initial and a final
stage. The initial mechanical relaxation stage is attributed to hopping
processes, the final thermal or structural relaxation stage to the decay of the
local double-well potentials. The energy landscape concept provides an
explanation for the equality of thermal and dielectric relaxation times. The
equality itself is once more demonstrated on the basis of literature data for
salol.Comment: 7 pages, 3 figures, 41 references, Workshop Disordered Systems,
Molveno 2006, submitted to Philosophical Magazin
Peer navigation improves diagnostic follow-up after breast cancer screening among Korean American women: results of a randomized trial
To test an intervention to increase adherence to diagnostic follow-up tests among Asian American women.
Korean American women who were referred for a diagnostic follow-up test (mainly diagnostic mammograms) and who had missed their follow-up appointment were eligible to participate in the study. Women from two clinics (n = 176) were randomly allocated to a usual care control arm or a peer navigator intervention arm. A 20-min telephone survey was administered to women in both study arms six months after they were identified to assess demographic and socio-economic characteristics and the primary outcome, self-reported completion of the recommended follow-up exam.
Among women who completed the survey at six-month follow-up, self-reported completion of follow-up procedures was 97% in the intervention arm and 67% in the control arm (p < 0.001). Based on an intent-to-treat analysis of all women who were randomized and an assumption of no completion of follow-up exam for women with missing outcome data, self-reported completion of follow-up was 61% in the intervention arm and 46% in the usual care control arm (p < 0.069).
Our results suggest that a peer navigator intervention to assist Korean American women to obtain follow-up diagnostic tests after an abnormal breast cancer screening test is efficacious
An Electron Fixed Target Experiment to Search for a New Vector Boson A' Decaying to e+e-
We describe an experiment to search for a new vector boson A' with weak
coupling alpha' > 6 x 10^{-8} alpha to electrons (alpha=e^2/4pi) in the mass
range 65 MeV < m_A' < 550 MeV. New vector bosons with such small couplings
arise naturally from a small kinetic mixing of the "dark photon" A' with the
photon -- one of the very few ways in which new forces can couple to the
Standard Model -- and have received considerable attention as an explanation of
various dark matter related anomalies. A' bosons are produced by radiation off
an electron beam, and could appear as narrow resonances with small production
cross-section in the trident e+e- spectrum. We summarize the experimental
approach described in a proposal submitted to Jefferson Laboratory's PAC35,
PR-10-009. This experiment, the A' Experiment (APEX), uses the electron beam of
the Continuous Electron Beam Accelerator Facility at Jefferson Laboratory
(CEBAF) at energies of ~1-4 GeV incident on 0.5-10% radiation length Tungsten
wire mesh targets, and measures the resulting e+e- pairs to search for the A'
using the High Resolution Spectrometer and the septum magnet in Hall A. With a
~1 month run, APEX will achieve very good sensitivity because the statistics of
e+e- pairs will be ~10,000 times larger in the explored mass range than any
previous search for the A' boson. These statistics and the excellent mass
resolution of the spectrometers allow sensitivity to alpha'/alpha one to three
orders of magnitude below current limits, in a region of parameter space of
great theoretical and phenomenological interest. Similar experiments could also
be performed at other facilities, such as the Mainz Microtron.Comment: 19 pages, 12 figures, 2 table
International Veterinary Epilepsy Task Force Consensus Proposal: Outcome of therapeutic interventions in canine and feline epilepsy
Common criteria for the diagnosis of drug resistance and the assessment of outcome are needed urgently as a prerequisite for standardized evaluation and reporting of individual therapeutic responses in canine epilepsy. Thus, we provide a proposal for the definition of drug resistance and partial therapeutic success in canine patients with epilepsy. This consensus statement also suggests a list of factors and aspects of outcome, which should be considered in addition to the impact on seizures. Moreover, these expert recommendations discuss criteria which determine the validity and informative value of a therapeutic trial in an individual patient and also suggest the application of individual outcome criteria. Agreement on common guidelines does not only render a basis for future optimization of individual patient management, but is also a presupposition for the design and implementation of clinical studies with highly standardized inclusion and exclusion criteria. Respective standardization will improve the comparability of findings from different studies and renders an improved basis for multicenter studies. Therefore, this proposal provides an in-depth discussion of the implications of outcome criteria for clinical studies. In particular ethical aspects and the different options for study design and application of individual patient-centered outcome criteria are considered
