Deep vein thrombosis and pulmonary embolus associated with a ruptured popliteal aneurysm – a cautionary note

Popliteal artery aneurysms representing 80% of peripheral artery aneurysms rarely rupture (a reported incidence of 0.1–2.8 %) and second commonest in frequency after aorto-iliac aneurysms. They usually present with pain, swelling, occlusion or distal embolisation and can cause diagnostic difficulties. We report a 78 year old man who was previously admitted to hospital with a pulmonary embolus secondary to deep venous thrombosis. He was heparinized then warfarinised and was readmitted with a ruptured popliteal aneurysm leading to a large pseudo aneurysm formation. The pulmonary embolus had been due to popliteal vein thrombosis and propagation of the clot. A thorough review of literature identified only one previously reported case of ruptured popliteal artery aneurysm and subsequent large pseudo aneurysm formation. We feel it is important to exclude a popliteal aneurysm in a patient with DVT. This may be more common than the published literature suggests

Chemoenzymatic elaboration of monosaccharides using engineered cytochrome P450_(BM3) demethylases

Polysaccharides comprise an extremely important class of biopolymers that play critical roles in a wide range of biological processes, but the synthesis of these compounds is challenging because of their complex structures. We have developed a chemoenzymatic method for regioselective deprotection of monosaccharide substrates using engineered Bacillus megaterium cytochrome P450 (P450_(BM3)) demethylases that provides a highly efficient means to access valuable intermediates, which can be converted to a wide range of substituted monosaccharides and polysaccharides. Demethylases displaying high levels of regioselectivity toward a number of protected monosaccharides were identified using a combination of protein and substrate engineering, suggesting that this approach ultimately could be used in the synthesis of a wide range of substituted mono- and polysaccharides for studies in chemistry, biology, and medicine

KECK HIRES Spectroscopy of APM 08279+5255

With an optical R-band magnitude of 15.2, the recently discovered z=3.911 BAL quasar APM 08279+5255 is an exceptionally bright high redshift source. Its brightness has allowed us to acquire a high signal-to-noise ratio (~100), high resolution (~6 km/s) spectrum using the HIRES echelle spectrograph on the 10-m Keck I telescope. Given the quality of the data, these observations provide an unprecedented view of associated and intervening absorption systems. Here we announce the availability of this spectrum to the general astronomical community and present a brief analysis of some of its main features.Comment: 21 pages including 5 figures. Accepted for publication by PAS

An Integrated Content and Metadata based Retrieval System for Art

In this paper we describe aspects of the Artiste project to develop a distributed content and metadata based analysis, retrieval and navigation system for a number of major European Museums. In particular, after a brief overview of the complete system, we describe the design and evaluation of some of the image analysis algorithms developed to meet the specific requirements of the users from the museums. These include a method for retrievals based on sub images, retrievals based on very low quality images and retrieval using craquelure type

Mechanical behaviour and environmental stability of continuous fibre-reinforced glass-ceramic matrix composites

The mechanical behaviour of three continuous Silicon carbide fibre-reinforced glass-ceramic matrix composites has been investigated at room and high temperatures. Commercially available composites with magnesium aluminosilicate, calcium aluminosilicate and barium magnesium aluminosilicate glass-ceramic matrices were considered. The materials were tested in the as-received and aged (heat-treated in a n oxidizing environment) condition. Four-point bend static tests and fiexural creep, fatigue and creep-fatigue tests were carried out a s well as a small quantity of tensile tests of aged composites. The experimental results have highlighted the importance of the carbon-rich layer at the fibre/matrix interface for obtaining "graceful" failures. At temperatures of 700 to 800 °C oxidative degradation of the interface results in significant strength reduction and a transition to brittle fracture mode. By rapid heat treatment of the materials at 1100°C for 1 h it is possible to seal the fibre ends by forming a silica "plug" which prevents oxygen ingress, retaining the carbon-rich interphase and composite behaviour. The results of the creep and creep-fatigue tests indicate low-cycle loading has a strong influence on the life of components at high temperatures

Density Variations in the NW Star Stream of M31

The Pan Andromeda Archeological Survey (PAndAS) CFHT Megaprime survey of the M31-M33 system has found a star stream which extends about 120 kpc NW from the center of M31. The great length of the stream, and the likelihood that it does not significantly intersect the disk of M31, means that it is unusually well suited for a measurement of stream gaps and clumps along its length as a test for the predicted thousands of dark matter sub-halos. The main result of this paper is that the density of the stream varies between zero and about three times the mean along its length on scales of 2 to 20 kpc. The probability that the variations are random fluctuations in the star density is less than 10^-5. As a control sample we search for density variations at precisely the same location in stars with metallicity higher than the stream, [Fe/H]=[0, -0.5] and find no variations above the expected shot noise. The lumpiness of the stream is not compatible with a low mass star stream in a smooth galactic potential, nor is it readily compatible with the disturbance caused by the visible M31 satellite galaxies. The stream's density variations appear to be consistent with the effects of a large population of steep mass function dark matter sub-halos, such as found in LCDM simulations, acting on an approximately 10Gyr old star stream. The effects of a single set of halo substructure realizations are shown for illustration, reserving a statistical comparison for another study.Comment: ApJ revised version submitte

Understanding Cytotoxicity and Cytostaticity in a High-Throughput Screening Collection.

