284 research outputs found
The Ecology and Evolution of Cancer: The Ultra-Microevolutionary Process
No full textAlthough tumorigenesis has been accepted as an evolutionary process (20, 102), many forces may operate differently in cancers than in organisms, as they evolve at vastly different time scales. Among such forces, natural selection, here defined as differential cellular proliferation among distinct somatic cell genotypes, is particularly interesting because its action might be thwarted in multicellular organisms (20, 29). In this review, selection is analyzed in two stages of cancer evolution: Stage I is the evolution between tumors and normal tissues, and Stage II is the evolution within tumors. The Cancer Genome Atlas (TCGA) data show a low degree of convergent evolution in Stage I, where genetic changes are not extensively shared among cases. An equally important, albeit much less highlighted, discovery using TCGA data is that there is almost no net selection in cancer evolution. Both positive and negative selection are evident but they neatly cancel each other out, rendering total selection ineffective in the absence of recombination. The efficacy of selection is even lower in Stage II, where neutral (non-Darwinian) evolution is increasingly supported by high-density sampling studies (81, 123). Because natural selection is not a strong deterministic force, cancers usually evolve divergently even in similar tissue environments
LLB MACRO-SPIN MODELLING OF NANOGRANULAR L1o FePt HIGH ANISOTROPY THIN FILMS
No full textNew recording media and recording methods are required if magnetic data storage is to continue the historic growth seen in the areal density, beyond the level currently imposed by the superparamagnetic limit. High anisotropy nano-granular L1o FePt thin films are currently being studied as a proposed material capable of continuing the exponential growth in areal density. FePt is so successful at maintaining a permanent magnetisation, that no applicable
magnetic field is capable of reversing the magnetisation, as in the recording process. Heat assisted magnetic recording is a proposed method of lowering the anisotropy, of the high anisotropy recording media, to a level that can be recorded in. In this thesis a nano-granular high anisotropy FePt thin film is modelled using the newly developed Landau-Lifshit-Bloch equation (to model the dynamic motion if the magnetisation) combined with a voronoi construction. The HAMR process is described over a range of maximum temperatures and modelled thin films of increasing anisotropy. It is shown that a 12000Oe applied field and a maximum temperature of Tc are required to reverse the magnetisation to the desired level. The model is used to demonstrate the lowering of the anisotropy field at elevated temperatures, allowing relatively low applied fields to set the magnetisation. The LLB equation also recovers the newly discovered fast acting linear reversal mode, at temperatures close to the Curie point
Rationale and design of the RIGHT trial: A multicenter, randomized, double-blind, placebo-controlled trial of anticoagulation prolongation versus no anticoagulation after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction
No full textInternational audienceFull text linksfull-text provider logoActionsFavoritesSharePage navigation Title & authors Abstract Similar articles Publication types MeSH terms Substances Related information LinkOut - more resourcesComparative StudyAm Heart J. 2020 Sep;227:19-30.doi: 10.1016/j.ahj.2020.06.005. Epub 2020 Jun 20.Rationale and design of the RIGHT trial: A multicenter, randomized, double-blind, placebo-controlled trial of anticoagulation prolongation versus no anticoagulation after primary percutaneous coronary intervention for ST-segment elevation myocardial infarctionYan Yan 1 , Xiao Wang 2 , Jincheng Guo 3 , Yongjun Li 4 , Hui Ai 5 , Wei Gong 6 , Bin Que 7 , Lei Zhen 8 , Jiapeng Lu 9 , Changsheng Ma 10 , Gilles Montalescot 11 , Shaoping Nie 12Affiliations PMID: 32663660 DOI: 10.1016/j.ahj.2020.06.005 AbstractBackground: Current guidelines recommend anticoagulation therapy during primary percutaneous coronary intervention (pPCI) for ST-segment elevation myocardial infarction (STEMI). However, whether anticoagulation should be continued after pPCI has not been well investigated.Methods/design: The RIGHT trial is a prospective, multicenter, randomized, double-blind, placebo-controlled trial in STEMI patients treated with pPCI evaluating the prolongation of anticoagulation after the procedure. Patients are randomized in a 1:1 fashion to receive either prolonged anticoagulant or matching placebo (no anticoagulation) for at least 48 hours after the procedure. When randomized to anticoagulation prolongation, the patient is assigned to intravenous unfractionated heparin (UFH) or subcutaneous enoxaparin or intravenous bivalirudin (same drug and same regimen at each center). The primary efficacy endpoint is the composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, stent thrombosis (definite) or urgent revascularization (any vessel) at 30 days. The primary safety endpoint is major bleeding (BARC 3-5) at 30 days. Based on a superiority design and assuming a 35% relative risk reduction (from 7% to 4.5%), 2856 patients will be enrolled, accounting for a 5% drop-out rate (α = 0.05 and power = 80%).Conclusion: The RIGHT trial tests the hypothesis that post-procedural anticoagulation is superior to no anticoagulation in reducing ischemic events in STEMI patients undergoing pPCI
Deletion of vitamin D receptor leads to premature emphysema/COPD by increased matrix metalloproteinases and lymphoid aggregates formation
