ALIX binds a YPX(3)L motif of the GPCR PAR1 and mediates ubiquitin-independent ESCRT-III/MVB sorting.

The sorting of signaling receptors to lysosomes is an essential regulatory process in mammalian cells. During degradation, receptors are modified with ubiquitin and sorted by endosomal sorting complex required for transport (ESCRT)-0, -I, -II, and -III complexes into intraluminal vesicles (ILVs) of multivesicular bodies (MVBs). However, it remains unclear whether a single universal mechanism mediates MVB sorting of all receptors. We previously showed that protease-activated receptor 1 (PAR1), a G protein-coupled receptor (GPCR) for thrombin, is internalized after activation and sorted to lysosomes independent of ubiquitination and the ubiquitin-binding ESCRT components hepatocyte growth factor-regulated tyrosine kinase substrate and Tsg101. In this paper, we report that PAR1 sorted to ILVs of MVBs through an ESCRT-III-dependent pathway independent of ubiquitination. We further demonstrate that ALIX, a charged MVB protein 4-ESCRT-III interacting protein, bound to a YPX(3)L motif of PAR1 via its central V domain to mediate lysosomal degradation. This study reveals a novel MVB/lysosomal sorting pathway for signaling receptors that bypasses the requirement for ubiquitination and ubiquitin-binding ESCRTs and may be applicable to a subset of GPCRs containing YPX(n)L motifs

Optimized CRISPR-mediated gene knockin reveals FOXP3-independent maintenance of human Treg identity

Regulatory T cell (Treg) therapy is a promising curative approach for a variety of immune-mediated conditions. CRISPR-based genome editing allows precise insertion of transgenes through homology-directed repair, but its use in human Tregs has been limited. We report an optimized protocol for CRISPR-mediated gene knockin in human Tregs with high-yield expansion. To establish a benchmark of human Treg dysfunction, we target the master transcription factor FOXP3 in naive and memory Tregs. Although FOXP3-ablated Tregs upregulate cytokine expression, effects on suppressive capacity in vitro manifest slowly and primarily in memory Tregs. Moreover, FOXP3-ablated Tregs retain their characteristic protein, transcriptional, and DNA methylation profile. Instead, FOXP3 maintains DNA methylation at regions enriched for AP-1 binding sites. Thus, although FOXP3 is important for human Treg development, it has a limited role in maintaining mature Treg identity. Optimized gene knockin with human Tregs will enable mechanistic studies and the development of tailored, next-generation Treg cell therapies

Role of strain in the blistering of hydrogen-implanted silicon

The authors investigated the physical mechanisms underlying blistering in hydrogen-implanted silicon by examining the correlation between implantation induced damage, strain distribution, and vacancy diffusion. Using Rutherford backscattering, scanning electron microscopy, and atomic force microscopy, they found that the depth of blisters coincided with that of maximum implantation damage. A model based on experimental results is presented showing the effect of tensile strain on the local diffusion of vacancies toward the depth of maximum damage, which promotes the nucleation and growth of platelets and ultimately blisters. © 2006 American Institute of Physics

Simulation-based reachability analysis for nonlinear systems using componentwise contraction properties

A shortcoming of existing reachability approaches for nonlinear systems is the poor scalability with the number of continuous state variables. To mitigate this problem we present a simulation-based approach where we first sample a number of trajectories of the system and next establish bounds on the convergence or divergence between the samples and neighboring trajectories. We compute these bounds using contraction theory and reduce the conservatism by partitioning the state vector into several components and analyzing contraction properties separately in each direction. Among other benefits this allows us to analyze the effect of constant but uncertain parameters by treating them as state variables and partitioning them into a separate direction. We next present a numerical procedure to search for weighted norms that yield a prescribed contraction rate, which can be incorporated in the reachability algorithm to adjust the weights to minimize the growth of the reachable set

Study on electrochemical properties of FeS2 in room temperature molten salt

In this paper, FeS2 electrodes have been prepared by using reactive codeposition methods. The electrochemical performances of FeS2 were studied in LiCl buffer Lewis neutral 1-methyl-3-ethylimidazolium chloride (MeEtImCl)/AlCl3 (room temperature molten salt) melts. The results show that FeS2 electrodes possess reversible Li ion intercalation and deintercalation behavior in the first step two electron processes.published_or_final_versio

Vertically aligned smooth ZnO nanorod films for planar device applications

The growth of smooth and continuous zinc oxide (ZnO) films, consisting of densely packed vertical ZnO nanorods with (002) crystal orientation on silicon substrates has been achieved in this work by a chemical solution method. These ZnO thin films have much stronger photoluminescence emission than those from discrete ZnO nanorods under identical conditions. Large area surface acoustic wave devices were fabricated on these films using conventional photolithography, and exhibited two well-defined resonant modes of the Sezawa wave and its harmonic mode

Postdialysis blood pressure rise predicts long-term outcomes in chronic hemodialysis patients: a four-year prospective observational cohort study

