Malcolm X and Symbolic Convergence Theory

The focus of this paper will be the application of symbolic convergence theory to the leadership attributes of Malcolm X. Symbolic Convergence Theory focuses on determining and identifying symbols in diverse communities and showing how the meanings for these symbols intersect to create shared results. In the case of Malcolm X, several ideas which initially sounded radical and frightening to many white people became more solid and reasonable when presented by themes consonant with mainstream American culture. By focusing on specific examples used by Malcolm X to present his ideas to diverse cultures, I hope to emphasize the importance of symbols and the vital role they play in creating an understanding across diverse communities

Affirmative Action and Implications for Effective Cultural Diversity Training

Diversity is an important factor in organizations today. As the workforce becomes more diverse in terms of gender, race, ethnicity, age, national origin, and other personal characteristics, employers are looking for ways to develop and manage the changes. Beginning with Affirmative Action, several approaches have been used to both ensure equal opportunity and encourage diversity. This paper will examine Affirmative Action both historically and in recent times and identify various approaches to training. An emphasis will be made on determining the effectiveness of current training and methods and determining recommendations for leaders to develop cultural competence

Assessing evidence and uncertainty:informed decision making in drug approval and replication target selection

This dissertation examines the general question of ``when do we have enough evidence?''. Informed decision making is considered in two contexts. Part I zooms in on the use of statistical evidence in regulatory decision making. Specifically, the evaluation of statistical evidence in the context of drug approval by the FDA in the United States. The evidential standards for psychotropic and cancer drugs are discussed using Bayes Factors. The Bayesian re-analyses revealed a substantial degree of variability in the strength of statistical evidence supporting the efficacy of novel psychotropic and cancer drugs approved by the FDA in the pasttwo decades. Although heterogeneity is to be expected due to the uniqueness of each drug evaluation, it is concerning that some drugs were approved despite the lack of statistical evidence of their efficacy or even evidence of their ineffectiveness. Part II considers decision making in the context of replication target selection in (clinical) psychology. To ensure that individual study results are not chance findings , studies are increasingly being replicated. However, given limited resources, only a small number of studies can be replicated. To make best use of the available resources, replication target selection should be systematic, justified, and transparently communicated. This dissertation describes the evidence considered when selecting replication targets in practice and presents formal suggestions for how to select replication projects in clinical psychology and psychology in general

Practical computation of matrix functions

AbstractSeveral new representations for an analytic function f(A) of a complex matrix A, and in particular for eAt and At, are derived, which also are numerically useful in that they avoid the computation of eigenvalues of A

h-Profile plots for the discovery and exploration of patterns in gene expression data with an application to time course data

<p>Abstract</p> <p>Background</p> <p>An ever increasing number of techniques are being used to find genes with similar profiles from microarray studies. Visualization of gene expression profiles can aid this process, potentially contributing to the identification of co-regulated genes and gene function as well as network development.</p> <p>Results</p> <p>We introduce the h-Profile plot to display gene expression profiles. Thumbnail versions of plots of gene expression profiles are plotted at coordinates such that profiles of similar shape are located in the same sector, with decreasing variance towards the origin. Negatively correlated profiles can easily be identified. A new method for selecting genes with fixed periodicity, but different phase and amplitude is described and used to demonstrate the use of the plots on cell cycle data.</p> <p>Conclusion</p> <p>Visualization tools for gene expression data are important and h-profile plots provide a timely contribution to the field. They allow the simultaneous visualization of many gene expression profiles and can be used for the identification of genes with similar or reversed profiles, the foundation step in many analyses.</p

Theoretical measures of relative performance of classifiers for high dimensional data with small sample sizes

We suggest a technique, related to the concept of 'detection boundary' that was developed by Ingster and by Donoho and Jin, for comparing the theoretical performance of classifiers constructed from small training samples of very large vectors. The resulting 'classification boundaries' are obtained for a variety of distance-based methods, including the support vector machine, distance-weighted discrimination and kth-nearest-neighbour classifiers, for thresholded forms of those methods, and for techniques based on Donoho and Jin's higher criticism approach to signal detection. Assessed in these terms, standard distance-based methods are shown to be capable only of detecting differences between populations when those differences can be estimated consistently. However, the thresholded forms of distance-based classifiers can do better, and in particular can correctly classify data even when differences between distributions are only detectable, not estimable. Other methods, including higher criticism classifiers, can on occasion perform better still, but they tend to be more limited in scope, requiring substantially more information about the marginal distributions. Moreover, as tail weight becomes heavier the classification boundaries of methods designed for particular distribution types can converge to, and achieve, the boundary for thresholded nearest neighbour approaches. For example, although higher criticism has a lower classification boundary, and in this sense performs better, in the case of normal data, the boundaries are identical for exponentially distributed data when both sample sizes equal 1

Simpler Evaluation of Predictions and Signature Stability for Gene Expression Data

