625 research outputs found

    Evidence for the Galactic X-ray Bulge II

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    A mosaic of 5 \ros~PSPC pointed observations in the Galactic plane (l25l\sim25^{\circ}) reveals X-ray shadows in the 0.52.00.5-2.0 keV band cast by distant molecular clouds. The observed on-cloud and off-cloud X-ray fluxes indicate that 15\sim15% and 37\sim37% of the diffuse X-ray background in this direction in the \tq~keV and 1.5 keV bands, respectively, originates behind the molecular gas which is located at \sim3 kpc from the Sun. The implication of the derived background X-ray flux beyond the absorbing molecular cloud is consistent with, and lends further support to recent observations of a Galactic X-ray bulge.Comment: 19 pages, 5 figures, 2 table

    Korrelator für Strategien für eine ökologisch anpassungsfähige städtebauliche und architektonische Entwicklung

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    40 years after “The limits to growth” the post oil boom economy affects countries in resource scarce environments like the Arabian Peninsula in the Middle East with expanding urbanization. Those cities and architectures are based on fossil fuel driven technologies to control the surrounding arid hot climate for the benefits of human comfort. As a result skyscrapers are flourishing out of desert sands. Their ecological footprint in terms of resource consumption and the resulting emissions is nearly six planet earths, but celebrated by imported quantitative evaluation methods from North America or Europe with platinum medals for sustainable building practices. This dichotomy displays the global quest for ‘sustainable’ development on the one hand side and the lack of integrating the inherent bio-climatic, socio-cultural and political-economical prerequisites of those newly developing countries on the other. Whereas traditional desert oases settlements have been as self-sufficient and self-organising systems perfectly interconnected with all prevalent natural resources and cultural conditions inherent to the region. Such integral understanding draws on the logic of the immanent relations of the natural, human and built environment or in other words on ecology. An ecological understanding is used in this work to determine the qualitative relationships of urban and architectural (built) environments in conjunction to prevalent natural (ecosphere) and human (anthroposhere) conditions. On the assumption that the built environment acts as levelling layer between the human and the natural environment in order to compensate bio-climate conditions for the comfort of social-cultural context desires, the main research question raises as such: How can cities and architectures become support systems (rather than energy and resource consumers) that have the properties to co-evolve as cooperative sub-systems with the surrounding natural and human preconditions under the rules of ecology in general? And in particular: How can the concept of a traditional self-sustaining desert oasis provide future strategies for sustainable development of cities and architecture? Rules of ecological systems are understood here as instruments to an appropriate urban planning that follows the principles of higher adaptability and self-organization patterns to generate conditions. System theories are consulted to determine principles and strategies of complex viable systems of nature. These then form the matrix for analysis of case studies on urbanization patterns of pre-and post-oil era in the Sultanate of Oman on the Arabian Peninsula and are used to extrapolate potentials and missing links within urban systems through support strategies. Those results are further transferred into a general model of interconnections (Correlator) of components of urbanism, architecture and technologies in conjunction to the natural and human environment. The resulting model provides a correlation matrix that orders elements and flows from the natural to the built environment via considering principles of human systems and strategies of ecological systems. It proposes a template of possible elements and strategies for interconnection, which determine the quality of adaptable, viable and thus ‘sustainable’ urban environments. The Correlator shows possibilities and fields of action for the holistic thinking of architecture and urbanism as support system and thus for the decision-making processes in planning, policy, and the design of the built environment. Finally this work demonstrates strategies for ‘sustainable development’ where the correlation matrix and the knowledge of the quality of ecological network connections proposes an aide-memoir to de-specify the tunnel-visioned expertise of past innovations and prioritizes ‘Vernetztes Denken’ for newly meaningful concepts for a new planning culture that enable viable urban and architectural development, not only within desert regions.40 Jahre nach "Die Grenzen des Wachstums" ermöglicht die Post Ölboom Wirtschaft Ländern in ressourcen_knappen Umgebungen wie der arabischen Halbinsel im Nahen Osten eine steigende Urbanisierung. Städte und Architekturen werden von fossilen Technologien gesteuert, um das aride heiße Klima für den menschlichen Komfort anzupassen. Als Ergebnis sprießen Wolkenkratzer aus dem Wüstensand. Deren ökologischer Fußabdruck in Bezug auf Ressourcenverbrauch und die daraus resultierenden Emissionen von fast sechs Planeten Erde floriert, werden aber von importierten quantitative Bewertungsmethoden aus Nord Amerika oder Europa mit Platin-Medaillen für nachhaltiges Bauen Praxis gefeiert. Es wird deutlich, dass die globale Suche nach "nachhaltiger" Entwicklung im Konflikt zu einer Integration von inhärenten bio-klimatischen und soziokulturelle Voraussetzungen dieser Entwicklungsländern steht. Städte materialisieren sich mittlerweile durch quantitative neo-liberale Wirtschaftsmotive, während traditionelle Wüstenoasen Siedlungen als autark und selbstorganisierende Systeme perfekt mit allen gängigen natürlichen Ressourcen und kulturellen Bedingungen der Region verbunden waren. Ein solches ganzheitliches Verständnis stützt sich auf die Logik von immanenten Wechselbeziehungen natürlicher, menschlicher und gebauter Umwelt oder mit anderen Worten auf Regeln der Ökologie. Ein ökologisches Verständnis wird in dieser Arbeit verwendet, um qualitative Zusammenhänge städtebaulicher und architektonischer Umgebungen in Verbindung zu natürlich (Ökosphäre) und menschlich (Anthroposphaere) herrschenden Bedingungen zu bringen. In der Annahme, dass die gebaute Umwelt als Ausgleichsschicht zwischen der menschlichen und der natürlichen Umwelt wirkt, um bio-klimatische Bedingungen dem Komfort im sozial-kulturellen Kontext zu kompensieren, ergibt sich die zentrale Forschungsfrage: Wie können Städte und Architekturen unterstützende Systeme (eher als Energie und Ressourcen Verbraucher) werden, die als kooperative Teilsysteme mit den umgebenden natürlichen und menschlichen Voraussetzungen nach den Regeln des Ökologie funktionieren? Und im speziellen: Wie kann das Konzept einer traditionellen selbsterhaltende Wüstenoase Zukunftsstrategien für eine nachhaltige Entwicklung der Städte und der Architektur liefern? Regeln ökologischer Systeme werden hier als Instrumente verstanden, um eine angemessene Stadtplanung, die den Prinzipien der höheren Anpassungsfähigkeit und Selbstorganisation Muster folgt, zu erzeugen. Systemtheorien werden konsultiert, um Prinzipien und Strategien von komplexen lebensfähigen Systemen zu ermitteln. Diese bilden dann die Analysematrix für Fallstudien an Urbanisierungsmustern aus Pre- und Post Öl-Aera im Sultanat Oman auf der arabischen Halbinsel und dienen dazu etwaige Potenziale und fehlende Verbindungen innerhalb urbaner Systeme und Support-Strategien zu extrapolieren. Diese Ergebnisse werden weiter transferiert in ein generelles Modell von Verbindungen (Correlator) der Komponenten von Stadt, Architektur und Technologien im Bezug auf ihre natürliche und menschliche Umwelt. Das resultierende Korrelationsmodell bietet eine Matrix, die Elemente und Flüsse von der natürlichen zur gebauten Umwelt in Einklang mit Prinzipien menschlicher Systeme und Strategien ökologischer Systeme stellt. Als Schablone möglicher Stadt- und Architekturkomponenten und Verbindungsstrategien, kann somit die Qualität hinlänglich ihrer Anpassungsfähigkeit, Lebensfähigkeit und somit "Nachhaltigkeit" eingestellt werden. Das Ergebnis zeigt Möglichkeiten und Handlungsfelder für ein ganzheitliches Denken auf, Architektur und Städtebau als Support-System zu sehen, um Entscheidungsfindungsprozesse in Planung, Politik und der Gestaltung gebauter Umwelt zu unterstützen. Der Korrelator und das Wissen um die Qualität ökologischer Netzwerkverbindungen ergibt somit eine Gedankenstütze für den Ansatz, Stadt, Mensch und Natur vernetzt zu denken, um sinnvolle Konzepte für lebensfähige Städte und Architekturen in spezifischen bio-klimatischen und soziokulturellen Gegebenheiten über Wüstenregionen hinaus zu ermöglichen

