The Starburst in the Central Kiloparsec of Markarian 231

We present VLBA observations at 0.33 and 0.61 GHz, and VLA observations between 5 and 22 GHz, of subkiloparsec scale radio emission from Mrk 231. In addition to jet components clearly associated with the AGN, we also find a smooth extended component of size 100 - 1000 pc most probably related to the purported massive star forming disk in Mrk 231. The diffuse radio emission from the disk is found to have a steep spectrum at high frequencies, characteristic of optically thin synchrotron emission. The required relativistic particle density in the disk can be produced by a star formation rate of 220 Msolar/yr in the central kiloparsec. At low frequencies the disk is absorbed, most likely by ionized gas with an emission measure of 8 x 10^5 pc cm-6. We have also identified 4 candidate radio supernovae that, if confirmed, represent direct evidence for ongoing star formation in the central kiloparsec.Comment: in press at ApJ for v. 519 July 1999, 14 page LaTeX document includes 6 postscript figure

The Time Machine: A Simulation Approach for Stochastic Trees

In the following paper we consider a simulation technique for stochastic trees. One of the most important areas in computational genetics is the calculation and subsequent maximization of the likelihood function associated to such models. This typically consists of using importance sampling (IS) and sequential Monte Carlo (SMC) techniques. The approach proceeds by simulating the tree, backward in time from observed data, to a most recent common ancestor (MRCA). However, in many cases, the computational time and variance of estimators are often too high to make standard approaches useful. In this paper we propose to stop the simulation, subsequently yielding biased estimates of the likelihood surface. The bias is investigated from a theoretical point of view. Results from simulation studies are also given to investigate the balance between loss of accuracy, saving in computing time and variance reduction.Comment: 22 Pages, 5 Figure

The BATSE experiment on the Gamma Ray Observatory: Solar flare hard x ray and gamma-ray capabilities

The Burst and Transient Source Experiment (BATSE) for the Gamma Ray Observatory (GRO) consists of eight detector modules that provide full-sky coverage for gamma-ray bursts and other transient phenomena such as solar flares. Each detector module has a thin, large-area scintillation detector (2025 sq cm) for high time-resolution studies, and a thicker spectroscopy detector (125 sq cm) to extend the energy range and provide better spectral resolution. The total energy range of the system is 15 keV to 100 MeV. These 16 detectors and the associated onboard data system should provide unprecedented capabilities for observing rapid spectral changes and gamma-ray lines from solar flares. The presence of a solar flare can be detected in real-time by BATSE; a trigger signal is sent to two other experiments on the GRO. The launch of the GRO is scheduled for June 1990, so that BATSE can be an important component of the Max '91 campaign

Prognostic DNA Methylation Biomarkers in High-risk Non–muscle-invasive Bladder Cancer:A Systematic Review to Identify Loci for Prospective Validation

Context: High-risk non–muscle-invasive bladder cancer (HR-NMIBC) represents over 30% of all incident urothelial bladder cancers (BCs); patients are at risk of progression, and 20–30% will die from BC within 5 yr. Current guidelines recommend induction and maintenance of intravesical bacillus Calmette-Guérin (BCG) or upfront radical cystectomy for highest-risk disease, treatments with markedly different morbidity, mortality, and patient burden. There are no validated biomarkers to facilitate such treatment decisions. Alterations in DNA methylation are commonplace in BC; hence, measurable changes in DNA methylation represent an opportunity for the discovery of such biomarkers.Objective: To systematically assess the evidence regarding DNA methylation markers as prognosticators for HR-NMIBC.Evidence acquisition: Standard systematic review methods were employed with searches undertaken in MEDLINE, EMBASE, and PubMed up to January 2019. Studies that included patients with HR-NMIBC and investigated the utility of DNA methylation biomarkers as prognostic tools were included.Evidence synthesis: Of 63 prognostic biomarker studies identified, 21 met the protocol-driven inclusion criteria and were directly relevant to HR-NMIBC patient outcomes: tumour recurrence (TR), tumour progression (TP), disease-specific survival (DSS), and overall survival (OS). These studies described 140 methylation markers; of these, the most promising were cadherin-13 (CDH13; hazard ratios [HRs]: 5.1 for TR, 6.6 for TP, 3.8–8.0 for OS), protocadherins (PCDHs; HRs: 4.7 for TR, 2.5 for TP, 3.0–4.8 for OS), Runt domain transcription factor 3 (RUNX3; HR: 5.1 for TP), Homeobox 9 (HOXA9; HR: 1.9 for TR), Islet-1 (ISL1; HRs: 1.7 for TR, 3.3 for TP), and PAX6 (HR: 2.2 for TR).Conclusions: This systematic review identifies a number of potentially useful prognostic methylation markers for HR-NMIBC. These loci (CDH13, PCDHs, RUNX3, HOXA9, ISL1, and PAX6) should be validated in prospective studies in order to translate benefit to patients.Patient summary: Early bladder cancer represents a more complex spectrum of disease than can be assessed by conventional methods Emerging studies on molecular markers will improve our understanding of this disease, and may enable more precise and personalised treatment.</p

