Laplace's rule of succession in information geometry

Laplace's "add-one" rule of succession modifies the observed frequencies in a sequence of heads and tails by adding one to the observed counts. This improves prediction by avoiding zero probabilities and corresponds to a uniform Bayesian prior on the parameter. The canonical Jeffreys prior corresponds to the "add-one-half" rule. We prove that, for exponential families of distributions, such Bayesian predictors can be approximated by taking the average of the maximum likelihood predictor and the \emph{sequential normalized maximum likelihood} predictor from information theory. Thus in this case it is possible to approximate Bayesian predictors without the cost of integrating or sampling in parameter space

Sequence sensitivity of breathing dynamics in heteropolymer DNA

We study the fluctuation dynamics of localized denaturation bubbles in heteropolymer DNA with a master equation and complementary stochastic simulation based on novel DNA stability data. A significant dependence of opening probability and waiting time between bubble events on the local DNA sequence is revealed and quantified for a biological sequence of the T7 bacteriophage. Quantitative agreement with data from fluorescence correlation spectroscopy (FCS) is demonstrated.Comment: 4 pages, 5 figures, to appear in Physical Review Letter

Bubble dynamics in DNA

The formation of local denaturation zones (bubbles) in double-stranded DNA is an important example for conformational changes of biological macromolecules. We study the dynamics of bubble formation in terms of a Fokker-Planck equation for the probability density to find a bubble of size n base pairs at time t, on the basis of the free energy in the Poland-Scheraga model. Characteristic bubble closing and opening times can be determined from the corresponding first passage time problem, and are sensitive to the specific parameters entering the model. A multistate unzipping model with constant rates recently applied to DNA breathing dynamics [G. Altan-Bonnet et al, Phys. Rev. Lett. 90, 138101 (2003)] emerges as a limiting case.Comment: 9 pages, 2 figure

MicroRNAs targeting oncogenes are down-regulated in pancreatic malignant transformation from benign tumors

BACKGROUND MicroRNA (miRNA) expression profiles have been described in pancreatic ductal adenocarcinoma (PDAC), but these have not been compared with pre-malignant pancreatic tumors. We wished to compare the miRNA expression signatures in pancreatic benign cystic tumors (BCT) of low and high malignant potential with PDAC, in order to identify miRNAs deregulated during PDAC development. The mechanistic consequences of miRNA dysregulation were further evaluated. METHODS Tissue samples were obtained at a tertiary pancreatic unit from individuals with BCT and PDAC. MiRNA profiling was performed using a custom microarray and results were validated using RT-qPCR prior to evaluation of miRNA targets. RESULTS Widespread miRNA down-regulation was observed in PDAC compared to low malignant potential BCT. We show that amongst those miRNAs down-regulated, miR-16, miR-126 and let-7d regulate known PDAC oncogenes (targeting BCL2, CRK and KRAS respectively). Notably, miR-126 also directly targets the KRAS transcript at a "seedless" binding site within its 3'UTR. In clinical specimens, miR-126 was strongly down-regulated in PDAC tissues, with an associated elevation in KRAS and CRK proteins. Furthermore, miR-21, a known oncogenic miRNA in pancreatic and other cancers, was not elevated in PDAC compared to serous microcystic adenoma (SMCA), but in both groups it was up-regulated compared to normal pancreas, implicating early up-regulation during malignant change. CONCLUSIONS Expression profiling revealed 21 miRNAs down-regulated in PDAC compared to SMCA, the most benign lesion that rarely progresses to invasive carcinoma. It appears that miR-21 up-regulation is an early event in the transformation from normal pancreatic tissue. MiRNA expression has the potential to distinguish PDAC from normal pancreas and BCT. Mechanistically the down-regulation of miR-16, miR-126 and let-7d promotes PDAC transformation by post-transcriptional up-regulation of crucial PDAC oncogenes. We show that miR-126 is able to directly target KRAS; re-expression has the potential as a therapeutic strategy against PDAC and other KRAS-driven cancers

Decay of isolated surface features driven by the Gibbs-Thomson effect in analytic model and simulation

A theory based on the thermodynamic Gibbs-Thomson relation is presented which provides the framework for understanding the time evolution of isolated nanoscale features (i.e., islands and pits) on surfaces. Two limiting cases are predicted, in which either diffusion or interface transfer is the limiting process. These cases correspond to similar regimes considered in previous works addressing the Ostwald ripening of ensembles of features. A third possible limiting case is noted for the special geometry of "stacked" islands. In these limiting cases, isolated features are predicted to decay in size with a power law scaling in time: A is proportional to (t0-t)^n, where A is the area of the feature, t0 is the time at which the feature disappears, and n=2/3 or 1. The constant of proportionality is related to parameters describing both the kinetic and equilibrium properties of the surface. A continuous time Monte Carlo simulation is used to test the application of this theory to generic surfaces with atomic scale features. A new method is described to obtain macroscopic kinetic parameters describing interfaces in such simulations. Simulation and analytic theory are compared directly, using measurements of the simulation to determine the constants of the analytic theory. Agreement between the two is very good over a range of surface parameters, suggesting that the analytic theory properly captures the necessary physics. It is anticipated that the simulation will be useful in modeling complex surface geometries often seen in experiments on physical surfaces, for which application of the analytic model is not straightforward.Comment: RevTeX (with .bbl file), 25 pages, 7 figures from 9 Postscript files embedded using epsf. Submitted to Phys. Rev. B A few minor changes made on 9/24/9

