NPSS Multidisciplinary Integration and Analysis

The objective of this task was to enhance the capability of the Numerical Propulsion System Simulation (NPSS) by expanding its reach into the high-fidelity multidisciplinary analysis area. This task investigated numerical techniques to convert between cold static to hot running geometry of compressor blades. Numerical calculations of blade deformations were iteratively done with high fidelity flow simulations together with high fidelity structural analysis of the compressor blade. The flow simulations were performed with the Advanced Ducted Propfan Analysis (ADPAC) code, while structural analyses were performed with the ANSYS code. High fidelity analyses were used to evaluate the effects on performance of: variations in tip clearance, uncertainty in manufacturing tolerance, variable inlet guide vane scheduling, and the effects of rotational speed on the hot running geometry of the compressor blades

MRI Markers and Functional Performance in Patients With CIS and MS: A Cross-Sectional Study

Introduction: Brain atrophy is a widely accepted marker of disease severity with association to clinical disability in multiple sclerosis (MS). It is unclear to which extent this association reflects common age effects on both atrophy and function. Objective: To explore how functional performance in gait, upper extremities and cognition is associated with brain atrophy in patients with Clinically Isolated Syndrome (CIS) and relapsing-remitting MS (RRMS), controlling for effects of age and sex. Methods: In 27 patients with CIS, 59 with RRMS (EDSS <= 3) and 63 healthy controls (HC), 3T MRI were analyzed for T2 lesion count (T2C), volume (T2V) and brain volumes [normalized brain volume (NBV), gray matter volume (NGMV), white matter volume (NWMV), thalamic volume (NThaIV)]. Functional performance was measured with short maximum walking speed (SMSW speed), 9-hole peg test (9HPT) and symbol digit modalities test (SDMT). Linear regression models were created for functional variables with stepwise inclusion of age, sex and MR imaging markers. Results: CIS differed from HC only in T2C and T2V. RRMS differed from HC in NBV, NGMV and NThaIV, T2C and T2V, but not in NWMV. A strong association with age was seen in HC, CIS and RRMS groups for NBV (r = -0.5 to -0.6) and NGMV (r = -0.6 to -0.8). Associations with age were seen in HC and RRMS but not CIS for NThaIV (r = -0.3; r = -0.5), T2C (r(s) = 0.3; r(s) = 0.2) and T2V (r(s) = 0.3; r(s) = 0.3). No effect of age was seen on NWMV. Correlations of functional performance with age in RRMS were seen for SMSW speed, 9HPTand SDMT (r = -0.27 to -0.46). Regression analyses yielded significant models only in the RRMS group for 9HPT, SMSW speed and EDSS. These included NBV, NGMV, NThaIV, NWMV, logT2V, age and sex as predictors. NThalV was the only MRI variable predicting a functional measure (9HPT(r)) with a higher standardized beta than age and sex (R2 = 0.36, p < 1e-04). Conclusion: Thalamic atrophy was a stronger predictor of hand function (9HPT) in RRMS, than age and sex. This underlines the clinical relevance of thalamic atrophy and the relevance of hand function as a clinical marker even in mildly disabled patients

GW25-e0848 The effects of anticoagulant therapy on coagulant state and platelet function following transcatheter closure of atrial septal defect

BACKGROUND: Motor cortex stimulation (MCS) was introduced in the early 1990s by Tsubokawa and his group for patients diagnosed with drug-resistant, central neuropathic pain. Inconsistencies concerning the details of this therapy and its outcomes and poor methodology of most clinical essays divide the neuromodulation society worldwide into "believers" and "nonbelievers." A European expert meeting was organized in Brussels, Belgium by the Benelux Neuromodulation Society in order to develop uniform MCS protocols in the preoperative, intraoperative, and postoperative courses. METHODS: An expert meeting was organized, and a questionnaire was sent out to all the invited participants before this expert meeting. An extensive literature research was conducted in order to enrich the results. RESULTS: Topics that were addressed during the expert meeting were 1) inclusion and exclusion criteria, 2) targeting and methods of stimulation, 3) effects of MCS, and 4) results from the questionnaire. CONCLUSIONS: Substantial commonalities but also important methodologic divergencies emerged from the discussion of MCS experts from 7 European Centers. From this meeting and questionnaire, all participants concluded that there is a need for more homogenous standardized protocols for MCS regarding patient selection, implantation procedure, stimulation parameters, and follow-up-course