Prognostic DNA Methylation Biomarkers in High-risk Non–muscle-invasive Bladder Cancer:A Systematic Review to Identify Loci for Prospective Validation

Context: High-risk non–muscle-invasive bladder cancer (HR-NMIBC) represents over 30% of all incident urothelial bladder cancers (BCs); patients are at risk of progression, and 20–30% will die from BC within 5 yr. Current guidelines recommend induction and maintenance of intravesical bacillus Calmette-Guérin (BCG) or upfront radical cystectomy for highest-risk disease, treatments with markedly different morbidity, mortality, and patient burden. There are no validated biomarkers to facilitate such treatment decisions. Alterations in DNA methylation are commonplace in BC; hence, measurable changes in DNA methylation represent an opportunity for the discovery of such biomarkers.Objective: To systematically assess the evidence regarding DNA methylation markers as prognosticators for HR-NMIBC.Evidence acquisition: Standard systematic review methods were employed with searches undertaken in MEDLINE, EMBASE, and PubMed up to January 2019. Studies that included patients with HR-NMIBC and investigated the utility of DNA methylation biomarkers as prognostic tools were included.Evidence synthesis: Of 63 prognostic biomarker studies identified, 21 met the protocol-driven inclusion criteria and were directly relevant to HR-NMIBC patient outcomes: tumour recurrence (TR), tumour progression (TP), disease-specific survival (DSS), and overall survival (OS). These studies described 140 methylation markers; of these, the most promising were cadherin-13 (CDH13; hazard ratios [HRs]: 5.1 for TR, 6.6 for TP, 3.8–8.0 for OS), protocadherins (PCDHs; HRs: 4.7 for TR, 2.5 for TP, 3.0–4.8 for OS), Runt domain transcription factor 3 (RUNX3; HR: 5.1 for TP), Homeobox 9 (HOXA9; HR: 1.9 for TR), Islet-1 (ISL1; HRs: 1.7 for TR, 3.3 for TP), and PAX6 (HR: 2.2 for TR).Conclusions: This systematic review identifies a number of potentially useful prognostic methylation markers for HR-NMIBC. These loci (CDH13, PCDHs, RUNX3, HOXA9, ISL1, and PAX6) should be validated in prospective studies in order to translate benefit to patients.Patient summary: Early bladder cancer represents a more complex spectrum of disease than can be assessed by conventional methods Emerging studies on molecular markers will improve our understanding of this disease, and may enable more precise and personalised treatment.</p

Kondo screening in d-wave superconductors in a Zeeman field and implications for STM spectra of Zn-doped cuprates

We consider the screening of an impurity moment in a d-wave superconductor under the influence of a Zeeman magnetic field. Using the Numerical Renormalization Group technique, we investigate the resulting pseudogap Kondo problem, in particular the field-induced crossover behavior in the vicinity of the zero-field boundary quantum phase transition. The impurity spectral function and the resulting changes in the local host density of states are calculated, giving specific predictions for high-field STM measurements on impurity-doped cuprates.Comment: 5 pages, 4 figs, (v2) remark on c-axis field added, discussion extended, (v3) final version as publishe

PTSD, psychological morbidity and marital dissatisfaction in colonial war veterans

Background: Forty years after Colonial War, veterans still show psychological disturbances affecting their marital and sexual satisfaction.Aims: This study analyzed the relationships between Post-Traumatic Stress Disorder (PTSD), number of PTSD symptoms and symptom clusters, psychological morbidity, marital dissatisfaction and sexual dissatisfaction; the variables that contributed to marital dissatisfaction and the mediator role of marital dissatisfaction and sexual dissatisfaction, in a sample of colonial War Veterans.Method: The sample included 138 Portuguese war veterans who answered Index of Marital Satisfaction; Index of Sexual Satisfaction; Beck Depression Inventory; State Trait Anxiety Inventory; Post-Traumatic Stress Disorder Scale.Results: PTSD, number of PTSD symptoms and symptom clusters were associated with psychological morbidity, marital and sexual dissatisfaction. Age, depression symptoms and sexual dissatisfaction contributed to marital dissatisfaction and the model explained 55% of the variance. Marital dissatisfaction mediated the relationship between depression symptoms and sexual dissatisfaction, as well as between number of PTSD symptoms and sexual dissatisfaction.Conclusions: Health professionals need to take into consideration the veteran's marital and sexual relationship in clinical routine consultations. As such, treating the veteran in the couple' context seems warranted.Bayer Portuguesa (B02/06

