Synthesis of missile autopilots robust to the presence of parametric variations

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Aeronautics and Astronautics, 1991.Includes bibliographical references (leaves 162-164).by Thomas John Urban.M.S

OmniMapFree: A unified tool to visualise and explore sequenced genomes

<p>Abstract</p> <p>• Background</p> <p>Acquiring and exploring whole genome sequence information for a species under investigation is now a routine experimental approach. On most genome browsers, typically, only the DNA sequence, EST support, motif search results, and GO annotations are displayed. However, for many species, a growing volume of additional experimental information is available but this is rarely searchable within the landscape of the entire genome.</p> <p>• Results</p> <p>We have developed a generic software which permits users to view a single genome in entirety either within its chromosome or supercontig context within a single window. This software permits the genome to be displayed at any scales and with any features. Different data types and data sets are displayed onto the genome, which have been acquired from other types of studies including classical genetics, forward and reverse genetics, transcriptomics, proteomics and improved annotation from alternative sources. In each display, different types of information can be overlapped, then retrieved in the desired combinations and scales and used in follow up analyses. The displays generated are of publication quality.</p> <p>• Conclusions</p> <p>OmniMapFree provides a unified, versatile and easy-to-use software tool for studying a single genome in association with all the other datasets and data types available for the organism.</p

Spacecraft Fire Detection: Smoke Properties and Transport in Low-Gravity

Results from a recent smoke particle size measurement experiment conducted on the International Space Station (ISS) are presented along with the results from a model of the transport of smoke in the ISS. The experimental results show that, for the materials tested, a substantial portion of the smoke particles are below 500 nm in diameter. The smoke transport model demonstrated that mixing dominates the smoke transport and that consequently detection times are longer than in normal gravity

Urban-Focused Comprehensive Economic Development Strategy (CEDS)