Scientific advances are raising expectations that patient-tailored treatment will soon be available. The development of resulting clinical approaches needs to be based on well-designed experimental and observational procedures that provide data to which proper biostatistical analyses are applied. Gene expression microarray and related technology are rapidly evolving. It is providing extremely large gene expression profiles containing many thousands of measurements. Choosing a subset from these gene expression measurements to include in a gene expression signature is one of the many challenges needing to be met. Choice of this signature depends on many factors, including the selection of patients in the training set. So the reliability and reproducibility of the resultant prognostic gene signature needs to be evaluated, in such a way as to be relevant to the clinical setting. A relatively straightforward approach is based on cross validation, with separate selection of genes at each iteration to avoid selection bias. Within this approach we developed two different methods, one based on forward selection, the other on genes that were statistically significant in all training blocks of data. We demonstrate our approach to gene signature evaluation with a well-known breast cancer data set

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Synthese und physiologische Funktion der chemischen Chaperone Ectoin und Hydroxyectoin

Eine unter Bakterien weit verbreitete Anpassungsstrategie an hyperosmotische Umgebungsbedingungen ist die Aufnahme oder die Synthese von osmotisch wirksamen Substanzen, die sogenannten kompatiblen Solute. In dieser Arbeit wurden hauptsächlich Aspekte aus dem Bereich der Synthese von den sogenannten kompatiblen Soluten aufgeklärt. Ein häufig genutztes kompatibles Solut in Bakterien ist das Tetrahydropyrimidinderivat Ectoin. Dieses kompatible Solut kann in einem weiteren enzymatischen Schritt durch eine Ectoin-Hydroxylase EctD zu Hydroxyectoin hydroxyliert werden. Um diese Hydroxylierungsreaktion besser zu verstehen, wurde in dieser Arbeit durch Röntgenstrukturanalysen die Kristallstruktur der Ectoin-Hydroxylase EctD aus V. salexigens in Zusammenarbeit mit der AG von Prof. Dr. K. Reuter (Universität Marburg) aufgeklärt. Die Ergebnisse aus der Kristallstruktur von EctD mit gebundenem Eisen, ein Vergleich des aktiven Zentrums der EctD Struktur mit Ectoin bindenden Substratproteinen aus Ectoin Transportern sowie der bioinformatische Vergleich von putativen EctD Proteinsequenzen führten zu einer Auswahl an Aminosäuren, die für eine Mutagenesestudie herangezogen wurden. Die Ergebnisse der Mutagenesestudie von hoch-konservierten Aminosäuren lieferten wichtige Informationen über deren Funktion und über den möglichen Synthesemechanismus des EctD Enzyms. Da man jedoch keine EctD Struktur mit gebundenem Substrat Ectoin oder Co-Substrat 2-Oxoglutarat erhalten konnte, wurden weitere potentielle Ectoin-Hydroxylasen aus verschiedenen Mikroorganismen kloniert und affinitätschromatographisch gereinigt. Alle gereinigten Ectoin-Hydroxylasen aus den Bakterien Sphingopyxis alaskensis, Geobacillus. sp. Y412MC10, Pseudomonas stutzeri A1501, Alkalilimnicola ehrlichi, Acidiphilium cryptum und Halomonas elongata sowie dem Crenarchaeon N. maritimus waren enzymatisch aktiv. Dazu wurden die genauen Essaybedingungen jeder Ectoin-Hydroxylase in Bezug auf pH-Wert, Temperatur, Salzkonzentration angepasst und optimiert. Danach erfolgte die enzymatische Charakterisierung und die Ermittlung der biochemischen Parameter wie Km, vmax und kcat. Durch weitere bioinformatische Analysen der ect Gene, die überwiegend als ein geschlossenes Gencluster in den Organismen organisiert sind, wurden weitere interessante Gene innerhalb des ect-Genclusters identifiziert. Dabei trat immer wieder ein für eine Aspartokinase kodierendes ask Gen auf. Die Aspartokinasen synthetisieren aus L-Aspartat den für die Ectoin Synthese wichtigen Vorläufer β-Aspartat-Semialdehyd im Zusammenschluss mit einem Asd Enzym. Im Genom des Bakteriums Pseudomonas stutzeri A1501 wurden zwei Gene für potentielle Aspartokinasen gefunden. Ein Gen befindet sich im ect-Gencluster und das zweite ask Gen ist an anderer Stelle im Genom lokalisiert. Die beiden Gene der Aspartokinasen wurden kloniert, die Proteine heterolog in E. coli produziert und durch enzymatische Tests charakterisiert. Diese Untersuchungen zeigten wichtige Unterschiede im Hinblick auf die Eigenschaften der beiden studierten Aspartokinasen in diesem Bakterium. In Wachstumsanalysen mit dem Actinomyceten Streptomyces coelicolor A3(2) wurde die physiologische Bedeutung der beiden kompatiblen Solute Ectoin und Hydroxyectoin untersucht. S. coelicolor wird durch Ectoin und Hydroxyectoin unter hohen osmotischen Bedingungen und hohen Temperaturen protektiert. Es konnte gezeigt werden, dass beim Einsatz eines 1:1 Gemischs von Ectoin und Hydroxyectoin diese Protektion am effektivsten ist. Des Weiteren wurde durch Transportstudien mit radioaktiv markiertem [14C]-Ectoin untersucht, bei welcher Salinität und bei welcher Temperatur die Aufnahme der kompatiblen Solute in S. coelicolor induziert wird. Durch die Kombination der beiden Stressfaktoren wie Hochsalz und hohe Temperatur, konnte gezeigt werden, dass in dieser Situation die Aufnahme am stärksten angeschaltet wird