Two-Particle Microrheology of quasi-2D Viscous Systems

We study the correlated motions of colloidal particles in a quasi-2D system (Human Serum Albumin (HSA) protein molecules at an air-water interface) for different surface viscosities $\eta_{s}$. We observe a transition in the behavior of the correlated motion, from 2-D interface dominated at high $\eta_{s}$ to bulk fluid-dependent at low $\eta_{s}$. The correlated motions can be scaled onto a master curve which captures the features of this transition. This master curve also characterizes the spatial dependence of the flow field of a viscous interface in response to a force. From the flow field and the correlated particle motions, we calculate a two-particle MSD (mean square displacement) for direct comparison with rheological measurements.Comment: 4 pages, 4 figures, submitted to PR

ATTITUDES AND PERCEPTIONS OF LIVING KIDNEY DONOR EVALUATION

poster abstractIntroduction: Attitudes and perceptions of living kidney donors are im-portant aspects to the organ donation process. Few patient-centered studies exist which focus on broad health outcomes and expectations of living kid-ney donors. This is of practical concern due to the trend of decreasing donor numbers observed in the last decade (U.S. Department of Health and Human Services, Health Resources and Services Administration, 2011). While fol-low-up care is a crucial part of the donation process, few studies address the importance of follow-up care and its implications on the health status of the donor following his/her donation. This study aims to evaluate attitudes and perceptions of living kidney donors regarding their total donation experience. Data collected will shape policy recommendations pertaining to the standard of follow-up care for living kidney donors. Methods: The present study uses an electronic survey tool to evaluate living kidney donors’ satisfaction with their post-donation follow-up care. All living kidney donors are eligible. Recruitment is via social networking sites with active donor members; successfully recruited participants receive an e-mail with the study information sheet and a link to the brief survey. Results: Completed survey responses are coded and analyzed using sta-tistical coding software. Data produced will illustrate any patient reported negative health outcomes across multiple transplant centers, attitudes about donor follow-up care, and policy recommendations

Photometric Decomposition of Barred Galaxies

We present a non-parametric method for decomposition of the light of disk galaxies into disk, bulge and bar components. We have developed and tested the method on a sample of 68 disk galaxies for which we have acquired I-band photometry. The separation of disk and bar light relies on the single assumption that the bar is a straight feature with a different ellipticity and position angle from that of the projected disk. We here present the basic method, but recognise that it can be significantly refined. We identify bars in only 47% of the more nearly face-on galaxies in our sample. The fraction of light in the bar has a broad range from 1.3% to 40% of the total galaxy light. If low-luminosity galaxies have more dominant halos, and if halos contribute to bar stability, the luminosity functions of barred and unbarred galaxies should differ markedly; while our sample is small, we find only a slight difference of low significance.Comment: Accepted to appear in AJ, 36 pages, 9 figures, full on-line figures available at http://www.physics.rutgers.edu/~sellwood/Reese.htm

A mitochondrial-focused genetic interaction map reveals a scaffold-like complex required for inner membrane organization in mitochondria.

To broadly explore mitochondrial structure and function as well as the communication of mitochondria with other cellular pathways, we constructed a quantitative, high-density genetic interaction map (the MITO-MAP) in Saccharomyces cerevisiae. The MITO-MAP provides a comprehensive view of mitochondrial function including insights into the activity of uncharacterized mitochondrial proteins and the functional connection between mitochondria and the ER. The MITO-MAP also reveals a large inner membrane-associated complex, which we term MitOS for mitochondrial organizing structure, comprised of Fcj1/Mitofilin, a conserved inner membrane protein, and five additional components. MitOS physically and functionally interacts with both outer and inner membrane components and localizes to extended structures that wrap around the inner membrane. We show that MitOS acts in concert with ATP synthase dimers to organize the inner membrane and promote normal mitochondrial morphology. We propose that MitOS acts as a conserved mitochondrial skeletal structure that differentiates regions of the inner membrane to establish the normal internal architecture of mitochondria

I can take the risk, but you should be safe: Self-other differences in situations involving physical safety

Prior research on self-other differences involving risk have found that individuals make riskier decisions for others than for the self in situations where risk taking is valued. We expand this research by examining whether the direction of self-other differences reverses when risk aversion is valued, as predicted by social values theory (Stone & Allgaier, 2008). Two studies tested for self-other differences in physical safety scenarios, a domain where risk aversion is valued. In Study 1, participants read physical safety and romantic relationship scenarios and selected what they would decide for themselves, what they would decide for a friend, or what they would predict their friend would decide. In Study 2, participants read public health scenarios and either decided or predicted for themselves and for a friend. In keeping with social values theory, participants made more risk-averse decisions for others than for themselves in situations where risk aversion is valued (physical safety scenarios) but more risk-taking decisions for others than for themselves in situations where risk taking is valued (relationship scenarios). Further, we show that these self-other differences in decision making do not arise from incorrectly predicting others’ behaviors, as participants predicted that others’ decisions regarding physical safety scenarios would be either similar (Experiment 1) or more risk taking (Experiment 2) than their own decisions

