Efficient parameterization of waverider geometries

This paper summarizes the results of investigations into the development of parametric waverider geometry models, with emphasis on their efficiency, in terms of their ability to cover a large feasible design space with a sufficiently small number of design variables to avoid the “curse of dimensionality.” The work presented here is focused on the parameterization of idealized waverider forebody geometries that provide the baseline shapes upon which more sophisticated and realistic hypersonic aircraft geometries can be built. Three different aspects of rationalizing the decisions behind the parametric geometry models developed using the osculating cones method are considered. Initially, three different approaches to the design method itself are discussed. Each approach provides direct control over different aspects of the geometry for which very specific shapes would be more complex to obtain indirectly, thus enabling the geometry to more efficiently meet any related design constraints. Then, a number of requirements and limitations are investigated that affect the available options for the parametric design-driving curves of the inverse design method. Finally, the performance advantages that open up with increasing flexibility of the design-driving curves in the context of a design optimization study are estimated. This allows one to reduce the risk of overparameterizing the geometry model, while still enabling a variety of meaningful shapes. Although the osculating cones method has mainly been used here, most of the findings also apply to other similar inverse design algorithms

Glypican-1 Mediates Both Prion Protein Lipid Raft Association and Disease Isoform Formation

In prion diseases, the cellular form of the prion protein, PrPC, undergoes a conformational conversion to the infectious isoform, PrPSc. PrPC associates with lipid rafts through its glycosyl-phosphatidylinositol (GPI) anchor and a region in its N-terminal domain which also binds to heparan sulfate proteoglycans (HSPGs). We show that heparin displaces PrPC from rafts and promotes its endocytosis, suggesting that heparin competes with an endogenous raft-resident HSPG for binding to PrPC. We then utilised a transmembrane-anchored form of PrP (PrP-TM), which is targeted to rafts solely by its N-terminal domain, to show that both heparin and phosphatidylinositol-specific phospholipase C can inhibit its association with detergent-resistant rafts, implying that a GPI-anchored HSPG targets PrPC to rafts. Depletion of the major neuronal GPI-anchored HSPG, glypican-1, significantly reduced the raft association of PrP-TM and displaced PrPC from rafts, promoting its endocytosis. Glypican-1 and PrPC colocalised on the cell surface and both PrPC and PrPSc co-immunoprecipitated with glypican-1. Critically, treatment of scrapie-infected N2a cells with glypican-1 siRNA significantly reduced PrPSc formation. In contrast, depletion of glypican-1 did not alter the inhibitory effect of PrPC on the β-secretase cleavage of the Alzheimer's amyloid precursor protein. These data indicate that glypican-1 is a novel cellular cofactor for prion conversion and we propose that it acts as a scaffold facilitating the interaction of PrPC and PrPSc in lipid rafts

Preparation and Analysis of the Geometry Models used in the 1st AIAA Geometry and Mesh Generation Workshop

The NASA High-Lift Common Research Model (HL-CRM) was the subject model chosen for the AIAA Geometry and Mesh Generation Workshop I (GMGW-1) and High-Lift Prediction Workshop III (HLPW-3). This paper describes how geometry models of the HLCRM were prepared for use in the workshops and reviews the analysis of their construction that was provided to workshop participants. The refinements made to the HL-CRM geometry model immediately after GMGW-1 are also presented

Fracture Tests to Study the Behaviour of Simulated Sub-Surface Flaws in a Reactor Pressure Vessel Steel - a Continuation of the NESC-IV project

The NESC-IV project (2000 - 2005) addressed the transferability of fracture toughness data from laboratory specimens to applications that assess the integrity of reactor pressure vessels. This project included a series of uniaxial bend tests on large beams with a simulated shallow, sub-surface flaw. The results of these experiments pointed towards a significant constraint-loss effect in the ductile-to-brittle transition temperature range of the used steel, but in view of the inherent scatter in fracture toughness of low alloy steels in the given regime, further testing was recommended. Therefore the scope of present project was to perform a set of six additional tests with nominally identical test piece geometry, material and loading arrangements, so as to obtain a statistically more relevant data set. The Institute for Energy contracted the Nuclear Research Institute in Rez to perform these experiments. Following the successful execution of the tests, a preliminary fracture mechanics analysis was made to compare estimates of the stress intensity values at failure with the material's Master Curve. The results confirmed the constraint-loss effect, which had been observed in the previous NESC-IV test series. Moreover it was found that some aspects needed further attention, such as detailed finite element modelling of the experimental arrangements and accurate characterization of the test material's fracture toughness. The latter should also consider material inhomogeneity issues.JRC.F.4-Safety of future nuclear reactor

