Comparison of Affymetrix GeneChip Expression Measures

Affymetrix GeneChip expression array technology has become a standard tool in medical science and basic biology research. In this system, preprocessing occurs before one obtains expression level measurements. Because the number of competing preprocessing methods was large and growing, in the summer of 2003 we developed a benchmark to help users of the technology identify the best method for their application. In conjunction with the release of a Bioconductor R package (affycomp), a webtool was made available for developers of preprocessing methods to submit them to a benchmark for comparison. There have now been over 30 methods compared via the webtool. Results: Background correction, one of the main steps in preprocessing, has the largest effect on performance. In particular, background correction appears to improve accuracy but, in general, worsen precision. The benchmark results put this balance in perspective. Furthermore, we have improved some of the original benchmark metrics to provide more detailed information regarding accuracy and precision. A handful of methods stand out as maintaining a useful balance. The affycomp package, now version 1.5.2, continues to be available as part of the Bioconductor project (http://www.bioconductor.org). The webtool continues to be available at http://affycomp.biostat.jhsph.edu

REDEFINING CpG ISLANDS USING A HIDEEN MARKOV MODEL

The DNA of most vertebrates is depleted in CpG dinucleotides; C followed by a G in the 5’ to 3’ direction. CpGs are the target for DNA methylation, a chemical modification of cytosine (C) heritable during cell division and the most well characterized epigenetic mechanism. The remaining CpGs tend to cluster in regions referred to as CpG islands (CGI). Knowing CGI locations is important because they mark functionally relevant epigenetic loci in development and disease. For various mammals, including human, a readily available and widely used list of CGI is available from the UCSC Genome Browser. This list was derived using algorithms that search for regions satisfying a definition of CGI proposed by Gardiner-Garden and Frommer more than 20 years ago. Recent findings, enabled by advances in technology that permit direct measurement of epigenetic endpoints at a whole-genome scale, motive the need to adapt the current CGI definition. In this paper we propose a procedure, guided by hidden Markov models, that permits an extensible approach to detecting CGI. The main advantage of our approach over others is that it summarized the evidence for CGI status as probability scores. This provides flexibility in the definition of a CGI and facilitates the creation of CGI lists for other species. The utility of this approach is demonstrated by generating the first CGI lists for invertebrates, and the fact that we can create CGI lists that substantially increases overlap with recently discovered epigenetic marks. A CGI list and the probability scores, as a function of genome location,for each specie are available at http://www.rafalab.org

Whole-cell cancer vaccination: from autologous to allogeneic tumor- and dendritic cell-based vaccines

The field of tumor vaccination is currently undergoing a shift in focus, from individualized tailor-made vaccines to more generally applicable vaccine formulations. Although primarily predicated by financial and logistic considerations, stemming from a growing awareness that clinical development for wide-scale application can only be achieved through backing from major pharmaceutical companies, these new approaches are also supported by a growing knowledge of the intricacies and minutiae of antigen presentation and effector T-cell activation. Here, the development of whole-cell tumor and dendritic cell (DC)-based vaccines from an individualized autologous set-up to a more widely applicable allogeneic approach will be discussed as reflected by translational studies carried out over the past two decades at our laboratories and clinics in the vrije universiteit medical center (VUmc) in Amsterdam, The Netherlands

Prosociality in business: a human empowerment framework

This study introduces a human empowerment framework to better understand why some businesses are more socially oriented than others in their policies and activities. Building on Welzel’s theory of emancipation, we argue that human empowerment—comprised of four components: action resources, emancipative values, social movement activity, and civic entitlements—enables, motivates, and entitles individuals to pursue social goals for their businesses. Using a sample of over 15,000 entrepreneurs from 43 countries, we report strong empirical evidence for two ecological effects of the framework components on prosociality. We find that human empowerment (1) lifts entrepreneurs’ willingness to choose a social orientation for their business, and (2) reinforces the gender effect on prosociality in business activity. We discuss the human empowerment framework’s added value in understanding how modernization processes fully leverage the potential of social business activities for societies

Help-Seeking Barriers Among Sexual and Gender Minority Individuals Who Experience Intimate Partner Violence Victimization

Sexual and gender minority (SGM) individuals experience intimate partner violence (IPV) victimization at disproportionate rates compared to cisgender and heterosexual individuals. Given the widespread consequences of experiencing IPV victimization, intervention and prevention strategies should identify readily accessible and culturally competent services for this population. SGM individuals who experience IPV victimization face unique individual-, interpersonal-, and systemic-level barriers to accessing informal and formal support services needed to recover from IPV. This chapter reviews IPV victimization prevalence rates among SGM individuals in the context of minority stress and highlights unique forms of IPV victimization affecting this population, namely identity abuse. The literature on help-seeking processes among IPV survivors in general and help-seeking patterns and barriers specifically among SGM individuals who experience IPV victimization in the context of minority stress (e.g., discrimination, internalized stigma, rejection sensitivity, identity concealment) are discussed. How minority stressors at individual, interpersonal, and structural levels act as barriers to help-seeking among SGM individuals experiencing IPV victimization is presented. The chapter concludes with a review of emerging evidence for interventions aimed at reducing help-seeking barriers among SGM individuals who face IPV victimization and a discussion of future directions for research on help-seeking barriers in this population

Cyber Insurance

This volume covers a wide spectrum of issues relating to economic and political development enabled by information and communication technology (ICT)