Molecular analysis of pediatric brain tumors identifies microRNAs in pilocytic astrocytomas that target the MAPK and NF-kappa B pathways

RT-qPCR confirms (a) up-regulation of miR-34a, miR-146a, miR-542-3p and miR-503 in pilocytic astrocytomas. (b) low expression of miR-124*, miR-129 and miR-129* in pilocytic astrocytomas. Relative expression shown as Log2 fold change compared to normal adult cerebellum and frontal lobe (normalized to miR-423-3p). Data represent two technical replicates ± SD. (ZIP 516 kb

История безопасности полетов: методология, опыт, перспективы

The formulation of the flight safety history problem is stated. The article shows that it is problematic to scientifically substantiate, systematize, analyze and generalize the theoretical and empirical flight safety material accumulated in various fields. From a historical perspective, the necessity for a socio-humanitarian assessment of the transformation processes of scientific and applied experience in the field of flight safety is substantiated. New multidisciplinary line of research, making use of a specific scientific apparatus and methodological tools, i.e., the history of flight safety, the subject basis of which covers social activities throughout the life cycle of all aerospace engineering (artificial flying objects in the Earth's atmosphere and space, aircraft, crews, passengers, other aerospace system specialists), including aeronautics, aviation, cosmonautics over a span of the entire history of mankind, is proposed. A brief overview of publications on the issue of flight safety is offered. The experience of flight safety history research is analyzed. The periodization of flight safety history in the XX–XXI centuries, giving prominence to three stages: 1. Generating ideas, technologies, flight safety systems (10–40s of the XX century). 2. Establishing the national and international systems to ensure flight safety, scientific research, personnel education and training in the field of flight safety (50–80s of the XX century). 3. Developing new ideas, technologies, projects, flight safety management systems, active ensuring of flight safety, etc. (since the 90s of the XX century), is proposed. The foundations of the conceptual model of the flight safety history are presented, the methodology, experience and prospects of research are considered. It is recommended to organize systematic studies of the flight safety history, covering the aspects of the world and domestic science, education and practice; to create a unified information system on the history of flight safety based on new information technologies, the ultimate aim of which can be a virtual worldwide museum of flight safety; to initiate a pilot project of the National Flight Safety Museum of Russia and to start its development in the year of the 100th anniversary of our civil aviation; in the future, to develop a new academic discipline "History of Flight Safety" for training aerospace industry specialists and researchers.Поставлена проблема истории безопасности полетов. Показано, что научно обоснованная систематизация, анализ и обобщение накопленного в разных сферах теоретического и эмпирического материала по безопасности полетов затруднены. Обоснована потребность в социогуманитарной оценке процессов трансформации научного и прикладного опыта в сфере безопасности полетов в историческом ракурсе. Предложено новое, располагающее специфическим научным аппаратом и методологическим инструментарием, мультидисциплинарное направление исследований – история безопасности полетов, предметное основание которого охватывает социальную деятельность на жизненном цикле всей аэрокосмической техники (искусственных летающих объектов в атмосфере Земли и космосе, летательных аппаратов, экипажей, пассажиров, других специалистов аэрокосмической системы) с охватом воздухоплавания, авиации, космонавтики за всю историю человечества. Сделан краткий обзор публикаций по проблеме безопасности полетов. Проанализирован опыт исследований истории безопасности полетов и предложена периодизация истории безопасности полетов в XX–XXI вв., в которой выделены три этапа: 1) зарождение идей, технологий, систем безопасности полетов (10–40-е гг. XX в.); 2) становление национальных и международных систем обеспечения безопасности полетов, научных исследований, обучения и подготовки кадров в области безопасности полетов (50–80-е гг. XX в.); 3) развитие новых идей, технологий, проектов, систем управления безопасности полетов, активного обеспечения безопасности полетов и др. (с 90-х гг. XX в.). Представлены основания концептуальной модели истории безопасности полетов, рассмотрены методология, опыт и перспективы исследований. Рекомендовано организовать систематические исследования истории безопасности полетов с охватом аспектов мировой и отечественной науки, образования и практики; создать единую информационную систему по истории безопасности полетов на основе новых информационных технологий, ядром которой может стать виртуальный всемирный музей безопасности полетов; инициировать пилотный проект национального музея безопасности полетов России и начать его разработку в год 100-летия нашей гражданской авиации; в перспективе разработать новую учебную дисциплину «История безопасности полетов» для обучения специалистов аэрокосмической отрасли и исследователей.