Considerations for the measurement of core, skin and mean body temperatures

Despite previous reviews and commentaries, significant misconceptions remain concerning deep-body (core) and skin temperature measurement in humans. Therefore, the authors have assembled the pertinent Laws of Thermodynamics and other first principles that govern physical and physiological heat exchanges. The resulting review is aimed at providing theoretical and empirical justifications for collecting and interpreting these data. The primary emphasis is upon deep-body temperatures, with discussions of intramuscular, subcutaneous, transcutaneous and skin temperatures included. These are all turnover indices resulting from variations in local metabolism, tissue conduction and blood flow. Consequently, inter-site differences and similarities may have no mechanistic relationship unless those sites have similar metabolic rates, are in close proximity and are perfused by the same blood vessels. Therefore, it is proposed that a gold standard deep-body temperature does not exist. Instead, the validity of each measurement must be evaluated relative to one\u27s research objectives, whilst satisfying equilibration and positioning requirements. When using thermometric computations of heat storage, the establishment of steady-state conditions is essential, but for clinically relevant states, targeted temperature monitoring becomes paramount. However, when investigating temperature regulation, the response characteristics of each temperature measurement must match the forcing function applied during experimentation. Thus, during dynamic phases, deep-body temperatures must be measured from sites that track temperature changes in the central blood volume

Thermal and cardiovascular strain imposed by motorcycle protective clothing under Australian summer conditions

Motorcycle protective clothing can be uncomfortably hot during summer, and this experiment was designed to evaluate the physiological significance of that burden. Twelve males participated in four, 90-min trials (cycling 30 W) across three environments (25, 30, 35 °C [all 40% relative humidity]). Clothing was modified between full and minimal injury protection. Both ensembles were tested at 25 °C, with only the more protective ensemble investigated at 30 and 35 °C. At 35 °C, auditory canal temperature rose at 0.02 °C min(-1) (SD 0.005), deviating from all other trials (p \u3c 0.05). The thresholds for moderate (\u3e38.5 °C) and profound hyperthermia (\u3e40.0 °C) were predicted to occur within 105 min (SD 20.6) and 180 min (SD 33.0), respectively. Profound hyperthermia might eventuate in ~10 h at 30 °C, but should not occur at 25 °C. These outcomes demonstrate a need to enhance the heat dissipation capabilities of motorcycle clothing designed for summer use in hot climates, but without compromising impact protection. Practitioner\u27s Summary: Motorcycle protective clothing can be uncomfortably hot during summer. This experiment was designed to evaluate the physiological significance of this burden across climatic states. In the heat, moderate (\u3e38.5 °C) and profound hyperthermia (\u3e40.0 °C) were predicted to occur within 105 and 180 min, respectively

Thermal and cardiovascular strain imposed by motorcycle protective clothing under Australian summer conditions

Motorcycle protective clothing can be uncomfortably hot during summer, and this experiment was designed to evaluate the physiological significance of that burden. Twelve males participated in four, 90-min trials (cycling 30 W) across three environments (25, 30, 35 °C [all 40% relative humidity]). Clothing was modified between full and minimal injury protection. Both ensembles were tested at 25 °C, with only the more protective ensemble investigated at 30 and 35 °C. At 35 °C, auditory canal temperature rose at 0.02 °C min(-1) (SD 0.005), deviating from all other trials (p \u3c 0.05). The thresholds for moderate (\u3e38.5 °C) and profound hyperthermia (\u3e40.0 °C) were predicted to occur within 105 min (SD 20.6) and 180 min (SD 33.0), respectively. Profound hyperthermia might eventuate in ~10 h at 30 °C, but should not occur at 25 °C. These outcomes demonstrate a need to enhance the heat dissipation capabilities of motorcycle clothing designed for summer use in hot climates, but without compromising impact protection. Practitioner\u27s Summary: Motorcycle protective clothing can be uncomfortably hot during summer. This experiment was designed to evaluate the physiological significance of this burden across climatic states. In the heat, moderate (\u3e38.5 °C) and profound hyperthermia (\u3e40.0 °C) were predicted to occur within 105 and 180 min, respectively

