Improve survival prediction using principal components of gene expression data

The purpose of many microarray studies is to find the association between gene expression and sample characteristics such as treatment type or sample phenotype. There has been a surge of efforts developing different methods for delineating the association. Aside from the high dimensionality of microarray data, one well recognized challenge is the fact that genes could be complicatedly inter-related, thus making many statistical methods inappropriate to use directly on the expression data. Multivariate methods such as principal component analysis （PCA） and clustering are often used as a part of the effort to capture the gene correlation, and the derived components or clusters are used to describe the association between gene expression and sample phenotype. We propose a method for patient population dichotomization using maximally selected test statistics in combination with the PCA method, which shows favorable results. The proposed method is compared with a currently well-recognized method.     

Characterisation of the low affinity interaction between rat cell adhesion molecules CD2 and CD48 by analytical ultracentrifugation

CD2 is a cell adhesion molecule found on the plasma membrane of T-lymphocytes. Its counter-receptor in rat is the structurally related CD48. This interaction is believed to contribute to the adhesion of T-cells to other cells such as cytotoxic targets and antigen presenting cells. Cell-cell adhesion involves the formation of multiple cell adhesion molecule complexes at the cell surface and if cell-cell de-adhesion is to occur, these complexes need to be disrupted. The affinities of cell adhesion molecule interactions are suggested to be relatively weak to allow this de-adhesion of cell-cell interactions. The CD2/CD48 interaction has been studied using recombinant extracellular proteins and the affinity of the interaction of soluble recombinant rat CD2–CD48 has been determined (at 37°C) using surface plasmon resonance (and shown to be weak), with the dissociation constant K_d=60–90 μm. The values determined by surface plasmon resonance results could be affected by the immobilisation of the ligand on the chip and any self-association on the chip. We used three different analytical ultracentrifuge procedures which each allowed the interaction to be studied in free solution without the need for an immobilisation medium. Both sedimentation equilibrium (using direct analysis of the concentration distribution and also modelling of molecular weight versus concentration data) and sedimentation velocity at 5°C yielded dissociation constants in the range of 20– 110 μm, supporting the surface plasmon resonance findings showing that binding between these cell adhesion molecules is relatively weak. These studies also ruled out the presence of any significant self-association of the reactants which could lead to systematic error in the surface plasmon resonance results. Accepted: 19 November 1996     

Bionics and Structural Biology： A Novel Approach for Bio-energy Production

Cellular metabolism is a very complex process. The biochemical pathways are fundamental structures of biology. These pathways possess a number of regeneration steps which facilitate energy shuttling on a massive scale. This facilitates the biochemical pathways to sustain the energy currency of the cells. This concept has been mimicked using electronic circuit components and it has been used to increase the efficiency of bio-energy generation. Six of the carbohydrate biochemical pathways have been chosen in which glycolysis is the principle pathway. All the six pathways are interrelated and coordinated in a complex manner. Mimic circuits have been designed for all the six biochemical pathways. The components of the metabolic pathways such as enzymes, cofactors etc., are substituted by appropriate electronic circuit components. Enzymes are related to the gain of transistors by the bond dissociation energies of enzyme-substrate molecules under consideration. Cofactors and coenzymes are represented by switches and capacitors respectively. Resistors are used for proper orientation of the circuits. The energy obtained from the current methods employed for the decomposition of organic matter is used to trigger the mimic circuits. A similar energy shuttle is observed in the mimic circuits and the percentage rise for each cycle of circuit functioning is found to be 78.90. The theoretical calculations have been made using a sample of domestic waste weighing 1.182 kg. The calculations arrived at finally speak of the efficiency of the novel methodology employed.     

Binding of nitrite and its reductive activation to nitric oxide at biomimetic copper centers

