Mode Specific Backscattering in a Quantum Point Contact.

We demonstrate a scanning gate grid measurement technique consisting in measuring the conductance of a quantum point contact (QPC) as a function of gate voltage at each tip position. Unlike conventional scanning gate experiments, it allows investigating QPC conductance plateaus affected by the tip at these positions. We compensate the capacitive coupling of the tip to the QPC and discover that interference fringes coexist with distorted QPC plateaus. We spatially resolve the mode structure for each plateau.

Dose matters! Optimisation of guideline adherence is associated with lower mortality in stable patients with chronic heart failure.

AIMS: Guidelines have been published for improving management of chronic heart failure (CHF). We examined the association between improved guideline adherence and risk for all-cause death in patients with stable systolic HF. METHODS: Data on ambulatory patients (2006-2010) with CHF and reduced ejection fraction (HF-REF) from the Austrian Heart Failure Registry (HIR Austria) were analysed. One-year clinical data and long-term follow-up data until all-cause death or data censoring were available for 1014 patients (age 65 [55-73], male 75%, NYHA class I 14%, NYHA II 56%, NYHA III/IV 30%). A guideline adherence indicator (GAI [0-100%]) was calculated for each patient at baseline and after 12 ± 3 months that considered indications and contraindications for ACE-I/ARB, beta blockers, and MRA. Patients were considered ΔGAI-positive if GAI improved to or remained at high levels (≥ 80%). ΔGAI50+ positivity was ascribed to patients achieving a dose of ≥ 50% of suggested target dose. RESULTS: Improvements in GAI and GAI50+ were associated with significant improvements in NYHA class and NT-proBNP (1728 [740-3636] to 970 [405-2348]) (p<0.001). Improvements in GAI50+, but not GAI, were independently predictive of lower mortality risk (HR 0.55 [95% CI 0.34-0.87; p=0.01]) after adjustment for a large variety of baseline parameters and hospitalisation for heart failure during follow-up. CONCLUSIONS: Improvement in guideline adherence with particular emphasis on dose escalation is associated with a decrease in long-term mortality in ambulatory HF-REF subjects surviving one year after registration.

[Diagnostics and therapy of heart failure]. / Diagnostik und Therapie der Herzinsuffizienz.

Heart failure represents one of the most common diseases in the western world with an estimated prevalence of 0.4-2% in Europe. The frequency and incidence is very age-dependant and chronic cardiac insufficiency has a high stage-dependant mortality. Aging of the population and prolongation of the lives of cardiac patients has led to an increasing prevalence of heart failure. However, average survival remains poor after hospitalization for a first episode of heart failure. Diagnostics and therapy of heart failure are subject to constant change due to ongoing progress in research and new randomized controlled trials. This review will focus on new developments and current guidelines for diagnosis and treatment of heart failure. Findings on natriuretic peptides and echocardiography in patients with preserved ejection fraction will be presented and innovative therapeutic measures, such as ivabradine will be discussed. Besides new drug developments insight into device therapy, such as MitraClip® and operative approaches for heart failure will be presented.

Thymine DNA glycosylase.

More than 50% of colon cancer-associated mutations in the p53 tumor suppressor gene are C-->T transitions. The majority of them locate in CpG dinucleotides and are thought to have arisen through spontaneous hydrolytic deamination of 5-methylcytosine. This deamination process gives rise to G.T mispairs that need to be repaired to G.C in order to avoid C-->T mutation. Similarly, deamination of cytosine generates G.U mispairs that also produce C-->T transitions if not repaired. Restoration of both G.T and G.U mismatches was shown to be mediated by a short-patch excision repair pathway, and one principal player implicated in this process may be thymine DNA glycosylase (TDG). Human TDG was discovered as an enzyme that has the potential to specifically remove thymine and uracil bases mispaired with guanine through hydrolysis of their N-glycosidic bond, thereby generating abasic sites in DNA and initiating a base excision repair reaction. The same protein was later found to interact physically and functionally with the retinoid receptors RAR and RXR, and this implicated an unexpected function of TDG in nuclear receptor-mediated transcriptional activation of gene expression. The objective of this chapter is to put together the results of different lines of experimentation that have explored the thymine DNA glycosylase since its discovery and to critically evaluate their implications for possible physiological roles of this enzyme.