This Comprehensive Economic Development Strategy (CEDS) is the outgrowth of a long running effort by the John S. Watson Institute for Public Policy at Thomas Edison State College (Watson Institute) to support economic and community development in New Jersey with a particular focus on urban areas in need of revitalization. The Watson Institute was previously awarded a United States Economic Development Administration (USEDA) grant to complete an economic analysis of the North Central New Jersey Region. The USEDA approved that analysis and awarded additional funds to continue our work, culminating in this CEDS plan. Several years ago, the Watson Institute recognized that there was an opportunity and need to engage in regional economic development planning and cooperation amongst members of the New Jersey Urban Mayors Association. Rapidly advancing technology and economies necessitate partnerships amongst local governments, non-profits, private firms, and universities to address broad economic development problems and reach long-term goals. Although many of the municipalities participating in the CEDS effort are not contiguous, they nonetheless share histories that have led to their current problems. Allowing geographic boundaries to limit the extent of opportunity is no longer a viable option for regions that want to see broad based and sustainable economic growth. The purpose of a CEDS is to bring together the public, non- profit, and private sectors to establish a comprehensive framework for economic growth and revitalization in a region. In this case, the “Region” is defined as 19 specific municipalities within a seven-county area of the state, including: Asbury Park, Bayonne, Bloomfield, East Orange, Elizabeth, Hoboken, Irvington, Jersey City, Lakewood, Neptune, New Brunswick, Newark, Orange, Passaic, Paterson, Perth Amboy, Plainfield, Roselle and Woodbridge. The geographic composition of this CEDS is unique in that the Region is not strictly speaking contiguous. What binds our Region together are the threads of common issues, opportunities, constraints, and the hope that, collectively, the communities can create solutions that would otherwise not be obtained individually. One of the most significant binding events of this region’s recent history is Superstorm Sandy. Minimizing disruption from natural disaster events is critical to any economic development goals and objectives of a community. There are a wide variety of reports and recommendations available to municipalities in helping them develop resiliency plans that are customized to meet the needs of their community. Discussions regarding resilient infrastructure have been an ongoing theme during this urban focused CEDS, and is reflected in several projects and initiatives focused on resiliency as well as it being a theme in projects that are not necessarily resiliency focused, but incorporate resiliency elements to reduce the stress put on other systems. Two of the more forward thinking projects included as part of resiliency strategies in this CEDS are the City of Hoboken’s flood wall and the Township of Woodbridge’s plan for a township wide microgrid. Although discussion about resiliency in general tends to focus on natural disaster, this CEDS discussion on resiliency also encompassed a wide variety of activities and topics. When at all possible, resilience focused projects should incorporate other resiliency related elements The steering committee met many times over the course of several years, for both the economic base analysis and for this CEDS plan. Steering committee members included representatives and officials from each community; non-profit organizations such as universities, community colleges, libraries and community-based organizations; and representatives of the private sector ranging from Fortune 100 corporations to small businesses. The steering committee’s work culminated in the Action Plan. The Action Plan serves as the roadmap that the Watson Institute, together with the New Jersey Urban Mayors Association and the CEDS steering committee itself, will use to implement sustainable economic development in the Region’s constituent municipalities. The challenges faced by the steering committee in formulating the CEDS plan were commensurate with those faced by each of the communities. The goals and objectives include: Enhancing, preserving and making resilient critical infrastructure assets; Promoting small business development; Addressing persistent and complex workforce issues; Marketing effectively to attract new businesses, residents and tourists; Promulgating best practices in economic development across all 19 communities; Providing adequate implementation assistance to execute the CEDS plan. The steering committee engaged in many planning exercises, including stakeholder and issues mapping, brainstorming, resource assessments, inventorying existing networks and programs, etc. The consulting team brought data, national economic development experience and certain stakeholder engagement techniques to elicit creative, non-linear thinking. The Watson Institute provided a Senior Fellow to meet and communicate with each community individually on multiple occasions to understand specific needs and encourage participation in the process. Following all these efforts, the steering committee agreed that, to be included in the CEDS plan, each action has to meet the following criteria: It must address one of the critical goals/objectives identified above, It must be realistic, clear and actionable, It must either require few local resources to implement or have a funding source identified, It must have a real and sustainable impact, and, It should be relatively short term to show progress and generate enthusiasm, It should be something that, if successful, can be quickly replicated across all 19 communities, It should have performance metrics that can be tracked and reported on. These criteria weighed considerably on the process and the steering committee’s deliberations. Unlike a “traditional” CEDS vested at the County or State level, with existing power structures and funding sources, this CEDS relies on the power of persuasion; the more effective utilization of existing resources; and the ability to realign stakeholders in a truly novel way

Retnla (Relmα/Fizz1) Suppresses Helminth-Induced Th2-Type Immunity

Retnla (Resistin-like molecule alpha/FIZZ1) is induced during Th2 cytokine immune responses. However, the role of Retnla in Th2-type immunity is unknown. Here, using Retnla−/− mice and three distinct helminth models, we show that Retnla functions as a negative regulator of Th2 responses. Pulmonary granuloma formation induced by the eggs of the helminth parasite Schistosoma mansoni is dependent on IL-4 and IL-13 and associated with marked increases in Retnla expression. We found that both primary and secondary pulmonary granuloma formation were exacerbated in the absence of Retlna. The number of granuloma-associated eosinophils and serum IgE titers were also enhanced. Moreover, when chronically infected with S. mansoni cercariae, Retnla−/− mice displayed significant increases in granulomatous inflammation in the liver and the development of fibrosis and progression to hepatosplenic disease was markedly augmented. Finally, Retnla−/− mice infected with the gastrointestinal (GI) parasite Nippostrongylus brasiliensis had intensified lung pathology to migrating larvae, reduced fecundity, and accelerated expulsion of adult worms from the intestine, suggesting Th2 immunity was enhanced. When their immune responses were compared, helminth infected Retnla−/− mice developed stronger Th2 responses, which could be reversed by exogenous rRelmα treatment. Studies with several cytokine knockout mice showed that expression of Retnla was dependent on IL-4 and IL-13 and inhibited by IFN-γ, while tissue localization and cell isolation experiments indicated that eosinophils and epithelial cells were the primary producers of Retnla in the liver and lung, respectively. Thus, the Th2-inducible gene Retnla suppresses resistance to GI nematode infection, pulmonary granulomatous inflammation, and fibrosis by negatively regulating Th2-dependent responses

