Yale University

About: Yale University is a education organization based out in New Haven, Connecticut, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 89824 authors who have published 220665 publications receiving 12834776 citations. The organization is also known as: Yale & Collegiate School.

Pan-cancer analysis of whole genomes

Abstract: Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1,2,3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10,11,12,13,14,15,16,17,18.

Initial Recombination of Ions

Abstract: The probability that a pair of ions of given initial separation will recombine with each other is computed from the laws of Brownian motion, which is the proper procedure whenever the Langevin factor equals unity, as in gases at high pressures. In the absence of forces other than the Coulomb attraction, the probability of escape equals the reciprocal of the Boltzmann factor. This result includes the correlation between temperature and pressure coefficients of the ionization by light particles previously predicted by Compton, Bennett and Stearns, if one allows their basic hypothesis about the laws which govern the initial separation of the ions. The effect of an electric field is to increase the fraction of escaping ions by a factor which in the incipient stage of the effect is proportional to the field intensity and independent of the initial distance, although it depends on the orientation of an ion pair. The predicted increase of the ionization current is a little more than one percent for every 100 volts/cm, which accounts for the observed effects of fields exceeding 1500 volts/cm. A reasonable amount of columnar recombination would help to explain the proportionately greater effects of weak fields. The inferred initial separations of the ions are apparently compatible with present knowledge of electron scattering and attachment.

Identification of ZO-1 : a high molecular weight polypeptide associated with the tight junction (zonula occludens) in a variety of epithelia

Abstract: A tight junction-enriched membrane fraction has been used as immunogen to generate a monoclonal antiserum specific for this intercellular junction. Hybridomas were screened for their ability to both react on an immunoblot and localize to the junctional complex region on frozen sections of unfixed mouse liver. A stable hybridoma line has been isolated that secretes an antibody (R26.4C) that localizes in thin section images of isolated mouse liver plasma membranes to the points of membrane contact at the tight junction. This antibody recognizes a polypeptide of approximately 225,000 D, detectable in whole liver homogenates as well as in the tight junction-enriched membrane fraction. R26.4C localizes to the junctional complex region of a number of other epithelia, including colon, kidney, and testis, and to arterial endothelium, as assayed by immunofluorescent staining of cryostat sections of whole tissue. This antibody also stains the junctional complex region in confluent monolayers of the Madin-Darby canine kidney epithelial cell line. Immunoblot analysis of Madin-Darby canine kidney cells demonstrates the presence of a polypeptide similar in molecular weight to that detected in liver, suggesting that this protein is potentially a ubiquitous component of all mammalian tight junctions. The 225-kD tight junction-associated polypeptide is termed "ZO-1."

Financial Development and Economic Growth in Underdeveloped Countries

Abstract: Publisher Summary This chapter discusses the financial development and economic growth in underdeveloped countries. An observed characteristic of the process of economic development over time, in a market-oriented economy using the price mechanism to allocate resources, is an increase in the number and variety of financial institutions and a substantial rise in the proportion not only of money but also of the total of all financial assets relative to GNP and to tangible wealth. Typical statements indicate that the financial system somehow accommodates—or, to the extent that it malfunctions, it restricts—growth of real per capita output. Such an approach places emphasis on the demand side for financial services; as the economy grows it generates additional and new demands for these services, which bring about a supply response in the growth of the financial system. In this view, the lack of financial institutions in underdeveloped countries is simply an indication of the lack of demand for their services.