Independent Orbiter Assessment (IOA): Analysis of the crew equipment subsystem

The results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL) are presented. The IOA approach features a top-down analysis of the hardware to determine failure modes, criticality, and potential critical (PCIs) items. To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. The independent analysis results coresponding to the Orbiter crew equipment hardware are documented. The IOA analysis process utilized available crew equipment hardware drawings and schematics for defining hardware assemblies, components, and hardware items. Each level of hardware was evaluated and analyzed for possible failure modes and effects. Criticality was assigned based upon the severity of the effect for each failure mode. Of the 352 failure modes analyzed, 78 were determined to be PCIs

Quantifying the relationship between mechanical loading and the skeletal response in pre- and early-pubertal girls

PURPOSEBefore exercise prescription for bone health can be recommended, the relationship between mechanical loading characteristics and the skeletal response need to be quantified. We asked i) does moderate impact exercise result in a greater gain in BMC than low impact exercise, ii) what are the loading characteristics associated with a moderate and low impact exercise program and does this differ from non-structured play?, and iii) does loading history affect the osteogenic response to a moderate or low impact program? METHODSSixty-eight pre- and early-pubertal girls (aged 8.9 +/- 0.2 yrs) were randomized to take part in a moderate or low impact exercise program 3 times/wk for 8.5 mnths. The number and type of loads associated with the exercise classes and non-structured play (recess) were assessed from video footage. The magnitude of load was assessed using a pedar in-sole mobile system. Hours of moderate and high impact organized sport were assessed from a physical activity questionnaire. RESULTSThe moderate and low impact exercise programs consisted of -400 impacts per class, but the jumping, hopping and dynamic activities performed during the moderate impact program produced forces ranging from 2 to 4 times body weight (BW) compared to -1 BW for the low impact program. Moderate impact exercise resulted in a 2.7% greater gain in BMC at the tibia compared to the low impact exercise. The moderate impact exercise program consisted of fewer low impacts (1-2 BW) and a higher number of moderate impacts (2-4BW) compared to those typically performed during non-structured play. There were greater gains in BMC in subjects participating in the moderate versus the low impact exercise programs who participated in 2 to 3 hours of moderate impact sports outside school (2.5% to 4.5%, p CONCLUSIONApproximately 400 impacts ranging 2-4 BW, 3 times/wk was enough stimuli to result in an osteogenic response in normally active girls; even in those actively involved in moderate impact sports outside school.<br /

A Phase III, Randomized, Multi-Center, Double Blind, Placebo Controlled Study of Safety and Efficacy of Lofexidine for Relief of Symptoms in Individuals Undergoing Inpatient Opioid Withdrawal

Background: Lofexidine is an alpha-2-adrenergic receptor agonist approved in the United Kingdom (UK) for the treatment of opioid withdrawal symptoms. Lofexidine has demonstrated better efficacy than placebo for reducing opioid withdrawal symptoms in patients undergoing opioid withdrawal with less reported hypotension than clonidine. Methods: Designed as an FDA registration trial, this 8-day, randomized, double-blind, placebo-controlled, parallel-group study in 264 patients dependent on short-acting opioids evaluated the efficacy of lofexidine hydrochloride in reducing withdrawal symptoms in patients undergoing opioid withdrawal. The primary efficacy measures were SOWS-Gossop on Day 3 and time-to-dropout. Secondary endpoints included the proportion of participants who were completers; area under the 5-day SOWS-Gossop – time curve (i.e., AUC1–5), and daily mean SOWS-Gossop, OOWS‐Handelsman, MCGI (subject and rater), and VAS-E scores. Participants received lofexidine HCl 3.2 mg daily in four divided doses or matching placebo on Days 1–5, followed by 2 days of placebo. Results: Lofexidine significantly decreased mean Day 3 SOWS scores compared to placebo, 6.32 versus 8.67, respectively, p = 0.0212. Fewer lofexidine patients were early terminators compared to placebo (59 versus 80, respectively); and non-completers in the lofexidine group remained in the study longer than those assigned to placebo (p = 0.0034). Secondary endpoints consistently favored lofexidine. Lofexidine was well tolerated in this trial. Conclusion: Lofexidine significantly decreased SOWS scores compared to placebo and demonstrated better retention rates in participants undergoing opioid withdrawal. Lofexidine potentially offers a useful non-opioid alternative to treat opioid withdrawal symptoms

