Assessment of Optimal Selected Prognostic Factors

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)     

The impact of climate change on the physical characteristics of the larger lakes in the English Lake District

1. The larger lakes of the English Lake District have been the subject of intensive scientific study for more than 60 years. Year‐to‐year variations in the weather have recently been shown to have a major effect on their physical characteristics. The area is mild but very wet and the dynamics of the lakes are strongly influenced by the movement of weather systems across the Atlantic. 2. Here, we combine the results of long‐term measurements and the projections from a Regional Climate Model (RCM) to assess the potential impact of climate change on the surface temperature and residence times of the lakes. 3. The RCM outputs used were produced by the U.K. Hadley Centre and are based on the IPCC ‘A2’ scenario for the emission of greenhouse gases. These suggest that winters in the area will be very much milder and wetter by the 2050s and that there will be a pronounced reduction in the summer rainfall. 4. An analysis of the meteorological data acquired between 1940 and 2000 shows that there have been progressive increases in the winter air temperature and in the rainfall which are correlated with the long‐term change in the North Atlantic Oscillation. The trends reported during the summer were less pronounced and were correlated with the increased frequency of anticyclonic days and a decrease in the frequency of westerly days in the British Isles. 5. A simple model of the year‐to‐year variations in surface temperatures showed that the highest winter temperatures were recorded in the deeper lakes and the highest summer temperatures in the lakes with the shallowest thermoclines. When this model was used to predict the surface temperatures of the lakes in the 2050s, the greatest winter increase (+1.08 °C) was observed in the shallowest lake and the greatest summer increase (+2.18 °C) in the lake with the shallowest thermocline. 6. The model used to estimate the seasonal variation in the residence time of the lakes showed that the most pronounced variations were recorded in lakes with a short residence time. Average winter residence times ranged from a minimum of 10 days to a maximum of 436 days and average summer values from a minimum of 23 days to a maximum of 215 days. When this model was used to predict the residence time of the lakes in the 2050s, the greatest winter decrease (−20%) was observed in the smallest lake and the greatest summer increase (+92%) in the lake with the shortest residence time. 7. The results are discussed in relation to trends reported elsewhere in Europe and the impact of changes in the atmospheric circulation on the dynamics of the lakes. The most serious limnological effects were those projected for the summer and included a general increase in the stability of the lakes and a decrease in the flushing rate of the lakes with short residence times.     

The effect of somatostatins (SRIF-14, 25 and 28), galanin and anti-SRIF on plasma growth hormone levels in Coho salmon (Oncorhynchus kisutch, Walbaum)

Porcine galanin, somatostatins (SRIF-25 and SRIF-28) and invariant SRIF-14, known to have inhibitory-stimulatory actions on growth hormone (GH) secretion in higher vertebrates, were tested for their ability to affect plasma GH levels in coho salmon. Peptides were administered by intraperitoneal injection of 10 or 100 ng g⁻¹ body weight. All three SRIFs decreased plasma GH concentrations, their activity following the order SRIF-14 > SRIF-28 > SRIF-25. Galanin and an anti-SRIF produced pronounced, although transient increases in plasma GH.     

Interaction of diphtheria toxin fragment A and of elongation factor 2 with Cibacron blue

Diphtheria toxin fragment A interacts with Cibacron blue in solution, although it is not retained by blue Sepharose columns. Difference spectral titration of fragment A with the dye gives a dissociation constant of the order of 10^–5 M and a 11 stoichiometry for the complex. In equilibrium dialysis experiments Cibacron blue behaves as a competitive inhibitor of the binding of NAD to diphtheria toxin fragment A. The dye inhibits in a non-competitive way the fragment A-catalysed transfer of ADP-ribose from NAD to elongation factor 2 (EF2). By affinity chromatography on blue Sepharose a binding of EF2 and of ADP-ribosyl-EF2 with the dye is also demonstrated. GDP, GTP and GDP(CH₂)P are able to displace EF2 from blue Sepharose.     

The fate of15N labeled nitrogen applied to mature citrus trees

Summary The efficiency and balance of nitrogen from one year's application was studied in a long-term fertigation experiment. Enriched nitrogen fertilizer, K¹⁵NO₃, was applied to a 22-year-old Shamouti orange tree with a history of high N applications (N₃) and to an N-starved tree (N₁). The distribution of N in the different parts of the trees and in the soil was determined after the experimental trees were excavated. Similar total recovery of the labeled fertilizer N was found in the trees and soil in both treatments (N₁−61.7% N₃−56%). However, the distribution between tree and soil was different. The amount of recovered residual fertilizer in the soil was much larger in the N₃ treatment than in N₁. The highest percentage of fertilizer N was found in the new organs,i.e. fruits, twigs and leaves. The roots and branches took up only 6–14% from the labeled fertilizer. Only 20.9% of the leaf N and 23.4% of the fruit N in the N₃ tree originated in the labeled fertilizer, indicating translocation of N from older parts of the tree to new growth. Evidence was found of storage of N in the wooded branches, while the roots contained a surprisingly small part of labeled fertilizer. Contribution 1599E.     

The physical map ofMus musculus chromosome 11 reveals evolutionary relationship with different syntenic groups of genes inHomo sapiens

Summary The physical localization of sequences homologous to three cloned genes was determined by in situ hybridization to metaphase chromosomes. Previous work had assigned the skeletal myosin heavy chain gene cluster (Myh), the functional locus for the cellular tumor antigen p53 (Trp53-1), and the cellular homologue of the viral erb-B oncogene (Erbb) toMus musculus chromosome 11 (MMU11). Our results provide regional assignments ofMyh andTrp53-1 to chromosome bands B2C, and ofErbb to bands A1A4. Taken together with in situ mapping of three other loci on MMU 11 (Hox-2 homeobox-containing gene cluster, theSparc protein, and theColla-1 collagen gene), which have been reported elsewhere, these data allowed us to construct a physical map of MMU11 and to compare it with the linkage map of this chromosome. The map positions of the homologous genes on human chromosomes suggest evolutionary relationships of distinct regions of MMU11 with six different human chromosome arms: 1p, 5q, 7p, 16p, 17p, and 17q. The delineation of conserved chromosome regions has important implications for the understanding of karyotype evolution in mammalian species and for the development of animal models of human genetic diseases.