Makar-Limanov's conjecture on free subalgebras

It is proved that over every countable field K there is a nil algebra R such that the algebra obtained from R by extending the field K contains noncommutative free subalgebras of arbitrarily high rank. It is also shown that over every countable field K there is an algebra R without noncommutative free subalgebras of rank two such that the algebra obtained from R by extending the field K contains a noncommutative free subalgebra of rank two. This answers a question of Makar-Limano

A size-dependent functionally graded sinusoidal plate model based on a modified couple stress theory

A size-dependent model for bending and free vibration of functionally graded plate is developed based on the modified couple stress theory and sinusoidal shear deformation theory. In the former theory, the small scale effect is taken into consideration, while the effect of shear deformation is accounted for in the latter theory. The equations of motion and boundary conditions are derived from Hamilton’s principle. Analytical solutions for the bending and vibration problems of simply supported plates are obtained. Numerical examples are presented to illustrate the influences of small scale on the responses of functionally graded microplates. The results indicate that the inclusion of small scale effects results in an increase in plate stiffness, and consequently, leads to a reduction of deflection and an increase in frequency. Such small scale effects are significant when the plate thickness is small, but become negligible with increasing plate thickness

Island coarsening in one-dimensional models with partially and completely reversible aggregation

Using computer simulations and scaling ideas, we study one-dimensional models of diffusion, aggregation and detachment of particles from islands in the post-deposition regime, i. e. without flux. The diffusion of isolated particles takes place with unit rate, aggregation occurs immediately upon contact with another particle or island, and detachment from an island occurs with rate epsilon = exp(-E/kT), where E is the related energy barrier. In the partially reversible model, dissociation is limited to islands of size larger than a critical value i, while in the completely reversible model there is no restriction to that process (infinite i). Extending previous simulation results for the completely reversible case, we observe that a peaked island size distribution in the intermediate time regime, in which the mean island size is increasing, crosses over to the theoretically predicted exponentially decreasing distribution at long times. It contrasts with the partially reversible model, in which peaked distributions are obtained until the long time frozen state, which is attained with a crossover time $\tau \sim \frac{i^3}{\epsilon}$. The mean island size at saturation varies as $S_{sat}\approx 2i+C\epsilon$ (C constant), while the completely reversible case shows an Ahrrenius dependence of the mean island size, $S\sim \epsilon^{-1/2}$. Thus, for different coverages, the effect of the critical size i on the geometric features is much stronger than that of epsilon, which may be used to infer the relevance of size-dependent detachment rates in real systems and other models.Comment: 14 pages,8 figures, accepted for publication in Physica

Heart failure around the world

With increasingly large sample sizes required to demonstrate event reduction, heart failure outcome trials are no longer being performed in a small group of selected patients and countries, but at a global scale with worldwide contribution of patients from countries with considerable differences in background therapy, socioeconomic status and healthcare practices. Recent studies have highlighted how socioeconomic determinants rather than geographical factors may underlie the heterogeneity of patient populations across the globe. Therefore, in this review, we evaluated (i) regional differences in patient characteristics and outcomes in recent epidemiologic studies; (ii) regional differences in worldwide representativeness of clinical trial populations; and (iii) the role of socioeconomic determinants in driving country differences in heart failure trial enrolment and clinical outcomes

The Ribosome Biogenesis Protein Nol9 Is Essential for Definitive Hematopoiesis and Pancreas Morphogenesis in Zebrafish.

Ribosome biogenesis is a ubiquitous and essential process in cells. Defects in ribosome biogenesis and function result in a group of human disorders, collectively known as ribosomopathies. In this study, we describe a zebrafish mutant with a loss-of-function mutation in nol9, a gene that encodes a non-ribosomal protein involved in rRNA processing. nol9sa1022/sa1022 mutants have a defect in 28S rRNA processing. The nol9sa1022/sa1022 larvae display hypoplastic pancreas, liver and intestine and have decreased numbers of hematopoietic stem and progenitor cells (HSPCs), as well as definitive erythrocytes and lymphocytes. In addition, ultrastructural analysis revealed signs of pathological processes occurring in endothelial cells of the caudal vein, emphasizing the complexity of the phenotype observed in nol9sa1022/sa1022 larvae. We further show that both the pancreatic and hematopoietic deficiencies in nol9sa1022/sa1022 embryos were due to impaired cell proliferation of respective progenitor cells. Interestingly, genetic loss of Tp53 rescued the HSPCs but not the pancreatic defects. In contrast, activation of mRNA translation via the mTOR pathway by L-Leucine treatment did not revert the erythroid or pancreatic defects. Together, we present the nol9sa1022/sa1022 mutant, a novel zebrafish ribosomopathy model, which recapitulates key human disease characteristics. The use of this genetically tractable model will enhance our understanding of the tissue-specific mechanisms following impaired ribosome biogenesis in the context of an intact vertebrate.The study was supported by Cancer Research UK (grant number C45041/A14953 to AC and LF), Wellcome Trust (grants number 084183/Z/07/Z to EBM and number 098051 to DLS and LLH), Specialist Programme from Bloodwise [12048], the Medical Research Council [MC_U105161083] and Ted’s Gang (to AJW), a Wellcome Trust strategic award to the Cambridge Institute for Medal Research [100140] and the Cambridge NIHR Biomedical Research Centre (to AJW and AC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.This is the final version of the article. It was first available from PLOS via http://dx.doi.org/10.1371/journal.pgen.100567

