Two-dimensional effects in laser-created plasmas measured with soft-x-ray laser interferometry

Includes bibliographical references (pages 056409-6).Soft-x-ray laser interferograms of laser-created plasmas generated at moderate irradiation intensities (1×1011-7×1012 W cm-2) with λ = 1.06 μm light pulses of ~13-ns-FWHM (full width at half maximum) duration and narrow focus (~30 μm) reveal the unexpected formation of an inverted density profile with a density minimum on axis and distinct plasma sidelobes. Model simulations show that this strong two dimensional hydrodynamic behavior is essentially a universal phenomena that is the result of plasma radiation induced mass ablation and cooling in the areas surrounding the focal spot

Application of extremely compact capillary discharge soft x-ray lasers to dense plasma diagnostics

Includes bibliographical references.Table-top capillary discharge soft x-ray lasers combine the advantages of a small size and a high repetition rate with an extremely high brightness similar to that of their laboratory-size predecessors. When utilized to probe high density plasmas their short wavelength results in a higher critical density, reduced refraction, decreased free-electron absorption, and higher resolution as compared to optical probes. These characteristics allow the design of experiments capable of measuring the evolution of plasmas with density-scale length products that are outside the reach of optical lasers. This paper reviews the use of a 46.9 nm wavelength Ne-like Ar capillary discharge table-top laser in dense plasma diagnostics, and reports soft x-ray laser interferometry results of spot-focus Nd:YAG laser plasmas created at moderate irradiation intensity (~7×1012 W cm-2) with ; ~13 ns pulse width duration laser pulses. The measurements produced electron density maps with densities up to 0.9×1021 cm-3 that show the development of a concave electron density profile that differ significantly from those of a classical expansion. This two-dimensional behavior, that was recently also observed in line-focus plasmas, is analyzed here for the case of spot-focus plasmas with the assistance of hydrodynamic model simulations. The results demonstrate the use of a table-top soft x-ray laser interferometer as a new high resolution tool for the study of high density plasma phenomena and the validation of hydrodynamic codes.This work was supported by the U.S. Department of Energy Grant No. DE-FG03-02NA00062 and by the National Science Foundation. Part of this work was performed under the auspices of the U.S. Department of Energy by the University of California, Lawrence Livermore National Laboratory through the Institute of Laser Science and Application, under Contract No. W-7405-Eng-48

Extremely compact soft X-ray lasers based on capillary discharges

Includes bibliographical references (page 522).Extremely compact high repetition rate soft X-ray lasers based on capillary discharge excitation have demonstrated average powers of a few milliWatt at 46.9 nm, milli-Joule-level pulse energy, peak spectral brightness several orders of magnitude larger than third-generation synchrotron beam lines, and excellent spatial coherence. Examples of the use of a capillary discharge soft X-ray laser in dense plasma diagnostics and laser ablation of materials are summarized

Tumour Cannabinoid CB1 Receptor and Phosphorylated Epidermal Growth Factor Receptor Expression Are Additive Prognostic Markers for Prostate Cancer

BACKGROUND: In cultured prostate cancer cells, down-regulation of epidermal growth factor receptor (EGFR) has been implicated in mediating the antiproliferative effect of the endogenous cannabinoid (CB) ligand anandamide. Using a well-characterised cohort of prostate cancer patients, we have previously reported that expression levels of phosphorylated EGFR (pEGFR-IR) and CB(1) receptor (CB(1)IR) in tumour tissue at diagnosis are markers of disease-specific survival, but it is not known whether the two markers interact in terms of their influence on disease severity at diagnosis and disease outcome. METHODOLOGY/PRINCIPAL FINDINGS: Data from a cohort of 419 patients who were diagnosed with prostate cancer at transurethral resection for voiding difficulties was used. Scores for both tumour CB(1)IR and pEGFR-IR were available in the database. Of these, 235 had been followed by expectancy until the appearance of metastases. For patients scored for both parameters, Cox proportional-hazards regression analyses using optimal cut-off scores indicated that the two measures provided additional diagnostic information not only to each other, but to that provided by the tumour stage and the Gleason score. When the cases were divided into subgroups on the basis of these cut-off scores, the patients with both CB(1)IR and pEGFR-IR scores above their cut-off had a poorer disease-specific survival and showed a more severe pathology at diagnosis than patients with high pEGFR-IR scores but with CB(1)IR scores below the cut-off. CONCLUSIONS/SIGNIFICANCE: These data indicate that a high tumour CB(1) receptor expression at diagnosis augments the deleterious effects of a high pEGFR expression upon disease-specific survival

