Design of a Programmable and Modular Neuromuscular Electrical Stimulator Integrated into a Wireless Body Sensor Network

Neuromuscular electrical stimulation finds application in several fields, from basic neurophysiology, to motor rehabilitation and cardiovascular conditioning. Despite the progressively increasing interest in this technique, its State-of-the-Art technology is mainly based on monolithic, mostly wired devices, leading to two main issues. First, these devices are often bulky, limiting their usability in applied contexts. Second, the possibility of interfacing these stimulation devices with external systems for the acquisition of electrophysiological and biomechanical variables to control the stimulation output is often limited. The aim of this work is to describe the design and development of an innovative electrical stimulator, specifically developed to contend with these issues. The developed device is composed of wireless modules that can be programmed and easily interfaced with third-party instrumentation. Moreover, benefiting from the system modular architecture, stimulation may be delivered concurrently to different sites while greatly reducing cable encumbrance. The main design choices and experimental tests are documented, evidencing the practical potential of the device in use-case scenarios

Turbulent jet through porous obstructions under Coriolis effect: an experimental investigation

The present study has the main purpose to experimentally investigate a turbulent momentum jet issued in a basin affected by rotation and in presence of porous obstructions. The experiments were carried out at the Coriolis Platform at LEGI Grenoble (FR). A large and unique set of velocity data was obtained by means of a Particle Image Velocimetry measurement technique while varying the rotation rate of the tank and the density of the canopy. The main differences in jet behavior in various flow configurations were assessed in terms of mean flow, turbulent kinetic energy and jet spreading. The jet trajectory was also detected. The results prove that obstructions with increasing density and increased rotation rates induce a more rapid abatement of both jet velocity and turbulent kinetic energy. The jet trajectories can be scaled by a characteristic length, which is found to be a function of the jet initial momentum, the rotation rate, and the drag exerted by the obstacles. An empirical expression for the latter is also proposed and validated

Tribodynamics of hydraulic actuated clutch system for engine-downsizing in heavy duty off-highway vehicles

Engine downsizing is desired for modern heavy-duty vehicles to enhance fuel economy and reduce emissions. However, the smaller engines usually cannot overcome the parasitic loads during engine start-up. A new clutch system is designed to disconnect the downsized engine from the parasitic losses prior to the idling speed. A multi-scale, multi-physics model is developed to study the clutch system. Multi-body dynamics is used to study the combined translational–rotational motions of the clutch components. A micro-scale contact model is incorporated to represent the frictional characteristics of the sliding surfaces. Although the clutch is designed for dry contact operation, leakage of actuating hydraulic fluid can affect the interfacial frictional characteristics. These are integrated into the multi-body dynamic analysis through tribometric studies of partially wetted surfaces using fresh and shear-degraded lubricants. Multi-scale simulations include sensitivity analysis of key operating parameters, such as contact pressure. This multi-physics approach is not hitherto reported in the literature. The study shows the importance of adhesion in dry clutch engagement, enabling full torque capacity. The same is also noted for any leakage of significantly shear-degraded lubricant into the clutch interfaces. However, the ingression of fresh lubricant into the contact is found to reduce the clutch torque capacity

Expression of vascular endothelial growth factor mRNA in non-small-cell lung carcinomas

The vascular endothelial growth factor (VEGF) has been shown to be strictly related to vascular permeability and endothelial cell growth under physiological and pathological conditions. In tumour development and progression, VEGF plays a pivotal role in the development of the tumoral vascular network, and useful information in the progression of human cancer can be obtained by analysing the vascular endothelial growth factor expression of the tumours. In this study, we investigated the vascular endothelial growth factor transcript expression in non-small-cell lung carcinomas to evaluate the significance of this factor in a group of cancers in which the vascular pattern has been shown to significantly affect progression. Surgical samples of 42 patients with NSCLC were studied using reverse transcription polymerase chain reaction (PCR) analysis and in situ hybridization. Thirty-three out of 42 cases (78.6%) showed VEGF transcript expression predominantly as transcripts for the secretory forms of VEGF (isoforms 121 and 165). In situ hybridization, performed on 24 out of 42 samples, showed that the VEGF transcript expression was in several cases present in the cytoplasm both of neoplastic and normal cells, even if the VEGF mRNA was less expressed in the corresponding non-tumoral part. The VEGF 121 expression was associated with hilar and/or mediastinal nodal involvement (P = 0.02), and, taken together, the VEGF isoforms were shown to significantly influence overall (P = 0.02) and disease-free survival (P = 0.03). As a regulator of tumour angiogenesis, VEGF may represent a useful indicator of progression and poor prognosis in non-small-cell lung carcinomas. © 1999 Cancer Research Campaig

HBeAg Levels Vary across the Different Stages of HBV Infection According to the Extent of Immunological Pressure and Are Associated with Therapeutic Outcome in the Setting of Immunosuppression-Driven HBV Reactivation

