Improvement of experimental testing and network training conditions with genome-wide microarrays for more accurate predictions of drug gene targets

BACKGROUND: Genome-wide microarrays have been useful for predicting chemical-genetic interactions at the gene level. However, interpreting genome-wide microarray results can be overwhelming due to the vast output of gene expression data combined with off-target transcriptional responses many times induced by a drug treatment. This study demonstrates how experimental and computational methods can interact with each other, to arrive at more accurate predictions of drug-induced perturbations. We present a two-stage strategy that links microarray experimental testing and network training conditions to predict gene perturbations for a drug with a known mechanism of action in a well-studied organism. RESULTS: S. cerevisiae cells were treated with the antifungal, fluconazole, and expression profiling was conducted under different biological conditions using Affymetrix genome-wide microarrays. Transcripts were filtered with a formal network-based method, sparse simultaneous equation models and Lasso regression (SSEM-Lasso), under different network training conditions. Gene expression results were evaluated using both gene set and single gene target analyses, and the drug’s transcriptional effects were narrowed first by pathway and then by individual genes. Variables included: (i) Testing conditions – exposure time and concentration and (ii) Network training conditions – training compendium modifications. Two analyses of SSEM-Lasso output – gene set and single gene – were conducted to gain a better understanding of how SSEM-Lasso predicts perturbation targets. CONCLUSIONS: This study demonstrates that genome-wide microarrays can be optimized using a two-stage strategy for a more in-depth understanding of how a cell manifests biological reactions to a drug treatment at the transcription level. Additionally, a more detailed understanding of how the statistical model, SSEM-Lasso, propagates perturbations through a network of gene regulatory interactions is achieved.Published versio

Quantum Field Theory and Unification in AdS5

We consider gauge bosons in the bulk of AdS5 in a two-brane theory that addresses the hierarchy problem. We show such a theory can be consistent with gauge coupling unification at a high scale. We discuss subtleties in this calculation and show how to regulate consistently in a bounded AdS5 background. Our regularization is guided by the holographic dual of the calculation.Comment: Published version, some typos correcte

Exploring the remuneration ‘black box’: establishing an organizational learning insight into changing remuneration committee ‘social worlds’

Current executive compensation research posits a need to extend analysis beyond principalagent theory in order to explore the complex social influences and processes implicated in Remuneration Committee (RemCo) decision-making (e.g. Bender, 2007; Kakabadse et al, 2006; Main et al., 2007), particularly given the current uproar surrounding reported levels and structuring of executive remuneration. We respond to this international need by highlighting how innovative organizational learning theorizing can be integrated into further investigations of the remuneration ‘Black Box’, in order to focus attention upon the nuances of what and how organizational learning takes place in the remuneration process. Additionally, we note the importance of investigating the main actors and particularly their performance of complex roles within their rapidly evolving ‘social worlds’. By exploring the organizational learning phenomena implicated in executive remuneration, we argue that practitioners, regulatory bodies etc. can appreciate further the implications of their respective decision-making

Positive Affect and Adjustment to Perceived Racism

This research provided the first empirical investigation of the role of positive affect in moderating the relationship between perceived racism and depressive symptoms. A sample of 215 racial and ethnic minority young adults completed measures of perceived racism, daily race–related stress, positive affect, optimism, and depressive symptoms. Hierarchical regression analyses revealed that positive affect and perceived racism accounted for a significant portion of the variance in depressive symptoms. Most notably, above and beyond the effects of optimism, positive affect interacted with perceived racism to weaken its influence on depression. Implications for future research directions that build on these initial findings are discussed

Responding to Discrimination as a Function of Meritocracy Beliefs and Personal Experiences: Testing the Model of Shattered Assumptions

We examined whether the model of shattered assumptions (Janoff-Bulman, 1992) could be applied to the reactions of victims of discrimination. Consistent with this model, it was hypothesized that those whose positive world assumptions are inconsistent with their negative experiences of discrimination would report more negative responses than those whose world assumptions match their experience. Disadvantaged group (both gender and ethnicity) members’ responses to discrimination (self-esteem, collective action, intergroup anxiety) were predicted from their meritocracy beliefs and personal experiences of discrimination. Regression analyses showed a significant interaction between meritocracy beliefs and personal discrimination such that among those who reported personal discrimination, stronger beliefs that the meritocracy exists predicted decreased self-esteem and collective action as well as increased intergroup anxiety. Among those who reported little personal discrimination, stronger beliefs that the meritocracy exists predicted increased self-esteem. Implications for promoting a critical view of the social system was discussed

Community Foundations Take the Lead: Promising Approaches to Building Inclusive and Equitable Communities

Features the work of several community foundations that have promoted racial equity, highlighting their successes and challenges

Evaluation of energy absorption of new concepts of aircraft composite subfloor intersections

Forty-one composite aircraft subfloor intersection specimens were tested to determine the effects of geometry and material on the energy absorbing behavior, failure characteristics, and post-crush structural integrity of the specimens. The intersections were constructed of twelve ply + or - 45 sub 6 laminates of either Kevlar 49/934 or AS-4/934 graphite-epoxy in heights of 4, 8, and 12 inches. The geometry of the specimens varied in the designs of the intersection attachment angle. Four different geometries were tested

Hope as a Source of Resilience in Later Adulthood

This research provided a preliminary investigation of how variations in trait and state hope are associated with positive adaptation to stress in later adulthood. Trait hope and neuroticism were measured by questionnaires and state hope, stress, and negative emotions were assessed daily for 45 days. Results from multilevel random coefficient modeling analyses suggested that daily hope provides protective benefits by keeping negative emotions low, while also contributing to adaptive recovery from stress. The dynamic linkages between daily hope, stress, and emotion were further moderated by individual differences in trait hope. Compared with those low in trait hope, high-hope individuals showed diminished stress reactivity and more effective emotional recovery