Gene expression profiling of brains from bovine spongiform encephalopathy (BSE)-infected cynomolgus macaques

BACKGROUND: Prion diseases are fatal neurodegenerative disorders whose pathogenesis mechanisms are not fully understood. In this context, the analysis of gene expression alterations occurring in prion-infected animals represents a powerful tool that may contribute to unravel the molecular basis of prion diseases and therefore discover novel potential targets for diagnosis and therapeutics. Here we present the first large-scale transcriptional profiling of brains from BSE-infected cynomolgus macaques, which are an excellent model for human prion disorders. RESULTS: The study was conducted using the GeneChip\uae Rhesus Macaque Genome Array and revealed 300 transcripts with expression changes greater than twofold. Among these, the bioinformatics analysis identified 86 genes with known functions, most of which are involved in cellular development, cell death and survival, lipid homeostasis, and acute phase response signaling. RT-qPCR was performed on selected gene transcripts in order to validate the differential expression in infected animals versus controls. The results obtained with the microarray technology were confirmed and a gene signature was identified. In brief, HBB and HBA2 were down-regulated in infected macaques, whereas TTR, APOC1 and SERPINA3 were up-regulated. CONCLUSIONS: Some genes involved in oxygen or lipid transport and in innate immunity were found to be dysregulated in prion infected macaques. These genes are known to be involved in other neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Our results may facilitate the identification of potential disease biomarkers for many neurodegenerative diseases

Модернизация конструкции биологического лабораторного комплекса

Объектом модернизации в данной работе является конструкция биологического лабораторного комплекса. Цель: модернизация конструкции биологического лабораторного комплекса. Результатом процесса модернизации является конструкция комплекса в CAD системе SolidWorks. В ходе работы: модернизирована конструкция комплекса под заданные характеристики, разработан сборочный чертеж, спроектирован технологический процесс изготовления детали типа фланец.The object of modernization in this work is the construction of a biological laboratory complex. Purpose: modernization of the biological laboratory complex. The result of the modernization process is the design of the complex in the CAD system SolidWorks. In the course of work: the design of the complex has been modernized for the given characteristics, an assembly drawing has been developed, a technological process has been designed for manufacturing a flange type part

curatedOvarianData: clinically annotated data for the ovarian cancer transcriptome

This article introduces a manually curated data collection for gene expression meta-analysis of patients with ovarian cancer and software for reproducible preparation of similar databases. This resource provides uniformly prepared microarray data for 2970 patients from 23 studies with curated and documented clinical metadata. It allows users to efficiently identify studies and patient subgroups of interest for analysis and to perform meta-analysis immediately without the challenges posed by harmonizing heterogeneous microarray technologies, study designs, expression data processing methods and clinical data formats. We confirm that the recently proposed biomarker CXCL12 is associated with patient survival, independently of stage and optimal surgical debulking, which was possible only through meta-analysis owing to insufficient sample sizes of the individual studies. The database is implemented as the curatedOvarianData Bioconductor package for the R statistical computing language, providing a comprehensive and flexible resource for clinically oriented investigation of the ovarian cancer transcriptome. The package and pipeline for producing it are available from http://bcb.dfci.harvard.edu/ovariancancer. Database URL: http://bcb.dfci.harvard.edu/ovariancance

Aberration in DNA Methylation in B-Cell Lymphomas Has a Complex Origin and Increases with Disease Severity

Despite mounting evidence that epigenetic abnormalities play a key role in cancer biology, their contributions to the malignant phenotype remain poorly understood. Here we studied genome-wide DNA methylation in normal B-cell populations and subtypes of B-cell non-Hodgkin lymphoma: follicular lymphoma and diffuse large B-cell lymphomas. These lymphomas display striking and progressive intra-tumor heterogeneity and also inter-patient heterogeneity in their cytosine methylation patterns. Epigenetic heterogeneity is initiated in normal germinal center B-cells, increases markedly with disease aggressiveness, and is associated with unfavorable clinical outcome. Moreover, patterns of abnormal methylation vary depending upon chromosomal regions, gene density and the status of neighboring genes. DNA methylation abnormalities arise via two distinct processes: i) lymphomagenic transcriptional regulators perturb promoter DNA methylation in a target gene-specific manner, and ii) aberrant epigenetic states tend to spread to neighboring promoters in the absence of CTCF insulator binding sites

An Experimental and Numerical Investigation of Flapping-Wing Propulsion

AIAA Paper No. 99-0995, 37th AIAA Aerospace Sciences Meeting, Reno, Nevada, Jan. 1999.Flapping-wing propulsion is investigated experimentally and numerically with direct comparisons between experimental and numerical thrust measurements for several geometrically simple configurations. Numerical simulations are performed using linear theory, and a previously developed, unsteady panel method that models one or two independently moving airfoils with three-degrees of freedom and non-linear deforming wakes. Experiments are carried out in the Naval Postgraduate School 5'×5' low-speed tunnel. A flapping mechanism that approximates the two-dimensional motions modeled by the panel code is suspended with cables in the wind tunnel, and thrust measurements are made by measuring the streamwise displacement of the model using a laser range-finder. The experimental flapping mechanism utilizes variable aspect-ratio wings and optional tip plates to investigate the effect of three-dimensionality. The device flaps two airfoils, each with two degrees of freedom and adjustable pitch and plunge amplitudes, and additional stationary wings may be attached up and/or downstream of the flapping wings to investigate interference effects

Development of CVD diamond radiation detectors

Diamond is a nearly ideal material for detecting ionizing radiation. Its outstanding radiation hardness, fast charge collection and low leakage current allow a diamond detector to be used in high ra diation, high temperature and in aggressive chemical media. We have constructed charged particle detectors using high quality CVD diamond. Characterization of the diamond samples and various detect ors are presented in terms of collection distance, $d=\mu E \tau$, the average distance electron-hole pairs move apart under the influence of an electric field, where $\mu$ is the sum of carrier mo bilities, $E$ is the applied electric field, and $\tau$ is the mobility weighted carrier lifetime. Over the last two years the collection distance increased from $\sim$ 75 $\mu$m to over 200 $\mu$ m. With this high quality CVD diamond a series of micro-strip and pixel particle detectors have been constructed. These devices were tested to determine their position resolution and signal to n oise performance. Diamond detectors were exposed to large fluences of pions, protons and neutrons to establish their radiation hardness properties. The results of these tests and their correlati on with the characterization studies are presented

Proton Irradiation of CVD Diamond Detectors for High Luminosity Experiments at the LHC

CVD diamond shows promising properties for use as a position sensitive detector for experiments in the highest radiation areas at the Large Hadron Collider. In order to study the radiation hardn ess of diamond we exposed CVD diamond detector samples to 24~GeV/$c$ and 500~MeV protons up to a fluence of $5\times 10^{15}~p/{\rm cm^2}$. We measured the charge collection distance, the ave rage distance electron hole pairs move apart in an external electric field, and leakage currents before, during, and after irradiation. The charge collection distance remains unchanged up to $1\ times 10^{15}~p/{\rm cm^2}$ and decreases by $\approx$40~\% at $5\times 10^{15}~p/{\rm cm^2}$. Leakage currents of diamond samples were below 1~pA before and after irradiation. The particle indu ced currents during irradiation correlate well with the proton flux. In contrast to diamond, a silicon diode, which was irradiated for comparison, shows the known large increase in leakage curren t. We conclude that CVD diamond detectors are radiation hard to 24~GeV/$c$ and 500~MeV protons up to at least $1\times 10^{15}~p/{\rm cm^2}$ without signal loss