HBeAg is a marker of HBV-activity, and HBeAg-loss predicts a favorable clinical outcome. Here, we characterize HBeAg-levels across different phases of HBV infection, their correlation with virological/biochemical markers and the virological response to anti-HBV therapy. Quantitative HBeAg (qHBeAg, DiaSorin) is assessed in 101 HBeAg+ patients: 20 with acute-infection, 20 with chronic infection, 32 with chronic hepatitis and 29 with immunosuppression-driven HBV-reactivation (HBV-R). A total of 15/29 patients with HBV-R are monitored for > 12 months after starting TDF/ETV. qHBeAg is higher in immunosuppression-driven HBV-R (median[IQR]:930[206-1945]PEIU/mL) and declines in chronic hepatitis (481[28-1393]PEIU/mL, p = 0.03), suggesting HBeAg production, modulated by the extent of immunological pressure. This is reinforced by the negative correlation between qHBeAg and ALT in acute infection (Rho = -0.66, p = 0.006) and chronic hepatitis (Rho = -0.35; p = 0.05). Interestingly, qHBeAg strongly and positively correlates with qHBsAg across the study groups, suggesting cccDNA as a major source of both proteins in the setting of HBeAg positivity (with limited contribution of integrated HBV-DNA to HBsAg production). Focusing on 15 patients with HBV-R starting TDF/ETV, virological suppression and HBeAg-loss are achieved in 60% and 53.3%. Notably, the combination of qHBeAg > 2000 PEIU/mL + qHBsAg > 52,000 IU/mL at HBV-R is the only factor predicting no HBeAg loss (HBeAg loss: 0% with vs. 72.7% without qHBeAg > 2000 PEIU/mL + qHBsAg > 52,000 IU/mL, p = 0.03). In conclusion, qHBeAg varies over the natural course of HBV infection, according to the extent of immunological pressure. In the setting of HBV-R, qHBeAg could be useful in predicting the treatment response under immunosuppression

Comparative proximity biotinylation implicates the small GTPase RAB18 in sterol mobilization and biosynthesis

Loss of functional RAB18 causes the autosomal recessive condition Warburg Micro syndrome. To better understand this disease, we used proximity biotinylation to generate an inventory of potential RAB18 effectors. A restricted set of 28 RAB18 interactions were dependent on the binary RAB3GAP1–RAB3GAP2 RAB18–guanine nucleotide exchange factor complex. Twelve of these 28 interactions are supported by prior reports, and we have directly validated novel interactions with SEC22A, TMCO4, and INPP5B. Consistent with a role for RAB18 in regulating membrane contact sites, interactors included groups of microtubule/membrane-remodeling proteins, membrane-tethering and docking proteins, and lipid-modifying/transporting proteins. Two of the putative interactors, EBP and OSBPL2/ORP2, have sterol substrates. EBP is a Δ8-Δ7 sterol isomerase, and ORP2 is a lipid transport protein. This prompted us to investigate a role for RAB18 in cholesterol biosynthesis. We found that the cholesterol precursor and EBP-product lathosterol accumulates in both RAB18-null HeLa cells and RAB3GAP1-null fibroblasts derived from an affected individual. Furthermore, de novo cholesterol biosynthesis is impaired in cells in which RAB18 is absent or dysregulated or in which ORP2 expression is disrupted. Our data demonstrate that guanine nucleotide exchange factor–dependent Rab interactions are highly amenable to interrogation by proximity biotinylation and may suggest that Micro syndrome is a cholesterol biosynthesis disorder

A mass-conservative semi-implicit volume of fluid method for the Navier–Stokes equations with high order semi-Lagrangian advection scheme

This paper deals with the development of a semi-implicit numerical method for the Navier–Stokes equations using the non-linear volumes of fluid (VOF) approach and a semi-Lagrangian scheme for the discretization of the advection contribution based on a high order reconstruction of the velocity field. The VOF approach guarantees high flexibility and is able to reproduce several phenomena that appear in real scenarios such as free surface flows, pressurized channels and jets. The discrete velocity field from the momentum conservation law is formally inserted into the discrete continuity equation, hence yielding a mildly non-linear system for the unknown hydraulic head which can be solved through a nested Newton-type algorithm. The computation of the non-linear convective diffusion contribution is then based on a high order reconstruction of the velocity field, which is furthermore constrained to exactly recover the original pointwise values of the numerical solution. As a consequence, the mass conservation is fully preserved while providing information about the main velocity field and its high order moments, later employed in the computation of the Lagrangian trajectories needed for the discretization of the convective and diffusive terms. Furthermore, the bottom friction and the tangential stresses can be directly computed from the high order velocity reconstruction. The method is derived in a general form with the only requirement to be structured in the z− direction, so that it applies to the three- and the two-dimensional cases with unstructured grids in the horizontal space. Convergence studies are carried out to demonstrate the accuracy of the reconstruction operator. Finally, the numerical scheme is validated against several benchmarks that include 2Dxz, 2Dxy and 3D non-hydrostatic flows with complex geometry in order to show the flexibility of the proposed algorithm, including a real-world application

Clinical applications of antibody avidity and immunoglobulin M testing in acute HCV infection

Acute hepatitis C is often asymptomatic, frequently remains undiagnosed and frequently evolves to chronic hepatitis. Early, short-term interferon treatment is efficacious in acute hepatitis C, and so underscores the importance of an early diagnosis and the need to distinguish acute infection from acute exacerbation of chronic HCV infection. The gold standard for the diagnosis of acute hepatitis C is demonstration of conversion to anti-HCV positivity, HCV RNA positivity or both, events that frequently occur before the patient comes to medical attention. Several laboratory approaches to assist with early diagnosis of acute hepatitis C have been developed. Our studies, reviewed here, show that testing for antibody avidity and anti-HCV immunoglobulin M allow diagnosis in up to 90% of cases of acute hepatitis C. ©2012 International Medical Press