Advanced Computed Tomography Inspection System (ACTIS): An overview of the technology and its application

The Advanced Computed Tomography Inspection System (ACTIS) was developed by NASA Marshall to support solid propulsion test programs. ACTIS represents a significant advance in state-of-the-art inspection systems. Its flexibility and superior technical performance have made ACTIS very popular, both within and outside the aerospace community. Through technology utilization efforts, ACTIS has been applied to inspection problems in commercial aerospace, lumber, automotive, and nuclear waste disposal industries. ACTIS has been used to inspect items of historical interest. ACTIS has consistently produced valuable results, providing information which was unattainable through conventional inspection methods. Although many successes have already been shown, the full potential of ACTIS has not yet been realized. It is currently being applied in the commercial aerospace industry by Boeing. Smaller systems, based on ACTIS technology, are becoming increasingly available. This technology has much to offer the small business and industry, especially in identifying design and process problems early in the product development cycle to prevent defects. Several options are available to businesses interested in this technology

A Computational Methodology to Screen Activities of Enzyme Variants

We present a fast computational method to efficiently screen enzyme activity. In the presented method, the effect of mutations on the barrier height of an enzyme-catalysed reaction can be computed within 24 hours on roughly 10 processors. The methodology is based on the PM6 and MOZYME methods as implemented in MOPAC2009, and is tested on the first step of the amide hydrolysis reaction catalyzed by Candida Antarctica lipase B (CalB) enzyme. The barrier heights are estimated using adiabatic mapping and are shown to give barrier heights to within 3kcal/mol of B3LYP/6-31G(d)//RHF/3-21G results for a small model system. Relatively strict convergence criteria (0.5kcal/(mol{\AA})), long NDDO cutoff distances within the MOZYME method (15{\AA}) and single point evaluations using conventional PM6 are needed for reliable results. The generation of mutant structure and subsequent setup of the semiempirical calculations are automated so that the effect on barrier heights can be estimated for hundreds of mutants in a matter of weeks using high performance computing

BioFET-SIM Web Interface: Implementation and Two Applications

We present a web interface for the BioFET-SIM program. The web interface allows to conveniently setup calculations based on the BioFET-SIM multiple charges model. As an illustration, two case studies are presented. In the first case, a generic peptide with opposite charges on both ends is inverted in orientation on a semiconducting nanowire surface leading to a corresponding change in sign of the computed sensitivity of the device. In the second case, the binding of an antibody/antigen complex on the nanowire surface is studied in terms of orientation and analyte/nanowire surface distance. We demonstrate how the BioFET-SIM web interface can aid in the understanding of experimental data and postulate alternative ways of antibody/antigen orientation on the nanowire surface

A computational method for the systematic screening of reaction barriers in enzymes:searching for Bacillus circulans xylanase mutants with greater activity towards a synthetic substrate

We present a semi-empirical (PM6-based) computational method for systematically estimating the effect of all possible single mutants, within a certain radius of the active site, on the barrier height of an enzymatic reaction. The intent of this method is not a quantitative prediction of the barrier heights, but rather to identify promising mutants for further computational or experimental study. The method is applied to identify promising single and double mutants of Bacillus circulans xylanase (BCX) with increased hydrolytic activity for the artificial substrate ortho-nitrophenyl β-xylobioside (ONPX2). The estimated reaction barrier for wild-type (WT) BCX is 18.5 kcal/mol, which is in good agreement with the experimental activation free energy value of 17.0 kcal/mol extracted from the observed kcat using transition state theory (Joshi et al., 2001). The PM6 reaction profiles for eight single point mutations are recomputed using FMO-MP2/PCM/6-31G(d) single points. PM6 predicts an increase in barrier height for all eight mutants while FMO predicts an increase for six of the eight mutants. Both methods predict that the largest change in barrier occurs for N35F, where PM6 and FMO predict a 9.0 and 15.8 kcal/mol increase, respectively. We thus conclude that PM6 is sufficiently accurate to identify promising mutants for further study. We prepared a set of all theoretically possible (342) single mutants in which every amino acid of the active site (except for the catalytically active residues E78 and E172) was mutated to every other amino acid. Based on results from the single mutants we construct a set of 111 double mutants consisting of all possible pairs of single mutants with the lowest barrier for a particular position and compute their reaction profile. None of the mutants have, to our knowledge, been prepared experimentally and therefore present experimentally testable predictions

