QCD-Factorization of inclusive B decays and |Vub|

Recent progress in the theoretical description of inclusive B to X_u l nu decays in the shape-function region is reported. Finite moments of the shape function are related to HQET parameters. Event fractions for several experimental cuts are presented, with a particular emphasis on the hadronic variable P+. The aim of this talk is to introduce the P+ spectrum, to compare it to the hadronic invariant mass spectrum and the charged-lepton energy spectrum, and to study the prospect of evaluating |Vub| in the presence of a large background from B to X_c decays.Comment: 8 pages, 7 figures, uses espcrc2.sty (included). Talk presented at the Sixth International Conference on Hyperons, Charm and Beauty Hadrons, IIT, Chicago, June 27--July 3 200

In vitro Zellkulturmodelle der Blut-Hirn-Schranke zur Untersuchung der Permeation und P-Glycoprotein-Interaktion von Arzneistoffen

Zielsetzung der vorliegenden Arbeit waren 1) die Isolierung, Kultivierung und Charakterisie-rung cerebraler Kapillarendothelzellen als Modellzellen für Zellkulturmodelle der Blut-Hirn-Schranke, 2) die Charakterisierung eines in vitro Permeationsmodells der Blut-Hirn-Schranke sowie 3) die Entwicklung eines Screening-Modells zur Untersuchung von Arzneistoff-Interaktionen mit P-Glycoprotein (P-gp). Die Zellisolierung erfolgte nach einer rein enzymatischen Methode aus Schweinehirn. Die Zellen zeigten gutes Wachstum und bildeten konfluente Monolayer, was mit Aktinfärbungen belegt wurde. Immunfärbungen des von-Willebrand-Faktors bestätigten den endothelialen Charakter der Zellen. Immunfärbungen des ABC-Transporters Mrp2 waren negativ. Die Ex-pression von P-Glycoprotein konnte dagegen nachgewiesen werden. Die Charakterisierung des in vitro Permeationsmodells der Blut-Hirn-Schranke erfolgte an-hand von Permeationsversuchen. Aufgrund der Untersuchungen wurden verschiedene Ein-flussfaktoren charakterisiert und standardisiert. Zwischen passiver parazellulärer bzw. transzellulärer Permeation, erleichterter Diffusion und aktivem Transport durch den ABC-Transporter P-Glycoprotein konnte differenziert werden. Zur Untersuchung von Arzneistoff-Interaktionen mit P-Glycoprotein wurden der Calcein-AM-MDR-Assay und der Calcein-AM-Kinetik-Assay. Mit dem Calcein-AM-MDR-Assay wurden Validierungssubstanzen richtig identifiziert und gut differenziert. Aufgrund der Untersuchun-gen mit dem Calcein-AM-Kinetik-Assay wurden Nicardipin und PSC-833 als non-kompetitive P-gp-Inhibitoren klassifiziert. Ritonavir, Taxol und Vinblastin wurden als kompetitive P-gp-Substrate eingestuft. Die Ergebnisse zeigen, dass das in vitro Permeationsmodell der Blut-Hirn-Schranke als indu-strietaugliches Permeations-Screening-Modell verwendet werden kann, und dass der Cal-cein-AM-MDR- und Calcein-AM-Kinetik-Assay gute Screening-Modelle zur Untersuchung von Arzneistoff-P-gp-Interaktionen darstellen

Ultra-high vacuum compatible induction-heated rod casting furnace

We report the design of a radio-frequency induction-heated rod casting furnace that permits the preparation of polycrystalline ingots of intermetallic compounds under ultra-high vacuum compatible conditions. The central part of the system is a bespoke water-cooled Hukin crucible supporting a casting mold. Depending on the choice of mold, typical rods have a diameter between 6 mm and 10 mm and a length up to 90 mm, suitable for single-crystal growth by means of float-zoning. The setup is all-metal sealed and may be baked out. We find that the resulting ultra-high vacuum represents an important precondition for processing compounds with high vapor pressures under a high-purity argon atmosphere up to 3 bar. Using the rod casting furnace, we succeeded to prepare large high-quality single crystals of two half-Heusler compounds, namely the itinerant antiferromagnet CuMnSb and the half-metallic ferromagnet NiMnSb.Comment: 5 pages, 4 figure

