BLOC-2 subunit HPS6 deficiency affects the tubulation and secretion of von Willebrand factor from mouse endothelial cells

Hermansky-Pudlak syndrome (HPS) is a recessive disorder with bleeding diathesis, which has been linked to platelet granule defects. Both platelet granules and endothelial Weibel-Palade bodies (WPBs) are members of lysosome-related organelles (LROs) whose formation is regulated by HPS protein associated complexes such as BLOC (biogenesis of lysosome organelles complex) -1, -2, -3, AP-3 (adaptor protein complex-3) and HOPS (homotypic fusion and protein sorting complex). Von Willebrand factor (VWF) is critical to hemostasis, which is stored in a highly-multimerized form as tubules in the WPBs. In this study, we found the defective, but varying, release of VWF into plasma after desmopressin (DDAVP) stimulation in HPS1 (BLOC-3 subunit), HPS6 (BLOC-2 subunit), and HPS9 (BLOC-1 subunit) deficient mice. In particular, VWF tubulation, a critical step in VWF maturation, was impaired in HPS6 deficient WPBs. This likely reflects a defective endothelium, contributing to the bleeding tendency in HPS mice or patients. The differentially defective regulated release of VWF in these HPS mouse models suggests the need for precise HPS genotyping before DDAVP administration to HPS patients

Tunable electronic transport properties of DyScO₃/SrTiO₃ polar heterointerface

Author name used in this publication: J. Y. Dai2010-2011 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Charge 4e4e superconductivity from pair density wave order in certain high temperature superconductors

A number of spectacular experimental anomalies\cite{li-2007,fujita-2005} have recently been discovered in certain cuprates, notably {\LBCO} and {\LNSCO}, which exhibit unidirectional spin and charge order (known as ``stripe order''). We have recently proposed to interpret these observations as evidence for a novel ``striped superconducting'' state, in which the superconducting order parameter is modulated in space, such that its average is precisely zero. Here, we show that thermal melting of the striped superconducting state can lead to a number of unusual phases, of which the most novel is a charge $4e$ superconducting state, with a corresponding fractional flux quantum $hc/4e$. These are never-before observed states of matter, and ones, moreover, that cannot arise from the conventional Bardeen-Cooper-Schrieffer (BCS) mechanism. Thus, direct confirmation of their existence, even in a small subset of the cuprates, could have much broader implications for our understanding of high temperature superconductivity. We propose experiments to observe fractional flux quantization, which thereby could confirm the existence of these states.Comment: 5 pages, 2 figures; new version in Nature Physics format with a discussion of the effective Josephson coupling J2 and minor changes. Mildly edited abstract. v3: corrected versio

Neural Network-Based Retinal Nerve Fiber Layer Profile Compensation for Glaucoma Diagnosis in Myopia: Model Development and Validation

BACKGROUND: Due to the axial elongation-associated changes in the optic nerve and retina in high myopia, traditional methods like optic disc evaluation and visual field are not able to correctly differentiate glaucomatous lesions. It has been clinically challenging to detect glaucoma in highly myopic eyes. OBJECTIVE: This study aimed to develop a neural network to adjust for the dependence of the peripapillary retinal nerve fiber layer (RNFL) thickness (RNFLT) profile on age, gender, and ocular biometric parameters and to evaluate the network's performance for glaucoma diagnosis, especially in high myopia. METHODS: RNFLT with 768 points on the circumferential 3.4-mm scan was measured using spectral-domain optical coherence tomography. A fully connected network and a radial basis function network were trained for vertical (scaling) and horizontal (shift) transformation of the RNFLT profile with adjustment for age, axial length (AL), disc-fovea angle, and distance in a test group of 2223 nonglaucomatous eyes. The performance of RNFLT compensation was evaluated in an independent group of 254 glaucoma patients and 254 nonglaucomatous participants. RESULTS: By applying the RNFL compensation algorithm, the area under the receiver operating characteristic curve for detecting glaucoma increased from 0.70 to 0.84, from 0.75 to 0.89, from 0.77 to 0.89, and from 0.78 to 0.87 for eyes in the highest 10% percentile subgroup of the AL distribution (mean 26.0, SD 0.9 mm), highest 20% percentile subgroup of the AL distribution (mean 25.3, SD 1.0 mm), highest 30% percentile subgroup of the AL distribution (mean 24.9, SD 1.0 mm), and any AL (mean 23.5, SD 1.2 mm), respectively, in comparison with unadjusted RNFLT. The difference between uncompensated and compensated RNFLT values increased with longer axial length, with enlargement of 19.8%, 18.9%, 16.2%, and 11.3% in the highest 10% percentile subgroup, highest 20% percentile subgroup, highest 30% percentile subgroup, and all eyes, respectively. CONCLUSIONS: In a population-based study sample, an algorithm-based adjustment for age, gender, and ocular biometric parameters improved the diagnostic precision of the RNFLT profile for glaucoma detection particularly in myopic and highly myopic eyes

TVL₁ Planarity Regularization for 3D Shape Approximation

The modern emergence of automation in many industries has given impetus to extensive research into mobile robotics. Novel perception technologies now enable cars to drive autonomously, tractors to till a field automatically and underwater robots to construct pipelines. An essential requirement to facilitate both perception and autonomous navigation is the analysis of the 3D environment using sensors like laser scanners or stereo cameras. 3D sensors generate a very large number of 3D data points when sampling object shapes within an environment, but crucially do not provide any intrinsic information about the environment which the robots operate within. This work focuses on the fundamental task of 3D shape reconstruction and modelling from 3D point clouds. The novelty lies in the representation of surfaces by algebraic functions having limited support, which enables the extraction of smooth consistent implicit shapes from noisy samples with a heterogeneous density. The minimization of total variation of second differential degree makes it possible to enforce planar surfaces which often occur in man-made environments. Applying the new technique means that less accurate, low-cost 3D sensors can be employed without sacrificing the 3D shape reconstruction accuracy

