Cardiac rehabilitation versus standard care after aortic aneurysm repair (Aneurysm CaRe): study protocol for a randomised controlled trial.

BACKGROUND: Abdominal and thoracic aortic aneurysms (A/TAA) are an important cause of mortality amongst the older population. Although A/TAA repair can be performed with low peri-operative risk, overall life expectancy remains poor in the years that follow surgery. The majority of deaths are caused by heart attack or stroke, which can both be prevented by cardiac rehabilitation (CR) in patients with clinically-manifest coronary artery disease. A Cochrane review has urged researchers to widen the use of CR to other populations with severe cardiovascular risk, and patients surviving A/TAA repair appear ideal candidates. However, it is unknown whether CR is feasible or acceptable to A/TAA patients, who are a decade older than those currently enrolling in CR. Aneurysm-CaRe is a feasibility randomised controlled trial (RCT) that will address these issues. METHODS AND DESIGN: Aneurysm-CaRe is a pilot RCT of CR versus standard care after A/TAA repair, with the primary objectives of estimating enrolment to a trial of CR after A/TAA repair and estimating compliance with CR amongst patients with A/TAA. Aneurysm-CaRe will randomise 84 patients at two sites. Patients discharged from hospital after elective A/TAA repair will be randomised to standard care or enrolment in their local CR programme with a protocolised approach to medical cardiovascular risk reduction. The primary outcome measures are enrolment in the RCT and compliance with CR. Secondary outcomes will include phenotypic markers of cardiovascular risk and smoking cessation, alongside disease-specific and generic quality-of-life measures. TRIAL REGISTRATION: ISRCTN 65746249 5 June 2014

Метафизическое значение категорий предмета и непредмета в логике, поясняемое примерами решения антиномии Рассела в теории типов и аксиоматической системе NBG

Метафизическое значение категорий предмета и непредмета в логике, поясняемое примерами решения антиномии Рассела в теории типов и аксиоматической системе NB

Mitochondrial phylogeography and demographic history of the Vicuña: implications for conservation

The vicuña (Vicugna vicugna; Miller, 1924) is a conservation success story, having recovered from near extinction in the 1960s to current population levels estimated at 275 000. However, lack of information about its demographic history and genetic diversity has limited both our understanding of its recovery and the development of science-based conservation measures. To examine the evolution and recent demographic history of the vicuña across its current range and to assess its genetic variation and population structure, we sequenced mitochondrial DNA from the control region (CR) for 261 individuals from 29 populations across Peru, Chile and Argentina. Our results suggest that populations currently designated as Vicugna vicugna vicugna and Vicugna vicugna mensalis comprise separate mitochondrial lineages. The current population distribution appears to be the result of a recent demographic expansion associated with the last major glacial event of the Pleistocene in the northern (18 to 22°S) dry Andes 14–12 000 years ago and the establishment of an extremely arid belt known as the 'Dry Diagonal' to 29°S. Within the Dry Diagonal, small populations of V. v. vicugna appear to have survived showing the genetic signature of demographic isolation, whereas to the north V. v. mensalis populations underwent a rapid demographic expansion before recent anthropogenic impacts

Quantitative principles of cis-translational control by general mRNA sequence features in eukaryotes.

BackgroundGeneral translational cis-elements are present in the mRNAs of all genes and affect the recruitment, assembly, and progress of preinitiation complexes and the ribosome under many physiological states. These elements include mRNA folding, upstream open reading frames, specific nucleotides flanking the initiating AUG codon, protein coding sequence length, and codon usage. The quantitative contributions of these sequence features and how and why they coordinate to control translation rates are not well understood.ResultsHere, we show that these sequence features specify 42-81% of the variance in translation rates in Saccharomyces cerevisiae, Schizosaccharomyces pombe, Arabidopsis thaliana, Mus musculus, and Homo sapiens. We establish that control by RNA secondary structure is chiefly mediated by highly folded 25-60 nucleotide segments within mRNA 5' regions, that changes in tri-nucleotide frequencies between highly and poorly translated 5' regions are correlated between all species, and that control by distinct biochemical processes is extensively correlated as is regulation by a single process acting in different parts of the same mRNA.ConclusionsOur work shows that general features control a much larger fraction of the variance in translation rates than previously realized. We provide a more detailed and accurate understanding of the aspects of RNA structure that directs translation in diverse eukaryotes. In addition, we note that the strongly correlated regulation between and within cis-control features will cause more even densities of translational complexes along each mRNA and therefore more efficient use of the translation machinery by the cell

High temperature optical absorption investigation into the electronic transitions in sol–gel derived C12A7 thin films

Optical absorption into 6 mm thick sol–gel derived films, annealed at 1300 °C of 12CaO·7Al2O3 calcium aluminate binary compound on MgO〈100〉 single crystal substrates was studied at temperatures ranging from room temperature to 300 °C. Experimental data were analysed in both Tauc and Urbach regions. The optical band gap decreased from 4.088 eV at 25 °C to 4.051 eV at 300 °C, while Urbach energy increased from 0.191 eV at 25 °C to 0.257 eV at 300 °C. The relationship between the optical band gap and the Urbach energy at different temperatures showed an almost linear relationship from which the theoretical values of 4.156 and 0.065 eV were evaluated for the band gap energy and Urbach energy of a 12CaO·7Al2O3 crystal with zero structural disorder at 0 K

