The Role of DNA Topoisomerase II In Drug Resistance and Sensitivity.

Intrinsic or acquired resistance of human tumors to chemotheraphy is often multifactorial. One of the factors involved in resistance is the nuclear enzyme DNA topoisomerase II (TopoII) which is known to be the target of a variety of cytotoxic drugs which are widely used in the clinic. A factor complicating TopoII research is the presence of two TopoII isoforms in human cells which are called TopoIIa and b. In this thesis the role of these isoforms in resistance in small cell lung carcinoma cell line models is examined and the regulation of TopoII expression in human ovarian tumors is investigated. .... Zie: Summary and conclusions

Critical theories for the pseudogap Kondo problem

We discuss quantum phase transitions in the pseudogap Kondo problem, which describes a magnetic moment coupled to conduction electrons with a power-law density of states, rho(omega) ~ |omega|^r. We show that different perturbative expansions, together with renormalization group techniques, provide effective low-energy field theories for the relevant critical fixed points. In particular, we review expansions near the lower-critical and upper-critical dimensions of the problem, being r=0 and r=1, respectively.Comment: 2 pages, 1 fig, submitted to SCES04 proceeding

From genome-wide association studies to disease mechanisms:celiac disease as a model for autoimmune diseases

Celiac disease is characterized by a chronic inflammatory reaction in the intestine and is triggered by gluten, a constituent derived from grains which is present in the common daily diet in the Western world. Despite decades of research, the mechanisms behind celiac disease etiology are still not fully understood, although it is clear that both genetic and environmental factors are involved. To improve the understanding of the disease, the genetic component has been extensively studied by genome-wide association studies. These have uncovered a wealth of information that still needs further investigation to clarify its importance. In this review, we summarize and discuss the results of the genetic studies in celiac disease, focusing on the "non-HLA" genes. We also present novel approaches to identifying the causal variants in complex susceptibility loci and disease mechanisms

Hidden Integrability of a Kondo Impurity in an Unconventional Host

We study a spin-1/2 Kondo impurity coupled to an unconventional host in which the density of band states vanishes either precisely at (``gapless'' systems) or on some interval around the Fermi level (``gapped''systems). Despite an essentially nonlinear band dispersion, the system is proven to exhibit hidden integrability and is diagonalized exactly by the Bethe ansatz.Comment: 4 pages, RevTe

Intestinal Barrier Function in Gluten-Related Disorders

Gluten-related disorders include distinct disease entities, namely celiac disease, wheat-associated allergy and non-celiac gluten/wheat sensitivity. Despite having in common the contact of the gastrointestinal mucosa with components of wheat and other cereals as a causative factor, these clinical entities have distinct pathophysiological pathways. In celiac disease, a T-cell mediate immune reaction triggered by gluten ingestion is central in the pathogenesis of the enteropathy, while wheat allergy develops as a rapid immunoglobulin E- or non-immunoglobulin E-mediated immune response. In non-celiac wheat sensitivity, classical adaptive immune responses are not involved. Instead, recent research has revealed that an innate immune response to a yet-to-be-defined antigen, as well as the gut microbiota, are pivotal in the development in this disorder. Although impairment of the epithelial barrier has been described in all three clinical conditions, its role as a potential pathogenetic co-factor, specifically in celiac disease and non-celiac wheat sensitivity, is still a matter of investigation. This article gives a short overview of the mucosal barrier of the small intestine, summarizes the aspects of barrier dysfunction observed in all three gluten-related disorders and reviews literature data in favor of a primary involvement of the epithelial barrier in the development of celiac disease and non-celiac wheat sensitivity

Kondo physics in a dissipative environment

We report nonperturbative results for the interacting quantum-critical behavior in a Bose-Fermi Kondo model describing a spin-1/2 coupled both to a fermionic band with a pseudogap density of states and to a dissipative bosonic bath. The model serves as a paradigm for studying the interplay between Kondo physics and low-energy dissipative modes in strongly correlated systems.Comment: 2 pages, 2 figures. Proceedings of The International Conference on Strongly Correlated Electron Systems (SCES'07), accepted for publication in Physica

Exactly Solvable Model of Superconducting Magnetic Alloys

A model describing the Anderson impurity in the Bardeen-Cooper-Schriffer superconductor is proven to exhibit hidden integrability and is diagonalized exactly by the Bethe ansatz.Comment: 10 pages, RevTEX, Phys. Lett. A. (in press

Metallic Ferromagnetism in the Kondo Lattice

Metallic magnetism is both ancient and modern, occurring in such familiar settings as the lodestone in compass needles and the hard drive in computers. Surprisingly, a rigorous theoretical basis for metallic ferromagnetism is still largely missing. The Stoner approach perturbatively treates Coulomb interactions when the latter need to be large, while the Nagaoka approach incorporates thermodynamically negligible electrons into a half-filled band. Here, we show that the ferromagnetic order of the Kondo lattice is amenable to an asymptotically exact analysis over a range of interaction parameters. In this ferromagnetic phase, the conduction electrons and local moments are strongly coupled but the Fermi surface does not enclose the latter (i.e. it is small). Moreover, non-Fermi liquid behavior appears over a range of frequencies and temperatures. Our results provide the basis to understand some long-standing puzzles in the ferromagnetic heavy fermion metals, and raises the prospect for a new class of ferromagnetic quantum phase transitions.Comment: 21 pages, 9 figures, including Supporting Informatio

Do quantum dots allow one access to pseudogap Kondo physics?

For the last decade, tunable quantum dot systems have allowed the investigation of Kondo physics wherein the quenching of a single spin on an artificial atom affects the conductance. The pseudogap Kondo model featuring a density of states $\rho(\epsilon)$ = C$|\epsilon|^{r}$, introduced by Withoff and Fradkin in 1990 was predicted to exhibit Kondo-like physics above a critical value of the Kondo coupling, J$_c$, which several groups have shown by numerical renormalization group (RG) is finite for r$< {1/2}$. Gonzalez-Buxton {\it{et al}} showed that the strong coupling limit of the particle-hole symmetric model leads to a non-trivial $\frac{\pi (1-r)}{2}$ phase shift at low temperatures indicating incomplete screening of the local moment, while away from particle-hole symmetry one generically flows towards a ground state with $\delta \sim \pi$. We examine the implications of this model for quantum dots whose leads are Fermi-liquid-like, yet possess a tunneling density of states which is suppressed at the Fermi energy as a power law.Comment: 2 pages, 1 figure, poster to be presented at SCES'04 Karlsruhe July 26-3