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.     

Role of early supervisory experience in supervisor performance.

Explores the role of early supervisory experience and cognitive ability in 1st-line supervisor performance. Similar to the F. L. Schmidt et al (see record 1986-31441-001) study of nonsupervisors, this research tested structural models hypothesizing relationships among supervisory experience, cognitive ability, supervisory knowledge and proficiency, and performance ratings, using a sample of 570 2nd-tour soldiers. The Schmidt et al model with an additional ability?→?experience path provided the best fit. The significant ability?→?experience path was interpreted as indicating that demonstrated ability contributes to soldiers being given the opportunity to obtain supervisory experience. Experience had a greater impact on supervisor proficiency than on supervisor knowledge. Ability had a greater impact on supervisor knowledge than on proficiency. Discussion focuses on the personal characteristics that might be involved in being assigned supervisory responsibilities. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Flow due to a sink near a vertical wall, in infinitely deep fluid

Flow caused by a point sink in an otherwise stagnant fluid is studied using numerical methods based on integral-equation techniques and an asymptotic solution for small Froude number. There is a vertical wall present on a plane close to the sink, so that the flow is fully three dimensional. The fluid is of infinite depth, but a free-surface bounds it above. Steady solutions are presented for various Froude numbers and distances of the source from the wall. It is shown that the numerical results and asymptotic formula are in good agreement for small Froude numbers, but the results suggest that the non-linear solution ultimately forms some limiting structure at sufficiently large Froude number.     

Linked influence of pH and cations on fatty-acid monolayer integrity related to high-quality Langmuir-Blodgett films

This study shows the connection between the morphological structure of transferred films and the chemical composition of the monolayer before transfer. The stability of a behenic acid monolayer depends on the linked influence of the type of cation and of the pH value in the aqueous subphase. The stability of the monolayer is assessed by the expansion of the solid-packed state and by the relaxation time. Its integrity is characterized by the number of crystal defects which appear in transferred Langmuir-Blodgett (LB) films as seen through Nomarski microscope observations. Both stability and integrity are greatly improved when Cd²⁺ or Mn²⁺are added to the subphase at pH 5.75 and 6 respectively. In these conditions, the transfer is very efficient and the LB films thus obtained are of very high quality. The pH values of the subphase at which the molecules of behenic acid are transformed into bivalent salts differ significantly according to the nature of the cation involved. Comparing infrared spectra of the LB films, it appeared that the relative amount of acid/salt found in the monolayer was practically the same with a subphase containing either Cd²⁺ at pH 5.75 or Mn²⁺ at pH 6. This suggests that the ratio of acidic and salt forms would be a key parameter for obtaining high-quality LB films.     

Link budget analysis for multistandard receiver architectures

As devices shrink, creating integrated circuits (ICs) that work with the required accuracy becomes more difficult due to issues related to device physics. Receivers are part of an area referred to as "mixed-signal design," meaning that both analog and digital circuitry will be on the same IC. This too presents many challenging issues, as the analog circuitry is highly sensitive to disruptions caused by the noisy digital circuitry. Therefore, accurate modeling and simulation is crucial in the design of wireless receivers to ensure the best possible operation of the fabricated IC. Through simulation and modeling a designer can determine if receiver architecture will meet the required specifications and pinpoint the possible problems before valuable time is spent developing the actual circuit. This article will present design issues for multistandard wireless receivers to give the reader an understanding of the challenges involved in link-budget analysis. TITAN (Toolbox for Integrated Transceiver Analysis), a link-budget analysis tool developed at The Ohio State University Analog VLSI Laboratory, will be presented as an example of a tool for receiver simulation. To determine design performance, various requirements must be translated to model parameters. Among the requirements for receivers are noise floor (NF), second- and third-order distortion (IP2 and IP3, respectively), reciprocal mixing, and phase noise. TITAN offers a graphical interface and encapsulated models to the designer, eliminating the possibility of formula corruption. The interface provides a more intuitive and sophisticated way of setting up the simulation and provides the designer with more readable results. Additionally, a blocking profile component allows the architecture to be tested across multiple standards.     

Glomerular and tubular function in glycogen storage disease

Urinary protein and calcium excretion were assessed in 77 patients with the hepatic glycogen storage diseases (GSD): 30 with GSD-I (median age 12.4 years, range 3.2-32.9 years), 25 with GSD-III (median age 10.5 years, range 4.2-31.3 years) and 22 with GSD-IX (median age 11.8 years, range 1.2-35.4 years). Inulin (Cinulin) and para-aminohippuric acid (CPAH) clearances were also measured in 33 of these patients. Those with GSD-I had significantly greater albumin (F = 15.07, P < 0.001), retinol-binding protein (RBP) (F = 14.66, P < 0.001), N-acetyl-beta-D-glucosaminidase (NAG) (F = 9.41, P < 0.001) and calcium (F = 7.41, P = 0.001) excretion than those with GSD-III and GSD-IX. GSD-I patients (n = 18) also had significantly higher Cinulin (F = 5.57, P = 0.009), but CPAH did not differ (F = 0.77, NS). Renal function was normal in GSD-III and GSD-IX patients. In GSD-I, Cinulin (r = -0.51, P = 0.03) and NAG excretion (r = -0.40, P = 0.03) were inversely correlated with age, whereas albumin excretion was positively correlated with age (r = +0.41, P = 0.03). RBP and calcium excretion were generally high throughout all age groups. Hyperfiltration in GSD-I is associated with renal tubular proteinuria that occurs before the onset of significant albuminuria. Deficiency of glucose-6-phosphatase within the proximal renal tubule may primarily cause tubular dysfunction, glomerular hyperfiltration being a secondary phenomenon.     

Introduction to the special section on neuropsychology and rehabilitation: The view from New York University.

30 yrs prior to this article, psychologists at the New York University Medical Center addressed issues at the interface of clinical neuropsychology and rehabilitation. The work gave rise to programs for interventions with people with cognitive deficits after brain damage, stroke, and traumatic brain injury. The expansion of this early work is discussed in reference to articles about instrument development, cognitive remediation programs, issues of program outcome, and problems in delivering neuropsychological services to individuals with brain trauma. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Physical attractiveness and self-perception of mental disorder.

Prior research has reported a relation between physical attractiveness and severity of mental disorder, with less attractive people being more maladjusted. However, because these two variables have been measured simultaneously, it has not been possible to separate cause from effect. To clarify this question, in this study we first measured physical attractiveness, social competence, and perceived risk of developing a mental disorder in 280 college women. Seven months later, we measured the subjects' self-perception of having a mental disorder. Women who were more attractive were higher in social competence and lower in perceived risk of mental disorder. More attractive women were also lower in self-perception of mental disorder 7 months later. This relation between attractiveness and self-perception of mental disorder remained significant even after controlling for the Time 1 measures (social competence, perceived risk of mental disorder, and age). The implications of these findings for the hypothesized role of attractiveness in the determination of adjustment are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)