Desensitization of mutant acetylcholine receptors in transgenic mice reduces the amplitude of neuromuscular synaptic currents

While the slow onset of desensitization of nicotinic acetylcholine receptors (AChRs), relative to the rate of acetylcholine removal, excludes this kinetic state from shaping synaptic responses in normal neuromuscular transmission, its role in neuromuscular disorders has not been examined. The slow-channel congenital myasthenic syndrome (SCCMS) is a disorder caused by point mutations in the AChR subunit-encoding genes leading to kinetically abnormal (slow) channels, reduced miniature endplate current amplitudes (MEPCs), and degeneration of the postsynaptic membrane. Because of this complicated picture of kinetic and structural change in the neuromuscular junction, it is difficult to assess the importance of the multiple factors that may be responsible for the reduced endplate current amplitudes, and ultimately the clinical syndrome. In order to address this we have used a transgenic mouse model for the SCCMS that has slow AChR ion channels and reduced endplate responsiveness in the absence of any of the degenerative changes. We found that the reduction in MEPC amplitudes in these mice could not be explained by either reduced AChR number or by reduced AChR channel conductance. Rather, we found that the mutant AChRs in situ manifested an activity-dependent reduction in sensitivity that caused diminished MEPC and endplate current amplitude with nerve stimulation. This observation demonstrates that the basis for the reduction in MEPC amplitudes in the SCCMS may be multifactorial. Moreover, these findings demonstrate that, under conditions that alter their rate of desensitization, the kinetic properties of nicotinic AChRs can control the strength of synaptic responses.     

New actinide ternary intermetallic compounds: synthesis, characterization and physical properties

Twelve new ternary intermetallic compounds of light actinide elements from Th to Pu, namely U₄Tc₇Si₆, U₄Tc₇Ge₆, Np₄Ru₇Ge₆, U₂Tc₃Si₅, Np₂Re₃Si₅, Pu₂Re₃Si₅, Th₂Mo₃Si₄, U₂Mo₃Si₄, U₂Mo₃Ge₄, Np₂Mo₃Si₄, Np₂Mo₃Ge₄, and Pu₂Mo₃Si₄, were obtained. The structures of these compounds are discussed as well as some preliminary physical property studies. Magnetic susceptibility measurements show that An₂Mo₃(Si or Ge)₄ compounds are paramagnetic at all temperatures studied and that U₄Tc₇Si₆ orders antiferromagnetically around 25 K. Mössbauer spectroscopy on Np₄Ru₇Ge₆ does not show a magnetic splitting down to 4.2 K.     

Impact and penetration by L/D ≤ 1 projectiles

Calculations of steel target penetration by L/D ≤ 1 tungsten and tungsten alloy projectiles have been extended to L/D = 1/32 over the velocity range 1.5 to 5 km/s. The ratio of crater to projectile diameter tends to 1 as L/D decreases over this entire velocity range. For impact velocities of 1.5 and 3 km/s, penetration depth normalized by projectile length, P/L, increases with decreasing projectile L/D up to a maximum value and then decreases for still lower L/D. Experiments at impact velocities of 2 and 3 km/s confirm these results. For 5 km/s impact velocity, the calculations show P/L increasing with decreasing projectile L/D over the entire range 1/32 ≤ L/D ≤ 1. The projectile L/D for which the maximum P/L occurs appears to depend on the impact velocity. P/L generally scales with impact velocity as P/L v^f(L/D) where f(L/D) ranges from 0 for a long rod to, we believe, 2 in the limit as projectile L/D approaches zero. The calculations show for 1/8 ≤ L/D ≤ 1/2, P/L v^0.9; for L/D = 1/16, P/L v^1.5; and for L/D = 1/32, the new results give P/L v^1.9.     