The reactivity of nitrite towards the copper(II) and copper(I) centers of a series of complexes with tridentate nitrogen donor ligands has been investigated. The ligands are bis[(1-methylbenzimidazol-2-yl)methyl]amine (1-bb), bis[2-(1-methylbenzimidazol-2-yl)ethyl]amine (2-bb), and bis[2-(3,5-dimethyl-1-pyrazolyl)ethyl]amine (ddah) and carry two terminal benzimidazole (1-bb, 2-bb) or pyrazole (ddah) rings and a central amine donor residue. While 2-bb and ddah form two adjacent six-membered chelate rings on metal coordination, 1-bb forms two smaller rings of five members. The binding affinity of nitrite and azide to the Cu(II) complexes (ClO₄ ⁻ as counterion) has been determined in solution. The association constants for the two ligands are similar, but nitrite is a slightly stronger ligand than azide when it binds as a bidentate donor. The X-ray crystal structure of the nitrite complex [Cu(ddah)(NO₂)]ClO₄ (final R=0.056) has been determined: triclinic P1ˉspace group, a=8.200(2) ?, b=9.582(3) ?, c=15.541(4) ?. It may be described as a perchlorate salt of a “supramolecular” species resulting from the assembly of two complex cations and one sodium perchlorate unit. The copper stereochemistry in the complex is intermediate between SPY and TBP, and nitrite binds to Cu(II) asymmetrically, with Cu-O distances of 2.037(2) and 2.390(3) ? and a nearly planar CuO₂N cycle. On standing, solutions of [Cu(ddah)(NO₂)]ClO₄ in methanol produce the dinuclear complex [Cu(ddah)(OMe)]₂(ClO₄)₂, containing dibridging methoxy groups. In fact the crystal structure analysis (final R=0.083) showed that the crystals are built up by dinuclear cations, arranged on a crystallographic symmetry center, and perchlorate anions. Electrochemical analysis shows that binding of nitrite to the Cu(II) complexes of 2-bb and ddah shifts the reduction potential of the Cu(II)/Cu(I) couple towards negative values by about 0.3 V. The thermodynamic parameters of the Cu(II)/Cu(I) electron transfer have also been analyzed. The mechanism of reductive activation of nitrite to nitric oxide by the Cu(I) complexes of 1-bb, 2-bb, and ddah has been studied. The reaction requires two protons per molecule of nitrite and Cu(I). Kinetic experiments show that the reaction is first order in [Cu(I)] and [H⁺] and exhibits saturation behavior with respect to nitrite concentration. The kinetic data show that [Cu(2-bb)]⁺ is more efficient than [Cu(1-bb)]⁺ and [Cu(ddah)]⁺ in reducing nitrite. Received: 19 November 1999 / Accepted: 20 January 2000     

Arsenic suppresses necrosis induced by selenite in human leukemia HL-60 cells

Selenium, an essential trace element for humans, has been shown to have anticancer effects. Arsenic, a possibly essential ultratrace element for humans, has been used in the treatment of leukemia. Anticancer effects of selenium and arsenic have been related to their ability to induce apoptosis. Because humans are exposed to diverse trace elements simultaneously, it is important to learn their interrelationship. In this study, we demonstrate that sodium selenite (Na₂SeO₃) causes apoptosis at 3 μM and necrosis at high concentrations (>3 μM) in HL-60 cells. Similarly, both sodium arsenite (NaAsO₂) at 50 μM and sodium arsenate (Na₂HAsO₄) induce apoptosis at 500 μM and necrosis at higher concentrations (>50 μM and >500 μM, respectively) in HL-60 cells. Arsenite/arsenate, but not selenite, enhances AP-1 DNA-binding activity. This finding indicates different mechanisms through which apoptosis is induced by these two elements. Interestingly, we observed that HL-60 cell necrosis induced by a high concentration (>3 μM) of selenite was essentially inhibited by arsenic (50 μM of NaAsO₂ or 500 μM of Na₂HAsO₄), which resulted in a net effect of apoptosis. Because AP-1 DNA-binding activity was not induced in the presence of a combination of necrotic amount of selenite and apoptotic amount of arsenite/arsenate, the observed apoptosis apparently was through the mechanism used by selenite. Our results suggest, for the first time, that the toxic necrotic effect of selenite can be neutralized by arsenite/arsenate at the cellular level. The U.S. Department of Agriculture, Agricultural Research Service, Northern Plains Area, is an equal opportunity/affirmative action employer and all agency services are available without discrimination. Mention of a trademark or proprietary product does not constitute a guarantee or warranty of the product by the U.S. Department of Agriculture and does not imply its approval to the exclusion of other products that may also be suitable.     

Protective effect of selenium treatment on diabetes-induced myocardial structural alterations

One of the main causes leading to mortality in diabetes is myocardial disease. Using streptozotocin (STZ)-induced diabetic animals, it has been possible to characterize diabetes-induced myocardial abnormalities. Interstitial and microvascular disorders are known to be a characteristic part of the diabetic cardiomyopathy and partly resist insulin therapy. Because diabetic damage is partly attributed to oxidative stress, antioxidant treatment may be able to reduce this damage. The aim of this study was to investigate the cardioprotective effect of sodium selenite, known as an antioxidant agent. The diabetes was induced by ip injection of 50 mg/kg body wt STZ. The duration of diabetes was 5 wk. The protected group received (ip) 5 μmol/kg body wt/d sodium selenite (Na₂SeO₃) over 4 wk following diabetes induction. Electron and light microscopic morphometry of heart samples revealed typical diabetic alterations consisting in an increase in collagen content, vacuolation, diminishing of the cardiomyocyte diameter, alteration in myofilaments and Z-lines of myofibers, and myofibrillary degeneration. Sodium selenite treatment could prevent the loss of myofibrills and reduction of myocyte diameter. In the sodium-selenite-treated diabetic rat heart, alterations of the discus intercalaris and nucleus were corrected, and degenerations seen in myofilaments and Z-lines were reversed by this treatment. Under these findings, one can suggest that sodium selenite treatment may alleviate late diabetic complications when it is used under control conditions.     