Identification and analysis of cassava genotype TME3 bacteria artificial chromosome libraries for characterization of the cassava mosaic disease

Cassava is an economically important crop in sub-Saharan Africa; however, its yield potential is constrained by cassava mosaic disease (CMD) infection. Classical genetics and biotechnology are being harnessed to overcome the disease and secure yields for farmers. The CMD2 resistance locus flanked by three simple sequence repeats (SSR) markers and one sequence characterized amplified region (SCAR) marker were mapped in West African genotypes and shown to impart qualitative resistant to all species of CMGs. However, gene(s) associated with the CMD2 locus and their mode of actions remains unknown. In an effort to discover gene(s) located in CMD2 locus region, TME3 BAC collections were screened for the presence of CMD2 flanking markers. CMD susceptible and resistant cassava genotypes were found to contain 100% of the markers flanking CMD2 locus. SNPs and nucleotide deletions were identified within the marker sequences but there was no evidence of trait and marker association. All the SSR markers flanking CMD2, and the more recently characterized CMD3 loci were to be located on chromosome 12. Through BAC pools library hybridization with marker probes, 130 BACs were identified, but only 23 BACs contained at least CMD2 specific two markers. Whole BAC sequencing identified five clones that mapped to the marker regions. BAC29 assembled into a 100 kb contig and encoded tandem repeats of three full length R genes (3.5 kb) and two partial repeats. These R genes were conserved and highly expressed in CMD susceptible and CMD resistant cassava genotypes. Promoter sequences derived from R genes showed similar transient expression of GUS as 35S promoter. On cassava genome V6.1 BAC29 sequences were mapped to chromosome 16, eliminating their potential role in CMD resistant.Keywords: Bacteria artificial chromosome, CMD2, cassava, cassava mosaic diseas

Efficient CRISPR/Cas9 genome editing of Phytoene desaturase in cassava

CRISPR/Cas9 has become a powerful genome-editing tool for introducing genetic changes into crop species. In order to develop capacity for CRISPR/Cas9 technology in the tropical staple cassava (Manihot esculenta), the Phytoene desaturase (MePDS) gene was targeted in two cultivars using constructs carrying gRNAs targeting two sequences within MePDS exon 13. After Agrobacterium-mediated delivery of CRISPR/Cas9 reagents into cassava cells, both constructs induced visible albino phenotypes within cotyledon-stage somatic embryos regenerating on selection medium and the plants regenerated therefrom. A total of 58 (cv. 60444) and 25 (cv. TME 204) plant lines were recovered, of which 38 plant lines (19 from each cultivar) were analyzed for mutagenesis. The frequency of plant lines showing albino phenotype was high, ranging from 90 to 100% in cv. TME 204. Observed albino phenotypes were comprised of full albinos devoid of green tissue and chimeras containing a mixture of white and green tissues. Sequence analysis revealed that 38/38 (100%) of the plant lines examined carried mutations at the targeted MePDS site, with insertions, deletions, and substitutions recorded. One putatively mono-allelic homozygous line (1/19) was found from cv. 60444, while 1 (1/19) and 4 (4/19) putatively bi-allelic homozygous lines were found in 60444 and TME204, respectively. The remaining plant lines, comprised mostly of the chimeras, were found to be putatively heterozygous. We observed minor (1 bp) nucleotide substitutions and or deletions upstream of the 5 0 and or downstream of the 3 0 targeted MePDS region. The data reported demonstrates that CRISPR/Cas9-mediated genome editing of cassava is highly efficient and relatively simple, generating multi-allelic mutations in both cultivars studied. Modification of MePDS described here generates visually detectable mutated events in a relatively short time frame of 6-8 weeks, and does not require sequencing to confirm editing at the target. It therefore provides a valuable platform to facilitate rapid assessment and optimization of CRISPR/Cas9 and other genome-editing technologies in cassava