A Coordinated X-ray and Optical Campaign of the Nearby Massive Binary δ\delta Orionis Aa: II. X-ray Variability

We present time-resolved and phase-resolved variability studies of an extensive X-ray high-resolution spectral dataset of the $\delta$ Orionis Aa binary system. The four observations, obtained with Chandra ACIS HETGS, have a total exposure time of ~479 ks and provide nearly complete binary phase coverage. Variability of the total X-ray flux in the range 5-25 $\AA$ is confirmed, with maximum amplitude of about +/-15% within a single ~125 ks observation. Periods of 4.76d and 2.04d are found in the total X-ray flux, as well as an apparent overall increase in flux level throughout the 9-day observational campaign. Using 40 ks contiguous spectra derived from the original observations, we investigate variability of emission line parameters and ratios. Several emission lines are shown to be variable, including S XV, Si XIII, and Ne IX. For the first time, variations of the X-ray emission line widths as a function of the binary phase are found in a binary system, with the smallest widths at phase=0.0 when the secondary $\delta$ Orionis Aa2 is at inferior conjunction. Using 3D hydrodynamic modeling of the interacting winds, we relate the emission line width variability to the presence of a wind cavity created by a wind-wind collision, which is effectively void of embedded wind shocks and is carved out of the X-ray-producing primary wind, thus producing phase-locked X-ray variability.Comment: 36 pages, 14 Tables, 19 Figures, accepted by ApJ, one of 4 related papers to be published togethe

Quantitative optical determination of the shape of Cu nanocrystals in a composite film

5 pages, 4 figures, 1 table.We demonstrate that optical extinction spectroscopy can be used to determine the effective shape of Cu nanocrystals (NCs) embedded in a transparent amorphous Al2O3 host both produced by pulsed laser deposition. The axial ratio of the NCs was extracted from the positions of the surface plasmon modes of the optical extinction spectra of the nanocomposite film. Comparison to the results obtained by grazing incidence small angle x-ray scattering shows excellent agreement. Thus, optical spectroscopy can be used as a simple, easily accessible, and versatile tool for the characterization of the NCs that form nanocomposite films.This work was supported by the European Union (BRITE Project No. 98-0616).Peer reviewe

Does deprivation affect breast cancer management?

We evaluated whether social deprivation affected decision-making for breast cancer surgery. Of 3419 patients, 53.6% had mastectomy and this was predicted by deprivation, age, tumour size and hospital, all of which retained significance on multivariate analysis, except deprivation. Pathological characteristics and surgical decision-making determined choice of operation not deprivation

A Coordinated X-ray and Optical Campaign on the Nearest Massive Eclipsing Binary, Delta Ori Aa: I. Overview of the X-ray Spectrum

We present an overview of four phase-constrained Chandra HETGS X-ray observations of Delta Ori A. Delta Ori A is actually a triple system which includes the nearest massive eclipsing spectroscopic binary, Delta Ori Aa, the only such object which can be observed with little phase-smearing with the Chandra gratings. Since the fainter star, Delta Ori Aa2, has a much lower X-ray luminosity than the brighter primary, Delta Ori A provides a unique system with which to test the spatial distribution of the X-ray emitting gas around Delta Ori Aa1 via occultation by the photosphere of and wind cavity around the X-ray dark secondary. Here we discuss the X-ray spectrum and X-ray line profiles for the combined observation, having an exposure time of nearly 500 ksec and covering nearly the entire binary orbit. Companion papers discuss the X-ray variability seen in the Chandra spectra, present new space-based photometry and ground-based radial velocities simultaneous with the X-ray data to better constrain the system parameters, and model the effects of X-rays on the optical and UV spectrum. We find that the X-ray emission is dominated by embedded wind shock emission from star Aa1, with little contribution from the tertiary star Ab or the shocked gas produced by the collision of the wind of Aa1 against the surface of Aa2. We find a similar temperature distribution to previous X-ray spectrum analyses. We also show that the line half-widths are about $0.3-0.5\times$ the terminal velocity of the wind of star Aa1. We find a strong anti-correlation between line widths and the line excitation energy, which suggests that longer-wavelength, lower-temperature lines form farther out in the wind. Our analysis also indicates that the ratio of the intensities of the strong and weak lines of \ion{Fe}{17} and \ion{Ne}{10} are inconsistent with model predictions, which may be an effect of resonance scatteringComment: accepted by ApJ; revised according to ApJ proo