New-onset atrial fibrillation in patients with worsening heart failure and coronary artery disease:an analysis from the COMMANDER-HF trial

Background: Atrial fibrillation (AF) in the presence of heart failure (HF) is associated with poor outcomes including a high-risk of stroke and other thromboembolic events. Identifying patients without AF who are at high-risk of developing this arrhythmia has important clinical implications. Aims: To develop a risk score to identify HF patients at high risk of developing AF. Methods: The COMMANDER-HF trial enrolled 5022 patients with HF and a LVEF ≤ 40%, history of coronary artery disease, and absence of AF at baseline (confirmed with an electrocardiogram). Patients were randomized to either rivaroxaban (2.5 mg bid) or placebo. New-onset AF was confirmed by the investigator at study visits. Results 241 (4.8%) patients developed AF during the follow-up (median 21 months). Older age (≥ 65 years), LVEF < 35%, history of PCI or CABG, White race, SBP < 110 mmHg, and higher BMI (≥ 25 kg/m2) were independently associated with risk of new-onset AF, whereas the use of DAPT was associated with a lower risk of new-onset AF. We then built a risk score from these variables (with good accuracy C-index = 0.71) and calibration across observed and predicted tertiles of risk. New-onset AF events rates increased steeply by increasing tertiles of the risk-score. Compared to tertile 1, the risk of new-onset AF was 2.5-fold higher in tertile 2, and 6.3-fold higher in tertile 3. Rivaroxaban had no effect in reducing new-onset AF. In time-updated models, new-onset AF was associated with a higher risk of subsequent all-cause death: HR (95%CI) 1.38 (1.11–1.73). Conclusions: A well-calibrated risk-score identified patients at risk of new-onset AF in the COMMANDER-HF trial. Patients who developed AF had a higher risk of subsequent death

Genetic mechanisms underlying spermatic and testicular traits within and among cattle breeds: systematic review and prioritization of GWAS results1

[EN] Reduced bull fertility imposes economic losses in bovine herds. Specifically, testicular and spermatic traits are important indicators of reproductive efficiency. Several genome-wide association studies (GWAS) have identified genomic regions associated with these fertility traits. The aims of this study were as follows: 1) to perform a systematic review of GWAS results for spermatic and testicular traits in cattle and 2) to identify key functional candidate genes for these traits. The identification of functional candidate genes was performed using a systems biology approach, where genes shared between traits and studies were evaluated by a guilt by association gene prioritization (GUILDify and ToppGene software) in order to identify the best functional candidates. These candidate genes were integrated and analyzed breeds. Results showed that GWAS for testicular-related traits have been developed for beef breeds only, whereas the majority of GWAS for spermatic-related traits were conducted using dairy breeds. comparing traits measured within the same study, the highest number of genes shared between different traits was observed, indicating a high impact of the population genetic structure and environmental effects. Several chromosomal regions were enriched for functional candidate genes associated with fertility traits. Moreover, multiple functional candidate genes were enriched for markers in a species-specific basis, taurine (Bos taurus) or indicine (Bos indicus). For the different candidate regions identified in the GWAS in the literature, functional candidate genes were detected as follows: B. Taurus chromosome X (BTX) (TEX11, IRAK, CDK16, ATP7A, ATRX, HDAC6, FMR1, L1CAM, MECP2, etc.), BTA17 (TRPV4 and DYNLL1), and BTA14 (MOS, FABP5, ZFPM2). These genes are responsible for regulating metabolic pathways or biological processes associated with fertility, such as progression of spermatogenesis, control of ciliary activity, development of Sertoli cells, DNA integrity in spermatozoa, and homeostasis of testicular cells. This study represents the first systematic review on male fertility traits in cattle using a system biology approach to identify key candidate genes for these traits.S

