The α5 subunit regulates the expression and function of α4*-containing neuronal nicotinic acetylcholine receptors in the ventral-tegmental area

Human genetic association studies have shown gene variants in the α5 subunit of the neuronal nicotinic receptor (nAChR) influence both ethanol and nicotine dependence. The α5 subunit is an accessory subunit that facilitates α4* nAChRs assembly in vitro. However, it is unknown whether this occurs in the brain, as there are few research tools to adequately address this question. As the α4*-containing nAChRs are highly expressed in the ventral tegmental area (VTA) we assessed the molecular, functional and pharmacological roles of α5 in α4*-containing nAChRs in the VTA. We utilized transgenic mice α5+/+(α4YFP) and α5-/-(α4YFP) that allow the direct visualization and measurement of α4-YFP expression and the effect of the presence (α5+/+) and absence of α5 (-/-) subunit, as the antibodies for detecting the α4* subunits of the nAChR are not specific. We performed voltage clamp electrophysiological experiments to study baseline nicotinic currents in VTA dopaminergic neurons. We show that in the presence of the α5 subunit, the overall expression of α4 subunit is increased significantly by 60% in the VTA. Furthermore, the α5 subunit strengthens baseline nAChR currents, suggesting the increased expression of α4* nAChRs to be likely on the cell surface. While the presence of the α5 subunit blunts the desensitization of nAChRs following nicotine exposure, it does not alter the amount of ethanol potentiation of VTA dopaminergic neurons. Our data demonstrates a major regulatory role for the α5 subunit in both the maintenance of α4*-containing nAChRs expression and in modulating nicotinic currents in VTA dopaminergic neurons. Additionally, the α5α4* nAChR in VTA dopaminergic neurons regulates the effect of nicotine but not ethanol on currents. Together, the data suggest that the α5 subunit is critical for controlling the expression and functional role of a population of α4*-containing nAChRs in the VTA.

Nedd4-2functionally interacts with ClC-5: involvement in constitutive albumin endocytosis in proximal tubule cells

Constitutive albumin uptake by the proximal tubule is achieved by a receptor-mediated process in which the Cl– channel, ClC-5, plays an obligate role. Here we investigated the functional interaction between ClC-5 and ubiquitin ligases Nedd4 and Nedd4-2 and their role in albumin uptake in opossum kidney proximal tubule (OK) cells. In vivo immunoprecipitation using an anti-HECT antibody demonstrated that ClC-5 bound to ubiquitin ligases, whereas glutathione S-transferase pull-downs confirmed that the C terminus of ClC-5 bound both Nedd4 and Nedd4-2. Nedd4-2 alone was able to alter ClC-5 currents in Xenopus oocytes by decreasing cell surface expression of ClC-5. In OK cells, a physiological concentration of albumin (10 μg/ml) rapidly increased cell surface expression of ClC-5, which was also accompanied by the ubiquitination of ClC-5. Albumin uptake was reduced by inhibiting either the lysosome or proteasome. Total levels of Nedd4-2 and proteasome activity also increased rapidly in response to albumin. Overexpression of ligase defective Nedd4-2 or knockdown of endogenous Nedd4-2 with small interfering RNA resulted in significant decreases in albumin uptake. In contrast, pathophysiological concentrations of albumin (100 and 1000 μg/ml) reduced the levels of ClC-5 and Nedd4-2 and the activity of the proteasome to the levels seen in the absence of albumin. These data demonstrate that normal constitutive uptake of albumin by the proximal tubule requires Nedd4-2, which may act via ubiquitination to shunt ClC-5 into the endocytic pathway.

Structures of μOconotoxins from Conusmarmoreus. Inhibitors of tetrodotoxin (TTX)-sensitive and TTX-resistant sodium channels in mammalian sensory neurons

The μO-conotoxins are an intriguing class of conotoxins targeting various voltage-dependent sodium channels and molluscan calcium channels. In the current study, we have shown MrVIA and MrVIB to be the first known peptidic inhibitors of the transient tetrodotoxin-resistant (TTX-R) Na+ current in rat dorsal root ganglion neurons, in addition to inhibiting tetrodotoxin-sensitive Na+ currents. Human TTX-R sodium channels are a therapeutic target for indications such as pain, highlighting the importance of the μO-conotoxins as potential leads for drug development. Furthermore, we have used NMR spectroscopy to provide the first structural information on this class of conotoxins. MrVIA and MrVIB are hydrophobic peptides that aggregate in aqueous solution but were solubilized in 50% acetonitrile/water. The three-dimensional structure of MrVIB consists of a small β-sheet and a cystine knot arrangement of the three-disulfide bonds. It contains four backbone “loops” between successive cysteine residues that are exposed to the solvent to varying degrees. The largest of these, loop 2, is the most disordered part of the molecule, most likely due to flexibility in solution. This disorder is the most striking difference between the structures of MrVIB and the known δ- and ω-conotoxins, which along with the μO-conotoxins are members of the O superfamily. Loop 2 of ω-conotoxins has previously been shown to contain residues critical for binding to voltage-gated calcium channels, and it is interesting to speculate that the flexibility observed in MrVIB may accommodate binding to both sodium and molluscan calcium channels.

