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

Examining short-term rentals' influence on tourists' well-being using Airbnb reviews

Smart tourism innovations are changing tourism. Tourists are increasingly demanding more authentic experiences and non-traditional accommodations (e.g., Airbnb) that offer closer connections to hosts and locals. Airbnb presents lodgings ranging from shared rooms and apartments to treehouses. Peer-to-peer accommodations create value for customers via reasonable prices, flexibility, ease of use, and local-guest interactive communication. Smart tourism has facilitated this new business ecosystem’s development within the sharing economy. This study sought to examine guests’ experiences in Bucharest Airbnb apartments and the main themes associated with these tourists’ subjective well-being. The sample of 750 online reviews were analysed using Leximancer, which revealed five themes—apartment, stay, old, host, and nice (view)— and their positive outcomes—recommend(ation), thank you(s), and value (for money). The results reveal that hosts’ friendliness contributes the most to guests’ affective wellbeing, which has theoretical and practical implications for Romania’s tourism industry.info:eu-repo/semantics/publishedVersio

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

Wine tourism: A multisensory experience

This study sought to identify the main themes of sensory experiences of Douro wineries shared online by tourists. Douro is a demarcated wine region famous for Port, which is on the United Nations Educational, Scientific and Cultural Organization’s World Heritage List. The research used 470 visitor reviews posted on the TripAdvisor website, which referred to experiences of the five regional wine brands that run wine hotels. Mixed content analyses extracted the main themes from the reviews, as well as identifying concepts associated with the five senses. The results include 12 main themes: wine, view, staff, room, hotel, food, restaurant, pool, service, Douro, delicious (food and wine) and comfort. Most concepts are linked with sight and taste, followed by hearing, with only a few reviews mentioning touch or smell. These findings have managerial implications for wine tourism, contributing to a better understanding of how sensory dimensions create memorable experiences for visitors.info:eu-repo/semantics/acceptedVersio

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

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Visitor experiences at UNESCO monasteries in Northeast Romania

The religious heritage of northeast Romania is one of the key attractions for visitors to the area. Known as ‘painted’ monasteries, the region’s churches highlight the rich religious culture of Romania, and they have been designated UNESCO World Heritage Sites. This study sought to identify the main dimensions of tourist experiences in the monasteries using mixed content analysis methods to collect data from Web reviews. The results include 10 themes: ‘monastery’, ‘painted (walls)’, ‘tower’, ‘visit’, ‘beautiful’ (place), ‘inside’ (painting), ‘famous’ (scene), ‘place’, ‘blue’ (colour) and ‘guide’. The Web reviews also reveal that tourists can feel connected to the Eastern Orthodox religion (e.g. most Romanian visitors) or they are more interested in the monasteries’ paintings and architecture. The majority of tourists value these structures for their status as UNESCO World Heritage Sites, seeing them as most notable for their old paintings, which have been preserved for many years and which are famed for their colours (i.e. Voronet Monastery’s blue paint).info:eu-repo/semantics/acceptedVersio