Weak localization and conductance fluctuations of a chaotic quantum dot with tunable spin-orbit coupling

In a two-dimensional quantum dot in a GaAs heterostructure, the spin-orbit scattering rate is substantially reduced below the rate in a bulk two-dimensional electron gas [B.I. Halperin et al, Phys. Rev. Lett. 86, 2106 (2001)]. Such a reduction can be undone if the spin-orbit coupling parameters acquire a spatial dependence, which can be achieved, e.g., by a metal gate covering only a part of the quantum dot. We calculate the effect of such spatially non-uniform spin-orbit scattering on the weak localization correction and the universal conductance fluctuations of a chaotic quantum dot coupled to electron reservoirs by ballistic point contacts, in the presence of a magnetic field parallel to the plane of the quantum dot.Comment: 4 pages, RevTeX; 2 figures. Substantial revision

A frequent variant in the Japanese population determines quasi-Mendelian inheritance of rare retinal ciliopathy.

Hereditary retinal degenerations (HRDs) are Mendelian diseases characterized by progressive blindness and caused by ultra-rare mutations. In a genomic screen of 331 unrelated Japanese patients, we identify a disruptive Alu insertion and a nonsense variant (p.Arg1933*) in the ciliary gene RP1, neither of which are rare alleles in Japan. p.Arg1933* is almost polymorphic (frequency = 0.6%, amongst 12,000 individuals), does not cause disease in homozygosis or heterozygosis, and yet is significantly enriched in HRD patients (frequency = 2.1%, i.e., a 3.5-fold enrichment; p-value = 9.2 × 10 <sup>-5</sup> ). Familial co-segregation and association analyses show that p.Arg1933* can act as a Mendelian mutation in trans with the Alu insertion, but might also associate with disease in combination with two alleles in the EYS gene in a non-Mendelian pattern of heredity. Our results suggest that rare conditions such as HRDs can be paradoxically determined by relatively common variants, following a quasi-Mendelian model linking monogenic and complex inheritance

Cost-effective sequence analysis of 113 genes in 1,192 probands with retinitis pigmentosa and Leber congenital amaurosis

Introduction: Retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) are two groups of inherited retinal diseases (IRDs) where the rod photoreceptors degenerate followed by the cone photoreceptors of the retina. A genetic diagnosis for IRDs is challenging since >280 genes are associated with these conditions. While whole exome sequencing (WES) is commonly used by diagnostic facilities, the costs and required infrastructure prevent its global applicability. Previous studies have shown the cost-effectiveness of sequence analysis using single molecule Molecular Inversion Probes (smMIPs) in a cohort of patients diagnosed with Stargardt disease and other maculopathies. Methods: Here, we introduce a smMIPs panel that targets the exons and splice sites of all currently known genes associated with RP and LCA, the entire RPE65 gene, known causative deep-intronic variants leading to pseudo-exons, and part of the RP17 region associated with autosomal dominant RP, by using a total of 16,812 smMIPs. The RP-LCA smMIPs panel was used to screen 1,192 probands from an international cohort of predominantly RP and LCA cases. Results and discussion: After genetic analysis, a diagnostic yield of 56% was obtained which is on par with results from WES analysis. The effectiveness and the reduced costs compared to WES renders the RP-LCA smMIPs panel a competitive approach to provide IRD patients with a genetic diagnosis, especially in countries with restricted access to genetic testing

Mechanical Stress Changes the Complex Interplay Between HO-1, Inflammation and Fibrosis, During Excisional Wound Repair

Contains fulltext : 152467.pdf (publisher's version ) (Open Access)Mechanical stress following surgery or injury can promote pathological wound healing and fibrosis, and lead to functional loss and esthetic problems. Splinted excisional wounds can be used as a model for inducing mechanical stress. The cytoprotective enzyme heme oxygenase-1 (HO-1) is thought to orchestrate the defense against inflammatory and oxidative insults that drive fibrosis. Here, we investigated the activation of the HO-1 system in a splinted and non-splinted full-thickness excisional wound model using HO-1-luc transgenic mice. Effects of splinting on wound closure, HO-1 promoter activity, and markers of inflammation and fibrosis were assessed. After seven days, splinted wounds were more than three times larger than non-splinted wounds, demonstrating a delay in wound closure. HO-1 promoter activity rapidly decreased following removal of the (epi)dermis, but was induced in both splinted and non-splinted wounds during skin repair. Splinting induced more HO-1 gene expression in 7-day wounds; however, HO-1 protein expression remained lower in the epidermis, likely due to lower numbers of keratinocytes in the re-epithelialization tissue. Higher numbers of F4/80-positive macrophages, alphaSMA-positive myofibroblasts, and increased levels of the inflammatory genes IL-1beta, TNF-alpha, and COX-2 were present in 7-day splinted wounds. Surprisingly, mRNA expression of newly formed collagen (type III) was lower in 7-day wounds after splinting, whereas, VEGF and MMP-9 were increased. In summary, these data demonstrate that splinting delays cutaneous wound closure and HO-1 protein induction. The pro-inflammatory environment following splinting may facilitate higher myofibroblast numbers and increase the risk of fibrosis and scar formation. Therefore, inducing HO-1 activity against mechanical stress-induced inflammation and fibrosis may be an interesting strategy to prevent negative effects of surgery on growth and function in patients with orofacial clefts or in patients with burns

Probabilistic multi-shape segmentation of knee extensor and flexor muscles

Abstract. Patients with chronic obstructive pulmonary disease (COPD) often exhibit skeletal muscle weakness in lower limbs. Analysis of the shapes and sizes of these muscles can lead to more effective therapy. Unfortunately, segmenting these muscles from one another is a challenging task due to a lack of image information in many areas. We present a fully automatic segmentation method that overcomes the inherent difficulties of this problem to accurately segment the different muscles. Our method enforces a multi-region shape prior on the segmentation to ensure feasibility and provides an energy minimizing probabilistic segmentation that indicates areas of uncertainty. Our experiments on 3D MRI datasets yield an average Dice similarity coefficient of 0.92 ± 0.03 with the ground truth.

Tactical Industry Allocation and Model Uncertainty

We use Bayesian model averaging to analyze industry return predictability in the presence of model uncertainty. The posterior analysis shows the importance of inflation and earnings yield in predicting industry returns. The out-of-sample performance of the Bayesian approach is, in general, superior to that of other statistical model selection criteria. However, the out-of-sample forecasting power of a naive i.i.d. forecast is similar to the Bayesian forecast. A variance decomposition into model risk, estimation risk, and forecast error shows that model risk is less important than estimation risk. Copyright (c)2008, The Eastern Finance Association.