Position Paper External Tank Thermal Protection System (TPS) Manually Sprayed fly-as-is Foam Certification

During manufacture of the existing External Tanks (ETs), the Thermal Protection System (TPS) foam manual spray application processes lacked the enhanced controls/procedures to ensure that defects produced were less than the critical size. Therefore the only remaining option to certify the "fly-as-is" foam is to verify ET120 tank hardware meets the new foam debris requirements. The ET project has undertaken a significant effort studying the existing "fly-as-is" TPS foam. This paper contains the findings of the study

A Unifying View on Recombination Spaces and Abstract Convex Evolutionary Search

This is the author accepted manuscript. The final version is available from Springer via the DOI in this record.Proceedings of EvoCOP 2019 - 19th European Conference on Evolutionary Computation, 24-26 April 2019, Leipzig, GermanyPrevious work proposed to unify an algebraic theory of fitness landscapes and a geometric framework of evolutionary algorithms (EAs). One of the main goals behind this unification is to develop an analytical method that verifies if a problem's landscape belongs to certain abstract convex landscapes classes, where certain recombination-based EAs (without mutation) have polynomial runtime performance. This paper advances such unification by showing that: (a) crossovers can be formally classified according to geometric or algebraic axiomatic properties; and (b) the population behaviour induced by certain crossovers in recombination-based EAs can be formalised in the geometric and algebraic theories. These results make a significant contribution to the basis of an integrated geometric-algebraic framework with which analyse recombination spaces and recombination-based EAs

NESC Peer-Review of the Flight Rationale for Expected Debris Report

Since the loss of Columbia on February 1, 2003, the Space Shuttle Program (SSP) has significantly improved the understanding of launch and ascent debris, implemented hardware modifications to reduce debris, and conducted tests and analyses to understand the risks associated with expected debris. The STS-114 flight rationale for expected debris relies on a combination of all three of these factors. A number of design improvements have been implemented to reduce debris at the source. The External Tank (ET) thermal protection system (TPS) foam has been redesigned and/or process improvements have been implemented in the following locations: the bipod closeout, the first ten feet of the liquid hydrogen (LH2) tank protuberance air load (PAL) ramp, and the LH2 tank-to-intertank flange closeout. In addition, the forward bipod ramp has been eliminated and heaters have been installed on the bipod fittings and the liquid oxygen (LO2) feedline forward bellows to prevent ice formation. The Solid Rocket Booster (SRB) bolt catcher has been redesigned. The Orbiter reaction control system (RCS) thruster cover "butcher paper" has been replaced with a material that sheds at a low velocity. Finally, the pad area has been cleaned to reduce debris during lift-off

TSS-1R Mission Failure Investigation Board

Reasons for the tether separation during the Tethered Satellite System (TSS-1) Mission are investigated. Lessons learned are presented

Spatial patterns of enzymatic activity in large water bodies: Ship-borne measurements of beta-D-glucuronidase activity as a rapid indicator of microbial water quality

This study used automated enzymatic activity measurements conducted from a mobile research vessel to detect the spatial variability of beta‑d‑glucuronidase (GLUC) activity in large freshwater bodies. The ship-borne observations provided the first high-resolution spatial data of GLUC activity in large water bodies as rapid indication of fecal pollution and were used to identify associations with hydrological conditions and land use. The utility of this novel approach for water quality screening was evaluated by surveys of the Columbia River, the Mississippi River and the Yahara Lakes, covering up to a 500 km river course and 50 km2 lake area. The ship-borne measurements of GLUC activity correlated with standard E. coli analyses (R2 = 0.71) and revealed the effects of (1) precipitation events and urban run-off on GLUC activity in surface waters, (2) localized point inlets of potential fecal pollution and (3) increasing GLUC signals along gradients of urbanization. We propose that this ship-borne water quality screening to be integrated into future water inventory programs as an initial or complementary tool (besides established fecal indicator parameters), due to its ability to provide near real-time spatial information on potential fecal contamination of large surface water resources and therefore being helpful to greatly reduce potential human health risks.Austrian Science Fund (FWF)Vienna University of TechnologyNorth Temperate Lakes–Long Term Ecological Researc

Allele-Specific Deletions in Mouse Tumors Identify Fbxw7 as Germline Modifier of Tumor Susceptibility

Genome-wide association studies (GWAS) have been successful in finding associations between specific genetic variants and cancer susceptibility in human populations. These studies have identified a range of highly statistically significant associations between single nucleotide polymorphisms (SNPs) and susceptibility to development of a range of human tumors. However, the effect of each SNP in isolation is very small, and all of the SNPs combined only account for a relatively minor proportion of the total genetic risk (5–10%). There is therefore a major requirement for alternative routes to the discovery of genetic risk factors for cancer. We have previously shown using mouse models that chromosomal regions harboring susceptibility genes identified by linkage analysis frequently exhibit allele-specific genetic alterations in tumors. We demonstrate here that the Fbxw7 gene, a commonly mutated gene in a wide range of mouse and human cancers, shows allele-specific deletions in mouse lymphomas and skin tumors. Lymphomas from three different F1 hybrids show 100% allele-specificity in the patterns of allelic loss. Parental alleles from 129/Sv or Spretus/Gla mice are lost in tumors from F1 hybrids with C57BL/6 animals, due to the presence of a specific non-synonymous coding sequence polymorphism at the N-terminal portion of the gene. A specific genetic test of association between this SNP and lymphoma susceptibility in interspecific backcross mice showed a significant linkage (p = 0.001), but only in animals with a functional p53 gene. These data therefore identify Fbxw7 as a p53-dependent tumor susceptibility gene. Increased p53-dependent tumor susceptibility and allele-specific losses were also seen in a mouse skin model of skin tumor development. We propose that analysis of preferential allelic imbalances in tumors may provide an efficient means of uncovering genetic variants that affect mouse and human tumor susceptibility