Identification of novel small molecule inhibitors of adenovirus gene transfer using a high throughput screening approach

Due to many favourable attributes adenoviruses (Ads) are the most extensively used vectors for clinical gene therapy applications. However, following intravascular administration, the safety and efficacy of Ad vectors are hampered by the strong hepatic tropism and induction of a potent immune response. Such effects are determined by a range of complex interactions including those with neutralising antibodies, blood cells and factors, as well as binding to native cellular receptors (coxsackie adenovirus receptor (CAR), integrins). Once in the bloodstream, coagulation factor X (FX) has a pivotal role in determining Ad liver transduction and viral immune recognition. Due to difficulties in generating a vector devoid of multiple receptor binding motifs, we hypothesised that a small molecule inhibitor would be of value. Here, a pharmacological approach was implemented to block adenovirus transduction pathways. We developed a high throughput screening (HTS) platform to identify the small molecule inhibitors of FX-mediated Ad5 gene transfer. Using an in vitro fluorescence and cell-based HTS, we evaluated 10,240 small molecules. Following sequential rounds of screening, three compounds, T5424837, T5550585 and T5660138 were identified that ablated FX-mediated Ad5 transduction with low micromolar potency. The candidate molecules possessed common structural features and formed part of the one pharmacophore model. Focused, mini-libraries were generated with structurally related molecules and in vitro screening revealed novel hits with similar or improved efficacy. The compounds did not interfere with Ad5:FX engagement but acted at a subsequent step by blocking efficient intracellular transport of the virus. In vivo, T5660138 and its closely related analogue T5660136 significantly reduced Ad5 liver transgene expression at 48 h post-intravenous administration of a high viral dose (1 × 10<sup>11</sup> vp/mouse). Therefore, this study identifies novel and potent small molecule inhibitors of the Ad5 transduction which may have applications in the Ad gene therapy setting

Common dysregulation network in the human prefrontal cortex underlies two neurodegenerative diseases.

Using expression profiles from postmortem prefrontal cortex samples of 624 dementia patients and non-demented controls, we investigated global disruptions in the co-regulation of genes in two neurodegenerative diseases, late-onset Alzheimer's disease (AD) and Huntington's disease (HD). We identified networks of differentially co-expressed (DC) gene pairs that either gained or lost correlation in disease cases relative to the control group, with the former dominant for both AD and HD and both patterns replicating in independent human cohorts of AD and aging. When aligning networks of DC patterns and physical interactions, we identified a 242-gene subnetwork enriched for independent AD/HD signatures. This subnetwork revealed a surprising dichotomy of gained/lost correlations among two inter-connected processes, chromatin organization and neural differentiation, and included DNA methyltransferases, DNMT1 and DNMT3A, of which we predicted the former but not latter as a key regulator. To validate the inter-connection of these two processes and our key regulator prediction, we generated two brain-specific knockout (KO) mice and show that Dnmt1 KO signature significantly overlaps with the subnetwork (P = 3.1 × 10(-12)), while Dnmt3a KO signature does not (P = 0.017)

Genetic basis of transcriptome diversity in Drosophila melanogaster

Understanding how DNA sequence variation is translated into variation for complex phenotypes has remained elusive but is essential for predicting adaptive evolution, for selecting agriculturally important animals and crops, and for personalized medicine. Gene expression may provide a link between variation in DNA sequence and organismal phenotypes, and its abundance can be measured efficiently and accurately. Here we quantified genomewide variation in gene expression in the sequenced inbred lines of the Drosophila melanogaster Genetic Reference Panel (DGRP), increasing the annotated Drosophila transcriptome by 11%, including thousands of novel transcribed regions (NTRs). We found that 42%of the Drosophila transcriptome is genetically variable in males and females, including the NTRs, and is organized into modules of genetically correlated transcripts. We found that NTRs often were negatively correlated with the expression of protein-coding genes, which we exploited to annotate NTRs functionally. We identified regulatory variants for the mean and variance of gene expression, which have largely independent genetic control. Expression quantitative trait loci (eQTLs) for the mean, but not for the variance, of gene expression were concentrated near genes. Notably, the variance eQTLs often interacted epistatically with local variants in these genes to regulate gene expression. This comprehensive characterization of population-scale diversity of transcriptomes and its genetic basis in the DGRP is critically important for a systems understanding of quantitative trait variation