A high-power vircator operating as an X-ray bremsstrahlung generator

Avircator capable of generating high-power X-ray pulses due to the multiple transitions of electrons through a thin anode foil transparent to X radiation has been created and put into operation for the first time. The vircator is created on the basis of a direct-action electron accelerator supplied from an inductive energy storage operating with a plasma opening switch. Self-consistent two-dimensional simulations of the electron beam dynamics in the vircator chamber are performed, and the spectra of the generated microwave radiation are determined. Self-consistent one-dimensional simulations of the beam dynamics with allowance for electron scattering in the foil were also carried out, and the X-ray bremsstrahlung spectra were measured. Results are presented from the first experiments on the generation of X-ray bremsstrahlung in vircators with thin (10 μm) and thick (100 μm) tantalum anode foils. For a thin foil, the X-ray (E _γ>30 keV) dose is eight times as high as that for a thick foil and the average photon energy is 30 keV (against 80 keV for a thick foil). __________ Translated from Fizika Plazmy, Vol. 30, No. 9, 2004, pp. 828–834. Original Russian Text Copyright ￠ 2004 by Selemir, Dubinov, Ryaslov, Kargin, Efimova, Loyko.     

Brainnetome and related projects

<正>The brain is organized as a hierarchy of complex networks on different temporal and spatial scales.The complex connectivities within the brain are presented in the anatomical architecture as well as dynamic activity.There have long been efforts to make a connection map of the brain[1],and this has now been achieved with the establishment of the     

Advance in a terrestrial biogeochemical model—DNDC model

Global climate change is one of the most important issues of contemporary environmental safety. Quantifying regional or global greenhouse gas (GHG) emissions and searching for appropriate mitigation measures have become a relatively hot issue in international global climate change studies. The high temporal and spatial variability of GHG emissions from soils makes their field measurement at regional or national scales impractical. To develop emission factors for a wide range of management practices such as those given in the Intergovernmental Panel on Climate Change Tier I methodology are often considered as a convenient technique to estimate emissions, but these can result in substantial errors when applied to specific geographical regions. Accordingly, considering the complexity of greenhouse gas production in soils, process-based models are required to quantify and predict the GHG emissions, and also interpret the intricate relationships among the gas emissions, the environmental factors and the ecological drivers. Several detailed biogeochemical process-based models of GHG emissions have been developed and accepted in recent years to provide regional scale estimate of GHG emissions and assess the mitigation measures. Among these the DNDC (Denitrification–Decomposition) model, as a process-based biogeochemical model, is capable of predicting the soil fluxes of all three terrestrial greenhouse gases: nitrous oxide (N₂O), carbon dioxide (CO₂), and methane (CH₄), as well as other important environmental and economic indicators such as crop production, ammonia (NH₃) volatilisation and nitrate NO₃^- leaching. Originally developed as a tool to simulate GHG emissions generated from agro-ecosystem, DNDC has since been expanded to include ecosystems such as rice paddies, grazed pastures, forests, and wetlands, and the model has attracted worldwide attention to simulate carbon and nitrogen biogeochemical cycles occurring in global ecosystems. This paper introduces the scientific basis underlying the modeling of greenhouse gas emissions from terrestrial soils, brings together the worldwide research undertaken on a wide range of ecosystems to test and verify, improve and modify, and apply the DNDC model to estimate GHG emissions from these systems, and furtherly sums up the advantages and disadvantages of the model for providing a reference for the application and development of the model. Most studies showed that there was a good agreement between the simulated and observed values of CO₂, CH₄ and N₂O emissions from arable, forest and grassland fields at different geographical locations over the world. However, some discrepancies still existed between observed and simulated seasonal patterns of CH₄ and N₂O emissions. Moreover, the DNDC model was mainly tested against experimental data on GHG emissions, but there were a few validations on NO₃^- leaching, soil water dynamics, NH₃ volatilisation which could greatly impact the GHG emissions. With the high development of society and economy, China had been facing a huge challenge between food production and environmental protection. Therefore, it was an urgent task to search optimal measures for optimizing land resource use, increasing crop productivity and reducing adverse environmental impacts. Process-based biogeochemical modeling, as with DNDC, can help in identifying optimal strategies to meet the needs. In future, the DNDC model need to not only improve the capability of predicting the GHG emissions, but also the accuracy of simulating the NO₃^- leaching and soil water dynamics for quantifying the non-point source pollution through modifying the parameters of the model or combining with other models, as SWAT model. The DNDC model will play more and more important role in future studies on global change.