Anaesthetic impairment of immune function is mediated via GABA(A) receptors.

BACKGROUND: GABA(A) receptors are members of the Cys-loop family of neurotransmitter receptors, proteins which are responsible for fast synaptic transmission, and are the site of action of wide range of drugs. Recent work has shown that Cys-loop receptors are present on immune cells, but their physiological roles and the effects of drugs that modify their function in the innate immune system are currently unclear. We are interested in how and why anaesthetics increase infections in intensive care patients; a serious problem as more than 50% of patients with severe sepsis will die. As many anaesthetics act via GABA(A) receptors, the aim of this study was to determine if these receptors are present on immune cells, and could play a role in immunocompromising patients. PRINCIPAL FINDINGS: We demonstrate, using RT-PCR, that monocytes express GABA(A) receptors constructed of α1, α4, β2, γ1 and/or δ subunits. Whole cell patch clamp electrophysiological studies show that GABA can activate these receptors, resulting in the opening of a chloride-selective channel; activation is inhibited by the GABA(A) receptor antagonists bicuculline and picrotoxin, but not enhanced by the positive modulator diazepam. The anaesthetic drugs propofol and thiopental, which can act via GABA(A) receptors, impaired monocyte function in classic immunological chemotaxis and phagocytosis assays, an effect reversed by bicuculline and picrotoxin. SIGNIFICANCE: Our results show that functional GABA(A) receptors are present on monocytes with properties similar to CNS GABA(A) receptors. The functional data provide a possible explanation as to why chronic propofol and thiopental administration can increase the risk of infection in critically ill patients: their action on GABA(A) receptors inhibits normal monocyte behaviour. The data also suggest a potential solution: monocyte GABA(A) receptors are insensitive to diazepam, thus the use of benzodiazepines as an alternative anesthetising agent may be advantageous where infection is a life threatening problem.

Nested sampling for materials: the case of hard spheres

The recently introduced nested sampling algorithm allows the direct and efficient calculation of the partition function of atomistic systems. We demonstrate its applicability to condensed phase systems with periodic boundary conditions by studying the three dimensional hard sphere model. Having obtained the partition function, we show how easy it is to calculate the compressibility and the free energy as functions of the packing fraction and local order, verifying that the transition to crystallinity has a very small barrier, and that the entropic contribution of jammed states to the free energy is negligible for packing fractions above the phase transition. We quantify the previously proposed schematic phase diagram and estimate the extent of the region of jammed states. We find that within our samples, the maximally random jammed configuration is surprisingly disordered.

A comparison of cage and nested-loop BDFM rotors

The Brushless Double-Fed Machine (BDFM) is a type of variable speed generator or drive. Using theoretical analysis of simple BDFM rotors this paper establishes trends in how rotor structures determine the rotor's equivalent circuit resistance, leakage inductance and turns ratio. The variation in measured parameters of five prototype rotors is then analysed in light of the trends found. Both the theory and experimental results suggest a significant performance advantage in using cage+loops type rotors as opposed to the simple nested loop type more usually employed.

Generalized vector control for brushless doubly fed machines with nested-loop rotor

This paper presents a generalized vector control system for a generic brushless doubly fed (induction) machine (BDFM) with nested-loop type rotor. The generic BDFM consists of p1/p2 pole-pair stator windings and a nested-loop rotor with N number of loops per nest. The vector control system is derived based on the basic BDFM equation in the synchronous mode accompanied with an appropriate synchronization approach to the grid. An analysis is performed for the vector control system using the generic BDFM vector model. The analysis proves the efficacy of the proposed approach in BDFM electromagnetic torque and rotor flux control. In fact, in the proposed vector control system, the BDFM torque can be controlled very effectively promising a high-performance BDFM shaft speed control system. A closed-loop shaft speed control system is composed based on the presented vector control system whose performance is examined both in simulations and experiments. The results confirm the high performance of the proposed approach in BDFM shaft speed control as well as a very close agreement between the simulations and experiments. Tests are performed on a 180-frame prototype BDFM. © 2012 IEEE.

Function propagation through nested systems

Concepts of function are central to design but statements about a device's functions can be interpreted in different ways. This raises problems for researchers trying to clarify the foundations of design theory and for those developing design support-tools that can represent and reason about function. By showing how functions relate systems to their sub-systems and super-systems, this article illustrates some limitations of existing function terminology and some problems with existing function statements. To address these issues, a system-relative function terminology is introduced. This is used to demonstrate that systems function not only with respect to their most local super-system, but also with respect to their more global super-systems. © 2012 Elsevier Ltd. All rights reserved.