Computational simulation of probabilistic lifetime strength for aerospace materials subjected to high temperature, mechanical fatigue, creep and thermal fatigue

This report presents the results of a fourth year effort of a research program, conducted for NASA-LeRC by the University of Texas at San Antonio (UTSA). The research included on-going development of methodology that provides probabilistic lifetime strength of aerospace materials via computational simulation. A probabilistic material strength degradation model, in the form of a randomized multifactor interaction equation, is postulated for strength degradation of structural components of aerospace propulsion systems subject to a number of effects or primitive variables. These primitive variables may include high temperature, fatigue or creep. In most cases, strength is reduced as a result of the action of a variable. This multifactor interaction strength degradation equation has been randomized and is included in the computer program, PROMISS. Also included in the research is the development of methodology to calibrate the above-described constitutive equation using actual experimental materials data together with regression analysis of that data, thereby predicting values for the empirical material constants for each effect or primitive variable. This regression methodology is included in the computer program, PROMISC. Actual experimental materials data were obtained from industry and the open literature for materials typically for applications in aerospace propulsion system components. Material data for Inconel 718 has been analyzed using the developed methodology

Deconjugation Kinetics of Glucuronidated Phase II Flavonoid Metabolites by B-glucuronidase from Neutrophils

Flavonoids are inactivated by phase II metabolism and occur in the body as glucuronides. Mammalian ß-glucuronidase released from neutrophils at inflammatory sites may be able to deconjugate and thus activate flavonoid glucuronides. We have studied deconjugation kinetics and pH optimum for four sources of ß-glucuronidase (human neutrophil, human recombinant, myeloid PLB-985 cells, Helix pomatia) with five flavonoid glucuronides (quercetin-3-glucuronide, quercetin-3'-glucuronide, quercetin-4'-glucuronide, quercetin-7-glucuronide, 3'-methylquercetin-3-glucuronide), 4-methylumbelliferyl-ß-D-glucuronide, and para-nitrophenol-glucuronide. All substrate-enzyme combinations tested exhibited first order kinetics. The optimum pH for hydrolysis was between 3.5-5, with appreciable hydrolysis activities up to pH 5.5. At pH 4, the Km ranged 44-fold from 22 µM for quercetin-4'-glucuronide with Helix pomatia ß-glucuronidase, to 981 µM for para-nitrophenol-glucuronide with recombinant ß-glucuronidase. Vmax (range: 0.735-24.012 µmol·min-1·unit-1 [1 unit is defined as the release of 1 µM 4-methylumbelliferyl-ß-D-glucuronide per min]) and the reaction rate constants at low substrate concentrations (k) (range: 0.002-0.062 min-1·(unit/L)-1 were similar for all substrates-enzyme combinations tested. In conclusion, we show that ß-glucuronidase from four different sources, including human neutrophils, is able to deconjugate flavonoid glucuronides and non-flavonoid substrates at fairly similar kinetic rates. At inflammatory sites in vivo the pH, neutrophil and flavonoid glucuronide concentrations seem favorable for deconjugation. However, it remains to be confirmed whether this is actually the case

Magnetic Behavior of Single La0.67_{0.67}Ca0.33_{0.33}MnO3_3 Nanotubes: Surface and Shape Effects

We report magnetization experiments in two magnetically isolated ferromagnetic nanotubes of perovskite La$_{0.67}$Ca$_{0.33}$MnO$_3$. The results show that the magnetic anisotropy is determined by the sample shape although the coercive field is reduced by incoherent magnetization reversal modes. The temperature dependence of the magnetization reveals that the magnetic behavior is dominated by grain surface properties. These measurements were acquired using a Silicon micro-mechanical oscillator working in its resonant mode. The sensitivity was enough to measure the magnetic properties of these two samples with a mass lower than 14 picograms and to obtain for the first time the magnetization loop for one isolated nanotube.Comment: 12 pages, 4 figures. Accepted for publication in Journal of Applied Physic

Alternative antibody for the detection of CA125 antigen: a European multicenter study for the evaluation of the analytical and clinical performance of the Access (R) OV Monitor assay on the UniCel (R) Dxl 800 Immunoassay System