Distribution harmonic state estimation based on a modified PSO considering parameters uncertainty

This paper presents a new algorithm based on a Modified Particle Swarm Optimization (MPSO) to estimate the harmonic state variables in a distribution networks. The proposed algorithm performs the estimation for both amplitude and phase of each injection harmonic currents by minimizing the error between the measured values from Phasor Measurement Units (PMUs) and the values computed from the estimated parameters during the estimation process. The proposed algorithm can take into account the uncertainty of the harmonic pseudo measurement and the tolerance in the line impedances of the network as well as the uncertainty of the Distributed Generators (DGs) such as Wind Turbines (WTs). The main features of the proposed MPSO algorithm are usage of a primary and secondary PSO loop and applying the mutation function. The simulation results on 34-bus IEEE radial and a 70-bus realistic radial test networks are presented. The results demonstrate that the speed and the accuracy of the proposed Distribution Harmonic State Estimation (DHSE) algorithm are very excellent compared to the algorithms such as Weight Least Square (WLS), Genetic Algorithm (GA), original PSO, and Honey Bees Mating Optimization (HBMO).

Go with the flow : optimal AUV path planning in coastal environments

This paper describes a novel optimum path planning strategy for long duration AUV operations in environments with time-varying ocean currents. These currents can exceed the maximum achievable speed of the AUV, as well as temporally expose obstacles. In contrast to most other path planning strategies, paths have to be defined in time as well as space. The solution described here exploits ocean currents to achieve mission goals with minimal energy expenditure, or a tradeoff between mission time and required energy. The proposed algorithm uses a parallel swarm search as a means to reduce the susceptibility to large local minima on the complex cost surface. The performance of the optimisation algorithms is evaluated in simulation and experimentally with the Starbug AUV using a validated ocean model of Brisbane’s Moreton Bay.

Distribution harmonic state estimation based on a hybrid PSO and SA algorithm considering parameters uncertainty

This paper presents a new algorithm based on a Hybrid Particle Swarm Optimization (PSO) and Simulated Annealing (SA) called PSO-SA to estimate harmonic state variables in distribution networks. The proposed algorithm performs estimation for both amplitude and phase of each harmonic currents injection by minimizing the error between the measured values from Phasor Measurement Units (PMUs) and the values computed from the estimated parameters during the estimation process. The proposed algorithm can take into account the uncertainty of the harmonic pseudo measurement and the tolerance in the line impedances of the network as well as uncertainty of the Distributed Generators (DGs) such as Wind Turbines (WT). The main feature of proposed PSO-SA algorithm is to reach quickly around the global optimum by PSO with enabling a mutation function and then to find that optimum by SA searching algorithm. Simulation results on IEEE 34 bus radial and a realistic 70-bus radial test networks are presented to demonstrate the speed and accuracy of proposed Distribution Harmonic State Estimation (DHSE) algorithm is extremely effective and efficient in comparison with the conventional algorithms such as Weight Least Square (WLS), Genetic Algorithm (GA), original PSO and Honey Bees Mating Optimization (HBMO) algorithm.

Prior storm experience moderates water surge perception and risk

Background How accurately do people perceive extreme water speeds and how does their perception affect perceived risk? Prior research has focused on the characteristics of moving water that can reduce human stability or balance. The current research presents the first experiment on people's perceptions of risk and moving water at different speeds and depths. Methods Using a randomized within-person 2 (water depth: 0.45, 0.90 m) ×3 (water speed: 0.4, 0.8, 1.2 m/s) experiment, we immersed 76 people in moving water and asked them to estimate water speed and the risk they felt. Results Multilevel modeling showed that people increasingly overestimated water speeds as actual water speeds increased or as water depth increased. Water speed perceptions mediated the direct positive relationship between actual water speeds and perceptions of risk; the faster the moving water, the greater the perceived risk. Participants' prior experience with rip currents and tropical cyclones moderated the strength of the actual–perceived water speed relationship; consequently, mediation was stronger for people who had experienced no rip currents or fewer storms. Conclusions These findings provide a clearer understanding of water speed and risk perception, which may help communicate the risks associated with anticipated floods and tropical cyclones.

Motor controller simulation and embedded implementation for a blood pump

This study was a step forward in modeling, simulation and microcontroller implementation of a high performance control algorithm for the motor of a blood pump. The rotor angle is sensed using three Hall effect sensors and an algorithm is developed to obtain better angular resolution from the three signals for better discrete-time updates of the controller. The performance of the system was evaluated in terms of actual and reference speeds, stator currents and power consumption over a range of reference speeds up to 4000 revolutions per minute. The use of fewer low cost Hall effect sensors compared to expensive high resolution sensors could reduce the cost of blood pumps for total artificial hearts.

