A Chromosomal Deletion and New Frameshift Mutation Cause ARSACS in an African-American

Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) is a rare, progressive, neurodegenerative disease characterized by ataxia, spasticity and polyneuropathy. First described in the French-Canadian population of Quebec in 1978, ARSACS has since been identified in multiple patients worldwide. In this clinical case report, we describe the evaluation of an 11-years-old African-American male who presented to neuromuscular clinic for assessment of a gait abnormality. He had a history of gross motor delay since early childhood, frequent falls and a below average IQ. Chromosomal microarray revealed a 1.422 megabase loss in the 13q12.12 region, which includes the SACS gene. Next Generation Sequencing then showed a novel, predicted to be pathogenic missense mutation (c.11824dup) of this gene. His clinical presentation and neurological imaging further confirmed the diagnosis of ARSACS. To our knowledge, this is the first reported case of this disease in the African-American population of the United States. This case report further highlights the growing trend of identifying genetic diseases previously restricted to single, ethnically isolated regions in many different ethnic groups worldwide

A Tale of Three Cities: Crime and Displacement after Hurricane Katrina

When Hurricane Katrina struck New Orleans in August 2005, it greatly disrupted both the physical and social structures of that community. One consequence of the hurricane was the displacement of large numbers of New Orleans residents to other cities, including Houston, San Antonio, and Phoenix. There has been media speculation that such a grand-scale population displacement led to increased crime in communities that were recipient of large numbers of displaced New Orleans residents. This study was a case study of three cities with somewhat different experiences with Katrina\u27s diaspora. Time series analysis was used to examine the pre- and post-Katrina trends in six Part I offenses (murder, robbery, aggravated assault, rape, burglary, and auto theft) to assess any impact of such large-scale population shifts on crime in host communities. Contrary to much popular speculation, only modest effects were found on crime. Social disorganization theory was used to frame both the analysis and the interpretation of these result

PhysicsGP: A Genetic Programming Approach to Event Selection

We present a novel multivariate classification technique based on Genetic Programming. The technique is distinct from Genetic Algorithms and offers several advantages compared to Neural Networks and Support Vector Machines. The technique optimizes a set of human-readable classifiers with respect to some user-defined performance measure. We calculate the Vapnik-Chervonenkis dimension of this class of learning machines and consider a practical example: the search for the Standard Model Higgs Boson at the LHC. The resulting classifier is very fast to evaluate, human-readable, and easily portable. The software may be downloaded at: http://cern.ch/~cranmer/PhysicsGP.htmlComment: 16 pages 9 figures, 1 table. Submitted to Comput. Phys. Commu

Nanoliposomal Nitroglycerin Exerts Potent Anti-Inflammatory Effects.

Nitroglycerin (NTG) markedly enhances nitric oxide (NO) bioavailability. However, its ability to mimic the anti-inflammatory properties of NO remains unknown. Here, we examined whether NTG can suppress endothelial cell (EC) activation during inflammation and developed NTG nanoformulation to simultaneously amplify its anti-inflammatory effects and ameliorate adverse effects associated with high-dose NTG administration. Our findings reveal that NTG significantly inhibits human U937 cell adhesion to NO-deficient human microvascular ECs in vitro through an increase in endothelial NO and decrease in endothelial ICAM-1 clustering, as determined by NO analyzer, microfluorimetry, and immunofluorescence staining. Nanoliposomal NTG (NTG-NL) was formulated by encapsulating NTG within unilamellar lipid vesicles (DPhPC, POPC, Cholesterol, DHPE-Texas Red at molar ratio of 6:2:2:0.2) that were ~155 nm in diameter and readily uptaken by ECs, as determined by dynamic light scattering and quantitative fluorescence microscopy, respectively. More importantly, NTG-NL produced a 70-fold increase in NTG therapeutic efficacy when compared with free NTG while preventing excessive mitochondrial superoxide production associated with high NTG doses. Thus, these findings, which are the first to reveal the superior therapeutic effects of an NTG nanoformulation, provide the rationale for their detailed investigation for potentially superior vascular normalization therapies

Utilizing the Alarm Taxonomy and Classification System (ATACS) to Redesign Landing Gear Warnings

Alarms have been in use for many decades, yet there still needs to be more clarity about what makes a good alarm. Vendors and government agencies have developed several useful handbooks describing the Do’s and Don’ts of effective alarm design; however, to date, we cannot find a comprehensive quantitative taxonomy or classification system that allows researchers to easily score and rank various alarm designs in any field—while using a common language that users, engineers, designers, and human factors professionals can understand. The Alarm Taxonomy and Classification System (ATACS) fills this gap in the literature by breaking alarms down into categorical characteristics, providing a quantitative methodology for scoring each characteristic, and outlining a process by which users, vendors, and human factors professionals can agree on the efficacy of the alarm in question. We discuss this process in detail and show how this system was used to improve landing gear warnings

