Search

Soft actuators (SAs) have been used in many compliant robotic structure and wearable devices, due to their safe interaction with the wearers. Despite advances, the capability of current SAs is limited by scalability, high hysteresis, and slow responses. In this paper, a new class of soft, scalable, and high-aspect ratio fiber-reinforced hydraulic SAs is introduced. The new SA uses a simple fabrication process of insertion where a hollow elastic rubber tube is directly inserted into a constrained hollow coil, eliminating the need for the manual wrapping of an inextensible fiber around a long elastic structure. To provide high adaptation to the user skin for wearable applications, the new SAs are integrated into flexible fabrics to form a wearable fabric sleeve. To monitor the SA elongation, a soft liquid metal-based fabric piezoresistive sensor is also developed. To capture the nonlinear hysteresis of the SA, a novel asymmetric hysteresis model which only requires five model parameters in its structure is developed and experimentally validated. The new SAs-driven wearable robotic sleeve is scalable, highly flexible, and lightweight. It can also produce a large amount of force of around 23 N per muscle at around 30% elongation, to provide useful assistance to the human upper limbs. Experimental results show that the soft fabric sleeve can augment a user’s performance when working against a load, evidenced by a significant reduction on the muscular effort, as monitored by electromyogram (EMG) signals. The performance of the developed SAs, soft fabric sleeve, soft liquid metal fabric sensor, and nonlinear hysteresis model reveal that they can effectively modulate the level of assistance for the wearer. The new technologies obtained from this work can be potentially implemented in emerging assistive applications, such as rehabilitation, defense, and industry.

Wound closure with surgical sutures is a critical challenge for flexible endoscopic surgeries. Substantial efforts have been introduced to develop functional and smart surgical sutures to either monitor wound conditions or ease the complexity of knot tying. Although research interests in smart sutures by soft robotic technologies have emerged for years, it is challenging to develop a soft robotic structure that possesses a similar physical structure as conventional sutures while offering a self-tightening knot or anchor to close the wound. This paper introduces a new concept of smart sutures that can be programmed to achieve desired and uniform tension distribution while offering self-tightening knots or automatically deploying secured anchors. The core technology is a soft hydraulic artificial muscle that can be elongated and contracted under applied fluid pressure. Each suture is equipped with a pressure locking mechanism to hold its temporary elongated state and to induce self-shrinking ability. The puncturing and holding force for the smart sutures with anchors are examined. Ex-vivo experiments on fresh porcine stomach and colon demonstrate the usefulness of the new smart sutures. The new approaches are expected to pave the way for the further development of smart sutures that will benefit research, training, and commercialization in the surgical field.

Lipoproteins play a key role in transport of cholesterol to and from tissues. Recent studies have also demonstrated that red blood cells (RBCs), which carry large quantities of free cholesterol in their membrane, play an important role in reverse cholesterol transport. However, the exact role of RBCs in systemic cholesterol metabolism is poorly understood. RBCs were incubated with autologous plasma or isolated lipoproteins resulting in a significant net amount of cholesterol moved from RBCs to HDL, while cholesterol from LDL moved in the opposite direction. Furthermore, the bi-directional cholesterol transport between RBCs and plasma lipoproteins was saturable and temperature-, energy-, and time-dependent, consistent with an active process. We did not find LDLR, ABCG1, or scavenger receptor class B type 1 in RBCs but found a substantial amount of ABCA1 mRNA and protein. However, specific cholesterol efflux from RBCs to isolated apoA-I was negligible, and ABCA1 silencing with siRNA or inhibition with vanadate and Probucol did not inhibit the efflux to apoA-I, HDL, or plasma. Cholesterol efflux from and cholesterol uptake by RBCs from Abca1+/+ and Abca1-/- mice were similar, arguing against the role of ABCA1 in cholesterol flux between RBCs and lipoproteins. Bioinformatics analysis identified ABCA7, ABCG5, lipoprotein lipase, and mitochondrial translocator protein as possible candidates that may mediate the cholesterol flux. Together, these results suggest that RBCs actively participate in cholesterol transport in the blood, but the role of cholesterol transporters in RBCs remains uncertain.