Purification, Overproduction, and Partial Characterization of β-RFAP Synthase, a Key Enzyme in the Methanopterin Biosynthesis Pathway†

Methanopterin is a folate analog involved in the C(1) metabolism of methanogenic archaea, sulfate-reducing archaea, and methylotrophic bacteria. Although a pathway for methanopterin biosynthesis has been described in methanogens, little is known about the enzymes and genes involved in the biosynthetic pathway. The enzyme β-ribofuranosylaminobenzene 5′-phosphate synthase (β-RFAP synthase) catalyzes the first unique step to be identified in the pathway of methanopterin biosynthesis, namely, the condensation of p-aminobenzoic acid with phosphoribosylpyrophosphate to form β-RFAP, CO(2), and inorganic pyrophosphate. The enzyme catalyzing this reaction has not been purified to homogeneity, and the gene encoding β-RFAP synthase has not yet been identified. In the present work, we report on the purification to homogeneity of β-RFAP synthase. The enzyme was purified from the methane-producing archaeon Methanosarcina thermophila, and the N-terminal sequence of the protein was used to identify corresponding genes from several archaea, including the methanogen Methanococcus jannaschii and the sulfate-reducing archaeon Archaeoglobus fulgidus. The putative β-RFAP synthase gene from A. fulgidus was expressed in Escherichia coli, and the enzymatic activity of the recombinant gene product was verified. A BLAST search using the deduced amino acid sequence of the β-RFAP synthase gene identified homologs in additional archaea and in a gene cluster required for C(1) metabolism by the bacterium Methylobacterium extorquens. The identification of a gene encoding a potential β-RFAP synthase in M. extorquens is the first report of a putative methanopterin biosynthetic gene found in the Bacteria and provides evidence that the pathways of methanopterin biosynthesis in Bacteria and Archaea are similar

Session IT 302-041 Using Knowledge-based Solid Modeling Techniques and Airfoil Design Data: A Case Study in Developing an Airfoil Seed Part Generator Abstract

This paper details a research project which encompassed the development of corporate best practices surrounding the use of company specific compressor and turbine design data in the generation of solid model geometry. Current solid modeling processes at Rolls-Royce Corporation for compressor and turbine engine airfoil geometry require a great deal of time and are prone to human error in the replacement of CAD geometry when design changes are made. A team of Purdue University students and faculty collaborated with Rolls-Royce Corporation to improve this process using knowledge-based tools within the Unigraphics (UG) NX 2 modeling tool set. A graphical user interface to import and manipulate aero data was developed and tested to ensure that it met design standards and maintained airfoil geometric integrity within the Rolls-Royce environment. Times for airfoil model replacement using the new application were recorded and compared to the previous method. Results demonstrated that the knowledge-based modeling applications had an average of 88.3 % time savings as well as allowed for automation of the solid model creation process of the airfoils. Suggestions for integration of such technique

A Systems Biology Approach for Identifying Hepatotoxicant Groups Based on Similarity in Mechanisms of Action and Chemical Structure

When evaluating compound similarity, addressing multiple sources of information to reach conclusions about common pharmaceutical and/or toxicological mechanisms of action is a crucial strategy. In this chapter, we describe a systems biology approach that incorporates analyses of hepatotoxicant data for 33 compounds from three different sources: a chemical structure similarity analysis based on the 3D Tanimoto coefficient, a chemical structure-based protein target prediction analysis, and a cross-study/cross-platform meta-analysis of in vitro and in vivo human and rat transcriptomics data derived from public resources (i.e., the diXa data warehouse). Hierarchical clustering of the outcome scores of the separate analyses did not result in a satisfactory grouping of compounds considering their known toxic mechanism as described in literature. However, a combined analysis of multiple data types may hypothetically compensate for missing or unreliable information in any of the single data types. We therefore performed an integrated clustering analysis of all three data sets using the R-based tool iClusterPlus. This indeed improved the grouping results. The compound clusters that were formed by means of iClusterPlus represent groups that show similar gene expression while simultaneously integrating a similarity in structure and protein targets, which corresponds much better with the known mechanism of action of these toxicants. Using an integrative systems biology approach may thus overcome the limitations of the separate analyses when grouping liver toxicants sharing a similar mechanism of toxicity