Clusterin, a haploinsufficient tumor suppressor gene in neuroblastomas

This article is available open access through the publisher’s website. Copyright @ 2009 The Authors.Background - Clusterin expression in various types of human cancers may be higher or lower than in normal tissue, and clusterin may promote or inhibit apoptosis, cell motility, and inflammation. We investigated the role of clusterin in tumor development in mouse models of neuroblastoma. Methods - We assessed expression of microRNAs in the miR-17-92 cluster by real-time reverse transcription–polymerase chain reaction in MYCN-transfected SH-SY5Y and SH-EP cells and inhibited expression by transfection with microRNA antisense oligonucleotides. Tumor development was studied in mice (n = 66) that were heterozygous or homozygous for the MYCN transgene and/or for the clusterin gene; these mice were from a cross between MYCN-transgenic mice, which develop neuroblastoma, and clusterin-knockout mice. Tumor growth and metastasis were studied in immunodeficient mice that were injected with human neuroblastoma cells that had enhanced (by clusterin transfection, four mice per group) or reduced (by clusterin short hairpin RNA [shRNA] transfection, eight mice per group) clusterin expression. All statistical tests were two-sided. Results - Clusterin expression increased when expression of MYCN-induced miR-17-92 microRNA cluster in SH-SY5Y neuroblastoma cells was inhibited by transfection with antisense oligonucleotides compared with scrambled oligonucleotides. Statistically significantly more neuroblastoma-bearing MYCN-transgenic mice were found in groups with zero or one clusterin allele than in those with two clusterin alleles (eg, 12 tumor-bearing mice in the zero-allele group vs three in the two-allele group, n = 22 mice per group; relative risk for neuroblastoma development = 4.85, 95% confidence interval [CI] = 1.69 to 14.00; P = .005). Five weeks after injection, fewer clusterin-overexpressing LA-N-5 human neuroblastoma cells than control cells were found in mouse liver or bone marrow, but statistically significantly more clusterin shRNA-transfected HTLA230 cells (3.27%, with decreased clusterin expression) than control-transfected cells (1.53%) were found in the bone marrow (difference = 1.74%, 95% CI = 0.24% to 3.24%, P = .026). Conclusions - We report, to our knowledge, the first genetic evidence that clusterin is a tumor and metastasis suppressor gene.Sport Aiding Medical Research for Kids (SPARKS), Great Ormond Street Hospital/National Health Service, the National Cancer Institute and University of Parma

Loss of Cyclin C or CDK8 provides ATR inhibitor resistance by suppressing transcription-associated replication stress.

The protein kinase ATR plays pivotal roles in DNA repair, cell cycle checkpoint engagement and DNA replication. Consequently, ATR inhibitors (ATRi) are in clinical development for the treatment of cancers, including tumours harbouring mutations in the related kinase ATM. However, it still remains unclear which functions and pathways dominate long-term ATRi efficacy, and how these vary between clinically relevant genetic backgrounds. Elucidating common and genetic-background specific mechanisms of ATRi efficacy could therefore assist in patient stratification and pre-empting drug resistance. Here, we use CRISPR-Cas9 genome-wide screening in ATM-deficient and proficient mouse embryonic stem cells to interrogate cell fitness following treatment with the ATRi, ceralasertib. We identify factors that enhance or suppress ATRi efficacy, with a subset of these requiring intact ATM signalling. Strikingly, two of the strongest resistance-gene hits in both ATM-proficient and ATM-deficient cells encode Cyclin C and CDK8: members of the CDK8 kinase module for the RNA polymerase II mediator complex. We show that Cyclin C/CDK8 loss reduces S-phase DNA:RNA hybrid formation, transcription-replication stress, and ultimately micronuclei formation induced by ATRi. Overall, our work identifies novel biomarkers of ATRi efficacy in ATM-proficient and ATM-deficient cells, and highlights transcription-associated replication stress as a predominant driver of ATRi-induced cell death