BACKGROUND: The American Joint Committee on Cancer (AJCC) staging for head and neck cutaneous squamous cell carcinoma (HNcSCC) stratifies risk poorly. We hypothesized that this results from prognostic heterogeneity within N and TNM groups. METHODS: Retrospective analysis of disease-specific survival (DSS) in a multicenter study of 1146 patients with nodal metastases from HNcSCC. RESULTS: The majority of patients were classified as pN2a or pN3b (83.1%) and TNM stage IV (90.6%). On multivariate analysis, there was statistically significant prognostic heterogeneity within these groups based on the number and size of nodal metastases, immunosuppression, and perineural invasion. When stage IV patients were categorized into low, moderate, and high-risk groups based on adverse features, there was wide variation in prognosis with 5-year DSS ranging from 90% to 60% (P < .001). CONCLUSIONS: The AJCC staging system stratifies risk poorly in HNcSCC due to significant prognostic heterogeneity within pN2a, pN3b, and stage IV groups.

HIV infection is known to be associated with cardiometabolic abnormalities; here we investigated the progression and causes of these abnormalities. Three groups of participants were recruited: HIV-negative subjects and two groups of treatment-naïve HIV-positive subjects, one group initiating antiretroviral treatment, the other remaining untreated. Intima-media thickness (cIMT) increased in HIV-positive untreated group compared to HIV-negative group, but treatment mitigated the difference. We found no increase in diabetes-related metabolic markers or in the level of inflammation in any of the groups. Total cholesterol, low density lipoprotein cholesterol and apoB levels were lower in HIV-positive groups, while triglyceride and Lp(a) levels did not differ between the groups. We found a statistically significant negative association between viral load and plasma levels of total cholesterol, LDL cholesterol, HDL cholesterol, apoA-I and apoB. HIV-positive patients had hypoalphalipoproteinemia at baseline, and we found a redistribution of sub-populations of high density lipoprotein (HDL) particles with increased proportion of smaller HDL in HIV-positive untreated patients, which may result from increased levels of plasma cholesteryl ester transfer protein in this group. HDL functionality declined in the HIV-negative and HIV-positive untreated groups, but not in HIV-positive treated group. We also found differences between HIV-positive and negative groups in plasma abundance of several microRNAs involved in lipid metabolism. Our data support a hypothesis that cardiometabolic abnormalities in HIV infection are caused by HIV and that antiretroviral treatment itself does not influence key cardiometabolic parameters, but mitigates those affected by HIV.

© The Author 2017. Aims The recent failures of HDL-raising therapies have underscored our incomplete understanding of HDL biology. Therefore there is an urgent need to comprehensively investigate HDL metabolism to enable the development of effective HDL-centric therapies. To identify novel regulators of HDL metabolism, we performed a joint analysis of human genetic, transcriptomic, and plasma HDL-cholesterol (HDL-C) concentration data and identified a novel association between trafficking protein, kinesin binding 2 (TRAK2) and HDL-C concentration. Here we characterize the molecular basis of the novel association between TRAK2 and HDL-cholesterol concentration. Methods and results Analysis of lymphocyte transcriptomic data together with plasma HDL from the San Antonio Family Heart Study (n = 1240) revealed a significant negative correlation between TRAK2 mRNA levels and HDL-C concentration, HDL particle diameter and HDL subspecies heterogeneity. TRAK2 siRNA-mediated knockdown significantly increased cholesterol efflux to apolipoprotein A-I and isolated HDL from human macrophage (THP-1) and liver (HepG2) cells by increasing the mRNA and protein expression of the cholesterol transporter ATP-binding cassette, sub-family A member 1 (ABCA1). The effect of TRAK2 knockdown on cholesterol efflux was abolished in the absence of ABCA1, indicating that TRAK2 functions in an ABCA1-dependent efflux pathway. TRAK2 knockdown significantly increased liver X receptor (LXR) binding at the ABCA1 promoter, establishing TRAK2 as a regulator of LXR-mediated transcription of ABCA1. Conclusion We show, for the first time, that TRAK2 is a novel regulator of LXR-mediated ABCA1 expression, cholesterol efflux, and HDL biogenesis. TRAK2 may therefore be an important target in the development of antiatherosclerotic therapies.

