287 research outputs found

    Compression tests of open-face truss-core sandwich panels

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    Compression tests of open-face truss core sandwich panel

    Compressive properties and column efficiency of metals reinforced on the surface with bonded filaments

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    Compressive properties and weight saving of metals reinforced on surface with resin bonded fiber

    Conceptual spatial representations for indoor mobile robots

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    We present an approach for creating conceptual representations of human-made indoor environments using mobile robots. The concepts refer to spatial and functional properties of typical indoor environments. Following ïŹndings in cognitive psychology, our model is composed of layers representing maps at diïŹ€erent levels of abstraction. The complete system is integrated in a mobile robot endowed with laser and vision sensors for place and object recognition. The system also incorporates a linguistic framework that actively supports the map acquisition process, and which is used for situated dialogue. Finally, we discuss the capabilities of the integrated system

    OmoMYC blunts promoter invasion by oncogenic MYC to inhibit gene expression characteristic of MYC-dependent tumors.

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    MYC genes have both essential roles during normal development and exert oncogenic functions during tumorigenesis. Expression of a dominant-negative allele of MYC, termed OmoMYC, can induce rapid tumor regression in mouse models with little toxicity for normal tissues. How OmoMYC discriminates between physiological and oncogenic functions of MYC is unclear. We have solved the crystal structure of OmoMYC and show that it forms a stable homodimer and as such recognizes DNA in the same manner as the MYC/MAX heterodimer. OmoMYC attenuates both MYC-dependent activation and repression by competing with MYC/MAX for binding to chromatin, effectively lowering MYC/MAX occupancy at its cognate binding sites. OmoMYC causes the largest decreases in promoter occupancy and changes in expression on genes that are invaded by oncogenic MYC levels. A signature of OmoMYC-regulated genes defines subgroups with high MYC levels in multiple tumor entities and identifies novel targets for the eradication of MYC-driven tumors

    Histone Acetylation-Mediated Regulation of the Hippo Pathway

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    The Hippo pathway is a signaling cascade recently found to play a key role in tumorigenesis therefore understanding the mechanisms that regulate it should open new opportunities for cancer treatment. Available data indicate that this pathway is controlled by signals from cell-cell junctions however the potential role of nuclear regulation has not yet been described. Here we set out to verify this possibility and define putative mechanism(s) by which it might occur. By using a luciferase reporter of the Hippo pathway, we measured the effects of different nuclear targeting drugs and found that chromatin-modifying agents, and to a lesser extent certain DNA damaging drugs, strongly induced activity of the reporter. This effect was not mediated by upstream core components (i.e. Mst, Lats) of the Hippo pathway, but through enhanced levels of the Hippo transducer TAZ. Investigation of the underlying mechanism led to the finding that cancer cell exposure to histone deacetylase inhibitors induced secretion of growth factors and cytokines, which in turn activate Akt and inhibit the GSK3 beta associated protein degradation complex in drug-affected as well as in their neighboring cells. Consequently, expression of EMT genes, cell migration and resistance to therapy were induced. These processes were suppressed by using pyrvinium, a recently described small molecule activator of the GSK 3 beta associated degradation complex. Overall, these findings shed light on a previously unrecognized phenomenon by which certain anti-cancer agents may paradoxically promote tumor progression by facilitating stabilization of the Hippo transducer TAZ and inducing cancer cell migration and resistance to therapy. Pharmacological targeting of the GSK3 beta associated degradation complex may thus represent a unique approach to treat cancer. © 2013 Basu et al

    BepiColombo-Mission Overview and Science Goals

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    BepiColombo is a joint mission between the European Space Agency, ESA, and the Japanese Aerospace Exploration Agency, JAXA, to perform a comprehensive exploration of Mercury. Launched on 20th October 2018 from the European spaceport in Kourou, French Guiana, the spacecraft is now en route to Mercury. Two orbiters have been sent to Mercury and will be put into dedicated, polar orbits around the planet to study the planet and its environment. One orbiter, Mio, is provided by JAXA, and one orbiter, MPO, is provided by ESA. The scientific payload of both spacecraft will provide detailed information necessary to understand the origin and evolution of the planet itself and its surrounding environment. Mercury is the planet closest to the Sun, the only terrestrial planet besides Earth with a self-sustained magnetic field, and the smallest planet in our Solar System. It is a key planet for understanding the evolutionary history of our Solar System and therefore also for the question of how the Earth and our Planetary System were formed. The scientific objectives focus on a global characterization ofMercury through the investigation of its interior, surface, exosphere, and magnetosphere. In addition, instrumentation onboard BepiColombo will be used to test Einstein's theory of general relativity. Major effort was put into optimizing the scientific return of the mission by defining a payload such that individual measurements can be interrelated and complement each other.Peer reviewe