Usability of Urban Air Mobility: Quantitative and Qualitative Assessments of Usage in Emergency Situations

The purpose of these four studies was to determine participants’ willingness to support the use of urban air mobility (UAM) in response to natural disasters, along with the preferred locations to establish vertiports. Study 1 assessed the willingness to support using a mixed factorial design. The findings demonstrated strong, robust support for the use of UAM when responding to natural disasters. Study 2 worked to create and validate a scale that could assess vertiports\u27 current and proposed locations. The Vertiport Usability Scale was developed and shown to have strong psychometric properties to validly assess vertiport locations through a multi-stage process. Study 3 used the Vertiport Usability Scale to understand the most highly preferred locations for vertiports in three conditions from a multi-stage process: temporary disaster locations, permanent disaster locations, and permanent consumer locations. Study 4 was conducted using qualitative methods to complement the earlier quantitative approaches. Through an initial survey and follow-on interview, three themes emerged related to UAM in response to natural disasters and vertiports: 1) human involvement in UAM operations, 2) scenarios for usage, and 3) setup and deployment of vehicles

A population study of the minicircles in Trypanosoma cruzi: predicting guide RNAs in the absence of empirical RNA editing

<p>Abstract</p> <p>Background</p> <p>The structurally complex network of minicircles and maxicircles comprising the mitochondrial DNA of kinetoplastids mirrors the complexity of the RNA editing process that is required for faithful expression of encrypted maxicircle genes. Although a few of the guide RNAs that direct this editing process have been discovered on maxicircles, guide RNAs are mostly found on the minicircles. The nuclear and maxicircle genomes have been sequenced and assembled for <it>Trypanosoma cruzi</it>, the causative agent of Chagas disease, however the complement of 1.4-kb minicircles, carrying four guide RNA genes per molecule in this parasite, has been less thoroughly characterised.</p> <p>Results</p> <p>Fifty-four CL Brener and 53 Esmeraldo strain minicircle sequence reads were extracted from <it>T. cruzi </it>whole genome shotgun sequencing data. With these sequences and all published <it>T. cruzi </it>minicircle sequences, 108 unique guide RNAs from all known <it>T. cruzi </it>minicircle sequences and two guide RNAs from the CL Brener maxicircle were predicted using a local alignment algorithm and mapped onto predicted or experimentally determined sequences of edited maxicircle open reading frames. For half of the sequences no statistically significant guide RNA could be assigned. Likely positions of these unidentified gRNAs in <it>T. cruzi </it>minicircle sequences are estimated using a simple Hidden Markov Model. With the local alignment predictions as a standard, the HMM had an ~85% chance of correctly identifying at least 20 nucleotides of guide RNA from a given minicircle sequence. Inter-minicircle recombination was documented. Variable regions contain species-specific areas of distinct nucleotide preference. Two maxicircle guide RNA genes were found.</p> <p>Conclusion</p> <p>The identification of new minicircle sequences and the further characterization of all published minicircles are presented, including the first observation of recombination between minicircles. Extrapolation suggests a level of 4% recombinants in the population, supporting a relatively high recombination rate that may serve to minimize the persistence of gRNA pseudogenes. Characteristic nucleotide preferences observed within variable regions provide potential clues regarding the transcription and maturation of <it>T. cruzi </it>guide RNAs. Based on these preferences, a method of predicting <it>T. cruzi </it>guide RNAs using only primary minicircle sequence data was created.</p

The Inception of a Long-Term Study of Elevation Change and Sediment Accretion in Three Forested Tidal Freshwater Wetlands and in the Restored Freshwater Marsh at Kimages Creek

Sediment accretion and the corresponding ability to keep pace with sea level rise in both mature forested tidal freshwater wetlands and restored wetland sites represent significant data gaps in the current body of literature pertaining to wetland sustainability. In order to address these data gaps, Surface Elevation Tables (SETs) were installed along with feldspar marker horizons to measure contemporary sediment accretion rates in three mature forested tidal freshwater wetlands, as well as accretion within a tidal marsh currently undergoing restoration. These are the first SETs installed in tidal forests in the James River watershed, and establish VCU Rice Rivers Center as a contributing partner in the NOAA Chesapeake Bay Sentinel Sites Cooperative