Genome modeling system: A knowledge management platform for genomics

In this work, we present the Genome Modeling System (GMS), an analysis information management system capable of executing automated genome analysis pipelines at a massive scale. The GMS framework provides detailed tracking of samples and data coupled with reliable and repeatable analysis pipelines. The GMS also serves as a platform for bioinformatics development, allowing a large team to collaborate on data analysis, or an individual researcher to leverage the work of others effectively within its data management system. Rather than separating ad-hoc analysis from rigorous, reproducible pipelines, the GMS promotes systematic integration between the two. As a demonstration of the GMS, we performed an integrated analysis of whole genome, exome and transcriptome sequencing data from a breast cancer cell line (HCC1395) and matched lymphoblastoid line (HCC1395BL). These data are available for users to test the software, complete tutorials and develop novel GMS pipeline configurations. The GMS is available at https://github.com/genome/gms

Towards an appreciation of ethics in social enterprise business models

How can a critical analysis of entrepreneurial intention inform an appreciation of ethics in social enterprise business models? In answering this question, we consider the ethical commitments that inform entrepreneurial action (inputs) and the hybrid organisations that emerge out of these commitments and actions (outputs). Ethical theory can be a useful way to re-orient the field of social enterprise so that it is more critical of bureaucratic (charitable) and market-driven (business) enterprises connected to neo-liberal doctrine. Social enterprise hybrid business models are therefore reframed as outcomes of both ethical and entrepreneurial intentions. We challenge the dominant conceptualisation of social enterprise as a hybrid blend of mission and market (purpose-versus-resource) by reframing hybridity in terms of the moral choice of economic system (redistribution, reciprocity and market) and social value orientation (personal, mutual or public benefit). We deconstruct the political foundations of charitable trading activities (CTAs), co-operative and mutual enterprises (CMEs) and socially responsible businesses (SRBs) by examining the rationalities (formal, social and substantive) and ethical commitments (utilitarian, communitarian, pragmatic) that underpin them. Whilst conceptual modelling of social enterprise is not new, this paper contributes to knowledge by developing a theory of social enterprise ethics based on the moral/political choices that are made by entrepreneurs (knowingly and unknowingly) when choosing between systems of economic exchange and social value orientation, then expressing it through a legal form

Evidence-based Kernels: Fundamental Units of Behavioral Influence

This paper describes evidence-based kernels, fundamental units of behavioral influence that appear to underlie effective prevention and treatment for children, adults, and families. A kernel is a behavior–influence procedure shown through experimental analysis to affect a specific behavior and that is indivisible in the sense that removing any of its components would render it inert. Existing evidence shows that a variety of kernels can influence behavior in context, and some evidence suggests that frequent use or sufficient use of some kernels may produce longer lasting behavioral shifts. The analysis of kernels could contribute to an empirically based theory of behavioral influence, augment existing prevention or treatment efforts, facilitate the dissemination of effective prevention and treatment practices, clarify the active ingredients in existing interventions, and contribute to efficiently developing interventions that are more effective. Kernels involve one or more of the following mechanisms of behavior influence: reinforcement, altering antecedents, changing verbal relational responding, or changing physiological states directly. The paper describes 52 of these kernels, and details practical, theoretical, and research implications, including calling for a national database of kernels that influence human behavior

The Somatic Genomic Landscape of Glioblastoma

We describe the landscape of somatic genomic alterations based on multi-dimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer

A Phase I dose-escalation study of LCL161, an oral IAP inhibitor, in patients with advanced solid tumors

Purpose LCL161 antagonizes the function of inhibitor of apoptosis proteins (IAPs), thereby promoting cancer cell death. This first-in-human, dose-escalation study assessed the maximum tolerated dose (MTD), safety, pharmacokinetics, and pharmacodynamics of LCL161 in patients with advanced solid tumors. Patients and Methods LCL161 was administered orally once-weekly on a 21-day cycle to adult patients with advanced solid tumors. An adaptive Bayesian Logistic Regression Model with overdose control guided dose escalation. A second part of the study assessed the relative bioavailability of tablet versus solution formulation. Results Fifty-three patients received at least one dose of LCL161 (range 10–3000 mg). LCL161 was well tolerated at doses up to 1800 mg, with cytokine release syndrome (CRS) the only dose-limiting toxicity (3/53; 6%) and most common grade 3/4 event (5/53; 9%). Although the MTD was not reached, a dose of 1800 mg was selected for further study given the occurrence of CRS at higher doses and evidence of pharmacodynamic activity at lower doses. LCL161 was rapidly absorbed. The tablet formulation of LCL161 was better tolerated than the solution with similar exposure, and the solution was discontinued. No patient had an objective response. LCL161 induced degradation of cellular IAP1 protein in the blood, skin, and tumor, and increased circulating cytokine levels consistent with LCL161’s mechanism of action. Conclusion Single-agent LCL161 administered in tablet formulation at a dose of 1800 mg once-weekly was well tolerated, with significant pharmacodynamic activity, warranting further investigation in future studies

Praxis, Volume 07, No. 02: Professionalization and the Writing Center, Part II

Contents: Reaching In, Reaching Out: A Tale of Administrative Experimentation and the Process of Administrative Inclusion / by Kelli Prejean -- The Professionalization of a University Writing Center Staff through a Professional Writing Internship Program / by Kevin Dvorak -- From Learning Adviser to Coordinator: A Professional Career Arc / by Chad Habel -- A Social Capital View of a Writing Center-WAC Partnership / by R. Mark Hall -- Writing Center Administration: Learning the Numbers Game / by Daniel Reardon -- Writing with Pictures: Immersive Technology and 21st Century Professional Development / by Russell Carpenter -- The Public Face: Working the Front Desk of the UWC / by Chris Edwards, Jamie Jesson, Lindsey Purvin, Ashley Busby, Anthony Fassi, Andrew Friedenthal, and Brian Gatten -- A Wealth of Opportunity: An Undergraduate Consultant-ant's Look into the Benefits of Working at a Writing Center / by Chris Edwards -- Toward a More Hybrid Discourse: Re-evaluating (NNS) Client/Consultant Relationships / by Matthew Schultz -- From Writing Center to Classroom and Back Again: Pursuing the Unknowns of Tutoring and Teaching / by Sarah Dees -- My Path to Management: Experience, Mentoring, Leadership, and Ambition / by Jane HirschhornUniversity Writing Cente