The effect of cigarette smoke exposure on the development of inflammation in lungs, gut and joints of TNFΔARE mice
The inflammatory cytokine TNF-alpha is a central mediator in many immune-mediated diseases, such as Crohn's disease (CD), spondyloarthritis (SpA) and chronic obstructive pulmonary disease (COPD). Epidemiologic studies have shown that cigarette smoking (CS) is a prominent common risk factor in these TNF-dependent diseases. We exposed TNF Delta ARE mice; in which a systemic TNF-alpha overexpression leads to the development of inflammation; to 2 or 4 weeks of air or CS. We investigated the effect of deregulated TNF expression on CS-induced pulmonary inflammation and the effect of CS exposure on the initiation and progression of gut and joint inflammation. Upon 2 weeks of CS exposure, inflammation in lungs of TNF Delta ARE mice was significantly aggravated. However, upon 4 weeks of CS-exposure, this aggravation was no longer observed. TNF Delta ARE mice have no increases in CD4+ and CD8+ T cells and a diminished neutrophil response in the lungs after 4 weeks of CS exposure. In the gut and joints of TNF Delta ARE mice, 2 or 4 weeks of CS exposure did not modulate the development of inflammation. In conclusion, CS exposure does not modulate gut and joint inflammation in TNF Delta ARE mice. The lung responses towards CS in TNF Delta ARE mice however depend on the duration of CS exposure
Complement C1q Activates Tumor Suppressor WWOX to Induce Apoptosis in Prostate Cancer Cells
BACKGROUND:Tissue exudates contain low levels of serum complement proteins, and their regulatory effects on prostate cancer progression are largely unknown. We examined specific serum complement components in coordinating the activation of tumor suppressors p53 and WWOX (also named FOR or WOX1) and kinases ERK, JNK1 and STAT3 in human prostate DU145 cells. METHODOLOGY/PRINCIPAL FINDINGS:DU145 cells were cultured overnight in 1% normal human serum, or in human serum depleted of an indicated complement protein. Under complement C1q- or C6-free conditions, WOX1 and ERK were mainly present in the cytoplasm without phosphorylation, whereas phosphorylated JNK1 was greatly accumulated in the nuclei. Exogenous C1q rapidly restored the WOX1 activation (with Tyr33 phosphorylation) in less than 2 hr. Without serum complement C9, p53 became activated, and hyaluronan (HA) reversed the effect. Under C6-free conditions, HA induced activation of STAT3, an enhancer of metastasis. Notably, exogenous C1q significantly induced apoptosis of WOX1-overexpressing DU145 cells, but not vehicle-expressing cells. A dominant negative and Y33R mutant of WOX1 blocked the apoptotic effect. C1q did not enhance p53-mediated apoptosis. By total internal reflection fluorescence (TIRF) microscopy, it was determined that C1q destabilized adherence of WOX1-expressing DU145 cells by partial detaching and inducing formation of clustered microvilli for focal adhesion particularly in between cells. These cells then underwent shrinkage, membrane blebbing and death. Remarkably, as determined by immunostaining, benign prostatic hyperplasia and prostate cancer were shown to have a significantly reduced expression of tissue C1q, compared to age-matched normal prostate tissues. CONCLUSIONS/SIGNIFICANCE:We conclude that complement C1q may induce apoptosis of prostate cancer cells by activating WOX1 and destabilizing cell adhesion. Downregulation of C1q enhances prostate hyperplasia and cancerous formation due to failure of WOX1 activation
Redox proteomics of the inflammatory secretome identifies a common set of redoxins and other glutathionylated proteins released in inflammation, influenza virus infection and oxidative stress
