MOBILITY21: Strategic Investments for Transportation Infrastructure & Technology

America's transportation infrastructure is the backbone of our economy. A strong infrastructure means a strong America - an America that competes globally, supports local and regional economic development, and creates jobs. Strategic investments in our transportation infrastructure are vital to our national security, economic growth, transportation safety and our technology leadership. This document outlines critical needs for our transportation infrastructure, identifies new technology drivers and proposes strategic investments for safe and efficient air, ground, rail and marine mobility of people and goods.Comment: A Computing Community Consortium (CCC) white paper, 4 page

A weighted genetic risk score using all known susceptibility variants to estimate rheumatoid arthritis risk

Background: There is currently great interest in the incorporation of genetic susceptibility loci into screening models to identify individuals at high risk of disease. Here, we present the first risk prediction model including all 46 known genetic loci associated with rheumatoid arthritis (RA). Methods: A weighted genetic risk score (wGRS) was created using 45 RA non-human leucocyte antigen (HLA) susceptibility loci, imputed amino acids at HLA-DRB1 (11, 71 and 74), HLA-DPB1 (position 9) HLA-B (position 9) and gender. The wGRS was tested in 11 366 RA cases and 15 489 healthy controls. The risk of developing RA was estimated using logistic regression by dividing the wGRS into quintiles. The ability of the wGRS to discriminate between cases and controls was assessed by receiver operator characteristic analysis and discrimination improvement tests. Results: Individuals in the highest risk group showed significantly increased odds of developing anti-cyclic citrullinated peptide-positive RA compared to the lowest risk group (OR 27.13, 95% CI 23.70 to 31.05). The wGRS was validated in an independent cohort that showed similar results (area under the curve 0.78, OR 18.00, 95% CI 13.67 to 23.71). Comparison of the full wGRS with a wGRS in which HLA amino acids were replaced by a HLA tag single-nucleotide polymorphism showed a significant loss of sensitivity and specificity. Conclusions: Our study suggests that in RA, even when using all known genetic susceptibility variants, prediction performance remains modest; while this is insufficiently accurate for general population screening, it may prove of more use in targeted studies. Our study has also highlighted the importance of including HLA variation in risk prediction models

Further Development Of Aperture: A Precise Extremely Large Reflective Telescope Using Re-Configurable Elements

One of the pressing needs for space ultraviolet-visible astronomy is a design to allow larger mirrors than the James Webb Space Telescope primary. The diameter of the rocket fairing limits the mirror diameter such that all future missions calling for mirrors up to 16 meters in diameter or larger will require a mirror that is deployed post-launch. In response to the deployment requirement, we address the issues of this concept called "A Precise Extremely Large Reflective Telescope Using Reconfigurable Elements (APERTURE) with both hardware experiments and software simulations... We designed and built several fixtures with O-rings to hold a membrane. We established a coating process to make a membrane that was coated on one side with Cr and the other side with Cr-Terfenol-D-NiCo. The Terfenol-D (T-D hereafter) is the MSM (Magnetic Smart Memory) we use. We bought and established a procedure for measuring a deformation over time and purchased a Shack Hartmann system from Imagine Optic (https://www.imagine-optic.com). The first substrate we used was DuPont (TM) Kapton polyimide film. Due to material creep, we found the stability over a 48-hour period with a Kapton substrate was not as good as desired (greater than 1 micron). We then switched to CP1 Polyimide. We found the CP1 much more stable to creep, being stable from about 3 hours to 48 hours to within a measurement error to below approximately 0.1 micron. We produced a 13 micron maximum deviation on a 50-millimeter-diameter piece of CP1 (25 microns thick). The T-D coating was about 2 microns, and the other layers, about 10 nanometers. The magnetic field at the base was about 0.1 teslas. We can make the T-D film at least 5 times thicker and the magnetic field at least 5 times stronger, and hence make deformations as much as 25 times larger. We have a formed a collaboration produced at the NIAC (NASA Innovative Advanced Concepts) mid-term review with Dr. Ron Shiri of Goddard Space Flight Center (GSFC) to explore making controlled deviations on lambda/14-lambda/20 scales which are required to bring a surface to the diffraction limit. We carried out only preliminary work on Si using a Coordinate Measuring Machine (CMM), which produced deviations on the 1 micron level. We are still working on a program to bring to GSFC a flat enough (radius of curvature greater than 10 microns) -coated a Si piece with Cr, T-D, NiCo. Then we plan to carry out tests with an interferometer. Further, we formed a new collaboration with Prof. Rajan Vaidyanathan of the University of Central Florida to replace the CP1 with a shape memory alloy (SMA). With his collaboration, we acquired new Federal funding outside of NASA to explore the use of SMAs (we use NiTi). Our preliminary results indicate that we can produce deformations greater than 1 micron on approximately 100 microns thick. Furthermore we have shown that the NiTi can deploy to better than 1 micron of its set original and then trained shape

A role of SCN9A in human epilepsies, as a cause of febrile seizures and as a potential modifier of Dravet syndrome

