Molekulare Karyotypisierung in der Diagnostik neurokognitiver Entwicklungsstörungen

Zusammenfassung: Die Ursache neurokognitiver Entwicklungsstörungen mit Intelligenzminderung stellt eine der häufigsten Fragestellungen in der genetischen Sprechstunde dar. Obwohl mehr als 400 krankheitsverursachende Einzelgendefekte bekannt sind, machen Chromosomenaberrationen derzeit den größten Anteil der bekannten Ursachen aus. Mittels hochauflösender Array-Techniken lassen sich nach Ausschluss des Down-Syndroms bei unselektionierten Patienten in 18% der Fälle relevante chromosomale Imbalancen nachweisen, wobei die Aberrationen nur in 4% der Fälle auch primär mikroskopisch sichtbar wären. Mit zunehmender Auflösung steigt jedoch auch die Rate an detektierten Kopienzahl-Normvarianten, welche die Beurteilung der Befunde erschweren können. Indikatoren für krankheitsrelevante Aberrationen sind Aberrationsgröße, Gengehalt und Segregation innerhalb der Familie. Eine Kausalität kann letztlich aber nur dann belegt werden, wenn Vergleichsfälle mit ähnlichem Genotyp und Phänotyp vorliege

Asymmetry Parameter of Λ Decay and the Intermediate Boson of Weak Interactions

The magnitude of the pion asymmetry parameter α- of the Λ → p + π- decay has been determinted [1] to be greater than or equal to (0.73 ± 0.14). The sign of this parameter, however, is rather hard to find. The results of Boldt et al. [2] anf the preliminary results of Birge and Fowler [3] indicated a positive sign for α-. Recently, however, Birge and Fowler [4] have reported a negative sign for α-, contrary to their own preliminary [3] results. In this Letter we wish to point out that the negative sign of α-, provides a favorable argument for the conjecture that the V-A four-fermion interaction may be mediated by a vector boson

Vascular adaptation to exercise in humans: Role of hemodynamic stimuli

On the 400th anniversary of Harvey’s Lumleian lectures, this review focuses on “hemodynamic” forces associated with the movement of blood through arteries in humans and the functional and structural adaptations that result from repeated episodic exposure to such stimuli. The late 20th century discovery that endothelial cells modify arterial tone via paracrine transduction provoked studies exploring the direct mechanical effects of blood flow and pressure on vascular function and adaptation in vivo. In this review, we address the impact of distinct hemodynamic signals that occur in response to exercise, the interrelationships between these signals, the nature of the adaptive responses that manifest under different physiological conditions, and the implications for human health. Exercise modifies blood flow, luminal shear stress, arterial pressure, and tangential wall stress, all of which can transduce changes in arterial function, diameter, and wall thickness. There are important clinical implications of the adaptation that occurs as a consequence of repeated hemodynamic stimulation associated with exercise training in humans, including impacts on atherosclerotic risk in conduit arteries, the control of blood pressure in resistance vessels, oxygen delivery and diffusion, and microvascular health. Exercise training studies have demonstrated that direct hemodynamic impacts on the health of the artery wall contribute to the well-established decrease in cardiovascular risk attributed to physical activity. © 2017 the American Physiological Society

Newly observed two-body decays of B mesons in a hybrid perspective

In consistency with the b --> c type of (quasi) two body decays, recently observed two body decays of B mesons are studied in a hybrid perspective in which their amplitude is given by a sum of factorizable and non-factorizable ones, and a role of the latter in these decays are discussed.Comment: 7 page

Towards resolution of the scalar meson nonet enigma

By the application of a linear mass spectrum to a composite system of both the pseudoscalar and scalar meson nonets, we find three mass relations for the masses of the scalar states which suggest the $q\bar{q}$ assignment for the scalar meson nonet: $a_0(1320),$ $K_0^\ast (1430),$ $f_0(1500),$ $f_0'(980).$Comment: 16 pages, LaTe

The Mixed Vector Current Correlator <0|T(V^3_\mu V^8_\nu )|0> To Two Loops in Chiral Perturbation Theory