Screening in Pregnancy and Fetal Medicine

Epilepsy is a common neurological disorder that affects over 70 million people worldwide. Despite the recent introduction of new antiseizure drugs (ASDs), about one-third of patients with epilepsy have seizures refractory to pharmacotherapy. Early identification of patients who will become refractory to ASDs could help direct such patients to appropriate non-pharmacological treatment, but the complexity in the temporal patterns of epilepsy could make such identification difficult. The target hypothesis and transporter hypothesis are the most cited theories trying to explain refractory epilepsy, but neither theory alone fully explains the neurobiological basis of pharmacoresistance. This review summarizes evidence for and against several major theories, including the pharmacokinetic hypothesis, neural network hypothesis, intrinsic severity hypothesis, gene variant hypothesis, target hypothesis, and transporter hypothesis. The discussion is mainly focused on the transporter hypothesis, where clinical and experimental data are discussed on multidrug transporter overexpression, substrate profiles of ASDs, mechanism of transporter upregulation, polymorphisms of transporters, and the use of transporter inhibitors. Finally, future perspectives are presented for the improvement of current hypotheses and the development of treatment strategies as guided by the current understanding of refractory epilepsy

ABC Transporters and the Alzheimer’s Disease Enigma

Alzheimer’s disease (AD) is considered the “disease of the twenty-first century.” With a 10-fold increase in global incidence over the past 100 years, AD is now reaching epidemic proportions and by all projections, AD patient numbers will continue to rise. Despite intense research efforts, AD remains a mystery and effective therapies are still unavailable. This represents an unmet need resulting in clinical, social, and economic problems. Over the last decade, a new AD research focus has emerged: ATP-binding cassette (ABC) transporters. In this article, we provide an overview of the ABC transporters ABCA1, ABCA2, P-glycoprotein (ABCB1), MRP1 (ABCC1), and BCRP (ABCG2), all of which are expressed in the brain and have been implicated in AD. We summarize recent findings on the role of these five transporters in AD, and discuss their potential to serve as therapeutic targets

Factorization and the Soft Overlap Contribution to Heavy-to-Light Form Factors

Using the formalism of soft-collinear effective theory, a complete separation of short- and long-distance contributions to heavy-to-light transition form factors at large recoil is performed. The universal functions $\zeta_M(E)$ parameterizing the ``soft overlap'' contribution to the form factors are defined in terms of matrix elements in the effective theory. Endpoint configurations corresponding to kinematic situations where one of the valence partons in the external mesons carries very small momentum are accounted for in terms of operators involving soft-collinear messenger fields. They contribute at leading order in $\Lambda_{\rm QCD}/E$ and spoil factorization. An analysis of operator mixing and renormalization-group evolution in the effective theory reveals that the intermediate scale $\sqrt{E\Lambda}$ is without significance to the soft functions $\zeta_M(E)$, and that the soft overlap contribution does not receive a significant perturbative (Sudakov) suppression.Comment: 30 pages, 6 figures. Erratum adde

Low-temperature properties of single-crystal CrB2_{2}

We report the low-temperature properties of $^{11}$B-enriched single-crystal CrB$_{2}$ as prepared from high-purity Cr and B powder by a solid-state reaction and optical float zoning. The electrical resistivity, $\rho_{\rm xx}$, Hall effect, $\rho_{\rm xy}$, and specific heat, $C$, are characteristic of an exchange-enhanced Fermi liquid ground state, which develops a slightly anisotropic spin gap $\Delta \approx 220\,{\rm K}$ below $T_{\rm N}=88\,{\rm K}$. This observation is corroborated by the absence of a Curie dependence in the magnetization for $T\to0$ reported in the literature. Comparison of $C$ with $d\rho_{\rm xx}/dT$, where we infer lattice contributions from measurements of VB$_2$, reveals strong antiferromagnetic spin fluctuations with a characteristic spin fluctuation temperature $T_{\rm sf}\approx 257\,{\rm K}$ in the paramagnetic state, followed by a pronounced second-order mean-field transition at $T_{\rm N}$, and unusual excitations around $\approx T_{\rm N}/2$. The pronounced anisotropy of $\rho_{\rm xx}$ above $T_{\rm N}$ is characteristic of an easy-plane anisotropy of the spin fluctuations consistent with the magnetization. The ratio of the Curie-Weiss to the N$\acute{\rm{e}}$el temperatures, $f=-\Theta_{\rm CW}/T_{\rm N}\approx 8.5$, inferred from the magnetization, implies strong geometric frustration. All physical properties are remarkably invariant under applied magnetic fields up to $14\,\,{\rm T}$, the highest field studied. In contrast to earlier suggestions of local-moment magnetism our study identifies CrB$_{2}$ as a weak itinerant antiferromagnet par excellence with strong geometric frustration.Comment: 15 pages, 9 figure