Foil-based atom chip for Bose-Einstein condensates

We describe a novel method of fabricating atom chips that are well suited to the production and manipulation of atomic Bose–Einstein condensates. Our chip was created using a silver foil and simple micro-cutting techniques without the need for photolithography. It can sustain larger currents than conventional chips, and is compatible with the patterning of complex trapping potentials. A near pure Bose–Einstein condensate of 4 × 104 87Rb atoms has been created in a magnetic microtrap formed by currents through wires on the chip. We have observed the fragmentation of atom clouds in close proximity to the silver conductors. The fragmentation has different characteristic features to those seen with copper conductors.

Sensor fault-resilient control of interior permanent-magnet synchronous motor drives

In a conventional ac motor drive using field-oriented control, a dc-link voltage, speed, and at least two current sensors are required. Hence, in the event of sensor failure, the performance of the drive system can be severely compromised. This paper presents a sensor fault-tolerant control strategy for interior permanent-magnet synchronous motor (IPMSM) drives. Three independent observers are proposed to estimate the speed, dc-link voltage, and currents of the machine. If a sensor fault is detected, the drive system isolates the faulty sensor while retaining the remaining functional ones. The signal is then acquired from the corresponding observer in order to maintain the operation of the drive system. The experimental results provided verify the effectiveness of the proposed approach.

Mitigation of distorted and unbalanced stator voltage of stand-alone doubly fed induction generators using repetitive control technique

Unbalanced or non-linear loads result in distorted stator currents and electromagnetic torque pulsations in stand-alone doubly fed induction generators (DFIGs). This study proposes the use of a proportional-integral repetitive control (PIRC) scheme so as to mitigate the levels of harmonic and unbalance at the stator terminals of the DFIG. The PIRC is structurally simpler and requires much less computation than existing methods. Analysis of the PIRC operation and the methodology to determine the control parameters is included. Simulation study as well as laboratory test measurements demonstrate clearly the effectiveness of the proposed PIRC control scheme.

Flying supercapacitors as power smoothing elements in wind generation

This paper presents a capacitor-clamped three-level inverter-based supercapacitor direct integration scheme for wind energy conversion systems. The idea is to increase the capacitance of clamping capacitors with the use of supercapacitors and allow their voltage to vary within a defined range. Even though this unique approach eliminates the need of interfacing dc-dc converters for supercapacitors, the variable voltage operation brings about several challenges. The uneven distribution of space vectors is the major modulation challenge. A space vector modulation method is proposed in this paper to address this issue and to generate undistorted currents even in the presence of dynamic changes in supercapacitor voltages. A supercapacitor voltage equalization algorithm is also presented. Moreover, control strategies of the proposed system are discussed in detail. Simulation and experimental results are presented to verify the efficacy of the proposed system in suppressing short-term wind power fluctuations.

Bit-stream-based space vector modulators

Bit-stream-based control, which uses one bit wide signals to control power electronics applications, is a new approach for controller design in power electronic systems. This study presents a novel family of three-phase space vector modulators, which are based on the bit-stream technique and suitable for three-phase inverter systems. Each of the proposed modulators simultaneously converts a two-phase reference to the three-phase domain and reduces switching frequencies to reasonable levels. The modulators do not require carrier oscillators, trigonometric functions or, in some cases, sector detectors. A complete three-phase modulator can be implemented in as few as 102 logic elements. The performance of the proposed modulators is compared through simulation and experimental testing of a 6 kW, three-phase DC-to-AC inverter. Subject to limits on the modulation index, the proposed modulators deliver spread-spectrum output currents with total harmonic distortion comparable to a standard carrier-based space vector pulse width modulator.

Direct integration of battery energy storage systems in distributed power generation

In this paper, a wind energy conversion system interfaced to the grid using a dual inverter is proposed. One of the two inverters in the dual inverter is connected to the rectified output of the wind generator while the other is directly connected to a battery energy storage system (BESS). This approach eliminates the need for an additional dc-dc converter and thus reduces power losses, cost, and complexity. The main issue with this scheme is uncorrelated dynamic changes in dc-link voltages that results in unevenly distributed space vectors. A detailed analysis on the effects of these variations is presented in this paper. Furthermore, a modified modulation technique is proposed to produce undistorted currents even in the presence of unevenly distributed and dynamically changing space vectors. An analysis on the battery charging/discharging process and maximum power point tracking of the wind turbine generator is also presented. Simulation and experimental results are presented to verify the efficacy of the proposed modulation technique and battery charging/discharging process.

Onset of Mediterranean outflow into the North Atlantic

Sediments cored along the southwestern Iberian margin during Integrated Ocean Drilling Program Expedition 339 provide constraints on Mediterranean Outflow Water (MOW) circulation patterns from the Pliocene epoch to the present day. After the Strait of Gibraltar opened (5.33 million years ago), a limited volume of MOW entered the Atlantic. Depositional hiatuses indicate erosion by bottom currents related to higher volumes of MOW circulating into the North Atlantic, beginning in the late Pliocene. The hiatuses coincide with regional tectonic events and changes in global thermohaline circulation (THC). This suggests that MOW influenced Atlantic Meridional Overturning Circulation (AMOC), THC, and climatic shifts by contributing a component of warm, saline water to northern latitudes while in turn being influenced by plate tectonics.