Common region of ALL-1 gene disrupted in epipodophyllotoxin-related secondary acute myeloid leukemia

Translocations at chromosomal band 11q23 characterize most de novo acute lymphoblastic leukemias (ALL) of infants, acute myeloid leukemias (AML) of infants and young children, and secondary AMLs following epipodophyllotoxin exposure. The chromosomal breakpoints at 11q23 have been cloned from isolated cases of de novo ALL and AML. Using an 859-base pair BamHI fragment of human ALL-1 complementary DNA that recognizes the genomic breakpoint region for de novo ALL and AML, we investigated two cases of secondary AML that followed etoposide-treated primary B-lineage ALL. In the first case, the translocation occurred between chromosomes 9 and 11 and the breakpoint at 11q23 localized to the same 9-kilobase region of the ALL-1 gene that is disrupted in most of the de novo leukemias. In the second case the translocation was between chromosomes 11 and 19. The breakpoint occurred outside of the ALL-1 breakpoint cluster region.     

The quality management journey: the progress of health facilities in Australia

Many facilities in Australia have taken the Total Quality Management (TQM) step. The objective of this study was to examine progress of adopted formal quality systems in health. Sixty per cent of organizations surveyed have adopted formal systems. Of these, Deming adherents are the most common, followed by eclectic choices. Only 35% considered the quality transition as reasonably easy. There was no relationship between accreditation and formal quality systems identified. The most common improvement techniques were: flow charts, histograms, and cause and effect diagrams. Quality practitioners are happy to use several tools exceptionally well rather than have many tools at their disposal. The greatest impediment to the adoption of quality was the lack of top management support. This study did not support the view that clinicians are not readily actively supporting quality initiatives. Total Quality Management is not a mature concept; however, Chief Executive Officers are assured that rewards will be realized over time.     

Sexual dimorphism of circulating somatotropin, insulin-like growth factor I and II, insulin-like growth factor binding proteins, and insulin: relationships to growth rate and carcass characteristics in growing lambs

The effects of sex and age on patterns of circulating somatotropin (ST) concentration and plasma IGF-I, IGF-II, insulin, and IGF binding protein-3 (IGFBP-3) were studied in ram, wether, and ewe lambs (n = 7 or 8) sampled at mean ages of 81 (I1) and 158 d (I2). Between 81 and 158 d of age, rams grew more rapidly than wethers (P < .01), and wethers grew more rapidly than ewes (P < .01). The sex differences in growth were reflected in empty body weight at slaughter: rams > wethers > ewes (P < .05). Mean plasma ST concentrations, ST pulse amplitude, and integrated plasma ST concentrations were greater (P < .05) in rams than in ewes at I1 and I2. Characteristics of the ST plasma profile in wethers were generally intermediate between those of rams and ewes. The interpulse interval was greater in ewes than in wethers at I2. The IGF-I and IGFBP-3 concentrations were greater in rams than in ewes at both sampling times. Plasma IGF-II was greater in ewes than in rams at I2. Mean plasma ST was approximately two thirds less at I2 than at I1 regardless of sex. Mean plasma ST and IGF-I at both ages were positively correlated with growth. Mean plasma ST at I2 was negatively correlated with fatness at slaughter. Sex and age significantly affected patterns of circulating ST and concentrations of IGF-I and IGFBP-3 in prepubertal growing lambs, under conditions for which growth rates and composition were also sexually dimorphic.     

Modeling Power Supply Noise in Delay Testing

Excessive power supply noise during test can cause overkill. This article discusses two models for supply noise in delay testing and their application to test compaction. The proposed noise models avoid complicated power network analysis, making them much faster than existing power noise analysis tools. can cause performance degradation and     

Adaptive alignment packaging for 2-D arrays of free-spaceoptical-interconnected optoelectronic systems

An adaptive alignment scheme for packaging two-dimensional (2D) arrays of optoelectronic systems interconnected by free-space optics is presented. A method of using three quadrant detectors to detect alignment errors in six degrees of freedom is described. However, the complexity of this system increases due to the interactions among the detected error signals. A novel control algorithm is presented to eliminate the interaction and simplify the design of the closed-loop feedback control. A computer simulation compares different algorithms and shows the effectiveness of the proposed algorithm. An experimental closed-loop feedback system demonstrated the principle of the error detection and correction of the proposed system with initial errors in multiple degrees of freedom