Genome reorganization in different cancer types: detection of cancer specific breakpoint regions

Background: Tumorigenesis is a multi-step process which is accompanied by substantial changes in genome organization. The development of these changes is not only a random process, but rather comprise specific DNA regions that are prone to the reorganization process. Results: We have analyzed previously published SNP arrays from three different cancer types (pancreatic adenocarcinoma, breast cancer and metastatic melanoma) and from non-malignant control samples. We calculated segmental copy number variations as well as breakpoint regions. Some of these regions were not randomly involved in genome reorganization since we detected fifteen of them in at least 20% of all tumor samples and one region on chromosome 9 where 43% of tumors have a breakpoint. Further, the top-15 breakpoint regions show an association to known fragile sites. The relevance of these common breakpoint regions was further confirmed by analyzing SNP arrays from 917 cancer cell lines. Conclusion: Our analyses suggest that genome reorganization is common in tumorigenesis and that some breakpoint regions can be found across all cancer types, while others exclusively occur in specific entities

Calculation of hadronic transition amplitudes in charm physics

Übergänge von Hadronen mit einem charm-Quark sind von wichtiger Bedeutung, da sie die Möglichkeit bieten, die CKM-Matrixelemente V_cd und V_cs zu bestimmen, sowie interessante Kanäle für die Suche nach neuer Physik zur Verfügung stellen. Quarks sind allerdings in Hadronen gebunden, und man braucht eine verlässliche Beschreibung dieses Effekts, um die zugrunde liegende Flavour-Dynamik untersuchen zu können. Dazu ist die Verwendung nichtperturbativer Methoden erforderlich, um entsprechende Übergangsamplituden bestimmen zu können. Die Ergebnisse solcher Berechnungen erlauben zudem umgekehrt auch einen Test der QCD und können zu einem tieferen Verständnis der Bindungsstruktur von Hadronen beitragen. In dieser Dissertation werden mit der Methode der QCD-Lichtkegelsummenregeln zwei Themengebiete untersucht. Das erste sind die Formfaktoren für die semileptonischen Zerfälle D →πℓ ν_ℓ und D → K ℓ ν_ℓ, für die - unter Nutzung neuester Ergebnisse - aktuelle Werte bestimmt werden. Da hier keine direkte Vorhersage im gesamten kinematischen Bereich möglich ist, werden sie unter Verwendung geeigneter Parametrisierungen extrapoliert und stimmen sehr gut mit dem Experiment überein. Das zweite Gebiet sind die Übergänge von Baryonen mit einem charm-Quark in Nukleonen. Auch hier werden die entsprechenden Übergangsformfaktoren, sowie zusätzlich die hadronischen Λ_c D^(*)N - und Σ_c D^(*)N -Kopplungskonstanten (unter Verwendung doppelter Dispersionsrelationen) berechnet. Letztere sind insbesondere für die Beschreibung hadronischer Wechselwirkungen von Bedeutung, wie der Produktion von charm-Quark-Hadronen in Proton-Antiproton-Kollisionen. Dabei tritt zudem das Problem auf, dass beide Paritätszustände der betrachteten Baryonen in die verwendete Darstellung einflie&szligen, zu deren Trennung eine konsistente Methode vorgestellt wird.Transitions of charmed hadrons are of significant importance, since they provide possibilities to extract the CKM matrix elements V_cd and V_cs from experimental data as well as interesting channels to search for new physics effects. However, quarks are bound in hadrons, and it is necessary to describe this effect in a reliable way, to study the underlying flavour dynamics. For this, one has to use nonperturbative tools, to determine the corresponding transition amplitudes. The results of such calculations can furthermore be of use, to test the predictions of QCD and to contribute to a deeper understanding of the structure of hadrons. In this thesis two topics are investigated using the method of QCD light-cone sum rules (LCSRs). The first topic consists in the form factors of the semileptonic decays D → πℓ ν_ℓ and D → K ℓ ν_ℓ, for which new results are calculated using up-to-date input values. Since LCSRs are not applicable in the whole range of kinematics, they are extrapolated by the use of appropriate parametrisations and the results agree well with experimental data. The second topic are the transitions of charmed baryons to a nucleon. Here the corresponding transition form factors and in addition the hadronic Λ_c D^(*)N and Σ_cD^(*)N coupling constants are calculated - the latter by the consideration of double dispersion relations. These coupling constants are of special interest for the description of hadronic interactions, like open charm production in proton-antiproton-collisions. Furthermore there appears the problem, that both parity states of a baryon contribute to the considered functional representation, for which a consistent way to seperate them is presented

Algebraic, Block and Multiplicative Preconditioners based on Fast Tridiagonal Solves on GPUs