Luminescence from erbium-doped silicon nanocrystals in silica: Excitation mechanisms

We develop a model for the excitation of erbium ions in erbium-doped silicon nanocrystals via coupling from confined excitons generated within the silicon nanoclusters. The model provides a phenomenological picture of the exchange mechanism and allows us to evaluate an effective absorption cross section for erbium of up to 7.3x10(-17) cm(2): four orders of magnitude higher than in stoichiometric silica. We address the origin of the 1.6 eV emission band associated with the silicon nanoclusters and determine absorption cross sections and excitonic lifetimes for nanoclusters in silica which are of the order of 1.02x10(-16) cm(2) and 20-100 mus, respectively. (C) 2002 American Institute of Physics

The CDK9 C-helix Exhibits Conformational Plasticity That May Explain the Selectivity of CAN508

Correct regulation of transcription is essential for maintaining a healthy cellular state. During transcription RNA polymerase II (Pol II) proceeds in a regulated manner through several transitions to ensure appropriate control of synthesis and enable correct processing of the pre-RNA. Shortly after initiation Pol II is caused to pause by the binding of factors, DSIF and NELF. To enable transition of Pol II into the elongation phase CDK9/cyclin T phosphorylates the C-terminal domain (CTD) of Pol II, DSIF and NELF. This phosphorylation releases the paused state and provides an alternative set of post-transcriptional modifications on the CTD to generate a binding platform for elongation, histone modifying and termination factors. CDK9/cyclin T is itself regulated within multicomponent complexes. A small activated complex, containing Brd4, recruits CDK9/cyclin T to active sites of transcription, thereby promoting the elongation of transcription. The role of CDK9/cyclin T in the regulation of transcription has resulted in its validation as a drug target against several disease states including cancer, HIV and cardiac hypertrophy.In this thesis, I present the crystallographic structures of a series of 2-amino-4-heteroaryl-pyrimidine compounds and the roscovitine derivative, (S)-CR8, bound to CDK9/cyclin T and CDK2/cyclin A. In combination with thermal denaturation data and kinetic analysis, these structures have suggested chemical modifications that might be made to increase the CDK9 specificity of these compounds. I have also validated the use of a mutated form of cyclin T for use in the development of CDK9/cyclin T inhibitors.In addition, I present both structural and kinetic analysis of the Brd4-CDK9/cyclin T interaction. I show that C-terminal fragments of Brd4 enhance the in vitro kinase activity of CDK9/cyclin T against the Pol II CTD. Furthermore, I demonstrate that this enhancement may be inhibited by Plk1-mediated phosphorylation of Brd4. Finally, I show that Brd4 binds to a site that spans CDK9 and cyclin T and I propose detailed molecular models of the Brd4-cyclin T interaction.This thesis is not currently available via ORA

Transthoracic echocardiography for imaging of the different coronary artery segments: a feasibility study

<p>Abstract</p> <p>Background</p> <p>Transthoracic echocardiography (TTE) may be used for direct inspection of various parts of the main coronary arteries for detection of coronary stenoses and occlusions. We aimed to assess the feasibility of TTE to visualise the complete segments of the left main (LM), left descending (LAD), circumflex (Cx) and right (RCA) coronary arteries.</p> <p>Methods</p> <p>One hundred and eleven patients scheduled for diagnostic coronary angiography because of chest pain or acute coronary syndrome had a TTE study to map the passage of the main coronary arteries. LAD, Cx and RCA were each divided into proximal, middle and distal segments. If any part of the individual segment of a coronary artery with antegrade blood flow was not visualised, the segment was labeled as not satisfactorily seen.</p> <p>Results</p> <p>Complete imaging of the LM was achieved in 98% of the patients. With antegrade directed coronary artery flow, the proximal, middle and distal segments of LAD were completely seen in 96%, 95% and 91% of patients, respectively. Adding the completely seen segments with antegrade coronary flow and segments with retrograde coronary flow, the proximal, middle and distal segments of LAD were adequately visualised in 96%, 96% and 93% of patients, respectively. With antegrade directed coronary artery flow, the proximal, middle and distal segments of Cx were completely seen in 88%, 61% and 3% and in RCA in 40%, 28% and 54% of patients. Retrograde coronary artery flow was correctly identified as verified by coronary angiography in seven coronary segments, mainly in the posterior descending artery (labeled as the distal segment of RCA) and distal LAD.</p> <p>Conclusions</p> <p>TTE is a feasible method for complete demonstration of coronary flow in the LM, the proximal Cx and the different segments of LAD, but less suitable for the RCA and mid and distal segments of the Cx. (ClinicalTrials.gov number NTC00281346.)</p

Aerodynamic investigations of ventilated brake discs.