The Cost of Poverty: The Perpetuating Cycle of Concentrated Poverty in New Jersey Cities • A Comprehensive Budgetary Analysis of Four Urban New Jersey Municipalities

This report examines the problem of concentrated poverty in the State of New Jersey. Both the individual and the long-term economic consequences of concentrated poverty are well- documented in social science research. The report adds to that knowledge by examining the practical, budgetary consequences faced by urban centers that are characterized by high poverty levels. The report focuses on four cities, which are represented in the New Jersey Urban Mayors Association (NJUMA) — Bridgeton, Passaic, Perth Amboy, and Trenton. While these regions vary considerably, they all share one important fact: their poverty rates are double or triple the New Jersey average. Clearly, these cities know all too well the struggles that come with concentrated poverty. Poverty in New Jersey is often highly concentrated, particularly in urban areas. New Jersey is ranked as one of the wealthiest states in the country, yet this average wealth ignores two important realities. First, poverty tends to be concentrated, so that a large portion of the State’s population lives in areas with poverty rates above 20%. Second, the official poverty threshold bears no relation to the basic cost of living in New Jersey, so that households with incomes up to two and a half times the poverty level still struggle just to make ends meet. By this measure, in 2014 a remarkable 2.8 million New Jersey residents lived under this true measure of poverty, including 800,000 children. Both the breadth and the concentration of poverty create serious challenges, particularly in urban areas. Residents in poor urban areas present significant service needs. Due to the limits of public and affordable housing even in low-income areas, citizens of NJUMA cities must spend over half their income on rent, leaving little else for other basic needs. The constraints produced by low incomes are exacerbated by multiple systemic barriers, including poor access to health care, reliance on inadequate transportation, poor quality education, and substandard or overcrowded housing. Personal barriers like limited English proficiency, large families, and lack of two wage earners can also act as barriers to economic empowerment. The deck is stacked against impoverished municipalities. In recent years, funding from the State to individual municipalities has dwindled markedly. In response, local property taxes have soared, generating an ever-increasing burden on nearly all New Jersey residents. But, in impoverished cities, the burden is even greater. Because an ever- increasing reliance on property taxes is layered over a diminishing tax base, a counterintuitive scenario has resulted, whereby the most impoverished municipalities shoulder an unmanageable municipal tax burden — a greater burden than even their wealthy neighbors. As the budget analysis in this report reveals, services other than public safety and public works make up an all too negligible portion of municipal budgets in the examined cities, despite the significant need for public services created by the dynamics of concentrated poverty. Urgent strategies are needed to alleviate concentrated poverty in New Jersey. We need to strengthen the safety-net for poverty-stricken families and their children, while at the same time addressing the budgetary system that unfairly burdens both income-strapped families and impoverished municipalities. If New Jersey is to make real progress on reducing the systemic poverty that traps far too many of our residents, the entire state must recognize and respond to this crisis. This means promoting family financial success through supportive work/family policies, adjusting the allocation of municipal budget State aid and support programming so that it prioritizes areas of concentrated need, and reimagining the fundamental structure of New Jersey’s property tax system