Exploring impulsive solar magnetic energy release and particle acceleration with focused hard X-ray imaging spectroscopy

How impulsive magnetic energy release leads to solar eruptions and how those eruptions are energized and evolve are vital unsolved problems in Heliophysics. The standard model for solar eruptions summarizes our current understanding of these events. Magnetic energy in the corona is released through drastic restructuring of the magnetic field via reconnection. Electrons and ions are then accelerated by poorly understood processes. Theories include contracting loops, merging magnetic islands, stochastic acceleration, and turbulence at shocks, among others. Although this basic model is well established, the fundamental physics is poorly understood. HXR observations using grazing-incidence focusing optics can now probe all of the key regions of the standard model. These include two above-the-looptop (ALT) sources which bookend the reconnection region and are likely the sites of particle acceleration and direct heating. The science achievable by a direct HXR imaging instrument can be summarized by the following science questions and objectives which are some of the most outstanding issues in solar physics (1) How are particles accelerated at the Sun? (1a) Where are electrons accelerated and on what time scales? (1b) What fraction of electrons is accelerated out of the ambient medium? (2) How does magnetic energy release on the Sun lead to flares and eruptions? A Focusing Optics X-ray Solar Imager (FOXSI) instrument, which can be built now using proven technology and at modest cost, would enable revolutionary advancements in our understanding of impulsive magnetic energy release and particle acceleration, a process which is known to occur at the Sun but also throughout the Universe

A single-label phenylpyrrolocytidine provides a molecular beacon-like response reporting HIV-1 RT RNase H activity

6-Phenylpyrrolocytidine (PhpC), a structurally conservative and highly fluorescent cytidine analog, was incorporated into oligoribonucleotides. The PhpC-containing RNA formed native-like duplex structures with complementary DNA or RNA. The PhpC-modification was found to act as a sensitive reporter group being non-disruptive to structure and the enzymatic activity of RNase H. A RNA/DNA hybrid possessing a single PhpC insert was an excellent substrate for HIV-1 RT Ribonuclease H and rapidly reported cleavage of the RNA strand with a 14-fold increase in fluorescence intensity. The PhpC-based assay for RNase H was superior to the traditional molecular beacon approach in terms of responsiveness, rapidity and ease (single label versus dual). Furthermore, the PhpC-based assay is amenable to high-throughput microplate assay format and may form the basis for a new screen for inhibitors of HIV-RT RNase H

TDP1 deficiency sensitizes human cells to base damage via distinct topoisomerase I and PARP mechanisms with potential applications for cancer therapy

Base damage and topoisomerase I (Top1)-linked DNA breaks are abundant forms of endogenous DNA breakage, contributing to hereditary ataxia and underlying the cytotoxicity of a wide range of anti-cancer agents. Despite their frequency, the overlapping mechanisms that repair these forms of DNA breakage are largely unknown. Here, we report that depletion of Tyrosyl DNA phosphodiesterase 1 (TDP1) sensitizes human cells to alkylation damage and the additional depletion of apurinic/apyrimidinic endonuclease I (APE1) confers hypersensitivity above that observed for TDP1 or APE1 depletion alone. Quantification of DNA breaks and clonogenic survival assays confirm a role for TDP1 in response to base damage, independently of APE1. The hypersensitivity to alkylation damage is partly restored by depletion of Top1, illustrating that alkylating agents can trigger cytotoxic Top1-breaks. Although inhibition of PARP activity does not sensitize TDP1-deficient cells to Top1 poisons, it confers increased sensitivity to alkylation damage, highlighting partially overlapping roles for PARP and TDP1 in response to genotoxic challenge. Finally, we demonstrate that cancer cells in which TDP1 is inherently deficient are hypersensitive to alkylation damage and that TDP1 depletion sensitizes glioblastoma-resistant cancer cells to the alkylating agent temozolomide