This thesis contributes to the field of sparse linear algebra, graph applications, and preconditioners for Krylov iterative solvers of sparse linear equation systems, by providing a (block) tridiagonal solver library, a generalized sparse matrix-vector implementation, a linear forest extraction, and a multiplicative preconditioner based on tridiagonal solves. The tridiagonal library, which supports (scaled) partial pivoting, outperforms cuSPARSE's tridiagonal solver by factor five while completely utilizing the available GPU memory bandwidth. For the performance optimized solving of multiple right-hand sides, the explicit factorization of the tridiagonal matrix can be computed. The extraction of a weighted linear forest (union of disjoint paths) from a general graph is used to build algebraic (block) tridiagonal preconditioners and deploys the generalized sparse-matrix vector implementation of this thesis for preconditioner construction. During linear forest extraction, a new parallel bidirectional scan pattern, which can operate on double-linked list structures, identifies the path ID and the position of a vertex. The algebraic preconditioner construction is also used to build more advanced preconditioners, which contain multiple tridiagonal factors, based on generalized ILU factorizations. Additionally, other preconditioners based on tridiagonal factors are presented and evaluated in comparison to ILU and ILU incomplete sparse approximate inverse preconditioners (ILU-ISAI) for the solution of large sparse linear equation systems from the Sparse Matrix Collection. For all presented problems of this thesis, an efficient parallel algorithm and its CUDA implementation for single GPU systems is provided

Influence of professional dental hygiene on oral and general health of retirement home residents: A comparative study

Objectives: The oral status of nursing home residents is poor. This could compromise general health. The controlled study investigated the influence of quarterly professional dental hygiene interventions on oral and general health of elderly. Material and Methods: 152 participants (mean age 84 years) of two residents' homes were examined. Parameters of general health, a questionnaire for caregivers, and oral parameters were evaluated at baseline and after 1 year. All caregivers were given one lesson on oral hygiene at baseline. In one home professional oral hygiene was performed every 3 months. Statistical analyses were done by Chi(2) test for nominal data and t-test for numeric data. Results: There were no significant differences between both homes regarding general health. Some oral parameters-if any-may be positively influenced by the intervention such as pocket depth, and Denture Hygiene Index and alterations of the mucosa. Conclusions: A quarterly professional hygiene is not able to influence general health and has-if any-little effect on oral health. This underlines the necessity for frequent interventions. An optimization of the health policy framework is necessary to allow caregivers more time for oral hygiene and to establish the accessibility of frequent professional health care for inhabitants in residents' homes

An Algorithmic Theory of Integer Programming

We study the general integer programming problem where the number of variables $n$ is a variable part of the input. We consider two natural parameters of the constraint matrix $A$: its numeric measure $a$ and its sparsity measure $d$. We show that integer programming can be solved in time $g(a,d)\textrm{poly}(n,L)$, where $g$ is some computable function of the parameters $a$ and $d$, and $L$ is the binary encoding length of the input. In particular, integer programming is fixed-parameter tractable parameterized by $a$ and $d$, and is solvable in polynomial time for every fixed $a$ and $d$. Our results also extend to nonlinear separable convex objective functions. Moreover, for linear objectives, we derive a strongly-polynomial algorithm, that is, with running time $g(a,d)\textrm{poly}(n)$, independent of the rest of the input data. We obtain these results by developing an algorithmic framework based on the idea of iterative augmentation: starting from an initial feasible solution, we show how to quickly find augmenting steps which rapidly converge to an optimum. A central notion in this framework is the Graver basis of the matrix $A$, which constitutes a set of fundamental augmenting steps. The iterative augmentation idea is then enhanced via the use of other techniques such as new and improved bounds on the Graver basis, rapid solution of integer programs with bounded variables, proximity theorems and a new proximity-scaling algorithm, the notion of a reduced objective function, and others. As a consequence of our work, we advance the state of the art of solving block-structured integer programs. In particular, we develop near-linear time algorithms for $n$-fold, tree-fold, and $2$-stage stochastic integer programs. We also discuss some of the many applications of these classes.Comment: Revision 2: - strengthened dual treedepth lower bound - simplified proximity-scaling algorith

Classical Motion in Random Potentials

We consider the motion of a classical particle under the influence of a random potential on R^d, in particular the distribution of asymptotic velocities and the question of ergodicity of time evolution.Comment: 45 pages, 3 figure

Einfluss von Kopienzahlvariationen auf die Tumorentwicklung

Tumorentstehung ist ein Prozess, bei dem die Abläufe innerhalb der Zelle schrittweise verändert werden. Die vielfältigen Interaktionen bei der Tumorentstehung sind jedoch bislang nicht vollständig erforscht. Bisher wurden vorwiegend Genexpressionsanalysen genutzt, die jedoch nur eine Zeitaufnahme aller Genexpressionen innerhalb der Zelle darstellen und somit allein nicht ausreichend zur Charakterisierung eines Tumors. Wir haben mithilfe von Affymetrix Mouse Diversity Genotyping Microarrays Mausbrustdrüsengewebe entsprechend unserem Dreistufen-Mausmodell analysiert und die Kopienzahländerungen berechnet. Wir fanden eine zunehmende stufenweise Änderung von den transgenen zu den Tumorproben. Die Berechnung von chromosomalen Segmenten mit gleicher Kopienzahl zeigte deutliche Fragmentmuster. Unsere Analysen zeigen, dass die Tumorentstehung ein schrittweiser Prozess ist, der sowohl durch Amplifikationen als auch Deletionen chromosomaler Abschnitte definiert ist. Wir fanden charakteristisch konservierte Fragmentierungsmuster und individuelle Unterschiede welche zur Tumorgenese beitragen

Good corporate social performance may lead to higher credit ratings

But only for firms whose countries share the same values, find Christian Klein, Christoph Stellner and Bernhard Zwerge