The heat dissipation and performance of a ventilated brake disc strongly depends on the aerodynamic characteristics of the flow through the rotor passages. The aim of this investigation was to provide an improved understanding of ventilated brake rotor flow phenomena, with a view to improving heat dissipation, as well as providing a measurement data set for validation of computational fluid dynamics methods. The flow fields at the exit of four different brake rotor geometries, rotated in free air, were measured using a five-hole pressure probe and a hot-wire anemometry system. The principal measurements were taken using two-component hot-wire techniques and were used to determine mean and unsteady flow characteristics at the exit of the brake rotors. Using phase-locked data processing, it was possible to reveal the spatial and temporal flow variation within individual rotor passages. The effects of disc geometry and rotational speed on the mean flow, passage turbulence intensity, and mass flow were determined. The rotor exit jet and wake flow were clearly observed as characterized by the passage geometry as well as definite regions of high and low turbulence. The aerodynamic flow characteristics were found to be reasonably independent of rotational speed but highly dependent upon rotor geometry

Therapy of human non-small-cell lung carcinoma using antibody targeting of a modified superantigen

Superantigens activate T-cells by linking the T-cell receptor to MHC class II on antigen-presenting cells, and novel reactivity can be introduced by fusing the superantigen to a targeting molecule. Thus, an antibody-targeted superantigen, which activates T cells to destroy tumour cells, might be used as cancer therapy. A suitable target is the 5T4 oncofetal antigen, which is expressed on many carcinomas. We constructed a fusion protein from a Fab of a monoclonal antibody recognizing the 5T4 antigen, and an engineered superantigen. The recombinant product 5T4FabV13-SEAD227A bound the 5T4 antigen expressed on the human non-small-cell lung cancer cell line Calu-1 with a Kd of 1.2 nM while the substitution of Asp227 to Ala in the superantigen moiety reduced binding activity to MHC class II. 5T4FabV13-SEAD227A tumour reactivity was demonstrated in 7/7 NSCLC samples by immunohistochemistry, while normal tissue reactivity was low to moderate. 5T4FabV13-SEAD227A induced significant T-cell-dependent in vitro killing of sensitive 5T4 bearing Calu-1 cells, with maximum lysis at 10−10M, while the capacity to lyse MHC class II expressing cells was approximately 1000 times less effective. Immunotherapy of 5T4FabV13-SEAD227A against human NSCLC was investigated in SCID mice reconstituted with human peripheral blood mononuclear cells. Mice carrying intreperitoneally growing Calu-1 cells showed significant reduction in tumour mass and number after intravenous therapy with 5T4FabV13-SEAD227A. Thus, 5T4FabV13-SEAD227A has highly attractive properties for therapy of human NSCLC. © 2001 Cancer Research Campaign http://www.bjcancer.co

Conservative kidney management and kidney supportive care:core components of integrated care for people with kidney failure

Integrated kidney care requires synergistic linkage between preventative care for people at risk for chronic kidney disease and health services providing care for people with kidney disease, ensuring holistic and coordinated care as people transition between acute and chronic kidney disease and the 3 modalities of kidney failure management: conservative kidney management, transplantation, and dialysis. People with kidney failure have many supportive care needs throughout their illness, regardless of treatment modality. Kidney supportive care is therefore a vital part of this integrated framework, but is nonexistent, poorly developed, and/or poorly integrated with kidney care in many settings, especially in low- and middle-income countries. To address this, the International Society of Nephrology has (i) coordinated the development of consensus definitions of conservative kidney management and kidney supportive care to promote international understanding and awareness of these active treatments; and (ii) identified key considerations for the development and expansion of conservative kidney management and kidney supportive care programs, especially in low resource settings, where access to kidney replacement therapy is restricted or not available. This article presents the definitions for conservative kidney management and kidney supportive care; describes their core components with some illustrative examples to highlight key points; and describes some of the additional considerations for delivering conservative kidney management and kidney supportive care in low resource settings.</p