The Mason Music & Memory Initiative (M3I)

Educational Objectives 1. Explain the benefits of a nonpharmacological intervention, such as the M3I, for persons with dementia. 2. Describe the work of M3I and its collaboration with students and faculty throughout the state. 3.Highlight lessons learned and future directions for the M3I

Duplex DNA from Sites of Helicase-Polymerase Uncoupling Links Non-B DNA Structure Formation to Replicative Stress

BACKGROUND: Replication impediments can produce helicase-polymerase uncoupling allowing lagging strand synthesis to continue for as much as 6 kb from the site of the impediment. MATERIALS AND METHODS: We developed a cloning procedure designed to recover fragments from lagging strand near the helicase halt site. RESULTS: A total of 62% of clones from a p53-deficient tumor cell line (PC3) and 33% of the clones from a primary cell line (HPS-19I) were within 5 kb of a G-quadruplex forming sequence. Analyses of a RACK7 gene sequence, that was cloned multiple times from the PC3 line, revealed multiple deletions in region about 1 kb from the cloned region that was present in a non-B conformation. Sequences from the region formed G-quadruplex and i-motif structures under physiological conditions. CONCLUSION: Defects in components of non-B structure suppression systems (e.g. p53 helicase targeting) promote replication-linked damage selectively targeted to sequences prone to G-quadruplex and i-motif formation

pH-Induced Folding of the Caspase-Cleaved Par-4 Tumor Suppressor: Evidence of Structure Outside of the Coiled Coil Domain

Prostate apoptosis response-4 (Par-4) is a 38 kDa largely intrinsically disordered tumor suppressor protein that functions in cancer cell apoptosis. Par-4 down-regulation is often observed in cancer while up-regulation is characteristic of neurodegenerative conditions such as Alzheimer’s disease. Cleavage of Par-4 by caspase-3 activates tumor suppression via formation of an approximately 25 kDa fragment (cl-Par-4) that enters the nucleus and inhibits Bcl-2 and NF-ƙB, which function in pro-survival pathways. Here, we have investigated the structure of cl-Par-4 using biophysical techniques including circular dichroism (CD) spectroscopy, dynamic light scattering (DLS), and intrinsic tyrosine fluorescence. The results demonstrate pH-dependent folding of cl-Par-4, with high disorder and aggregation at neutral pH, but a largely folded, non-aggregated conformation at acidic p

Modest Interference with Actin Dynamics in Primary T Cell Activation by Antigen Presenting Cells Preferentially Affects Lamellal Signaling

Dynamic subcellular distributions of signaling system components are critical regulators of cellular signal transduction through their control of molecular interactions. Understanding how signaling activity depends on such distributions and the cellular structures driving them is required for comprehensive insight into signal transduction. In the activation of primary murine T cells by antigen presenting cells (APC) signaling intermediates associate with various subcellular structures, prominently a transient, wide, and actin-associated lamellum extending from an interdigitated T cell:APC interface several micrometers into the T cell. While actin dynamics are well established as general regulators of cellular organization, their role in controlling signaling organization in primary T cell:APC couples and the specific cellular structures driving it is unresolved. Using modest interference with actin dynamics with a low concentration of Jasplakinolide as corroborated by costimulation blockade we show that T cell actin preferentially controls lamellal signaling localization and activity leading downstream to calcium signaling. Lamellal localization repeatedly related to efficient T cell function. This suggests that the transient lamellal actin matrix regulates T cell signaling associations that facilitate T cell activation

Characteristics of US public schools with reported cases of novel influenza A (H1N1)