Protein cysteines can form transient disulfides with glutathione (GSH), resulting in the production of glutathionylated proteins, and this process is regarded as a mechanism by which the redox state of the cell can regulate protein function. Most studies on redox regulation of immunity have focused on intracellular proteins. In this study we have used redox proteomics to identify those proteins released in glutathionylated form by macrophages stimulated with lipopolysaccharide (LPS) after pre-loading the cells with biotinylated GSH. Of the several proteins identified in the redox secretome, we have selected a number for validation. Proteomic analysis indicated that LPS stimulated the release of peroxiredoxin (PRDX) 1, PRDX2, vimentin (VIM), profilin1 (PFN1) and thioredoxin 1 (TXN1). For PRDX1 and TXN1, we were able to confirm that the released protein is glutathionylated. PRDX1, PRDX2 and TXN1 were also released by the human pulmonary epithelial cell line, A549, infected with influenza virus. The release of the proteins identified was inhibited by the anti-inflammatory glucocorticoid, dexamethasone (DEX), which also inhibited tumor necrosis factor (TNF)-α release, and by thiol antioxidants (N-butanoyl GSH derivative, GSH-C4, and N-acetylcysteine (NAC), which did not affect TNF-α production. The proteins identified could be useful as biomarkers of oxidative stress associated with inflammation, and further studies will be required to investigate if the extracellular forms of these proteins has immunoregulatory functions
Seesaw Neutrino Signals at the Large Hadron Collider
We discuss the scenario with gauge singlet fermions (right-handed neutrinos)
accessible at the energy of the Large Hadron Collider. The singlet fermions
generate tiny neutrino masses via the seesaw mechanism and also have sizable
couplings to the standard-model particles. We demonstrate that these two facts,
which are naively not satisfied simultaneously, are reconciled in the
five-dimensional framework in various fashions, which make the seesaw mechanism
observable. The collider signal of tri-lepton final states with transverse
missing energy is investigated for two explicit examples of the observable
seesaw, taking account of three types of neutrino mass spectrum and the
constraint from lepton flavor violation. We find by showing the significance of
signal discovery that the collider experiment has a potential to find signals
of extra dimensions and the origin of small neutrino masses.Comment: 27 pages, 4 figure
MicroRNAs in pulmonary arterial remodeling
Pulmonary arterial remodeling is a presently irreversible pathologic hallmark of pulmonary arterial hypertension (PAH). This complex disease involves pathogenic dysregulation of all cell types within the small pulmonary arteries contributing to vascular remodeling leading to intimal lesions, resulting in elevated pulmonary vascular resistance and right heart dysfunction. Mutations within the bone morphogenetic protein receptor 2 gene, leading to dysregulated proliferation of pulmonary artery smooth muscle cells, have been identified as being responsible for heritable PAH. Indeed, the disease is characterized by excessive cellular proliferation and resistance to apoptosis of smooth muscle and endothelial cells. Significant gene dysregulation at the transcriptional and signaling level has been identified. MicroRNAs are small non-coding RNA molecules that negatively regulate gene expression and have the ability to target numerous genes, therefore potentially controlling a host of gene regulatory and signaling pathways. The major role of miRNAs in pulmonary arterial remodeling is still relatively unknown although research data is emerging apace. Modulation of miRNAs represents a possible therapeutic target for altering the remodeling phenotype in the pulmonary vasculature. This review will focus on the role of miRNAs in regulating smooth muscle and endothelial cell phenotypes and their influence on pulmonary remodeling in the setting of PAH
Low-Energy Probes of a Warped Extra Dimension
We investigate a natural realization of a light Abelian hidden sector in an
extended Randall-Sundrum (RS) model. In addition to the usual RS bulk we
consider a second warped space containing a bulk U(1)_x gauge theory with a
characteristic IR scale of order a GeV. This Abelian hidden sector can couple
to the standard model via gauge kinetic mixing on a common UV brane. We show
that if such a coupling induces significant mixing between the lightest U(1)_x
gauge mode and the standard model photon and Z, it can also induce significant
mixing with the heavier U(1)_x Kaluza-Klein (KK) modes. As a result it might be
possible to probe several KK modes in upcoming fixed-target experiments and
meson factories, thereby offering a new way to investigate the structure of an
extra spacetime dimension.Comment: 26 pages, 1 figure, added references, corrected minor typos, same as
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