Manipulation of lipid rafts in neuronal cells

Lipid rafts are specialized plasma membrane micro-domains highly enriched in cholesterol, sphingolipids and glycosylphosphatidylinositol (GPI) anchored proteins. Lipid rafts are thought to be located in the exofacial leaflet of plasma membranes. Functionally, lipid rafts are involved in intracellular trafficking of proteins and lipids, secretory and endocytotic pathways, signal transduction, inflammation and in cell-surface proteolysis. There has been substantial interest in lipid rafts in brain, both with respect to normal functioning and with certain neurodegenerative diseases. Based on the impact of lipid rafts on multitude biochemical pathways, modulation of lipid rafts is used to study related disease pathways and probably offers a target for pharmacological intervention. Lipid rafts can be targeted by modulation of its main components, namely cholesterol and sphingolipids. Other approaches include the modulation of membrane dynamics and it has been reported that protein-lipid interactions can vary the occurrence and composition of these membrane micro-domains. The present review summarizes the possibilities to modulate lipid rafts with focus on neuronal cells. Keywords: Lipid raft, cholesterol, membrane fluidity, statin, cyclodextrine, docosahexaenoic acid

Regulating Mobile Mental Health Apps

Mobile medical apps (MMAs) are a fast‐growing category of software typically installed on personal smartphones and wearable devices. A subset of MMAs are aimed at helping consumers identify mental states and/or mental illnesses. Although this is a fledgling domain, there are already enough extant mental health MMAs both to suggest a typology and to detail some of the regulatory issues they pose. As to the former, the current generation of apps includes those that facilitate self‐assessment or self‐help, connect patients with online support groups, connect patients with therapists, or predict mental health issues. Regulatory concerns with these apps include their quality, safety, and data protection. Unfortunately, the regulatory frameworks that apply have failed to provide coherent risk‐assessment models. As a result, prudent providers will need to progress with caution when it comes to recommending apps to patients or relying on app‐generated data to guide treatment

Duplication of modules facilitates the evolution of functional specialization

The evolution of simulated robots with three different architectures is studied. We compared a non-modular feed forward network, a hardwired modular and a duplication-based modular motor control network. We conclude that both modular architectures outperform the non-modular architecture, both in terms of rate of adaptation as well as the level of adaptation achieved. The main difference between the hardwired and duplication-based modular architectures is that in the latter the modules reached a much higher degree of functional specialization of their motor control units with regard to high level behavioral functions. The hardwired architectures reach the same level of performance, but have a more distributed assignment of functional tasks to the motor control units. We conclude that the mechanism through which functional specialization is achieved is similar to the mechanism proposed for the evolution of duplicated genes. It is found that the duplication of multifunctional modules first leads to a change in the regulation of the module, leading to a differentiation of the functional context in which the module is used. Then the module adapts to the new functional context. After this second step the system is locked into a functionally specialized state. We suggest that functional specialization may be an evolutionary absorption state

Design and application of squeeze film dampers for turbomachinery stabilization

The steady-state transient response of the squeeze film damper bearing was investigated. Both the steady-state and transient equations for the hydrodynamic bearing forces are derived; the steady-state equations were used to determine the damper equivalent stiffness and damping coefficients. These coefficients are used to find the damper configuration which will provide the optimum support characteristics based on a stability analysis of the rotor-bearing system. The effects of end seals and cavitated fluid film are included. The transient analysis of rotor-bearing systems was conducted by coupling the damping and rotor equations and integrating forward in time. The effects of unbalance, cavitation, and retainer springs are included. Methods of determining the stability of a rotor-bearing system under the influence of aerodynamic forces and internal shaft friction are discussed

Quasi-Normal Modes of Brane-Localised Standard Model Fields

We present here a detailed study of the quasi-normal spectrum of brane-localised Standard Model fields in the vicinity of D-dimensional black-holes. A variety of such backgrounds (Schwarzschild, Reissner-Nordstrom and Schwarzszchild-(Anti) de Sitter) are investigated. The dependence of the quasi-normal spectra on the dimensionality D, spin of the field s, and multipole number l is analyzed. Analytical formulae are obtained for a number of limiting cases: in the limit of large multipole number for Schwarzschild, Schwarzschild-de Sitter and Reissner-Nordstrom black holes, in the extremal limit of the Schwarzschild-de Sitter black hole, and in the limit of small horizon radius in the case of Schwarzschild-Anti de Sitter black holes. We show that an increase in the number of hidden, extra dimensions results in the faster damping of all fields living on the brane, and that the localization of fields on a brane affects the QN spectrum in a number of additional ways, both direct and indirect.Comment: 13 pages, 4 figures, to be published in Phys. Rev.