Osteocytes and mechanical loading: The Wnt connection

Bone adapts to the mechanical forces that it experiences. Orthodontic tooth movement harnesses the cell‐ and tissue‐level properties of mechanotransduction to achieve alignment and reorganization of the dentition. However, the mechanisms of action that permit bone resorption and formation in response to loads placed on the teeth are incompletely elucidated, though several mechanisms have been identified. Wnt/Lrp5 signalling in osteocytes is a key pathway that modulates bone tissue's response to load. Numerous mouse models that harbour knock‐in, knockout and transgenic/overexpression alleles targeting genes related to Wnt signalling point to the necessity of Wnt/Lrp5, and its localization to osteocytes, for proper mechanotransduction in bone. Alveolar bone is rich in osteocytes and is a highly mechanoresponsive tissue in which components of the canonical Wnt signalling cascade have been identified. As Wnt‐based agents become clinically available in the next several years, the major challenge that lies ahead will be to gain a more complete understanding of Wnt biology in alveolar bone so that improved/expedited tooth movement becomes a possibility

Rydberg Wave Packets are Squeezed States

We point out that Rydberg wave packets (and similar ``coherent" molecular packets) are, in general, squeezed states, rather than the more elementary coherent states. This observation allows a more intuitive understanding of their properties; e.g., their revivals.Comment: 7 pages of text plus one figure available in the literature, LA-UR 93-2804, to be published in Quantum Optics, LaTe

Mutagenesis Reveals a Role for Epidermal Growth Factor Receptor Extracellular Subdomain IV in Ligand Binding

The extracellular domain of the epidermal growth factor (EGF) receptor (EGFR) comprises four subdomains (I-IV) and mediates binding of several different polypeptide ligands, including EGF, transforming growth factor-alpha, and heparin-binding EGF. Previous studies have predominantly implicated subdomain III in ligand binding. To investigate a possible role for sequences in subdomain IV, we constructed several mutant EGFRs in which clusters of charged or aromatic amino acids were replaced with alanine. Analysis of stably transfected Chinese hamster ovary cells expressing mutant EGFRs confirmed that they were present on the cell surface at levels approaching that of the wild-type receptor. Although tyrosine phosphorylation of most mutants was markedly induced by EGF, a cluster mutation (mt25) containing four alanine substitutions in the span of residues 521-527 failed to respond. EGF-induced tyrosine phosphorylation of an alternative mutant (DeltaEN) with amino acids 518-589 deleted was also greatly diminished. Larger doses of EGF or heparin-binding EGF induced only weak tyrosine phosphorylation of mt25, whereas the response to transforming growth factor-alpha was undetectable. These results suggest that mt25 might be defective with respect to either ligand binding or receptor dimerization. Quantitative analyses showed that binding of (125)I-EGF to mt25 and DeltaEN was reduced to near background levels, whereas binding of EGF to other cluster mutants was reduced 60-70% compared with wild-type levels. Among the mutants, only mt25 and DeltaEN failed to form homodimers or to transphosphorylate HER2/Neu in response to EGF treatment. Collectively, our results are the first to provide direct evidence that discrete subdomain IV residues are required for normal binding of EGF family ligands. Significantly, they were obtained with the full-length receptor in vivo, rather than a soluble truncated receptor, which has been frequently used for structure/function studies of the EGFR extracellular region

The Stark effect in linear potentials

We examine the Stark effect (the second-order shift in the energy spectrum due to an external constant force) for two 1-dimensional model quantum mechanical systems described by linear potentials, the so-called quantum bouncer (defined by V(z) = Fz for z>0 and V(z) infinite for z<0) and the symmetric linear potential (given by V(z) = F|z|). We show how straightforward use of the most obvious properties of the Airy function solutions and simple Taylor expansions give closed form results for the Stark shifts in both systems. These exact results are then compared to other approximation techniques, such as perturbation theory and WKB methods. These expressions add to the small number of closed-form descriptions available for the Stark effect in model quantum mechanical systems.Comment: 15 pages. To appear in Eur. J. Phys. Needs Institute of Physics (iopart) style file

Analytic results for Gaussian wave packets in four model systems: II. Autocorrelation functions

The autocorrelation function, A(t), measures the overlap (in Hilbert space) of a time-dependent quantum mechanical wave function, psi(x,t), with its initial value, psi(x,0). It finds extensive use in the theoretical analysis and experimental measurement of such phenomena as quantum wave packet revivals. We evaluate explicit expressions for the autocorrelation function for time-dependent Gaussian solutions of the Schrodinger equation corresponding to the cases of a free particle, a particle undergoing uniform acceleration, a particle in a harmonic oscillator potential, and a system corresponding to an unstable equilibrium (the so-called `inverted' oscillator.) We emphasize the importance of momentum-space methods where such calculations are often more straightforwardly realized, as well as stressing their role in providing complementary information to results obtained using position-space wavefunctions.Comment: 18 pages, RevTeX, to appear in Found. Phys. Lett, Vol. 17, Dec. 200