CGHAnalyzer: a stand-alone software package for cancer genome analysis using array-based DNA copy number data

SUMMARY: This synopsis provides an overview of array-based comparative genomic hybridization data display, abstraction and analysis using CGHAnalyzer, a software suite, designed specifically for this purpose. CGHAnalyzer can be used to simultaneously load copy number data from multiple platforms, query and describe large, heterogeneous datasets and export results. Additionally, CGHAnalyzer employs a host of algorithms for microarray analysis that include hierarchical clustering and class differentiation. AVAILABILITY: CGHAnalyzer, the accompanying manual, documentation and sample data are available for download at http://acgh.afcri.upenn.edu. This is a Java-based application built in the framework of the TIGR MeV that can run on Microsoft Windows, Macintosh OSX and a variety of Unix-based platforms. It requires the installation of the free Java Runtime Environment 1.4.1 (or more recent) (http://www.java.sun.com).     

An Assessment of Habitat Diversity and Transformation on La Réunion Island (Mascarene Islands,Indian Ocean) as a Basis for Identifying Broad-scale Conservation Priorities

Most natural habitat in the Mascarene Islands (Mauritius, La Réunion and Rodrigues) has been transformed. Although urbanisation, agriculture and alien plant invasions have transformed large areas in La Réunion, the island has by far the greatest area of intact habitats in the Mascarenes, but remaining natural areas are under threat. We propose a protocol for defining a system of habitat types and for using these to provide a preliminary assessment of conservation priorities for La Réunion. The protocol draws on existing data and expert knowledge to map habitat types, assesses the extent of habitat transformation, and quantifies heterogeneity between habitat types based on climate, topography and geology. The pattern of habitat transformation was uneven among the nineteen habitat types identified. While three habitats have lost > 95% of their original area, four still retain> 80% of their original extent. Habitat types could be grouped into the following categories: (i) transformed habitats with low levels of plant endemism, (ii) habitats confined to homogenous geology with high levels of plantendemism, and (iii) species-rich heterogeneous habitats on diverse geological types. Priority habitats were also identified using municipalities as a basis for implementation. Urgent action is required for several habitat types where a large part of the original extent has been transformed. Three municipalities which contain more than 10 habitat types should receive conservation priority. The analysis provides the basis for setting conservation priorities in La Réunion at the regional and local scale. Implications of the results are discussed with reference to requirements for finer-scale conservation planning.     

The use of smoke acid as an alternative coagulating agent for natural rubber sheets' production

A comparative study of rubber sheets obtained using formic, acetic, and smoke acid as coagulants is shown for latex obtained from native Amazonian trees and also from commercial cultivated trees. The evaluation of both processes of coagulation was carried out by spectroscopic and physical-chemical analysis, showing no differences in the rubber sheets obtained. This new method of rubber sheet preparation was introduced into Amazonian rainforest rubber tapper communities, which are actually producing in large scale. The physical-mechanical properties were similar among a large sheets made by different rubber tapper communities using this new method.     

Potent pyrimidinetrione-based inhibitors of MMP-13 with enhanced selectivity over MMP-14

Through the use of computational modeling, a series of pyrimidinetrione-based inhibitors of MMP-13 was designed based on a lead inhibitor identified through file screening. Incorporation of a biaryl ether moiety at the C-5 position of the pyrimidinetrione ring resulted in a dramatic enhancement of MMP-13 potency. Protein crystallography revealed that this moiety binds in the S(1)(') pocket of the enzyme. Optimization of the C-4 substituent of the terminal aromatic ring led to incorporation of selectivity versus MMP-14 (MT-1 MMP). Structure activity relationships of the biaryl ether substituent are presented as is pharmacokinetic data for a compound that meets our in vitro potency and selectivity goals.     

Arylphthalazines: identification of a new phthalazine chemotype as inhibitors of VEGFR kinase

A novel class of 4-arylamino-phthalazin-1-yl-benzamides is described as inhibitors of vascular endothelial growth factor receptor II (VEGFR-2). Several compounds display potent VEGFR-2 inhibitory activity with an IC50 as low as 0.078 microM in an HTRF enzymatic assay. These compounds are relatively selective against a small kinase panel.     

Isosteric ramatroban analogs: selective and potent CRTH-2 antagonists

The chemoattractant receptor-homologous molecule expressed on T(H)2 cells (CRTH-2), also found on eosinophils and basophils, is a prostaglandin D2 receptor involved in the recruitment of these cell types during an inflammatory response. In this report, we describe the synthesis and optimization of a ramatroban isostere that is a selective and potent antagonist of CRTH-2 which may be useful in the treatment of certain diseases.