<p>Abstract</p> <p>Background</p> <p>The blood pressure (BP) of a proportion of chronic hemodialysis (HD) patients rises after HD. We investigated the influence of postdialysis BP rise on long-term outcomes.</p> <p>Methods</p> <p>A total of 115 prevalent HD patients were enrolled. Because of the fluctuating nature of predialysis and postdialysis BP, systolic BP (SBP) and diastolic BP before and after HD were recorded from 25 consecutive HD sessions during a 2-month period. Patients were followed for 4 years or until death or withdrawal.</p> <p>Results</p> <p>Kaplan-Meier estimates revealed that patients with average postdialysis SBP rise of more than 5 mmHg were at the highest risk of both cardiovascular and all-cause mortality as compared to those with an average postdialysis SBP change between -5 to 5 mmHg and those with an average postdialysis SBP drop of more than 5 mmHg. Furthermore, multivariate Cox regression analysis indicated that both postdialysis SBP rise of more than 5 mmHg (HR, 3.925 [95% CI, 1.410-10.846], <it>p </it>= 0.008) and high cardiothoracic (CT) ratio of more than 50% (HR, 7.560 [95% CI, 2.048-27.912], <it>p </it>= 0.002) independently predicted all-cause mortality. We also found that patients with an average postdialysis SBP rise were associated with subclinical volume overload, as evidenced by the significantly higher CT ratio (<it>p </it>= 0.008).</p> <p>Conclusions</p> <p>A postdialysis SBP rise in HD patients independently predicted 4-year cardiovascular and all-cause mortality. Considering postdialysis SBP rise was associated with higher CT ratio, intensive evaluation of cardiac and volume status should be performed in patients with postdialysis SBP rise.</p

Plasma hydrogenation of strained Si/SiGe/Si heterostructure for layer transfer without ion implantation

We have developed an innovative approach without the use of ion implantation to transfer a high-quality thin Si layer for the fabrication of silicon-on-insulator wafers. The technique uses a buried strained SiGe layer, a few nanometers in thickness, to provide H trapping centers. In conjunction with H plasma hydrogenation, lift-off of the top Si layer can be realized with cleavage occurring at the depth of the strained SiGe layer. This technique avoids irradiation damage within the top Si layer that typically results from ion implantation used to create H trapping regions in the conventional ion-cut method. We explain the strain-facilitated layer transfer as being due to preferential vacancy aggregation within the strained layer and subsequent trapping of hydrogen, which lead to cracking in a well controlled manner. © 2005 American Institute of Physics

H-induced platelet and crack formation in hydrogenated epitaxial Si/Si <inf>0.98</inf>B <inf>0.02</inf>/Si structures

An approach to transfer a high-quality Si layer for the fabrication of silicon-on-insulator wafers has been proposed based on the investigation of platelet and crack formation in hydrogenated epitaxial Si Si0.98 B0.02 Si structures grown by molecular-beam epitaxy. H-related defect formation during hydrogenation was found to be very sensitive to the thickness of the buried Si0.98 B0.02 layer. For hydrogenated Si containing a 130 nm thick Si0.98 B0.02 layer, no platelets or cracking were observed in the B-doped region. Upon reducing the thickness of the buried Si0.98 B0.02 layer to 3 nm, localized continuous cracking was observed along the interface between the Si and the B-doped layers. In the latter case, the strains at the interface are believed to facilitate the (100)-oriented platelet formation and (100)-oriented crack propagation. © 2006 American Institute of Physics

Mini-open anterior spine surgery for anterior lumbar diseases

Minimally invasive surgeries including endoscopic surgery and mini-open surgery are current trend of spine surgery, and its main advantages are shorter recovery time and cosmetic benefits, etc. However, mini-open surgery is easier and less technique demanding than endoscopic surgery. Besides, anterior spinal fusion is better than posterior spinal fusion while considering the physiological loading, back muscle function, etc. Therefore, we aimed to introduce the modified “mini-open anterior spine surgery” (MOASS) and to evaluate the feasibility, effectiveness and safety in the treatment of various anterior lumbar diseases with this technique. A total of 61 consecutive patients (46 female, 15 male; mean age 58.2 years) from 1997 to 2004 were included in this study, with an average follow-up of 24–52 (mean 43) months. The disease entities included vertebral fracture (20), failed back surgery (13), segmental instability or spondylolisthesis (10), infection (8), herniated disc (5), undetermined lesion for biopsy (4), and hemivertebra (1). Lesions involved 13 cases at T12–L1, 18 at L1–L2, 18 at L2–L3, 22 at L3–L4 and 11 at L4–L5 levels. All patients received a single stage anterior-only procedure for their anterior lumbar disease. We used the subjective clinical results, Oswestry disability index, fusion rate, and complications to evaluate our clinical outcome. Most patients (91.8%) were subjectively satisfied with the surgery and had good-to-excellent outcomes. Mean operation time was 85 (62–124) minutes, and mean blood loss was 136 (minimal-250) ml in the past 6 years. Hospital stay ranged from 4–26 (mean 10.6) days. Nearly all cases had improved back pain (87%), physical function (90%) and life quality (85%). Most cases (95%) achieved solid or probable solid bony fusion. There were no major complications. Therefore, MOASS is feasible, effective and safe for patients with various anterior lumbar diseases