    Differential effects of selective inhibitors targeting the PI3K/AKT/mTOR pathway in acute lymphoblastic leukemia

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    Purpose: Aberrant PI3K/AKT/mTOR signaling has been linked to oncogenesis and therapy resistance in various malignancies including leukemias. In Philadelphia chromosome (Ph) positive leukemias, activation of PI3K by dysregulated BCR-ABL tyrosine kinase (TK) contributes to the pathogenesis and development of resistance to ABL-TK inhibitors (TKI). The PI3K pathway thus is an attractive therapeutic target in BCR-ABL positive leukemias, but its role in BCR-ABL negative ALL is conjectural. Moreover, the functional contribution of individual components of the PI3K pathway in ALL has not been established. Experimental design: We compared the activity of the ATP-competitive pan-PI3K inhibitor NVP-BKM120, the allosteric mTORC1 inhibitor RAD001, the ATP-competitive dual PI3K/mTORC1/C2 inhibitors NVP-BEZ235 and NVP-BGT226 and the combined mTORC1 and mTORC2 inhibitors Torin 1, PP242 and KU-0063794 using long-term cultures of ALL cells (ALL-LTC) from patients with B-precursor ALL that expressed the BCR-ABL or TEL-ABL oncoproteins or were BCR-ABL negative. Results: Dual PI3K/mTOR inhibitors profoundly inhibited growth and survival of ALL cells irrespective of their genetic subtype and their responsiveness to ABL-TKI. Combined suppression of PI3K, mTORC1 and mTORC2 displayed greater antileukemic activity than selective inhibitors of PI3K, mTORC1 or mTORC1 and mTORC2. Conclusions: Inhibition of the PI3K/mTOR pathway is a promising therapeutic approach in patients with ALL. Greater antileukemic activity of dual PI3K/mTORC1/C2 inhibitors appears to be due to the redundant function of PI3K and mTOR. Clinical trials examining dual PI3K/mTORC1/C2 inhibitors in patients with B-precursor ALL are warranted, and should not be restricted to particular genetic subtypes

