The metastasis inducer CCN1 (CYR61) activates the fatty acid synthase (FASN)-driven lipogenic phenotype in breast cancer cells

The angiogenic inducer CCN1 (Cysteine-rich 61, CYR61) is differentially activated in metastatic breast carcinomas. However, little is known about the precise mechanisms that underlie the pro-metastatic actions of CCN1. Here, we investigated the impact of CCN1 expression on fatty acid synthase (FASN), a metabolic oncogene thought to provide cancer cells with proliferative and survival advantages. Forced expression of CCN1 in MCF-7 cells robustly up-regulated FASN protein expression and also significantly increased FASN gene promoter activity 2- to 3-fold, whereas deletion of the sterol response element-binding protein (SREBP) binding site in the FASN promoter completely abrogated CCN1-driven transcriptional activation. Pharmacological blockade of MAPK or PI-3´K activation similarly prevented the ability of CCN1 to induce FASN gene activation. Pharmacological inhibition of FASN activity with the mycotoxin cerulenin or the small compound C75 reversed CCN1-induced acquisition of estrogen independence and resistance to hormone therapies such as tamoxifen and fulvestrant in anchorage-independent growth assays. This study uncovers FASNdependent endogenous lipogenesis as a new mechanism controlling the metastatic phenotype promoted by CCN1. Because estrogen independence and progression to a metastatic phenotype are hallmarks of therapeutic resistance and mortality in breast cancer, this previously unrecognized CCN1-driven lipogenic phenotype represents a novel metabolic target to clinically manage metastatic disease progression.Fil: Menendez, Javier A.. Instituto Catalán de Oncología; España. Institut d; EspañaFil: Vellón, Luciano. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Espinoza, Ingrid. University Of Mississippi; Estados UnidosFil: Lupu, Ruth. Mayo Clinic Cancer Center; Estados Unido

Security policy refinement using data integration: a position paper.

In spite of the wide adoption of policy-based approaches for security management, and many existing treatments of policy verification and analysis, relatively little attention has been paid to policy refinement: the problem of deriving lower-level, runnable policies from higher-level policies, policy goals, and specifications. In this paper we present our initial ideas on this task, using and adapting concepts from data integration. We take a view of policies as governing the performance of an action on a target by a subject, possibly with certain conditions. Transformation rules are applied to these components of a policy in a structured way, in order to translate the policy into more refined terms; the transformation rules we use are similar to those of global-as-view database schema mappings, or to extensions thereof. We illustrate our ideas with an example. Copyright 2009 ACM

Adaptive self-management of teams of autonomous vehicles

Unmanned Autonomous Vehicles (UAVs) are increasingly deployed for missions that are deemed dangerous or impractical to perform by humans in many military and disaster scenarios. Collaborating UAVs in a team form a Self- Managed Cell (SMC) with at least one commander. UAVs in an SMC may need to operate independently or in sub- groups, out of contact with the commander and the rest of the team in order to perform specific tasks, but must still be able to eventually synchronise state information. The SMC must also cope with intermittent and permanent communication failures as well permanent UAV failures. This paper describes a failure management scheme that copes with both communication link and UAV failures, which may result in temporary disjoint sub-networks within the SMC. A communication management protocol is proposed to control UAVs performing disconnected individual operations, while maintaining the SMCs structure by trying to ensure that all members of the mission regardless of destination or task, can communicate by moving UAVs to act as relays or by allowing the UAVs to rendezvous at intermittent intervals. Copyright 2008 ACM.Accepted versio

Expressive Policy Analysis with Enhanced System Dynamicity

Despite several research studies, the effective analysis of policy based systems remains a significant challenge. Policy analysis should at least (i) be expressive (ii) take account of obligations and authorizations, (iii) include a dynamic system model, and (iv) give useful diagnostic information. We present a logic-based policy analysis framework which satisfies these requirements, showing how many significant policy-related properties can be analysed, and we give details of a prototype implementation. Copyright 2009 ACM

A 2-D Analysis of the Stability of Boundary Layer Flow on Single and Multilayer Compliant Coatings

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The Tethered Moon

Cosmic collisions between terrestrial planets resemble somewhat the life cycle of the phoenix: worlds collide, are consumed in flame, and after the debris has cleared, shiny new worlds emerge aglow with possibilities. And glow they do, for they are molten. How brightly they glow, and for how long, is determined by their atmospheres and their moons. A reasonable initial condition on Earth after the Moon-forming impact is that it begins as a hot global magma ocean. We therefore begin our study with the mantle as a liquid ocean with a surface temperature on the order of 3000-4000 K at a time some 100-1000 years after the impact, by which point we can hope that early transients have settled down

A goal-based approach to policy refinement

As the interest in using policy-based approaches for systems management grows, it is becoming increasingly important to develop methods for performing analysis and refinement of policy specifications. Although this is an area that researchers have devoted some attention to, none of the proposed solutions address the issue of deriving implementable policies from high-level goals. A key part of the solution to this problem is having the ability to identify the operations, available on the underlying system, which can achieve a given goal. This paper presents an approach by which a formal representation of a system, based on the Event Calculus, can be used in conjunction with abductive reasoning techniques to derive the sequence of operations that will allow a given system to achieve a desired goal. Additionally it outlines how this technique might be used for providing tool support and partial automation for policy refinement. Building on previous work on using formal techniques for policy analysis, the approach presented here applies a transformation of both policy and system behaviour specifications into a formal notation that is based on Event Calculus. Finally, it shows how the overall process could be used in conjunction with UML modelling and illustrates this by means of an example. 1