Right atrial area and right ventricular outflow tract akinetic length predict sustained tachyarrhythmia in repaired tetralogy of Fallot

AIMS: Repaired tetralogy of Fallot (rtoF) patients are at risk of atrial or ventricular tachyarrhythmia and sudden cardiac death. Risk stratification for arrhythmia remains difficult. We investigated whether cardiac anatomy and function predict arrhythmia. METHODS: One-hundred-and-fifty-four adults with rtoF, median age 30.8 (21.9–40.2) years, were studied with a standardised protocol including cardiovascular magnetic resonance (CMR) and prospectively followed up over median 5.6 (4.6–7.0) years for the pre-specified endpoints of new-onset atrial or ventricular tachyarrhythmia (sustained ventricular tachycardia/ventricular fibrillation). RESULTS: Atrial tachyarrhythmia (n = 11) was predicted by maximal right atrial area indexed to body surface area (RAAi) on four-chamber cine-CMR (Hazard ratio 1.17, 95% Confidence Interval 1.07–1.28 per cm(2)/m(2); p = 0.0005, survival receiver operating curve; ROC analysis, area under curve; AUC 0.74 [0.66–0.81]; cut-off value 16 cm(2)/m(2)). Atrial arrhythmia-free survival was reduced in patients with RAAi ≥ 16 cm(2)/m(2) (logrank p = 0.0001). Right ventricular (RV) restrictive physiology on echocardiography (n = 38) related to higher RAAi (p = 0.02) and had similar RV dilatation compared with remaining patients. Ventricular arrhythmia (n = 9) was predicted by CMR RV outflow tract (RVOT) akinetic area length (Hazard ratio 1.05, 95% Confidence Interval 1.01–1.09 per mm; p = 0.003, survival ROC analysis, AUC 0.77 [0.83–0.61]; cut-off value 30 mm) and decreased RV ejection fraction (Hazard ratio 0.93, 95% Confidence Interval 0.87–0.99 per %; p = 0.03). Ventricular arrhythmia-free survival was reduced in patients with RVOT akinetic region length > 30 mm (logrank p = 0.02). CONCLUSION: RAAi predicts atrial arrhythmia and RVOT akinetic region length predicts ventricular arrhythmia in late follow-up of rtoF. These are simple, feasible measurements for inclusion in serial surveillance and risk stratification of rtoF patients

Moving frame aand its application in the error analysis of point contact gearing

2005-2006 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Uptake of oxLDL and IL-10 production by macrophages requires PAFR and CD36 recruitment into the same lipid rafts

Macrophage interaction with oxidized low-density lipoprotein (oxLDL) leads to its differentiation into foam cells and cytokine production, contributing to atherosclerosis development. In a previous study, we showed that CD36 and the receptor for platelet-activating factor (PAFR) are required for oxLDL to activate gene transcription for cytokines and CD36. Here, we investigated the localization and physical interaction of CD36 and PAFR in macrophages stimulated with oxLDL. We found that blocking CD36 or PAFR decreases oxLDL uptake and IL-10 production. OxLDL induces IL-10 mRNA expression only in HEK293T expressing both receptors (PAFR and CD36). OxLDL does not induce IL-12 production. The lipid rafts disruption by treatment with βCD reduces the oxLDL uptake and IL-10 production. OxLDL induces co-immunoprecipitation of PAFR and CD36 with the constitutive raft protein flotillin-1, and colocalization with the lipid raft-marker GM1-ganglioside. Finally, we found colocalization of PAFR and CD36 in macrophages from human atherosclerotic plaques. Our results show that oxLDL induces the recruitment of PAFR and CD36 into the same lipid rafts, which is important for oxLDL uptake and IL-10 production. This study provided new insights into how oxLDL interact with macrophages and contributing to atherosclerosis development

The Perceived Benefits of an Artificial Intelligence-Embedded Mobile App Implementing Evidence-Based Guidelines for the Self-Management of Chronic Neck and Back Pain: Observational Study

BACKGROUND: Chronic musculoskeletal neck and back pain are disabling conditions among adults. Use of technology has been suggested as an alternative way to increase adherence to exercise therapy, which may improve clinical outcomes. OBJECTIVE: The aim was to investigate the self-perceived benefits of an artificial intelligence (AI)-embedded mobile app to self-manage chronic neck and back pain. METHODS: A total of 161 participants responded to the invitation. The evaluation questionnaire included 14 questions that were intended to explore if using the AI rehabilitation system may (1) increase time spent on therapeutic exercise, (2) affect pain level (assessed by the 0-10 Numerical Pain Rating Scale), and (3) reduce the need for other interventions. RESULTS: An increase in time spent on therapeutic exercise per day was observed. The median Numerical Pain Rating Scale scores were 6 (interquartile range [IQR] 5-8) before and 4 (IQR 3-6) after using the AI-embedded mobile app (95% CI 1.18-1.81). A 3-point reduction was reported by the participants who used the AI-embedded mobile app for more than 6 months. Reduction in the usage of other interventions while using the AI-embedded mobile app was also reported. CONCLUSIONS: This study demonstrated the positive self-perceived beneficiary effect of using the AI-embedded mobile app to provide a personalized therapeutic exercise program. The positive results suggest that it at least warrants further study to investigate the physiological effect of the AI-embedded mobile app and how it compares with routine clinical care