Rough Sets and Nuclear Safety

It is well-known that rough set theory can be applied successfully to rough classification and knowledge discovery. Our work is concerned with finding methods for using rough sets to identify classes in datasets, finding dependencies in relations and discovering rules which are hidden in databases by means of decision tables and algorithm D. We use these methods to analyze and control aspects of nuclear energy generation.     

Common deletion polymorphisms in the human genome

The locations and properties of common deletion variants in the human genome are largely unknown. We describe a systematic method for using dense SNP genotype data to discover deletions and its application to data from the International HapMap Consortium to characterize and catalogue segregating deletion variants across the human genome. We identified 541 deletion variants (94% novel) ranging from 1 kb to 745 kb in size; 278 of these variants were observed in multiple, unrelated individuals, 120 in the homozygous state. The coding exons of ten expressed genes were found to be commonly deleted, including multiple genes with roles in sex steroid metabolism, olfaction and drug response. These common deletion polymorphisms typically represent ancestral mutations that are in linkage disequilibrium with nearby SNPs, meaning that their association to disease can often be evaluated in the course of SNP-based whole-genome association studies.     

Gene silencing in cancer by histone H3 lysine 27 trimethylation independent of promoter DNA methylation

Epigenetic silencing in cancer cells is mediated by at least two distinct histone modifications, polycomb-based histone H3 lysine 27 trimethylation (H3K27triM) and H3K9 dimethylation. The relationship between DNA hypermethylation and these histone modifications is not completely understood. Using chromatin immunoprecipitation microarrays (ChIP-chip) in prostate cancer cells compared to normal prostate, we found that up to 5% of promoters (16% CpG islands and 84% non-CpG islands) were enriched with H3K27triM. These genes were silenced specifically in prostate cancer, and those CpG islands affected showed low levels of DNA methylation. Downregulation of the EZH2 histone methyltransferase restored expression of the H3K27triM target genes alone or in synergy with histone deacetylase inhibition, without affecting promoter DNA methylation, and with no effect on the expression of genes silenced by DNA hypermethylation. These data establish EZH2-mediated H3K27triM as a mechanism of tumor-suppressor gene silencing in cancer that is potentially independent of promoter DNA methylation.     

The structure of H5N1 avian influenza neuraminidase suggests new opportunities for drug design

The worldwide spread of H5N1 avian influenza has raised concerns that this virus might acquire the ability to pass readily among humans and cause a pandemic. Two anti-influenza drugs currently being used to treat infected patients are oseltamivir (Tamiflu) and zanamivir (Relenza), both of which target the neuraminidase enzyme of the virus. Reports of the emergence of drug resistance make the development of new anti-influenza molecules a priority. Neuraminidases from influenza type A viruses form two genetically distinct groups: group-1 contains the N1 neuraminidase of the H5N1 avian virus and group-2 contains the N2 and N9 enzymes used for the structure-based design of current drugs. Here we show by X-ray crystallography that these two groups are structurally distinct. Group-1 neuraminidases contain a cavity adjacent to their active sites that closes on ligand binding. Our analysis suggests that it may be possible to exploit the size and location of the group-1 cavity to develop new anti-influenza drugs.     

The crystal-like anatomical uniformity of the striate cortex

The visual field is topographically mapped onto the primary visual cortex (V1), forming a retinotopic map which is far more detailed for the foveal regions than for the periphery. We found that receptive field (RF) size in monkey V1 increases with eccentricity, and that a 1—2 m² V1 region contains roughly a complete set of machinery necessary to analyze a visual-field area whose size is about that of the RFs of the cells. This allows V1 to be anatomically uniform, and is in sharp contrast with the retina.     

Energetic landscape of alpha-lytic protease optimizes longevity through kinetic stability.

During the evolution of proteins the pressure to optimize biological activity is moderated by a need for efficient folding. For most proteins, this is accomplished through spontaneous folding to a thermodynamically stable and active native state. However, in the extracellular bacterial alpha-lytic protease (alphaLP) these two processes have become decoupled. The native state of alphaLP is thermodynamically unstable, and when denatured, requires millennia (t1/2 approximately 1,800 years) to refold. Folding is made possible by an attached folding catalyst, the pro-region, which is degraded on completion of folding, leaving alphaLP trapped in its native state by a large kinetic unfolding barrier (t1/2 approximately 1.2 years). alphaLP faces two very different folding landscapes: one in the presence of the pro-region controlling folding, and one in its absence restricting unfolding. Here we demonstrate that this separation of folding and unfolding pathways has removed constraints placed on the folding of thermodynamically stable proteins, and allowed the evolution of a native state having markedly reduced dynamic fluctuations. This, in turn, has led to a significant extension of the functional lifetime of alphaLP by the optimal suppression of proteolytic sensitivity.     

An aqueous extract of Liu Wei Di Huang Wan alters the labeling of blood constituents with Technetium-99m

The Liu Wei Di Huang Wan is a formula of a traditional Chinese medicine that is used to treat asthma patients and has been shown to have several important properties,such as antioxidant and free radical scavenging activities.The influence of an extract of Liu Wei Di Huang Wan on the labeling of blood constituents with technetium-99m was investigated.Anticoagulated blood(Wistar rats) was incubated with the extract,stannous chloride and technetium-99m,as sodium pertechnetate.Samples were centrifuged and aliquots of plasma and blood cells were separated and precipitated with trichloroacetic acid,to obtain soluble and insoluble fractions of the blood constituents.The percentage of radioactivity(%ATI) in all the fractions was determined.The analysis of the results shows that the extract at the highest concentration used(70 mg/mL) decreased significantly(P<0.05) the %ATI(from 96.48 ± 1.19 to 54.46 ± 7.38) on blood cells compartment,(from 81.11 ± 4.15 to 61.33 ± 4.74) on insoluble fractions of blood cells and(from 65.91 ± 2.44 to 13.15 ± 3.62) on insoluble fractions of plasma.In conclusion,the results suggest that the substances present on this extract can alter this labeling process,probably due to(i) redox properties(antioxidant and chelator activities) and/or(ii) specific actions in the binding sites where the 99mTc would be bound on the blood constituents.As a consequence,precaution is suggested on the interpretation of the nuclear medicine results from performed with blood constituents labeled with 99m Tc in patients that have undertaken LWDHW,although the current findings were obtained in experimental animal models.