A follow-up study of a large Utah family with significant linkage to chromosome 2q24 led us to identify a new febrile seizure (FS) gene, SCN9A encoding Na(v)1.7. In 21 affected members, we uncovered a potential mutation in a highly conserved amino acid, p.N641Y, in the large cytoplasmic loop between transmembrane domains I and II that was absent from 586 ethnically matched population control chromosomes. To establish a functional role for this mutation in seizure susceptibility, we introduced the orthologous mutation into the murine Scn9a ortholog using targeted homologous recombination. Compared to wild-type mice, homozygous Scn9a(N641Y/N641Y) knockin mice exhibit significantly reduced thresholds to electrically induced clonic and tonic-clonic seizures, and increased corneal kindling acquisition rates. Together, these data strongly support the SCN9A p.N641Y mutation as disease-causing in this family. To confirm the role of SCN9A in FS, we analyzed a collection of 92 unrelated FS patients and identified additional highly conserved Na(v)1.7 missense variants in 5% of the patients. After one of these children with FS later developed Dravet syndrome (severe myoclonic epilepsy of infancy), we sequenced the SCN1A gene, a gene known to be associated with Dravet syndrome, and identified a heterozygous frameshift mutation. Subsequent analysis of 109 Dravet syndrome patients yielded nine Na(v)1.7 missense variants (8% of the patients), all in highly conserved amino acids. Six of these Dravet syndrome patients with SCN9A missense variants also harbored either missense or splice site SCN1A mutations and three had no SCN1A mutations. This study provides evidence for a role of SCN9A in human epilepsies, both as a cause of FS and as a partner with SCN1A mutations

Barriers and facilitators to adherence to group exercise in institutionalized older people living with dementia: a systematic review

Objectives Research suggests targeted exercise is important for people living with dementia, especially those living in residential care. The aim of this review was to collect and synthesize evidence on the known barriers and facilitators to adherence to group exercise of institutionalized older people living with dementia. Methods We searched all available electronic databases. Additionally, we searched trial registries (clinicaltrial.gov, and WHO ICTRP) for ongoing studies. We searched for and included papers from January 1990 until September 2017 in any language. We included randomized, non-randomized trials. Studies were not eligible if participants were either healthy older people or people suffering from dementia but not living in an institution. Studies were also excluded if they were not focused on barriers and facilitators to adherence to group exercise. Results Using narrative analysis, we identified the following themes for barriers: bio-medical reasons and mental wellbeing and physical ability, relationships dynamics, and socioeconomic reasons. The facilitators were grouped under the following thematic frames: bio-medical benefits and benefits related to physical ability, feelings and emotions and confidence improvements, therapist and group relationships dynamics and activity related reasons. Conclusions We conclude that institutionalized older people living with dementia, even those who are physically frail, incontinent and/or have mild dementia can demonstrate certain level of exercise adherence, and therefore can respond positively to exercise programs. Tailored, individually-adjusted and supported physical activity, led by a knowledgeable, engaging and well communicating therapist/facilitator improves the adherence to group exercise interventions of institutionalized older people living with dementia

The Atacama Cosmology Telescope: Two-Season ACTPol Spectra and Parameters

We present the temperature and polarization angular power spectra measured by the Atacama Cosmology Telescope Polarimeter (ACTPol). We analyze night-time data collected during 2013-14 using two detector arrays at 149 GHz, from 548 deg$^2$ of sky on the celestial equator. We use these spectra, and the spectra measured with the MBAC camera on ACT from 2008-10, in combination with Planck and WMAP data to estimate cosmological parameters from the temperature, polarization, and temperature-polarization cross-correlations. We find the new ACTPol data to be consistent with the LCDM model. The ACTPol temperature-polarization cross-spectrum now provides stronger constraints on multiple parameters than the ACTPol temperature spectrum, including the baryon density, the acoustic peak angular scale, and the derived Hubble constant. Adding the new data to planck temperature data tightens the limits on damping tail parameters, for example reducing the joint uncertainty on the number of neutrino species and the primordial helium fraction by 20%.Comment: 23 pages, 25 figure

Genetics of rheumatoid arthritis contributes to biology and drug discovery

A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological datasets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)1. Here, we performed a genome-wide association study (GWAS) meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating ~10 million single nucleotide polymorphisms (SNPs). We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 1012–4. We devised an in-silico pipeline using established bioinformatics methods based on functional annotation5, cis-acting expression quantitative trait loci (cis-eQTL)6, and pathway analyses7–9 – as well as novel methods based on genetic overlap with human primary immunodeficiency (PID), hematological cancer somatic mutations and knock-out mouse phenotypes – to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery

The SUMMA Platform Prototype

We present the first prototype of the SUMMA Platform: an integrated platform for multilingual media monitoring. The platform contains a rich suite of low-level and high-level natural language processing technologies: automatic speech recognition of broadcast media, machine translation, automated tagging and classification of named entities, semantic parsing to detect relationships between entities, and automatic construction / augmentation of factual knowledge bases. Implemented on the Docker platform, it can easily be deployed, customised, and scaled to large volumes of incoming media streams

Women's Leadership in the State Legislature

Minnesota stands out nationally for the number of women serving in the state legislature and holding leadership positions. How have women leaders made a difference in the legislative decision-making process? What barriers still remain for women in politics and how can these be overcome? Join us to explore these questions with House Majority Leader Joyce Peppin, Deputy Minority Leader Erin Murphy, President of the Senate Sandra Pappas, and Assistant Senate Minority Leader Michelle Benson. The conversation will be moderated by former Speaker of the House, Steve Sviggum.Center for the Study of Politics and Governance, Humphrey School of Public Affairs, UM