Objective The 2009 pandemic of influenza A (H1N1) has disproportionately affected children and young adults, resulting in attention by public health officials and the news media on schools as important settings for disease transmission and spread. We aimed to characterize US schools affected by novel influenza A (H1N1) relative to other schools in the same communities. Methods A database of US school-related cases was obtained by electronic news media monitoring for early reports of novel H1N1 influenza between April 23 and June 8, 2009. We performed a matched case–control study of 32 public primary and secondary schools that had one or more confirmed cases of H1N1 influenza and 6815 control schools located in the same 23 counties as case schools. Results Compared with controls from the same county, schools with reports of confirmed cases of H1N1 influenza were less likely to have a high proportion of economically disadvantaged students (adjusted odds ratio (aOR) 0.385; 95% confidence interval (CI) 0.166–0.894) and less likely to have older students (aOR 0.792; 95% CI 0.670–0.938). Conclusions We conclude that public schools with younger, more affluent students may be considered sentinels of the epidemic and may have played a role in its initial spread.National Institute of Allergy and Infectious Diseases (U.S.) (R21AI073591-01)National Institutes of Health (U.S.)Canadian Institutes of Health Research (PAN-83152)Canadian Institutes of Health Research (CAT-86857)Google (Firm) (Research Grant

Scantegrity II Municipal Election at Takoma Park: The First E2E Binding Governmental Election with Ballot Privacy

On November 3, 2009, voters in Takoma Park, Maryland, cast ballots for the mayor and city council members using the Scantegrity II voting system—the first time any end-to-end (E2E) voting system with ballot privacy has been used in a binding governmental election. This case study describes the various efforts that went into the election—including the improved design and implementation of the voting system, streamlined procedures, agreements with the city, and assessments of the experiences of voters and poll workers. The election, with 1728 voters from six wards, involved paper ballots with invisible-ink confirmation codes, instant-runoff voting with write-ins, early and absentee (mail-in) voting, dual-language ballots, provisional ballots, privacy sleeves, any-which-way scanning with parallel conventional desktop scanners, end-to-end verifiability based on optional web-based voter verification of votes cast, a full hand recount, thresholded authorities, three independent outside auditors, fully-disclosed software, and exit surveys for voters and pollworkers. Despite some glitches, the use of Scantegrity II was a success, demonstrating that E2E cryptographic voting systems can be effectively used and accepted by the general public.United States. Dept. of Defense (IASP grant H98230-08-1-0334)United States. Dept. of Defense (IASP grant H98230-09-1-0404)National Science Foundation (U.S.) (Grant no. CNS 0831149

Laser Sounder Approach for Global Measurement of Tropospheric CO2 Mixing Ratio from Space

We report progress in assessing the feasibility of a new satellite-based laser-sounding instrument to measure CO2 and other trace gas abundances in the lower troposphere from space

Natural adaptation and human selection of northeast African sheep genomes

African sheep manifest diverse but distinct physio-anatomical traits, which are the outcomes of natural- and human-driven selection. Here, we generated 34.8 million variants from 150 indigenous northeast African sheep genomes sequenced at an average depth of ∼54× for 130 samples (Ethiopia, Libya) and ∼20× for 20 samples (Sudan). These represented sheep from diverse environments, tail morphology and post-Neolithic introductions to Africa. Phylogenetic and model-based admixture analysis provided evidence of four genetic groups corresponding to altitudinal geographic origins, tail morphotypes and possible historical introduction and dispersal of the species into and across the continent. Running admixture at higher levels of K (6 ≤ K ≤ 25), revealed cryptic levels of genome intermixing as well as distinct genetic backgrounds in some populations. Comparative genomic analysis identified targets of selection that spanned conserved haplotype structures overlapping clusters of genes and gene families. These were related to hypoxia responses, ear morphology, caudal vertebrae and tail skeleton length, and tail fat-depot structures. Our findings provide novel insights underpinning morphological variation and response to human-driven selection and environmental adaptation in African indigenous sheep

Scantegrity Responds to Rice Study on Usability of the Scantegrity II Voting System

This note is a response to, and critique of, recent work by Acemyan, Kortum, Bryne, and Wallach regarding the usability of end-to-end verifiable voting systems, and in particular, to their analysis of the usability of the Scantegrity II voting system. Their work is given in a JETS paper [Ace14] and was presented at EVT/WOTE 2014; it was also described in an associated press release [Rut14]. We find that their study lacked an appropriate control voting system with which to compare effectiveness, and thus their conclusions regarding Scantegrity II are unsupported by the evidence they present. Furthermore, their conclusions are contradicted by the successful deployment experiences of Scantegrity II at Takoma Park