Previous in vitro and in vivo studies demonstrated that HIV protein nef plays a key role in impairing cellular and systemic cholesterol metabolism in HIV disease, but clinical support for these findings is lacking. Here we present the data of comparative lipidomic analysis (330 lipid species) of plasma samples from HIV-negative subjects, patients infected with WT HIV-1 strain and patients infected with nef-deficient strain of HIV-1. We determine which effects of HIV on plasma lipidome are explained by the presence of nef. The data can be used to evaluate cardiovascular risk in HIV disease and to assess the role of nef in HIV-induced disturbances in systemic lipid metabolism. The full impact of nef deficiency on lipid and lipoprotein metabolism in HIV-infected patients is presented in the accompanying study "Lipid Metabolism in Patients Infected with Nef-deficient HIV-1 Strain" [1].

IgA nephropathy (IgAN) is one of the most common primary glomerulonephritis. Previously identified genome-wide association study (GWAS) loci explain only a fraction of disease risk. To identify novel susceptibility loci in Han Chinese, we conduct a four-stage GWAS comprising 8,313 cases and 19,680 controls. Here, we show novel associations at ST6GAL1 on 3q27.3 (rs7634389, odds ratio (OR)=1.13, P=7.27 × 10(-10)), ACCS on 11p11.2 (rs2074038, OR=1.14, P=3.93 × 10(-9)) and ODF1-KLF10 on 8q22.3 (rs2033562, OR=1.13, P=1.41 × 10(-9)), validate a recently reported association at ITGAX-ITGAM on 16p11.2 (rs7190997, OR=1.22, P=2.26 × 10(-19)), and identify three independent signals within the DEFA locus (rs2738058, P=1.15 × 10(-19); rs12716641, P=9.53 × 10(-9); rs9314614, P=4.25 × 10(-9), multivariate association). The risk variants on 3q27.3 and 11p11.2 show strong association with mRNA expression levels in blood cells while allele frequencies of the risk variants within ST6GAL1, ACCS and DEFA correlate with geographical variation in IgAN prevalence. Our findings expand our understanding on IgAN genetic susceptibility and provide novel biological insights into molecular mechanisms underlying IgAN.

Deepwater offshore oil and gas developments require an assessment to be made of the risk of infrastructure damage from submarine slides. The likelihood and magnitude of submarine slides, and the consequent impact loading on seabed infrastructure in the path of the debris from the slide, must be estimated. Export pipelines are especially vulnerable to impact from submarine slides, because of their length and the need to cross canyons and other seabed features that are potential paths for the flowing debris. Characterising the debris material represents a particular challenge, as the original soil, which is typically characterised using conventional geotechnical methods, evolves through remoulding and water entrainment into a viscous fluid. Because of this transition from soil to fluid, characterisation of the strength of flowing fine-grained sediment has been addressed separately within a soil mechanics framework and a fluid mechanics framework, resulting in two different approaches for expressing the strain-rate-dependent strength of debris flows, and the consequential impact loads on pipelines. In this paper we compare the two approaches, and show that the geotechnical characterisation of fine-grained sediments can be extended into the liquid range in a continuous fashion. This is supported by a series of undrained shear strength measurements on two different remoulded soils, from fall cone tests, vane shear (including viscometer) tests, T-bar and ball penetrometer tests. Analysis of the results shows that the variation in shear strength over the solid and liquid ranges can be described by a unique function of water content, for a given soil. Furthermore, the effects of rate of shearing are well captured by a dimensionless function of the normalised strain rate. The geotechnical approach also accounts for the observed strength reduction due to intense shearing.

Public-Private Partnerships (PPPs) in defense have gained momentum in various countries around the world over the past decade. This research project explores the experiences and evolutions of PPPs in the United Kingdom (UK), the United States (U.S.), Australia, and Singapore. Each of these countries has its own unique fiscal system, operating environment, and defense focus. It is timely to study how defense PPPs has evolved around the world since their inception in the UK in the 1990s. Through the study of these four countries' journeys into defense PPPs, the objective of this project is to first determine whether there are any key common denominators that steer the countries toward the adoption of PPPs to meet their defense needs. The next objective is to determine whether PPPs are suitable for defense acquisitions. The final objective is to determine whether there are specific areas in defense that are more suitable than others for PPPs., The original document contains color images.