The persistent dynamic secrets of senescence

While the beneficial versus detrimental implications of the senescence-associated secretome remain an issue of debate, time-resolved analyses of its composition, regulatory mechanisms and functional consequences have been largely missing. The dynamic activity of NOTCH is now shown to direct two distinct senescence phenotypes, by first promoting a pro-senescent TGF-{beta}1-dependent secretome, followed by a second wave of pro-inflammatory, senescence-clearing cytokines

D3-D7 Quark-Gluon Plasmas at Finite Baryon Density

We present the string dual to SU(Nc) N=4 SYM, coupled to Nf massless fundamental flavors, at finite temperature and baryon density. The solution is determined by two dimensionless parameters, both depending on the 't Hooft coupling $\lambda_h$ at the scale set by the temperature T: $\epsilon_h\sim\lambda_h Nf/Nc$, weighting the backreaction of the flavor fields and $\tilde\delta\sim\lambda_h^{-1/2}nb/(Nf T^3)$, where $nb$ is the baryon density. For small values of these two parameters the solution is given analytically up to second order. We study the thermodynamics of the system in the canonical and grand-canonical ensembles. We then analyze the energy loss of partons moving through the plasma, computing the jet quenching parameter and studying its dependence on the baryon density. Finally, we analyze certain "optical" properties of the plasma. The whole setup is generalized to non abelian strongly coupled plasmas engineered on D3-D7 systems with D3-branes placed at the tip of a generic singular Calabi-Yau cone. In all the cases, fundamental matter fields are introduced by means of homogeneously smeared D7-branes and the flavor symmetry group is thus a product of abelian factors.Comment: 27 pages; v2: 29 pages, 1 (new) figure, new section 4.4 on optical properties, references, comments added; v3: eq. (3.19), comments and a reference adde

Holographic Duals of Quark Gluon Plasmas with Unquenched Flavors

We review the construction of gravitational solutions holographically dual to N=1 quiver gauge theories with dynamical flavor multiplets. We focus on the D3-D7 construction and consider the finite temperature, finite quark chemical potential case where there is a charged black hole in the dual solution. Discussed physical outputs of the model include its thermodynamics (with susceptibilities) and general hydrodynamic properties.Comment: Lecture presented at the Workshop "AdS/CFT and Novel Approaches to Hadron and Heavy Ion Physics", Kavli Institute of Theoretical Physics (KITPC), Beijing, China, 13 October 2010. Review article to be published in Communications in Theoretical Physics. 27 pages, 2 figure

International consensus definition of low anterior resection syndrome

BACKGROUND: Low anterior resection syndrome is pragmatically defined as disordered bowel function after rectal resection leading to a detriment in quality of life. This broad characterization does not allow for precise estimates of prevalence. The low anterior resection syndrome score was designed as a simple tool for clinical evaluation of low anterior resection syndrome. Although the low anterior resection syndrome score has good clinical utility, it may not capture all important aspects that patients may experience. OBJECTIVE: The aim of this collaboration was to develop an international consensus definition of low anterior resection syndrome that encompasses all aspects of the condition and is informed by all stakeholders. DESIGN: This international patient-provider initiative used an online Delphi survey, regional patient consultation meetings, and an international consensus meeting. PARTICIPANTS: Three expert groups participated: patients, surgeons, and other health professionals from 5 regions (Australasia, Denmark, Spain, Great Britain and Ireland, and North America) and in 3 languages (English, Spanish, and Danish). MAIN OUTCOME MEASURE: The primary outcome measured was the priorities for the definition of low anterior resection syndrome. RESULTS: Three hundred twenty-five participants (156 patients) registered. The response rates for successive rounds of the Delphi survey were 86%, 96%, and 99%. Eighteen priorities emerged from the Delphi survey. Patient consultation and consensus meetings refined these priorities to 8 symptoms and 8 consequences that capture essential aspects of the syndrome. LIMITATIONS: Sampling bias may have been present, in particular, in the patient panel because social media was used extensively in recruitment. There was also dominance of the surgical panel at the final consensus meeting despite attempts to mitigate this. CONCLUSIONS: This is the first definition of low anterior resection syndrome developed with direct input from a large international patient panel. The involvement of patients in all phases has ensured that the definition presented encompasses the vital aspects of the patient experience of low anterior resection syndrome. The novel separation of symptoms and consequences may enable greater sensitivity to detect changes in low anterior resection syndrome over time and with intervention

The GEYSERS optical testbed: a platform for the integration, validation and demonstration of cloud-based infrastructure services

The recent evolution of cloud services is leading to a new service transformation paradigm to accommodate network infrastructures in a cost-scalable way. In this transformation, the network constitutes the key to efficiently connect users to services and applications. In this paper we describe the deployment, validation and demonstration of the optical integrated testbed for the “GEneralized architecture for dYnamic infrastructure SERviceS” (GEYSERS) project to accommodate such cloud based Infrastructure Services. The GEYSERS testbed is composed of a set of local physical testbeds allocated in the facilities of the GEYSERS partners. It is built up based on the requirements specification, architecture definition and per-layer development that constitutes the whole GEYSERS ecosystem, and validates the procedures on the GEYSERS prototypes. The testbed includes optical devices (layer 1), switches (layer 2), and IT resources deployed in different local testbeds provided by the project partners and interconnected among them to compose the whole testbed layout. The main goal of the GEYSERS testbed is twofold. On one hand, it aims at providing a validation ground for the architecture, concepts and business models proposed by GEYSERS, sustained by two main paradigms: Infrastructure as a Service (IaaS) and the coupled provisioning of optical network and IT resources. On the other hand, it is used as a demonstration platform for testing the software prototypes within the project and to demonstrate to the research and business community the project approach and solutions. In this work, we discuss our experience in the deployment of the testbed and share the results and insights learned from our trials in the process. Additionally, the paper highlights the most relevant experiments carried out in the testbed, aimed at the validation of the overall GEYSERS architecture

Role of cellular senescence and NOX4-mediated oxidative stress in systemic sclerosis pathogenesis.

Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by progressive fibrosis of skin and numerous internal organs and a severe fibroproliferative vasculopathy resulting frequently in severe disability and high mortality. Although the etiology of SSc is unknown and the detailed mechanisms responsible for the fibrotic process have not been fully elucidated, one important observation from a large US population study was the demonstration of a late onset of SSc with a peak incidence between 45 and 54 years of age in African-American females and between 65 and 74 years of age in white females. Although it is not appropriate to consider SSc as a disease of aging, the possibility that senescence changes in the cellular elements involved in its pathogenesis may play a role has not been thoroughly examined. The process of cellular senescence is extremely complex, and the mechanisms, molecular events, and signaling pathways involved have not been fully elucidated; however, there is strong evidence to support the concept that oxidative stress caused by the excessive generation of reactive oxygen species may be one important mechanism involved. On the other hand, numerous studies have implicated oxidative stress in SSc pathogenesis, thus, suggesting a plausible mechanism in which excessive oxidative stress induces cellular senescence and that the molecular events associated with this complex process play an important role in the fibrotic and fibroproliferative vasculopathy characteristic of SSc. Here, recent studies examining the role of cellular senescence and of oxidative stress in SSc pathogenesis will be reviewed