In utero exposure to cigarette smoking, environmental tobacco smoke and reproductive hormones in US girls approaching puberty

BACKGROUND/AIMS: Evidence is unclear whether prenatal smoking affects age at menarche and pubertal development, and its impact upon hormones has not been well studied. We aim to identify potential pathways through which prenatal smoking and environmental tobacco smoke (ETS) affect reproductive hormones in girls approaching puberty. METHODS: We examined the association between prenatal smoking, current ETS and luteinizing hormone (LH) and inhibin B (InB) in 6- to 11-year-old girls in the 3rd National Health and Nutrition Examination Survey, 1988-1994. Parents/guardians completed interviewer-assisted questionnaires on health and demographics at the time of physical examination. Residual blood samples were analyzed for reproductive hormones in 2008. RESULTS: Of 660 girls, 19 and 39% were exposed to prenatal smoke and current ETS, respectively. Accounting for multiple pathways in structural equation models, prenatally exposed girls had significantly lower LH (β = -0.205 log-mIU/ml, p < 0.0001) and InB (β = -0.162, log-pg/ml, p < 0.0001). Prenatal smoking also influenced LH positively and InB negatively indirectly through BMI-for-age. ETS was positively associated with LH, but not with InB. CONCLUSION: Exposure to maternal smoking may disrupt reproductive development manifesting in altered hormone levels near puberty

Betreuungsindex in Pflegeheimen: Entwicklung und Validierung eines neuen Instruments zur Beurteilung von Betreuungsqualität in Pflegeheimen

Zusammenfassung: Hintergrund: Derzeit gibt es in der Literatur kein geeignetes Instrument zur Beurteilung der Betreuungsqualität in Pflegeheimen. Die Autoren haben deshalb ein neues Instrument, den Betreuungsindex in Pflegeheimen (Nursing Home Care Index, NCI), konzipiert und getestet. Material und Methode: Betreuungsqualität wird in der Literatur in 8Dimensionen definiert. Es wurde ein Fragebogen mit 42Fragen aus 12validierten Messinstrumenten entwickelt. Der Originalfragebogen wurde mit 320Mitarbeitern aus 15Alteneinrichtungen getestet. Die Daten wurden mithilfe einer Faktorenanalyse und Cronbachsα untersucht und auf 3Faktoren und 16Fragen reduziert. Das revidierte Instrument wurde in einer weiteren Studie mit 136Mitarbeitern auf seine Anwendbarkeit überprüft. Ergebnisse: Als Ergebnis der Faktorenanalyse konnten 16Items mit einer 3-Faktoren-Struktur, d.h. soziale Teilhabe, emotionales Wohlbefinden und Selbstbestimmung, identifiziert werden. Diese 3Faktoren erklären 51,2% der Gesamtvarianz. Die Reliabilität der Gesamtskala beträgt 0,87, die der 3Subskalen Selbstbestimmung 0,86, emotionales Wohlbefinden 0,71 und soziale Beziehungen bzw. Teilhabe 0,78. Die Gesamtpunktezahl des NCI erlaubt eine Kategorisierung der Betreuungsqualität in den 3Abstufungen gut, ausreichend und dringender Verbesserungsbedarf. Schlussfolgerungen: Der NCI hat eine doppelte Funktion. Einerseits dient er Mitarbeitern und dem Heimmanagement als internes Qualitätssicherungsinstrument. Andererseits könnte es zukünftig Angehörigen von potenziellen Heimbewohnern die Möglichkeit bieten, die Betreuungsqualität verschiedener Pflegeheime zu vergleiche

Site-specific perturbations of alpha-synuclein fibril structure by the Parkinson's disease associated mutations A53T and E46K.