While mechanisms of cytotoxicity and cytostaticity have been studied extensively from the biological side, relatively little is currently understood regarding areas of chemical space leading to cytotoxicity and cytostasis in large compound collections. Predicting and rationalizing potential adverse mechanism-of-actions (MoAs) of small molecules is however crucial for screening library design, given the link of even low level cytotoxicity and adverse events observed in man. In this study, we analyzed results from a cell-based cytotoxicity screening cascade, comprising 296 970 nontoxic, 5784 cytotoxic and cytostatic, and 2327 cytostatic-only compounds evaluated on the THP-1 cell-line. We employed an in silico MoA analysis protocol, utilizing 9.5 million active and 602 million inactive bioactivity points to generate target predictions, annotate predicted targets with pathways, and calculate enrichment metrics to highlight targets and pathways. Predictions identify known mechanisms for the top ranking targets and pathways for both phenotypes after review and indicate that while processes involved in cytotoxicity versus cytostaticity seem to overlap, differences between both phenotypes seem to exist to some extent. Cytotoxic predictions highlight many kinases, including the potentially novel cytotoxicity-related target STK32C, while cytostatic predictions outline targets linked with response to DNA damage, metabolism, and cytoskeletal machinery. Fragment analysis was also employed to generate a library of toxicophores to improve general understanding of the chemical features driving toxicity. We highlight substructures with potential kinase-dependent and kinase-independent mechanisms of toxicity. We also trained a cytotoxic classification model on proprietary and public compound readouts, and prospectively validated these on 988 novel compounds comprising difficult and trivial testing instances, to establish the applicability domain of models. The proprietary model performed with precision and recall scores of 77.9% and 83.8%, respectively. The MoA results and top ranking substructures with accompanying MoA predictions are available as a platform to assess screening collections.Biotechnology and Biological Sciences Research Council, AstraZenec

Multi-objective engineering shape optimization using differential evolution interfaced to the Nimrod/O tool

This paper presents an enhancement of the Nimrod/O optimization tool by interfacing DEMO, an external multiobjective optimization algorithm. DEMO is a variant of differential evolution – an algorithm that has attained much popularity in the research community, and this work represents the first time that true multiobjective optimizations have been performed with Nimrod/O. A modification to the DEMO code enables multiple objectives to be evaluated concurrently. With Nimrod/O’s support for parallelism, this can reduce the wall-clock time significantly for compute intensive objective function evaluations. We describe the usage and implementation of the interface and present two optimizations. The first is a two objective mathematical function in which the Pareto front is successfully found after only 30 generations. The second test case is the three-objective shape optimization of a rib-reinforced wall bracket using the Finite Element software, Code_Aster. The interfacing of the already successful packages of Nimrod/O and DEMO yields a solution that we believe can benefit a wide community, both industrial and academic

UBC-Nepal expedition: The use of oral antioxidants does not alter cerebrovascular function at sea-level or high-altitude

Hypoxia is associated with an increased systemic and cerebral formation of free radicals and associated reactants that may be linked to impaired cerebral vascular function a neurological sequela. To what extent oral antioxidants prophylaxis impacts cerebrovascular function in humans throughout the course of acclimatization to the hypoxia of terrestrial high-altitude has not been examined. Thus, the purpose of the current study was to examine the influence of orally ingested antioxidants at clinically relevant doses (vitamin C, E, and alpha-lipoic acid) on cerebrovascular regulation at sea-level (344 m; n = 12; female n = 2 participants), and at high altitude (5050 m; n = 9; female n = 2), in a randomized, placebo-controlled, and double-blinded crossover design. Hypercapnic and hypoxic cerebrovascular reactivity tests of the internal carotid (ICA)] were conducted at sea-level, while global and regional cerebral blood flow [i.e. ICA and vertebral artery (VA)] were assessed after 10–12 days following arrival at 5050 m. At sea-level, acute administration of antioxidants did not alter cerebral hypoxic cerebrovascular reactivity (pre vs. post: 1.5 ± 0.7 vs. 1.2 ± 0.8 %∆CBF/-%∆SpO2; P = 0.96), or cerebral hypercapnic cerebrovascular reactivity (pre vs. post: 5.7 ± 2.0 vs. 5.8 ± 1.9 %∆CBF/∆mmHg; P = 0.33). Furthermore, global cerebral blood flow (P = 0.43), as well as cerebral vascular conductance (ICA P = 0.08; VA P = 0.32), were unaltered at 5050 m following antioxidant administration. In conclusion, these data show that an oral antioxidant cocktail known to attenuate systemic oxidative stress failed to alter cerebrovascular function at sea-level and cerebral blood flow during acclimatization to high-altitude