    Bounding the role of black carbon in the climate system: A scientific assessment

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    Black carbon aerosol plays a unique and important role in Earth's climate system. Black carbon is a type of carbonaceous material with a unique combination of physical properties. This assessment provides an evaluation of black‐carbon climate forcing that is comprehensive in its inclusion of all known and relevant processes and that is quantitative in providing best estimates and uncertainties of the main forcing terms: direct solar absorption; influence on liquid, mixed phase, and ice clouds; and deposition on snow and ice. These effects are calculated with climate models, but when possible, they are evaluated with both microphysical measurements and field observations. Predominant sources are combustion related, namely, fossil fuels for transportation, solid fuels for industrial and residential uses, and open burning of biomass. Total global emissions of black carbon using bottom‐up inventory methods are 7500 Gg yr −1 in the year 2000 with an uncertainty range of 2000 to 29000. However, global atmospheric absorption attributable to black carbon is too low in many models and should be increased by a factor of almost 3. After this scaling, the best estimate for the industrial‐era (1750 to 2005) direct radiative forcing of atmospheric black carbon is +0.71 W m −2 with 90% uncertainty bounds of (+0.08, +1.27) W m −2 . Total direct forcing by all black carbon sources, without subtracting the preindustrial background, is estimated as +0.88 (+0.17, +1.48) W m −2 . Direct radiative forcing alone does not capture important rapid adjustment mechanisms. A framework is described and used for quantifying climate forcings, including rapid adjustments. The best estimate of industrial‐era climate forcing of black carbon through all forcing mechanisms, including clouds and cryosphere forcing, is +1.1 W m −2 with 90% uncertainty bounds of +0.17 to +2.1 W m −2 . Thus, there is a very high probability that black carbon emissions, independent of co‐emitted species, have a positive forcing and warm the climate. We estimate that black carbon, with a total climate forcing of +1.1 W m −2 , is the second most important human emission in terms of its climate forcing in the present‐day atmosphere; only carbon dioxide is estimated to have a greater forcing. Sources that emit black carbon also emit other short‐lived species that may either cool or warm climate. Climate forcings from co‐emitted species are estimated and used in the framework described herein. When the principal effects of short‐lived co‐emissions, including cooling agents such as sulfur dioxide, are included in net forcing, energy‐related sources (fossil fuel and biofuel) have an industrial‐era climate forcing of +0.22 (−0.50 to +1.08) W m −2 during the first year after emission. For a few of these sources, such as diesel engines and possibly residential biofuels, warming is strong enough that eliminating all short‐lived emissions from these sources would reduce net climate forcing (i.e., produce cooling). When open burning emissions, which emit high levels of organic matter, are included in the total, the best estimate of net industrial‐era climate forcing by all short‐lived species from black‐carbon‐rich sources becomes slightly negative (−0.06 W m −2 with 90% uncertainty bounds of −1.45 to +1.29 W m −2 ). The uncertainties in net climate forcing from black‐carbon‐rich sources are substantial, largely due to lack of knowledge about cloud interactions with both black carbon and co‐emitted organic carbon. In prioritizing potential black‐carbon mitigation actions, non‐science factors, such as technical feasibility, costs, policy design, and implementation feasibility play important roles. The major sources of black carbon are presently in different stages with regard to the feasibility for near‐term mitigation. This assessment, by evaluating the large number and complexity of the associated physical and radiative processes in black‐carbon climate forcing, sets a baseline from which to improve future climate forcing estimates.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99106/1/jgrd50171.pd

    No Exit? Withdrawal Rights and the Law of Corporate Reorganizations

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    Bankruptcy scholarship is largely a debate about the comparative merits of a mandatory regime on one hand and bankruptcy by free design on the other. By the standard account, the current law of corporate reorganization is mandatory. Various rules that cannot be avoided ensure that investors’ actions are limited and they do not exercise their rights against specialized assets in a way that destroys the value of a business as a whole. These rules solve collective action problems and reduce the risk of bargaining failure. But there are costs to a mandatory regime. In particular, investors cannot design their rights to achieve optimal monitoring as they could in a system of bankruptcy by free design. This Article suggests that the academic debate has missed a fundamental feature of the law. Bankruptcy operates on legal entities, not on firms in the economic sense. For this reason, sophisticated investors do not face a mandatory regime at all. The ability of investors to place assets in separate entities gives them the ability to create specific withdrawal rights in the event the firm encounters financial distress. There is nothing mandatory about rules like the automatic stay when assets can be partitioned off into legal entities that are beyond the reach of the bankruptcy judge. Thus, by partitioning assets of one economic enterprise into different legal entities, investors can create a tailored bankruptcy regime. In this way, legal entities serve as building blocks that can be combined to create specific and varied but transparent investor withdrawal rights. This regime of tailored bankruptcy has been unrecognized and underappreciated and may be preferable to both mandatory and free design regimes. By allowing a limited number of investors to opt out of bankruptcy in a particular, discrete, and visible way, investors as a group may be able to both limit the risk of bargaining failure and at the same time enjoy the disciplining effect that a withdrawal right brings with it

    Evasion of anti-growth signaling: a key step in tumorigenesis and potential target for treatment and prophylaxis by natural compounds

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    The evasion of anti-growth signaling is an important characteristic of cancer cells. In order to continue to proliferate, cancer cells must somehow uncouple themselves from the many signals that exist to slow down cell growth. Here, we define the anti-growth signaling process, and review several important pathways involved in growth signaling: p53, phosphatase and tensin homolog (PTEN), retinoblastoma protein (Rb), Hippo, growth differentiation factor 15 (GDF15), AT-rich interactive domain 1A (ARID1A), Notch, insulin-like growth factor (IGF), and KrĂŒppel-like factor 5 (KLF5) pathways. Aberrations in these processes in cancer cells involve mutations and thus the suppression of genes that prevent growth, as well as mutation and activation of genes involved in driving cell growth. Using these pathways as examples, we prioritize molecular targets that might be leveraged to promote anti-growth signaling in cancer cells. Interestingly, naturally-occurring phytochemicals found in human diets (either singly or as mixtures) may promote anti-growth signaling, and do so without the potentially adverse effects associated with synthetic chemicals. We review examples of naturally-occurring phytochemicals that may be applied to prevent cancer by antagonizing growth signaling, and propose one phytochemical for each pathway. These are: epigallocatechin-3-gallate (EGCG) for the Rb pathway, luteolin for p53, curcumin for PTEN, porphyrins for Hippo, genistein for GDF15, resveratrol for ARID1A, withaferin A for Notch and diguelin for the IGF1-receptor pathway. The coordination of anti-growth signaling and natural compound studies will provide insight into the future application of these compounds in the clinical setting
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