A mechanism for the inhibition of DNA-PK-mediated DNA sensing by a virus

The innate immune system is critical in the response to infection by pathogens and it is activated by pattern recognition receptors (PRRs) binding to pathogen associated molecular patterns (PAMPs). During viral infection, the direct recognition of the viral nucleic acids, such as the genomes of DNA viruses, is very important for activation of innate immunity. Recently, DNA-dependent protein kinase (DNA-PK), a heterotrimeric complex consisting of the Ku70/Ku80 heterodimer and the catalytic subunit DNA-PKcs was identified as a cytoplasmic PRR for DNA that is important for the innate immune response to intracellular DNA and DNA virus infection. Here we show that vaccinia virus (VACV) has evolved to inhibit this function of DNA-PK by expression of a highly conserved protein called C16, which was known to contribute to virulence but by an unknown mechanism. Data presented show that C16 binds directly to the Ku heterodimer and thereby inhibits the innate immune response to DNA in fibroblasts, characterised by the decreased production of cytokines and chemokines. Mechanistically, C16 acts by blocking DNA-PK binding to DNA, which correlates with reduced DNA-PK-dependent DNA sensing. The C-terminal region of C16 is sufficient for binding Ku and this activity is conserved in the variola virus (VARV) orthologue of C16. In contrast, deletion of 5 amino acids in this domain is enough to knockout this function from the attenuated vaccine strain modified vaccinia virus Ankara (MVA). In vivo a VACV mutant lacking C16 induced higher levels of cytokines and chemokines early after infection compared to control viruses, confirming the role of this virulence factor in attenuating the innate immune response. Overall this study describes the inhibition of DNA-PK-dependent DNA sensing by a poxvirus protein, adding to the evidence that DNA-PK is a critical component of innate immunity to DNA viruses

Cardiac troponin measurement at the point of care: educational recommendations on analytical and clinical aspects by the IFCC Committee on Clinical Applications of Cardiac Bio-Markers (IFCC C-CB).

The International Federation of Clinical Chemistry and Laboarator Medicine (IFCC) Committee on Clinical Applications of Cardiac Bio-Markers (C-CB) has provided evidence-based educational resources to aid and improve the understanding of important analytical and clinical aspects of cardiac biomarkers. The present IFCC C-CB educational report focuses on recommendations for appropriate use, analytical performance, and gaps in clinical studies related to the use of cardiac troponin (cTn) by point of care (POC) measurement, often referred to as a point of care testing (POCT). The use of high-sensitivity (hs)-cTn POC devices in accelerated diagnostic protocols used in emergency departments or outpatient clinics investigating acute coronary syndrome has the potential for improved efficacy, reduction of length of stay and reduced costs in the health care system. POCT workflow integration includes location of the instrument, assignment of collection and testing responsibility to (non-lab) staff, instrument maintenance, in-service and recurrent training, quality control, proficiency assessments, discrepant result trapping, and troubleshooting and inventory management

Hyperglycemia and prostate cancer recurrence in men treated for localized prostate cancer.

Background:Obesity is consistently linked with prostate cancer (PCa) recurrence and mortality, though the mechanism is unknown. Impaired glucose regulation, which is common among obese individuals, has been hypothesized as a potential mechanism for PCa tumor growth. In this study, we explore the relationship between serum glucose at time of treatment and risk of PCa recurrence following initial therapy.Methods:The study group comprised 1734 men treated with radical prostatectomy (RP) or radiation therapy (RT) for localized PCa between 2001-2010. Serum glucose levels closest to date of diagnosis were determined. PCa recurrence was determined based on PSA progression (nadir PSA+2 for RT; PSA0.2 for RP) or secondary therapy. Multivariate Cox regression was performed to determine whether glucose level was associated with biochemical recurrence after adjusting for age, race, body mass index, comorbidity, diagnosis of diabetes, Gleason Sum, PSA, treatment and treatment year.Results:Recurrence was identified in 16% of men over a mean follow-up period of 41 months (range 1-121 months). Those with elevated glucose (100 mg/dl) had a 50% increased risk of recurrence (HR 1.5, 95% CI: 1.1-2.0) compared with those with a normal glucose level (<100 mg/dl). This effect was seen in both those undergoing RP (HR 1.9, 95% CI: 1.0-3.6) and those treated with RT (HR 1.4, 95% CI: 1.0-2.0).Conclusions:Glucose levels at the time of PCa diagnosis are an independent predictor of PCa recurrence for men undergoing treatment for localized disease