Whirl Motion of a Seal Test Rig with Squeeze-Film Dampers

This paper presents the experimental behavior and dynamic analysis of a high speed test rig with rolling element bearings mounted in squeeze film oil damper bearings. The test rotor is a double overhung configuration with rolling element ball bearings mounted in uncentered squeeze-film oil dampers. The damper design is similar to that employed with various high-speed aircraft HP gas turbines. The dynamic performance of the test rig with the originally installed dampers with an effective damper length of length 0.23-inch was unacceptable. The design speed of 40,000 RPM could not be safely achieved as nonsynchronous whirling at the overhung seal test disk and high amplitude critical speed response at the drive spline section occurred at 32,000 RPM. In addition to the self excited stability and critical speed problems, it was later seen from FFT data analysis, that a region of supersynchronous dead band whirling occurs between 10,000 to 15,000 RPM which can lead to bearing distress and wear. The system was analyzed using both linear and nonlinear techniques. The extended length damper design resulting from the analysis eliminated the rotor subsynchronous whirling, high amplitude critical speed, and the dead band whirling region allowing the system to achieve a speed of 45,000 RPM. However, nonlinear analysis shows that damper lockup could occur with high rotor unbalance at 33,000 RPM, even with the extended squeeze-film dampers. The control of damper lockup will be addressed in a future paper

Stability Analysis of a High-Speed Seal Test Rotor With Marginal and Extended Squeeze-Film Dampers: Theoretical and Experimental Results

A case study of a high-speed seal test rotor shows how rotor dynamic analysis can be used to diagnose the source of high vibrations and evaluate a proposed remedy. Experimental results are compared with the synchronous and non-synchronous whirl response analysis of a double overhung, high-speed seal test rotor with ball bearings supported in 5.84- and 12.7-mm-long, un-centered squeeze-film oil dampers. Test performance with the original damper of length 5.84 mm was marginal. Non-synchronous whirling occurred at the overhung seal test disk and there was a high amplitude synchronous response near the drive spline above 32,000 rpm. Nonlinear synchronous unbalance and time transient whirl studies were conducted on the seal test rotor with the original and extended damper lengths. With the original damper design, the nonlinear synchronous response showed that unbalance could cause damper lockup at 33,000 rpm. Alford cross-coupling forces were also included at the overhung seal test disk for the whirl analysis. Sub-synchronous whirling at the seal test disk was observed in the nonlinear time transient analysis. With the extended damper length of 12.7 mm, the sub-synchronous motion was eliminated and the rotor unbalance response was acceptable to 45,000 rpm with moderate rotor unbalance. Seal test rotor orbits and vibration levels with the extended squeeze film dampers showed smooth operation to 40,444 rpm

The mathematical description of the electrosynthesis of composites of oxy-hydroxycompounds cobalt with polypyrrole overooxidazed

The electrosynthesis of the composite with of the overoxidized polypyrrole with cobalt oxy-hydroxide in strongly acidic media has been described mathematically, using linear stability theory and bifurcation analysis. The steadystates stability conditions and oscillatory and monotonic instability requirements have been described too. The system´s behavior was compared with behavior of other systems with overoxidation, electropolymerization of heterocyclic compounds and electrosynthesis of the cobalt oxy-hydroxides

Risk of respiratory depression with opioids and concomitant gabapentinoids.

Introduction:The combination of opioids and central nervous system depressants such as benzodiazepines and barbiturates has an additive effect on the frequency of oversedation and respiratory depression requiring naloxone use in hospitalized patients. Gabapentinoids (gabapentin and pregabalin) are frequently prescribed with opioids for their opioid-sparing and adjuvant analgesic effects. There is limited literature on the risk of respiratory depression due to the combination of opioids and gabapentinoids requiring naloxone administration. Methods:This retrospective study evaluated patients who were prescribed opioids and at least one dose of naloxone between March 1, 2014 and September 30, 2016. The primary objective of this study was to compare the frequency of respiratory depression among patients who received naloxone and opioids (non-gabapentinoid group) with those who received naloxone, opioids, and gabapentinoids (gabapentinoid group). Secondary objectives included comparing the association of oversedation, using the Pasero Opioid-induced Sedation Scale, and various risk factors with those in the gabapentinoid group. Results:A total of 153 patient episodes of naloxone administration (102 in the non-gabapentinoid and 51 in the gabapentinoid groups) in 125 unique patients were included in the study. For the primary objective, there were 33 episodes of respiratory depression associated with the non-gabapentinoid group (33/102=32.4%) versus 17 episodes of respiratory depression with the gabapentinoid group (17/51=33.3%) (p=0.128). Secondary objectives showed a significant association between respiratory depression and surgery in the previous 24 hours (p=0.036) as well as respiratory depression and age >65 years (p=0.031) for patients in the non-gabapentinoid group compared to the gabapentinoid group. Conclusion:There was no significant association of respiratory depression in the gabapentinoid group versus the non-gabapentinoid group. There was an increased risk of respiratory depression in the gabapentinoid group, specifically in patients who had surgery within the previous 24 hours