PMCID: PMC3591419This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Parkinson's disease (PD) is pathologically characterized by the presence of Lewy bodies (LBs) in dopaminergic neurons of the substantia nigra. These intracellular inclusions are largely composed of misfolded α-synuclein (AS), a neuronal protein that is abundant in the vertebrate brain. Point mutations in AS are associated with rare, early-onset forms of PD, although aggregation of the wild-type (WT) protein is observed in the more common sporadic forms of the disease. Here, we employed multidimensional solid-state NMR experiments to assess A53T and E46K mutant fibrils, in comparison to our recent description of WT AS fibrils. We made de novo chemical shift assignments for the mutants, and used these chemical shifts to empirically determine secondary structures. We observe significant perturbations in secondary structure throughout the fibril core for the E46K fibril, while the A53T fibril exhibits more localized perturbations near the mutation site. Overall, these results demonstrate that the secondary structure of A53T has some small differences from the WT and the secondary structure of E46K has significant differences, which may alter the overall structural arrangement of the fibrils

SLITHER: a web server for generating contiguous conformations of substrate molecules entering into deep active sites of proteins or migrating through channels in membrane transporters

Many proteins use a long channel to guide the substrate or ligand molecules into the well-defined active sites for catalytic reactions or for switching molecular states. In addition, substrates of membrane transporters can migrate to another side of cellular compartment by means of certain selective mechanisms. SLITHER (http://bioinfo.mc.ntu.edu.tw/slither/or http://slither.rcas.sinica.edu.tw/) is a web server that can generate contiguous conformations of a molecule along a curved tunnel inside a protein, and the binding free energy profile along the predicted channel pathway. SLITHER adopts an iterative docking scheme, which combines with a puddle-skimming procedure, i.e. repeatedly elevating the potential energies of the identified global minima, thereby determines the contiguous binding modes of substrates inside the protein. In contrast to some programs that are widely used to determine the geometric dimensions in the ion channels, SLITHER can be applied to predict whether a substrate molecule can crawl through an inner channel or a half-channel of proteins across surmountable energy barriers. Besides, SLITHER also provides the list of the pore-facing residues, which can be directly compared with many genetic diseases. Finally, the adjacent binding poses determined by SLITHER can also be used for fragment-based drug design

The Figure Rating Scale as an Index of Weight Status of Women on Videotape

Objective: To determine whether Stunkard's Figure Rating Scale (FRS) is a valid and reliable index of weight status when an unbiased observer assigns the figure ratings of adult women viewed on videotape. Research Methods and Procedures: Seventy‐two women drawn from a community sample participated in a videotaped study in which height and weight were measured. The FRS is a rating scale displaying 9 silhouettes ranging from very thin to very obese. Women were assigned a figure rating “in‐person” by a research assistant (FRS used as a 17‐point scale) and by additional research assistants viewing women only on videotape (FRS used as both a 17‐ and 9‐point scale). Pearson's correlation coefficients were calculated for in‐person figure ratings, mean videotape figure ratings, and BMI. Results: BMI and in‐person figure ratings were highly correlated ( r = 0.91), as were BMI and both mean 17‐point videotape figure ratings and mean 9‐point videotape figure ratings ( r = 0.89 and 0.87, respectively). Inter‐rater agreement for in‐person figure ratings and mean 17‐point videotape figure ratings was 0.86, and agreement between in‐person figure ratings and mean 9‐point videotape figure ratings was 0.82. Discussion: The FRS can be used as an index of women's weight status by an unbiased observer, with subjects viewed in‐person or on videotape.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93750/1/oby.2006.249.pd