Hallmarks of cancer-the new testament.

Diagnosis and treatment of disease demand a sound understanding of the underlying mechanisms, determining any Achilles' heel that can be targeted in effective therapies. Throughout history, this endeavour to decipher the origin and mechanism of transformation of a normal cell into cancer has led to various theories-from cancer as a curse to an understanding at the level of single-cell heterogeneity, meaning even among a single sub-type of cancer there are myriad molecular challenges to overcome. With increasing insight into cancer genetics and biology, the disease has become ever more complex to understand. The complexity of cancer as a disease was distilled into key traits by Hanahan and Weinberg in their seminal 'Hallmarks of Cancer' reviews. This lucid conceptualization of complex cancer biology is widely accepted and has helped advance cancer therapeutics by targeting the various hallmarks but, with the advancement in technologies, there is greater granularity in how we view cancer as a disease, and the additional understanding over the past decade requires us to revisit the hallmarks of cancer. Based on extensive study of the cancer research literature, we propose four novel hallmarks of cancer, namely, the ability of cells to regress from a specific specialized functional state, epigenetic changes that can affect gene expression, the role of microorganisms and neuronal signalling, to be included in the hallmark conceptualization along with evidence of various means to exploit them therapeutically

Answering Non-Monotonic Queries in Relational Data Exchange

Relational data exchange is the problem of translating relational data from a source schema into a target schema, according to a specification of the relationship between the source data and the target data. One of the basic issues is how to answer queries that are posed against target data. While consensus has been reached on the definitive semantics for monotonic queries, this issue turned out to be considerably more difficult for non-monotonic queries. Several semantics for non-monotonic queries have been proposed in the past few years. This article proposes a new semantics for non-monotonic queries, called the GCWA*-semantics. It is inspired by semantics from the area of deductive databases. We show that the GCWA*-semantics coincides with the standard open world semantics on monotonic queries, and we further explore the (data) complexity of evaluating non-monotonic queries under the GCWA*-semantics. In particular, we introduce a class of schema mappings for which universal queries can be evaluated under the GCWA*-semantics in polynomial time (data complexity) on the core of the universal solutions.Comment: 55 pages, 3 figure

High recombination rates and hotspots in a Plasmodium falciparum genetic cross

Using the universal P2/P8 primers, we were able to obtain the gene segments of chromo-helicase-DNA binding protein (CHD)-Z and CHD-W from ten species of ardeid birds including Chinese egret (Egretta eulophotes), little egret (E. garzetta), eastern reef egret (E. sacra), great egret (Ardea alba), grey heron (A. cinerea), Chinese pond-heron (Ardeola bacchus), cattle egret (Bubulcus ibis), black-crowned night-heron (Nycticorax nycticorax), cinnamon bittern (Ixobrychus cinnamomeus) and yellow bittern (I. sinensis). Based on conserved regions inside the P2/P8-derived sequences, we designed new PCR primers for sex identification in these ardeid species. Using agarose gel electrophoresis, the PCR products showed two bands for females (140 bp derived from CHD-W and the other 250 bp from CHD-ZW), whereas the males showed only the 250 bp band. The results indicated that our new primers could be used for accurate and convenient sex identification in ardeid species.National Natural Science Foundation of China[30970380, 40876077]; Fujian Natural Science Foundation of China[2008S0007, 2009J01195

Running GAGs: myxoid matrix in tumor pathology revisited: What’s in it for the pathologist?

Ever since Virchow introduced the entity myxoma, abundant myxoid extracellular matrix (ECM) has been recognized in various reactive and neoplastic lesions. Nowadays, the term “myxoid” is commonly used in daily pathological practice. But what do today’s pathologists mean by it, and what does the myxoid ECM tell the pathologist? What is known about the exact composition and function of the myxoid ECM 150 years after Virchow? Here, we give an overview of the composition and constituents of the myxoid ECM as known so far and demonstrate the heterogeneity of the myxoid ECM among different tumors. We discuss the possible role of the predominant constituents of the myxoid ECM and attempt to relate them to differences in clinical behavior. Finally, we will speculate on the potential relevance of this knowledge in daily pathological practice

Energetic particle influence on the Earth's atmosphere

This manuscript gives an up-to-date and comprehensive overview of the effects of energetic particle precipitation (EPP) onto the whole atmosphere, from the lower thermosphere/mesosphere through the stratosphere and troposphere, to the surface. The paper summarizes the different sources and energies of particles, principally galactic cosmic rays (GCRs), solar energetic particles (SEPs) and energetic electron precipitation (EEP). All the proposed mechanisms by which EPP can affect the atmosphere are discussed, including chemical changes in the upper atmosphere and lower thermosphere, chemistry-dynamics feedbacks, the global electric circuit and cloud formation. The role of energetic particles in Earth’s atmosphere is a multi-disciplinary problem that requires expertise from a range of scientific backgrounds. To assist with this synergy, summary tables are provided, which are intended to evaluate the level of current knowledge of the effects of energetic particles on processes in the entire atmosphere