Autoantibodies to the insulin receptor. Effect on the insulin-receptor interaction in IM-9 lymphocytes

The serum of some patients with insulin-resistant "diabetes" contains antibodies that bind to and block the cell membrane receptors for insulin. In this report, we have characterized the effects of the antireceptor antibodies on the interaction of (125)I-insulin with its receptor on the human lymphoblastoid cell line IM-9. Up to 95% of specific insulin binding can be inhibited by pretreatment of the cells with these immunoglobulins. The onset of the inhibitory effect is time- and temperature-dependent, and the effect is reversed extremely slowly if the cells are suspended in a large excess of antibody-free buffer. These features of antibody binding can be easily distinguished from those for insulin binding to its receptor. The inhibitory effect of the antibodies can be reversed by exposure of the cells to conditions known to elute surface immunoglobulins. The three antireceptor sera studied appear to alter the insulin-receptor interaction in different ways. Two antisera markedly reduce receptor affinity through combined effects on the insulin association and dissociation rates, and, additionally, have smaller effects on available receptor number. A third antiserum primarily affects available receptor number and has little effect on receptor affinity. All three antisera inhibit the capacity of insulin to promote negatively cooperative site-site interactions among insulin receptors. The data suggest that these autoantibodies to the insulin receptor bind to different determinants on the receptor and may therefore be useful as unique probes of insulin receptor structure and function.     

Experimental automobile-pedestrian injuries

Fifteen fresh cadaver impacts were conducted in simulation of pedestrian-automobile accidents. The test sled configuration simulated an automobile bumper and hood in "standard" and "nosedive" situations as well as "hard" and "soft" impact surfaces. Instrumentation and film demonstrated large axial compression forces in the struck leg and considerable angular velocity of the torso in all modes. Dissection revealed primary injury at the impact site at low velocities with added remote injury at high velocities. Fracture of the lateral tibial plateau was most common. Lowering the bumper height offered the greatest protection against injury at moderate impact velocities.     

Licorice-induced hypertension and syndromes of apparent mineralocorticoid excess

Excessive ingestion of licorice induces a syndrome of hypokalemia and hypertension that reflects increased activation of renal mineralocorticoid receptors by cortisol. A similar syndrome of cortisol-dependent mineralocorticoid excess occurs in congenital deficiency of the enzyme 11 beta-hydroxysteroid dehydrogenase, which normally inactivates cortisol to cortisone. It has been shown that licorice inhibits 11 beta-dehydrogenase, preventing local inactivation of cortisol and allowing cortisol inappropriate access to intrinsically nonspecific renal mineralocorticoid receptors. Further studies with licorice and its derivatives have revealed a widespread role for 11 beta-dehydrogenase in regulating tissue sensitivity to cortisol. Deficient 11 beta-dehydrogenase activity provides a novel pathogenetic mechanism for hypertension, and current research suggests that several common forms of hypertension can be explained by the mechanisms that operate in licorice-induced hypertension.     

Quantal transmitter release at somatic motor-nerve terminals: stochastic analysis of the subunit hypothesis

Here we analyze the problem of determining whether experimentally measured spontaneous miniature end-plate currents (MEPCs) indicate that quanta are composed of subunits. The properties of MEPCs at end plates with or without secondary clefts at the neuromuscular junction are investigated, using both stochastic and deterministic models of the action of a quantum of transmitter. It is shown that as the amount of transmitter in a quantum is increased above about 4000 acetylcholine (ACh) molecules there is a linear increase in the size of the MEPC. It is possible to then use amplitude-frequency histograms of such MEPCs to detect a subunit structure, as there is little potentiation effect above 4000 ACh molecules. Autocorrelation and power spectral analyses of such histograms establish that their subunit structure can be detected if the coefficient of variation of the subunit size is less than about 0.12 or, if electrical noise is added, about 0.1. Positive gradients relate the rise time and half-decay times of MEPCs to their amplitude, even in the absence of potentiating effects; these gradients are shallower at motor nerve terminals that possess secondary clefts. The effect of asynchronous release of subunits is also investigated. The criteria determined by this analysis for identifying a subunit composition in the quantum are applied to an amplitude-frequency histogram of MEPCs recorded from a small group of active zones at a visualized amphibian motor-nerve terminal. This did not provide evidence for a subunit structure.     

NaCl doping and the conductivity of agar phantoms

A recipe for manipulating the conductivity of agar impedance-imaging phantoms through their NaCl (salt) content is reexamined. The conductivities at frequencies 100 kHz and below are characterized for phantoms created with the recipe. The data are compared against the recipe's predictive formula for conductivity as a function of salt content. Based on analysis of the data a modified version of the conductivity formula is generated. The modified predictive formula better approximates the observed NaCl dependence of conductivity in phantoms with salt concentrations under 0.1 M. The experimental data also provide verification for the asymptotic dependence of contact impedance on frequency and phantom conductivity. The results of these experiments will be helpful in better constructing agar phantoms to electrical specifications for future impedance-imaging experiments.     

Development of an automated testing system for vehicle infotainment system

A current premium vehicle is implemented with a variety of information, entertainment, and communication functions, which are generally referred as an infotainment system. During vehicle development, testing of the infotainment system at an overall level is conventionally carried out manually by an expert who can observe at a customer level. This approach has significant limitations with regard to test coverage and effectiveness due to the complexity of the system functions and human’s capability. Hence, it is highly demanded by car manufacturers for an automated infotainment testing system, which replicates a human expert encompassing relevant sensory modalities relating to control (i.e., touch) and observation (i.e., sight and sound) of the system under test. This paper describes the design, development, and evaluation of such a system that consists of simulation of vehicle network, vision-based inspection, automated navigation of features, random cranking waveform generation, sound detection, and test automation. The system developed is able to: stimulate a vehicle system across a wide variety of initialisation conditions, exercise each function, check for system responses, and record failure situations for post-testing analysis.     

Demonstration of multi-core photonic crystal fibre in an optical interconnect

A novel microstructured fibre has been created for use in an optical interconnection system. The fibre has low crosstalk with a high density of cores corresponding to 1150 channels/mm/sup 2/. A repeating pseudorandom binary sequence has been used to demonstrate a four-channel transmit/receive system using vertical cavity surface emitting lasers as both emitters and detectors.