No full textDeficiency of vitamin D is associated with accelerated decline in lung function. Vitamin D is a ligand for nuclear hormone vitamin D receptor (VDR), and upon binding it modulates various cellular functions. The level of VDR is reduced in lungs of patients with chronic obstructive pulmonary disease (COPD) which led us to hypothesize that deficiency of VDR leads to significant alterations in lung phenotype that are characteristics of COPD/emphysema associated with increased inflammatory response. We found that VDR knock-out (VDR(-/-)) mice had increased influx of inflammatory cells, phospho-acetylation of nuclear factor-kappaB (NF-κB) associated with increased proinflammatory mediators, and up-regulation of matrix metalloproteinases (MMPs) MMP-2, MMP-9, and MMP-12 in the lung. This was associated with emphysema and decline in lung function associated with lymphoid aggregates formation compared to WT mice. These findings suggest that deficiency of VDR in mouse lung can lead to an early onset of emphysema/COPD because of chronic inflammation, immune dysregulation, and lung destruction
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An inverse model study of abrupt climate change during last ice age
No full texttextGeologic records and climate model simulations suggest that changes in the meridional heat transport in the Atlantic Ocean were involved in the abrupt warming events – the so-called Dansgaard-Oeschger Interstadials (DOIs) – that punctuated an otherwise cold Greenland climate during the last glacial period. However, the role of Northern Hemisphere (NH) ice sheets in these events remains a subject of controversy. Here we report on the first attempt to combine quantitatively a paleo-temperature proxy with simplified ocean models, with the specific purpose of extracting information about the changes in mass balance of the NH ice sheets during the last glaciation. A Greenland paleotemperature record is combined with the climate models using Bayesian Stochastic Inversion (BSI) in order to estimate the changes that would be required to alter the Atlantic Ocean mass and heat transports between ~30 and 39 thousand years ago. The mean sea level changes implied by changes in NH ice sheet mass balance agree in amplitude and timing with reconstructions from the geologic record, which gives some support to the freshwater forcing hypothesis. Our results are unaffected by uncertainties in the representation of vertical buoyancy transport in the tropical ocean, in large part because the global adjustments to high latitude freshening bypass the tropics and affect sinking rate in the opposite pole. However, the solutions are sensitive to assumptions about physical processes at polar latitudes. We find that the inversion reproduces the gradual changes in sea level and Antarctic temperature inferred from the independent evidence provided by proxy records. The Greenland warm event lasting over 3000 years (DOI 8) can be explained by sustained growth of NH ice sheet and reduced supply of icebergs to the North Atlantic. Our results indicate a more involved role of the NH ice sheets than previously thought, in which both collapse and subsequent growth would be required to explain the full series of the long (> 3000 years) warm events recorded in Greenland ice.Physic
Performance Degradation Prediction Based on a Gaussian Mixture Model and Optimized Support Vector Regression for an Aviation Piston Pump
No full textPerformance degradation prediction plays a key role in realizing aviation pump health management and condition-based maintenance. Thus, this paper proposes a new approach that combines a Gaussian mixture model (GMM) and optimized support vector regression (SVR) to predict aviation pumps’ degradation processes based on the pump outlet pressure signals. Different from other feature extraction methods in which the information of intrinsic mode functions (IMFs) is not fully utilized, some useful IMF components are firstly chosen, and the corresponding multi-domain features are extracted from each selected component. Considering that it is not the case that all features are equally sensitive to degradation assessment, PCA is used to select more sensitive degradation features. Since the distribution of these extracted features is a stochastic process in feature space, meanwhile, self-information quantity can describe the uncertainty of system by measuring the average information quantity contained in the probability distribution, self-information quantity based on GMM is defined as degradation index (DI) to describe the degradation degree of the pump quantitatively. Finally, an SVR model is constructed to predict the degradation status of the pump. To achieve higher prediction accuracy, phase space reconstruction theory is first employed to determine the number of the inputs of the SVR model, then a new method combining particle swarm optimization (PSO) with grid search (GS) is developed to optimize the parameters of the SVR model. Finally, both the online data and historical data are utilized for the construction of the SVR model, respectively. The effectiveness of the proposed approach is validated by full life cycle data collected from an aviation pump test rig. The results demonstrate that the DI extracted from pump outlet pressure signals can effectively identify and track the current deterioration stage, and the established SVR model has better prediction ability when compared with previously published methods
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