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1.
The identification and assessment of prognostic factors is one of the major tasks in clinical research. The assessment of one single prognostic factor can be done by recently established methods for using optimal cutpoints. Here, we suggest a method to consider an optimal selected prognostic factor from a set of prognostic factors of interest. This can be viewed as a variable selection method and is the underlying decision problem at each node of various tree building algorithms. We propose to use maximally selected statistics where the selection is defined over the set of prognostic factors and over all cutpoints in each prognostic factor. We demonstrate that it is feasible to compute the approximate null distribution. We illustrate the new variable selection test with data of the German Breast Cancer Study Group and of a small study on patients with diffuse large B‐cell lymphoma. Using the null distribution for a p‐value adjusted regression trees algorithm, we adjust for the number of variables analysed at each node as well. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)  相似文献   
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Developments in insect transgenesis using transposons combined with available mass rearing technology for insects such as the Medfly, Ceratitis capitata, provide opportunity for the production of protein for industrial, agricultural and healthcare purposes on a very large scale. In this study, we report the germ-line transformation and expression of a cDNA encoding human growth hormone (hGH) in transgenic Drosophila using the Minos transposon. Production and secretion of a bioactive hGH into the haemolymph of transgenic larvae was demonstrated by immunoblot analysis, ELISA and a proliferation bioassay. Stable expression of hGH was observed over 50 generations. The results indicate that mass reared transgenic diptera with a rapid period of larval growth could provide cost effective production systems for the manufacture of therapeutic and other high value proteins.  相似文献   
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Detecting similarities between local binding surfaces can facilitate identification of enzyme binding sites and prediction of enzyme functions, and aid in our understanding of enzyme mechanisms. Constructing a template of local surface characteristics for a specific enzyme function or binding activity is a challenging task, as the size and shape of the binding surfaces of a biochemical function often vary. Here we introduce the concept of signature binding pockets, which captures information on preserved and varied atomic positions at multiresolution levels. For proteins with complex enzyme binding and activity, multiple signatures arise naturally in our model, forming a signature basis set that characterizes this class of proteins. Both signatures and signature basis sets can be automatically constructed by a method called SOLAR (Signature Of Local Active Regions). This method is based on a sequence-order-independent alignment of computed binding surface pockets. SOLAR also provides a structure-based multiple sequence fragment alignment to facilitate the interpretation of computed signatures. By studying a family of evolutionarily related proteins, we show that for metzincin metalloendopeptidase, which has a broad spectrum of substrate binding, signature and basis set pockets can be used to discriminate metzincins from other enzymes, to predict the subclass of metzincins functions, and to identify specific binding surfaces. Studying unrelated proteins that have evolved to bind to the same NAD cofactor, we constructed signatures of NAD binding pockets and used them to predict NAD binding proteins and to locate NAD binding pockets. By measuring preservation ratio and location variation, our method can identify residues and atoms that are important for binding affinity and specificity. In both cases, we show that signatures and signature basis set reveal significant biological insight.  相似文献   
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The fruit fly Drosophila embryo is one of the most important model organisms in genetics and developmental biology research. To better understand the biomechanical properties involved in Drosophila embryo research, this work presents a mechanical characterization of living Drosophila embryos through the stages of embryogenesis. Measurements of the mechanical forces of Drosophila embryos are implemented using a novel, in situ, and minimally invasive force sensing tool with a resolution in the range of microN. The measurements offer an essential understanding of penetration force profiles during the microinjection of Drosophila embryos. Sequentially quantitative evaluation and analysis of the mechanical properties, such as Young's modulus, stiffness, and mechanical impedance of living Drosophila embryos are performed by extracting the force measurements throughout the stages of embryogenesis. Experimental results illustrate the changing mechanical properties of Drosophila embryos during development, and thus mathematical models are proposed. The evaluation provides a critical step toward better understanding of the biomechanical properties of Drosophila embryos during embryogenesis, and could contribute to more efficient and significant genetic and embryonic development research on Drosophila.  相似文献   
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AimThe aim of this study was to determine the Inflection Points (IPs) of flattening filter free (FFF) CyberKnife dose profiles for cone-based streotactic radiotherapy. In addition, dosimetric field sizes were determined.BackgroundThe increased need for treatment in the early stages of cancer necessitated the treatment of smaller tumors. However, efforts in that direction required the modeling accuracy of the beam. Removal of the flattening filter (FF) from the path of x-ray beam has provided the solution to those efforts, but required a different normalization approach for the beam to ensure the delivery of the dose accurately. As a solution, researchers proposed a normalization factor based on IPs.Materials and methodsMeasurements using microDiamond (PTW 60019), Diode SRS (PTW 60018) and Monte Carlo (MC) calculations of dose profiles were completed at SAD 80 cm and 5 cm depth for 15–60 mm cones. Performance analysis of detectors with respect to MC calculation was carried out. Gamma evaluation method was used to determine achievable acceptability criteria for FFF CyberKnife beams.ResultsAcceptability within (3%–0.5 mm) was found to be anachievable criterion for all dose profile measurements of the cone beams used in this study. To determine the IP, the first and second derivatives of the dose profile were determined via the cubic spline interpolation technique.ConclusionDerivatives of the interpolated profiles showed that locations of IPs and 50% isodose points coincide.  相似文献   
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Fatty acids, which are essential nutritional components, are also involved in cardiovascular and metabolic diseases. Here we report a human cell surface receptor that we name free fatty acid receptor (FFAR), because it is specifically activated by medium to long-chain free fatty acids. The receptor belongs to the class of seven-transmembrane, G-protein coupled receptors (GPCRs) and also mediates responses to antidiabetic drugs of the thiazolidinedione type. It is expressed in skeletal muscle, heart, liver, and pancreatic beta-cells. Stimulation of FFAR increases the intracellular calcium concentration in cells expressing the receptor in a native (pancreatic beta-cell line) or in a recombinant form. In view of the nature of the activating substances, their physiological role in the body, and the tissue distribution of FFAR we suggest the term "nutrient sensing receptor" for receptors acting at the interface between dietary components and signalling molecules.  相似文献   
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Abstract

Field experiments were carried out at the Teaching and Research Farm of the Abubakar Tafawa Balewa University, Bauchi during the rainy season of 2005. The study was carried out with sole objective of evaluating the efficacy of six selected plant materials (sweetsop, red pepper, garlic, neem, mahogany and gmalina) against the major insect pests of cowpea variety, Dan Sokoto. The experiment was laid down in randomised complete block design with seven treatments. Each treatment was replicated three times. The results of the study showed that all the plant materials used were significantly (p < 0.05) better than control where no plant material was used in controlling the population of B. tabaci, E. dolichi, M. sjostedti and C. tomentosicollis at 1, 2 and 3 days after application of the treatments. Similarly the effects of these plant materials on the number of seeds/pod showed a significant (p < 0.05) difference between plots treated with plant materials and control. On the grain yield of the crop, all the plant materials showed significant effect except mahogany and the control which were statistically similar. Furthermore, the order of level of control indicated that sweet sop has (70.7%), garlic (69.3%), neem (61.0%), red pepper (54.0%), ash (30.9%), and mahogany (3.5%). The result of the present finding therefore recommends the use of sweet sop, garlic and neem as they were found to be the most promising in the control of major cowpea insect pests.  相似文献   
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