Structural analysis of MDM2 RING separates degradation from regulation of p53 transcription activity

MDM2–MDMX complexes bind the p53 tumor-suppressor protein, inhibiting p53's transcriptional activity and targeting p53 for proteasomal degradation. Inhibitors that disrupt binding between p53 and MDM2 efficiently activate a p53 response, but their use in the treatment of cancers that retain wild-type p53 may be limited by on-target toxicities due to p53 activation in normal tissue. Guided by a novel crystal structure of the MDM2–MDMX–E2(UbcH5B)–ubiquitin complex, we designed MDM2 mutants that prevent E2–ubiquitin binding without altering the RING-domain structure. These mutants lack MDM2's E3 activity but retain the ability to limit p53′s transcriptional activity and allow cell proliferation. Cells expressing these mutants respond more quickly to cellular stress than cells expressing wild-type MDM2, but basal p53 control is maintained. Targeting the MDM2 E3-ligase activity could therefore widen the therapeutic window of p53 activation in tumors

Massive stars as thermonuclear reactors and their explosions following core collapse

Nuclear reactions transform atomic nuclei inside stars. This is the process of stellar nucleosynthesis. The basic concepts of determining nuclear reaction rates inside stars are reviewed. How stars manage to burn their fuel so slowly most of the time are also considered. Stellar thermonuclear reactions involving protons in hydrostatic burning are discussed first. Then I discuss triple alpha reactions in the helium burning stage. Carbon and oxygen survive in red giant stars because of the nuclear structure of oxygen and neon. Further nuclear burning of carbon, neon, oxygen and silicon in quiescent conditions are discussed next. In the subsequent core-collapse phase, neutronization due to electron capture from the top of the Fermi sea in a degenerate core takes place. The expected signal of neutrinos from a nearby supernova is calculated. The supernova often explodes inside a dense circumstellar medium, which is established due to the progenitor star losing its outermost envelope in a stellar wind or mass transfer in a binary system. The nature of the circumstellar medium and the ejecta of the supernova and their dynamics are revealed by observations in the optical, IR, radio, and X-ray bands, and I discuss some of these observations and their interpretations.Comment: To be published in " Principles and Perspectives in Cosmochemistry" Lecture Notes on Kodai School on Synthesis of Elements in Stars; ed. by Aruna Goswami & Eswar Reddy, Springer Verlag, 2009. Contains 21 figure

The transcriptional repressor protein NsrR senses nitric oxide directly via a [2Fe-2S] cluster

The regulatory protein NsrR, a member of the Rrf2 family of transcription repressors, is specifically dedicated to sensing nitric oxide (NO) in a variety of pathogenic and non-pathogenic bacteria. It has been proposed that NO directly modulates NsrR activity by interacting with a predicted [Fe-S] cluster in the NsrR protein, but no experimental evidence has been published to support this hypothesis. Here we report the purification of NsrR from the obligate aerobe Streptomyces coelicolor. We demonstrate using UV-visible, near UV CD and EPR spectroscopy that the protein contains an NO-sensitive [2Fe-2S] cluster when purified from E. coli. Upon exposure of NsrR to NO, the cluster is nitrosylated, which results in the loss of DNA binding activity as detected by bandshift assays. Removal of the [2Fe-2S] cluster to generate apo-NsrR also resulted in loss of DNA binding activity. This is the first demonstration that NsrR contains an NO-sensitive [2Fe-2S] cluster that is required for DNA binding activity

What is the potential of p53 isoforms as a predictive biomarker in the treatment of cancer?

Introduction: For decades, p53 was researched as a single protein with alterations described as mutants. The discovery of 12 human p53 isoforms expressed from 9 transcripts changed this perception, eloquently explaining the numerous roles p53 plays, including apoptosis, senescence, and regeneration. Area covered: Here, we summarise the p53 isoforms and their relevance to cancer to establish an understanding and theorise on potential applications of the isoforms in clinical practice. Expert commentary: Pertaining to the different expression of isoforms in different tumors, it is concluded that the clinical use of isoforms as prognostic and predictive biomarkers will be different depending on the cell type, the tissue origin of the tumors, the position of the TP53 mutation and the driver-oncogene.</p

Quantum Gravity in 2+1 Dimensions: The Case of a Closed Universe

In three spacetime dimensions, general relativity drastically simplifies, becoming a ``topological'' theory with no propagating local degrees of freedom. Nevertheless, many of the difficult conceptual problems of quantizing gravity are still present. In this review, I summarize the rather large body of work that has gone towards quantizing (2+1)-dimensional vacuum gravity in the setting of a spatially closed universe.Comment: 61 pages, draft of review for Living Reviews; comments, criticisms, additions, missing references welcome; v2: minor changes, added reference