WISE/NEOWISE observations of Active Bodies in the Main Belt

We report results based on mid-infrared photometry of 5 active main belt objects (AMBOs) detected by the Wide-field Infrared Survey Explorer (WISE) spacecraft. Four of these bodies, P/2010 R2 (La Sagra), 133P/Elst-Pizarro, (596) Scheila, and 176P/LINEAR, showed no signs of activity at the time of the observations, allowing the WISE detections to place firm constraints on their diameters and albedos. Geometric albedos were in the range of a few percent, and on the order of other measured comet nuclei. P/2010 A2 was observed on April 2-3, 2010, three months after its peak activity. Photometry of the coma at 12 and 22 {\mu}m combined with ground-based visible-wavelength measurements provides constraints on the dust particle mass distribution (PMD), dlogn/dlogm, yielding power-law slope values of {\alpha} = -0.5 +/- 0.1. This PMD is considerably more shallow than that found for other comets, in particular inbound particle fluence during the Stardust encounter of comet 81P/Wild 2. It is similar to the PMD seen for 9P/Tempel 1 in the immediate aftermath of the Deep Impact experiment. Upper limits for CO2 & CO production are also provided for each AMBO and compared with revised production numbers for WISE observations of 103P/Hartley 2.Comment: 32 Pages, including 5 Figure

Concentración, segregación y movilidad residencial de los extranjeros en Barcelona

El artículo analiza la dinámica residencial de la población extranjera en la ciudad de Barcelona, considerando tres aspectos que centran su distribución: la concentración en el territorio, la segregación residencial en relación con la población de la ciudad y la movilidad residencial en interrelación con su región metropolitana. Se realiza un análisis temporal que sigue la evolución de estos elementos a lo largo de la década, con el objetivo de aportar una visión de conjunto de los cambios observados. El análisis contempla la utilización de diferentes fuentes estadísticas y detalla el comportamiento de las nacionalidades con más efectivos en Barcelona. Los resultados indican un desplazamiento de las áreas de concentración desde el centro histórico hacia la periferia de la ciudad, un descenso de la segregación vinculado a una mayor dispersión territorial y una fuerte movilidad residencial dentro de la Región Metropolitana que afecta especialmente a los municipios situados en la periferia más próxima a la ciudad.L'article analitza la dinàmica residencial de la població estrangera a la ciutat de Barcelona, considerant tres dels aspectes que en centren la distribució: la concentració en el territori, la segregació residencial en relació amb la població de la ciutat i la mobilitat residencial en interrelació amb la seva regió metropolitana. S'hi realitza una anàlisi temporal que ressegueix l'evolució d'aquests elements al llarg de la darrera dècada, amb l'objectiu d'aportar una visió de conjunt dels canvis observats. L'estudi contempla la utilització de diferents fonts estadístiques i detalla el comportament de les nacionalitats amb més efectius a Barcelona. Els resultats indiquen un desplaçament de les àrees de concentració des del centre històric cap a la perifèria de la ciutat, un descens de la segregació lligat a una dispersió territorial més gran i una forta mobilitat residencial dins de la Regió Metropolitana que afecta especialment els municipis situats a la perifèria més pròxima a la ciutat.L'article analyse la dynamique résidentielle de la population étrangère dans la ville de Barcelone en se concentrant sur trois aspects de sa distribution : la concentration sur le territoire, la ségrégation et la mobilité résidentielle au sein de la région métropolitaine. L'évolution de ces trois facteurs a été suivie pendant une décennie dans le but d'obtenir une vision globale des changements observés. Diverses sources statistiques qui détaillent le comportement des populations les plus nombreuses habitant Barcelone ont été utilisées. Les résultats montrent un déplacement des zones de concentration des étrangers depuis le centre historique vers les périphéries, une diminution de la ségrégation due à la croissante dispersion territoriale, et finalement une forte mobilité résidentielle dans la Région Métropolitaine, particulièrement dans les communes les plus proches de Barcelone.Three aspects of foreigners' residential mobility in the city of Barcelona are studied in this paper: territorial concentration, segregation and residential change within the metropolitan region. To obtain a global view, these three elements are followed for a decade. Several data bases, specifying the behaviour of major nationalities, are used. Results firstly show that foreigners are gradually moving out of the historical centre and into the periphery. Secondly, that there is a strong intra-metropolitan mobility, particularly so in the municipalities nearest to the central city. Finally, as foreigners are more widely distributed throughout the territory, they are also becoming less segregated