Improving Phase Change Memory Performance with Data Content Aware Access

A prominent characteristic of write operation in Phase-Change Memory (PCM) is that its latency and energy are sensitive to the data to be written as well as the content that is overwritten. We observe that overwriting unknown memory content can incur significantly higher latency and energy compared to overwriting known all-zeros or all-ones content. This is because all-zeros or all-ones content is overwritten by programming the PCM cells only in one direction, i.e., using either SET or RESET operations, not both. In this paper, we propose data content aware PCM writes (DATACON), a new mechanism that reduces the latency and energy of PCM writes by redirecting these requests to overwrite memory locations containing all-zeros or all-ones. DATACON operates in three steps. First, it estimates how much a PCM write access would benefit from overwriting known content (e.g., all-zeros, or all-ones) by comprehensively considering the number of set bits in the data to be written, and the energy-latency trade-offs for SET and RESET operations in PCM. Second, it translates the write address to a physical address within memory that contains the best type of content to overwrite, and records this translation in a table for future accesses. We exploit data access locality in workloads to minimize the address translation overhead. Third, it re-initializes unused memory locations with known all-zeros or all-ones content in a manner that does not interfere with regular read and write accesses. DATACON overwrites unknown content only when it is absolutely necessary to do so. We evaluate DATACON with workloads from state-of-the-art machine learning applications, SPEC CPU2017, and NAS Parallel Benchmarks. Results demonstrate that DATACON significantly improves system performance and memory system energy consumption compared to the best of performance-oriented state-of-the-art techniques.Comment: 18 pages, 21 figures, accepted at ACM SIGPLAN International Symposium on Memory Management (ISMM

Strength and durability of composite concretes using municipal wastes

The influence of different types of polyethylene (PE) substitutions as partial aggregate replacement of micro-steel fiber reinforced self-consolidating concrete (SCC) incorporating incinerator fly ash was investigated. The study focuses on the workability and hardened properties including mechanical, permeability properties, sulfate resistance and microstructure. Regardless of the polyethylene type, PE substitutions slightly decreased the compressive and flexural strength of SSC initially, however, the difference was compensated at later ages. SEM analysis of the interfacial transition zone showed that there was chemical interaction between PE and the matrix. Although PE substitutions increased the permeable porosity and sorptivity, it significantly improved the sulfate resistance of SCC. The influence of PE shape and size on workability and strength was found to be more important than its type. When considering the disposal of PE wastes and saving embodied energy, consuming recycled PE as partial aggregate replacement was more advantageous over virgin PE aggregate replaced concrete

Hepatoprotective effects of Spirulina maxima in patients with non-alcoholic fatty liver disease: a case series

<p>Abstract</p> <p>Introduction</p> <p>Non-alcoholic fatty liver diseases range from simple steatosis to non-alcoholic steatohepatitis. The "two hits" hypothesis is widely accepted for its pathogenesis: the first hit is an increased fat flux to the liver, which predisposes our patient to a second hit where increasing free fatty acid oxidation into the mitochondria leads to oxidative stress, lipoperoxidation and a chain reaction with increased ROS. Clinical indications include abdominal cramps, meteorism and fatigue. Most patients, however, are asymptomatic, and diagnosis is based on aminotransferase elevation and ultrasonography (or "brilliant liver"). Spirulina maxima has been experimentally proven to possess <it>in vivo </it>and <it>in vitro </it>hepatoprotective properties by maintaining the liver lipid profile. This case report evaluates the hepatoprotective effects of orally supplied Spirulina maxima.</p> <p>Case presentation</p> <p>Three Hispanic Mexican patients (a 43-year-old man, a 77-year-old man and a 44-year-old woman) underwent ultrasonography and were treated with 4.5 g/day of Spirulina maxima for three months. Their blood samples before and after the treatment determined triacylglycerols, total cholesterol, high-density lipoprotein cholesterol, alanine aminotransferase and low-density lipoprotein cholesterol levels. The results were assessed using ultrasound.</p> <p>Conclusion</p> <p>Treatment had therapeutic effects as evidenced by ultrasonography and the aminotransferase data. Hypolipidemic effects were also shown. We conclude that Spirulina maxima may be considered an alternative treatment for patients with non-alcoholic fatty liver diseases and dyslipidemic disorder.</p