    Optimal Time-Convex Hull under the Lp Metrics

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    We consider the problem of computing the time-convex hull of a point set under the general LpL_p metric in the presence of a straight-line highway in the plane. The traveling speed along the highway is assumed to be faster than that off the highway, and the shortest time-path between a distant pair may involve traveling along the highway. The time-convex hull TCH(P){TCH}(P) of a point set PP is the smallest set containing both PP and \emph{all} shortest time-paths between any two points in TCH(P){TCH}(P). In this paper we give an algorithm that computes the time-convex hull under the LpL_p metric in optimal O(nlogn)O(n\log n) time for a given set of nn points and a real number pp with 1p1\le p \le \infty

    Community Gardens: An Exploration of Urban Agriculture in the Bronx, New York City

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    Urban agriculture/community gardening in the Bronx has multiple roles, including health-promoting, economic, environmental, and cultural. These roles are particularly important in light of urban sustainability issues and environmental justice concerns, such as differential access to open space, recreation, and fresh produce in poorer communities and communities of color, as well as differential environmental and health impacts of unsustainable practices on these communities. The gardens generally help promote a sense of place - a focus for communities - which often have little access to safe parks or recreational space within their neighborhoods, and create a center for community cultural and educational activities. The Bronx currently has about 175 community gardens administered by Operation Green Thumb, as well as a number of community gardens operated by non-profit entities, such as the Parks Council, and community gardens on private property. On average, the Bronx community gardens use about 75% of their land for growing vegetables, and many gardens supply the farming families and others in the neighborhood with much of their vegetables for the year. This study investigates urban agricultural practices in the Bronx to assess how community gardens improve quality-of-life for the proximate populations. Through semi-structured interviews of the gardeners, visits to observe the gardens, and a spatial analysis of community socio-demographic characteristics using Geographic Information System (GIS), we examine the social, political, cultural, environmental, food security, and health benefits of community gardening. This is part of a larger study comparing urban agricultural practices in the Bronx and Curitiba, Brazil

    Characterization of Urban Agricultural Practices and Gardeners’ Perceptions in Bronx Community Gardens, New York City.

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    This study investigates urban agricultural practices in the community gardens in the Bronx, New York City, United States, due to their historical role of helping bring peace and a sense of community to areas that suffered from violence and social injustice. Through semi-structured interviews with the gardeners, visits to observe the gardens, and a spatial analysis of community socio-demographic characteristics using Geographic Information Systems (GIS), we characterize the community gardens visited, and survey the gardeners’ perceptions regarding the benefits and challenges that are involved in the activity. The GISc analysis results showed that there is a much higher rate of poverty in block group populations living within a quarter mile of the community gardens and there is also a significantly higher Hispanic population in block groups living close to the gardens than those further away. The community gardens visited can be characterized as places where the activity of growing plants is a way to socialize within the community, a source of fresh vegetables and fruits, a way to beautify the neighborhood, and a place for education. Regarding the gardeners’ perceptions, it was unanimous that in the garden they enjoy being together with family and community, appreciating nature, and receiving therapeutic benefits that gardening brings. However, some have spoken about their fears of losing the gardens, since they are still not protected by the City, and are prone to take-over by developers

    Discovery of Small-Molecule Stabilizers of 14-3-3 Protein-Protein Interactions via Dynamic Combinatorial Chemistry

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    Protein-protein interactions (PPIs) play an important role in numerous biological processes such as cell-cycle regulation and multiple diseases. The family of 14-3-3 proteins is an attractive target as they serve as binding partner to various proteins and are therefore capable of regulating their biological activities. Discovering small-molecule modulators, in particular stabilizers, of such complexes via traditional screening approaches is a challenging task. Herein, we pioneered the first application of dynamic combinatorial chemistry (DCC) to a PPI target, to find modulators of 14-3-3 proteins. Evaluation of the amplified hits from the DCC experiments for their binding affinity via surface plasmon resonance (SPR), revealed that the low-micromolar (KD 15-16 μM) acylhydrazones are 14-3-3/synaptopodin PPI stabilizers. Thus, DCC appears to be ideally suited for the discovery of not only modulators but even the more elusive stabilizers of notoriously challenging PPIs
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