The isospin-breaking correlator of the product of flavor octet vector currents, $V^3_\mu$ and $V^8_\nu$, $\Pi^{38}_{\mu\nu}(q^2)$ is computed to next-to-next- to-leading (two-loop) order in Chiral Perturbation Theory. Large corrections to both the magnitude and $q^2$-dependence of the one-loop result are found, and the reasons for the slow convergence of the chiral series for the correlator given. The two-loop expression involves a single ${\cal O}(q^6)$ counterterm, present also in the two-loop expressions for $\Pi^{33}_{\mu\nu}(q^2)$ and $\Pi^{88}_{\mu\nu}(q^2)$, which counterterm contributes a constant to the scalar correlator $\Pi^{38}(q^2)$. The feasibility of extracting the value of this counterterm from other sources is discussed. Analysis of the slope of the correlator with respect to $q^2$ using QCD sum rules is shown to suggest that, even to two-loop order, the chiral series for the correlator may not yet be well-converged.Comment: 32 pages, uses REVTEX and epsfig.sty with 7 uuencoded figures. Entire manuscript available as a ps file at http://www.physics.adelaide.edu.au/theory/home.html Also available via anonymous ftp at ftp://adelphi.adelaide.edu.au/pub/theory/ADP-95-27.T181.p

η→π0γγ\eta \to \pi^0 \gamma \gamma decay within unitarized chiral perturbation theory

We improve the calculations of the $\eta \to \pi^0 \gamma \gamma$ decay within the context of meson chiral lagrangians. We use a chiral unitary approach for the meson-meson interaction, thus generating the $a_0(980)$ resonance and fixing the longstanding sign ambiguity on its contribution. This also allows us to calculate the loops with one vector meson exchange, thus removing a former source of uncertainty. In addition we ensure the consistency of the approach with other processes. First, by using vector meson dominance couplings normalized to agree with radiative vector meson decays. And, second, by checking the consistency of the calculations with the related $\gamma \gamma \to \pi^0 \eta$ reaction. We find an $\eta \to \pi^0 \gamma \gamma$ decay width of $0.47\pm 0.10$ eV, in clear disagreement with published data but in remarkable agreement with the most recent measurement.Comment: 15 pages, 10 figures, published versio

Study of 3-prong Hadronic τ\tau Decays with Charged Kaons

Using a sample of 4.7/fb integrated luminosity accumulated with the CLEO-II detector at the Cornell Electron Storage Ring (CESR), we have measured the branching fractions of the tau lepton into $K^- h^+ \pi^- \nu_\tau$ and $K^- K^+ \pi^- \nu_\tau$ relative to $h^- h^+ h^- \nu_\tau; K^- h^+ \pi^- \pi^0\nu_\tau$ and $K^- K^+ \pi^- \pi^0\nu_\tau$ relative to $h^- h^+ h^- \pi^0 \nu_\tau$. The relative branching fractions are: (5.16+-0.20+-0.50)*$10^{-2}$, (1.52+-0.14+-0.29)*$10^{-2}$, (2.54+-0.44+-0.39)*$10^{-2}$ and $<0.0154$ at 95% C.L., respectively. Coupled with additional experimental information, we use our results to extract information on the structure of three-prong tau decays to charged kaons.Comment: 16 pages postscript file also available through http://w4.lns.cornell.edu/public/CLN

Influence of Various Polymorphic Variants of Cytochrome P450 Oxidoreductase (POR) on Drug Metabolic Activity of CYP3A4 and CYP2B6

Cytochrome P450 oxidoreductase (POR) is known as the sole electron donor in the metabolism of drugs by cytochrome P450 (CYP) enzymes in human. However, little is known about the effect of polymorphic variants of POR on drug metabolic activities of CYP3A4 and CYP2B6. In order to better understand the mechanism of the activity of CYPs affected by polymorphic variants of POR, six full-length mutants of POR (e.g., Y181D, A287P, K49N, A115V, S244C and G413S) were designed and then co-expressed with CYP3A4 and CYP2B6 in the baculovirus-Sf9 insect cells to determine their kinetic parameters. Surprisingly, both mutants, Y181D and A287P in POR completely inhibited the CYP3A4 activity with testosterone, while the catalytic activity of CYP2B6 with bupropion was reduced to approximately ∼70% of wild-type activity by Y181D and A287P mutations. In addition, the mutant K49N of POR increased the CLint (Vmax/Km) of CYP3A4 up to more than 31% of wild-type, while it reduced the catalytic efficiency of CYP2B6 to 74% of wild-type. Moreover, CLint values of CYP3A4-POR (A115V, G413S) were increased up to 36% and 65% of wild-type respectively. However, there were no appreciable effects observed by the remaining two mutants of POR (i.e., A115V and G413S) on activities of CYP2B6. In conclusion, the extent to which the catalytic activities of CYP were altered did not only depend on the specific POR mutations but also on the isoforms of different CYP redox partners. Thereby, we proposed that the POR-mutant patients should be carefully monitored for the activity of CYP3A4 and CYP2B6 on the prescribed medication