Alterations in gene expression and sensitivity to genotoxic stress following HdmX or Hdm2 knockdown in human tumor cells harboring wild-type p53

While half of all human tumors possess p53 mutations, inactivation of wild-type p53 can also occur through a variety of mechanisms that do not involve p53 gene mutation or deletion. Our laboratory has been interested in tumor cells possessing wild-type p53 protein and elevated levels of HdmX and/or Hdm2, two critical negative regulators of p53 function. In this study we utilized RNAi to knockdown HdmX or Hdm2 in MCF7 human breast cancer cells, which harbor wild-type p53 and elevated levels of HdmX and Hdm2 then examined gene expression changes and effects on cell growth. Cell cycle and growth assays confirmed that the loss of either HdmX or Hdm2 led to a significant growth inhibition and G1 cell cycle arrest. Although the removal of overexpressed HdmX/2 appears limited to an anti-proliferative effect in MCF7 cells, the loss of HdmX and/or Hdm2 enhanced cytotoxicity in these same cells exposed to DNA damage. Through the use of Affymetrix GeneChips and subsequent RT-qPCR validations, we uncovered a subset of anti-proliferative p53 target genes activated upon HdmX/2 knockdown. Interestingly, a second set of genes, normally transactivated by E2F1 as cells transverse the G1-S phase boundary, were found repressed in a p21-dependent manner following HdmX/2 knockdown. Taken together, these results provide novel insights into the reactivation of p53 in cells overexpressing HdmX and Hdm2

On the Existence of Multiple Positive Solutions for a Semilinear Problem in Exterior Domains

In this paper, we study the existence and nonexistence of multiple positive solutions for problem # # # # # # # # # # # #u +K(x)u p = 0 in# . u > 0 in# , u # H 1 loc (# # C(# ). u # # ## = 0, u # > 0 as |x| ## where# = R N \ # is an exterior domain in R N , # # R N is a bounded domain with smooth boundary and N > 2. # 0, p > 1 are some given constants. K(x) satisfies: K(x) # C # loc (# and #C, #, M > 0 such that, |K(x)| # C|x| l for any |x| # M, wit

A Reasonable Semantic Web

The realization of Semantic Web reasoning is central to substantiating the Semantic Web vision. However, current mainstream research on this topic faces serious challenges, which forces us to question established lines of research and to rethink the underlying approaches. We argue that reasoning for the Semantic Web should be understood as "shared inference," which is not necessarily based on deductive methods. Model-theoretic semantics (and sound and complete reasoning based on it) functions as a gold standard, but applications dealing with large-scale and noisy data usually cannot afford the required runtimes. Approximate methods, including deductive ones, but also approaches based on entirely different methods like machine learning or nature-inspired computing need to be investigated, while quality assurance needs to be done in terms of precision and recall values (as in information retrieval) and not necessarily in terms of soundness and completeness of the underlying algorithms

Implementing QoS Management for Workflow Systems

Workflow management systems (WfMSs) have been used to support various types of business processes. As organizations adopt new working models, such as e-commerce, new challenges arise for workflow systems. One such challenge is that of quality of service (QoS) management. QoS management includes mechanisms that specify, compute, monitor, and control the quality of service of the products or services to be delivered. A good management of QoS directly impacts the success of organizations participating in e-commerce activities by better fulfilling customer expectations and achieving customer satisfaction. In this paper we present an implementation of a comprehensive QoS model for workflows we have specified earlier. While the implementation is being carried out for the METEOR workflow management system, the ideas presented here can also be applied to other workflow systems. In this work we describe the components that have been changed, or added, and discuss how they interact to enable the specification, computation, and monitoring of QoS

The state of the art in flow visualization: Partition-based techniques

Flow visualization has been a very active subfield of scientific visualization in recent years. From the resulting large variety of methods this paper discusses partition-based techniques. The aim of these approaches is to partition the flow in areas of common structure. Based on this partitioning, subsequent visualization techniques can be applied. A classification is suggested and advantages/disadvantages of the different techniques are discussed as well.

Maintaining Transitive Closure of Graphs in SQL

It is common knowledge that relational calculus and even SQL are not expressive enough to express recursive queries such as the transitive closure. In a real database system, one can overcome this problem by storing a graph together with its transitive closure and maintaining the latter whenever updates to the former occur. This leads to the concept of an incremental evaluation system, or IES. Much is already known about the theory of IES but very little has been translated into practice. The purpose of this paper is to fill in this gap by providing a gentle introduction to and an overview of some recent theoretical results on IES. The introduction is through the translation into SQL of three interesting positive maintenance results that have practical importance -- the maintenance of the transitive closure of acyclic graphs, of undirected graphs, and of arbitrary directed graphs. Interestingly, these examples also allow us to show the relationship between power and cost ..

A survey of the semantic specification of sensors

Abstract. Semantic sensor networks use declarative descriptions of sensors promote reuse and integration, and to help solve the difficulties of installing, querying and maintaining complex, heterogeneous sensor networks. This paper reviews the state of the art for the semantic specification of sensors, one of the fundamental technologies in the semantic sensor network vision. Twelve sensor ontologies are reviewed and analysed for the range and expressive power of their concepts. The reasoning and search technology developed in conjunction with these ontologies is also reviewed, as is technology for annotating OGC standards with links to ontologies. Sensor concepts that cannot be expressed accurately by current sensor ontologies are also discussed.