Single-cell analysis: visualizing pharmaceutical and metabolite uptake in cells with label-free 3D mass spectrometry imaging

Detecting metabolites and parent compound within a cell type is now a priority for pharmaceutical development. In this context, three-dimensional secondary ion mass spectrometry (SIMS) imaging was used to investigate the cellular uptake of the antiarrhythmic agent amiodarone, a phospholipidosis-inducing pharmaceutical compound. The high lateral resolution and 3D imaging capabilities of SIMS combined with the multiplex capabilities of ToF mass spectrometric detection allows for the visualization of pharmaceutical compound and metabolites in single cells. The intact, unlabeled drug compound was successfully detected at therapeutic dosages in macrophages (cell line: NR8383). Chemical information from endogenous biomolecules was used to correlate drug distributions with morphological features. From this spatial analysis, amiodarone was detected throughout the cell with the majority of the compound found in the membrane and subsurface regions and absent in the nuclear regions. Similar results were obtained when the macrophages were doped with amiodarone metabolite, desethylamiodarone. The FWHM lateral resolution measured across an intracellular interface in a high lateral resolution ion images was approximately 550 nm. Overall, this approach provides the basis for studying cellular uptake of pharmaceutical compounds and their metabolites on the single cell level

O-GlcNAc Modification of NFκB p65 Inhibits TNF-α-Induced Inflammatory Mediator Expression in Rat Aortic Smooth Muscle Cells

BACKGROUND: We have shown that glucosamine (GlcN) or O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc) treatment augments O-linked-N-acetylglucosamine (O-GlcNAc) protein modification and attenuates inflammatory mediator expression, leukocyte infiltration and neointima formation in balloon injured rat carotid arteries and have identified the arterial smooth muscle cell (SMC) as the target cell in the injury response. NFκB signaling has been shown to mediate the expression of inflammatory genes and neointima formation in injured arteries. Phosphorylation of the p65 subunit of NFκB is required for the transcriptional activation of NFκB. This study tested the hypothesis that GlcN or PUGNAc treatment protects vascular SMCs against tumor necrosis factor (TNF)-α induced inflammatory stress by enhancing O-GlcNAcylation and inhibiting TNF-α induced phosphorylation of NFκB p65, thus inhibiting NFκB signaling. METHODOLOGY/PRINCIPAL FINDINGS: Quiescent rat aortic SMCs were pretreated with GlcN (5 mM), PUGNAc (10(-4) M) or vehicle and then stimulated with TNF-α (10 ng/ml). Both treatments inhibited TNF-α-induced expression of chemokines [cytokine-induced neutrophil chemoattractant (CINC)-2β and monocyte chemotactic protein (MCP)-1] and adhesion molecules [vascular cell adhesion molecule (VCAM)-1 and P-Selectin]. Both treatments inhibited TNF-α induced NFκB p65 activation and promoter activity, increased NFκB p65 O-GlcNAcylation and inhibited NFκB p65 phosphorylation at Serine 536, thus promoting IκBα binding to NFκB p65. CONCLUSIONS: There is a reciprocal relationship between O-GlcNAcylation and phosphorylation of NFκB p65, such that increased NFκB p65 O-GlcNAc modification inhibits TNF-α-Induced expression of inflammatory mediators through inhibition of NFκB p65 signaling. These findings provide a mechanistic basis for our previous observations that GlcN and PUGNAc treatments inhibit inflammation and remodeling induced by acute endoluminal arterial injury

Features generated for computational splice-site prediction correspond to functional elements

<p>Abstract</p> <p>Background</p> <p>Accurate selection of splice sites during the splicing of precursors to messenger RNA requires both relatively well-characterized signals at the splice sites and auxiliary signals in the adjacent exons and introns. We previously described a feature generation algorithm (FGA) that is capable of achieving high classification accuracy on human 3' splice sites. In this paper, we extend the splice-site prediction to 5' splice sites and explore the generated features for biologically meaningful splicing signals.</p> <p>Results</p> <p>We present examples from the observed features that correspond to known signals, both core signals (including the branch site and pyrimidine tract) and auxiliary signals (including GGG triplets and exon splicing enhancers). We present evidence that features identified by FGA include splicing signals not found by other methods.</p> <p>Conclusion</p> <p>Our generated features capture known biological signals in the expected sequence interval flanking splice sites. The method can be easily applied to other species and to similar classification problems, such as tissue-specific regulatory elements, polyadenylation sites, promoters, etc.</p