A36 The TP53 mutations in the Russian patients with de novo DLBCL

BackgroundTP53 dysfunction is implicated in lymphomagenesis and disease progression. Information about the frequency and spectrum of TP53 mutations in the Russian pathients with diffuse large B-cell lymphoma (DLBCL) in the current version of the IARC TP53 Mutation Database R17 is not represented. The goal of this work was to study the frequency, spectrum and functional significance of TP53 mutations in Russian patients with DLBCL.Material and methodsAt the present time the pilot group of 14 patients were included in the study. Diagnosis was assessed according to the criteria of the WHO classification system. Genomic DNA was isolated from formalin-fixed, paraffin embedded tissue blocks. Direct sequence analysis of gene TP53 was performed according to the IARC protocol, 2010 update.ResultsIn two patients were identified single nucleotide substitutions that are not described in the current version of the PubMed database. All of mutations occurred in the DNA-binding domain of p53. The nonsense mutation Arg196Ter was detected in one patient. Previously it was shown that formation of this premature stop codon might activate the nonsense-mediated RNA decay pathway. The second patient had two missense mutations – Leu130Phe and Arg156Cys. The first of them leads to p53 inactivation according to the analysis of the functional importance of amino acid substitutions using service PolyPhen-2.ConclusionWe detected TP53 mutation in 14% cases. The mutational rate in our study is in good agreement with other studies where the frequency of the TP53 mutations in patients with DLBCL ranged mostly from 13% to 23%

How much laser power can propagate through fusion plasma?

Propagation of intense laser beams is crucial for inertial confinement fusion, which requires precise beam control to achieve the compression and heating necessary to ignite the fusion reaction. The National Ignition Facility (NIF), where fusion will be attempted, is now under construction. Control of intense beam propagation may be ruined by laser beam self-focusing. We have identified the maximum laser beam power that can propagate through fusion plasma without significant self-focusing and have found excellent agreement with recent experimental data, and suggest a way to increase that maximum by appropriate choice of plasma composition with implication for NIF designs. Our theory also leads to the prediction of anti-correlation between beam spray and backscatter and suggests the indirect control of backscatter through manipulation of plasma ionization state or acoustic damping.Comment: 15 pages, 4 figures, submitted to Plasma Physics and Controlled Fusio

Spatial Pattern Formation in External Noise: Theory and Simulation

Spatial pattern formation in excitable fluctuating media was researched analytically from the point of view of the order parameters concept. The reaction-diffusion system in external noise is considered as a model of such medium. Stochastic equations for the unstable mode amplitudes (order parameters), dispersion equations for the unstable mode averaged amplitudes, and the Fokker-Planck equation for the order parameters have been obtained. The developed theory makes it possible to analyze different noise-induced effects, including the variation of boundaries of ordering and disordering phase transitions depending on the parameters of external noiseComment: 22 pages, 10 figure

The Relationship between Epigenetic Age and Myocardial Infarction/Acute Coronary Syndrome in a Population-Based Nested Case-Control Study

We investigated the relationship between ‘epigenetic age’ (EA) derived from DNA methylation (DNAm) and myocardial infarction (MI)/acute coronary syndrome (ACS). A random population sample was examined in 2003/2005 (n = 9360, 45–69, the HAPIEE project) and followed up for 15 years. From this cohort, incident MI/ACS (cases, n = 129) and age- and sex-stratified controls (n = 177) were selected for a nested case-control study. Baseline EA (Horvath’s, Hannum’s, PhenoAge, Skin and Blood) and the differences between EA and chronological age (CA) were calculated (ΔAHr, ΔAHn, ΔAPh, ΔASB). EAs by Horvath’s, Hannum’s and Skin and Blood were close to CA (median absolute difference, MAD, of 1.08, –1.91 and –2.03 years); PhenoAge had MAD of −9.29 years vs. CA. The adjusted odds ratios (ORs) of MI/ACS per 1–year increments of ΔAHr, ΔAHn, ΔASB and ΔAPh were 1.01 (95% CI 0.95–1.07), 1.01 (95% CI 0.95–1.08), 1.02 (95% CI 0.97–1.06) and 1.01 (0.93–1.09), respectively. When classified into tertiles, only the highest tertile of ΔAPh showed a suggestion of increased risk of MI/ACS with OR 2.09 (1.11–3.94) independent of age and 1.84 (0.99–3.52) in the age- and sex-adjusted model. Metabolic modulation may be the likely mechanism of this association. In conclusion, this case-control study nested in a prospective population-based cohort did not find strong associations between accelerated epigenetic age markers and risk of MI/ACS. Larger cohort studies are needed to re-examine this important research question