Background: Cancer antigen CA125 is known as a valuable marker for the management of ovarian cancer. Methods: The analytical and clinical performance of the Access OV Monitor Immunoassay System (Beckman Coulter) was evaluated at five different European sites and compared with a reference system, defined as CA125 on the Elecsys System (Roche Diagnostics). Results: Total imprecision (%CV) of the OV Monitor ranged between 3.1% and 8.8%, and inter-laboratory reproducibility between 4.7% and 5.0%. Linearity upon dilution showed a mean recovery of 100% (SD+8.1%). Endogenous interferents had no influence on OV Monitor levels (mean recoveries: hemoglobin 107%, bilirubin 103%, triglycericles 103%). There was no high-dose hook effect up to 27,193 kU/L. Clinical performance investigated in sera from 1811 individuals showed a good correlation between the Access OV Monitor and Elecsys CA125 (R = 0.982, slope = 0.921, intercept = + 1.951). OV Monitor serum levels were low in healthy individuals (n = 267, median = 9.7 kU/L, 95th percentile = 30.8 kU/L), higher in individuals with various benign diseases (n = 549, medians = 10.9-16.4 kU/L, 95th percentiles = 44.2-355 kU/L) and even higher in individuals suffering from various cancers (n = 995, medians= 12.4-445 kU/L; 95th percentiles = 53.4-4664 kU/L). Optimal diagnostic accuracy for cancer detection against the relevant benign control group by the OV Monitor was found for ovarian cancer {[}area under the curve (AUC) 0.898]. Results for the reference CA125 assay were comparable (AUC 0.899). Conclusions: The Access OV Monitor provides very good methodological characteristics and demonstrates an excellent analytical and clinical correlation with Elecsys CA125. The best diagnostic accuracy for the OV Monitor was found in ovarian cancer. Our results also suggest a clinical value of the OV Monitor in other cancers

Significance of Dopamine Transmission in the Rat Medial Prefrontal Cortex for Conditioned Fear

Previous studies have demonstrated activation of dopamine transmission in the medial prefrontal cortex (mPFC) by conditioned fear stimuli. Therefore, the present study investigated the functional significance of mPFC dopamine for a conditioned fear response to a tone. We examined the effects of inhibition or stimulation of mPFC dopamine transmission by local microinfusion of the D1/D2-receptor antagonist cis-flupenthixol or the indirect dopamine receptor agonist d-amphetamine, respectively, in a classical fear-conditioning paradigm in Wistar rats. Rats received tone-shock pairings and were later exposed to the tone alone. Freezing was used as measure of conditioned fear. Presence of the drugs in the mPFC during the tone-shock pairings did not affect freezing during subsequent presentation of the tone alone. However, when cis-flupenthixol and d-amphetamine were present in the mPFC during presentation of the tone alone, freezing to the tone was reduced. We demonstrated that the decreased freezing could be explained neither by state dependency nor infusion-induced alterations in activity. Our data indicate that mPFC dopamine transmission is important for the retrieval/expression, but not the formation, of conditioned fear. The reduction of conditioned fear by prefrontal infusion of both cis-flupenthixol and d-amphetamine may reflect normal expression of conditioned fear requires an optimal level of mPFC dopamine activit

Travelling on Graphs with Small Highway Dimension

We study the Travelling Salesperson (TSP) and the Steiner Tree problem (STP) in graphs of low highway dimension. This graph parameter was introduced by Abraham et al. [SODA 2010] as a model for transportation networks, on which TSP and STP naturally occur for various applications in logistics. It was previously shown [Feldmann et al. ICALP 2015] that these problems admit a quasi-polynomial time approximation scheme (QPTAS) on graphs of constant highway dimension. We demonstrate that a significant improvement is possible in the special case when the highway dimension is 1, for which we present a fully-polynomial time approximation scheme (FPTAS). We also prove that STP is weakly NP-hard for these restricted graphs. For TSP we show NP-hardness for graphs of highway dimension 6, which answers an open problem posed in [Feldmann et al. ICALP 2015]

Immunotherapy of lung cancer: An update

In Germany lung cancer is the leading cause of cancer-associated death in men. Surgery, chemotherapy and radiation may enhance survival of patients suffering from lung cancer but the enhancement is typically transient and mostly absent with advanced disease; eventually more than 90% of lung cancer patients will die of disease. New approaches to the treatment of lung cancer are urgently needed. Immunotherapy may represent one new approach with low toxicity and high specificity but implementation has been a challenge because of the poor antigenic characterization of these tumors and their ability to escape immune responses. Several different immunotherapeutic treatment strategies have been developed. This review examines the current state of development and recent advances with respect to non-specific immune stimulation, cellular immunotherapy ( specific and non-specific), therapeutic cancer vaccines and gene therapy for lung cancer. The focus is primarily placed on immunotherapeutic cancer treatments that are already in clinical trial or well progressed in preclinical studies. Although there seems to be a promising future for immunotherapy in lung cancer, presently there is not standard immunotherapy available for clinical routine

Former of Turn Trajectory of Sliding Valve Shaft of Gas Line

Former of turn trajectory of sliding valve shaft of gas line, that allows to provide desired motion trajectory of sliding valve and its full closing, is considered in that paper. Imitation model of that former, research results, which allow to detect influence of gain factor and time constant of position controller on value of speed error, that has impact on delay of output coordinate from setting, and that results to delay of sliding valve motion process to setting position point, are shown

Decay of Sexual Trait Genes in an Asexual Parasitoid Wasp.

Trait loss is a widespread phenomenon with pervasive consequences for a species’ evolutionary potential. The genetic changes underlying trait loss have only been clarified in a small number of cases. None of these studies can identify whether the loss of the trait under study was a result of neutral mutation accumulation or negative selection. This distinction is relatively clear-cut in the loss of sexual traits in asexual organisms. Male-specific sexual traits are not expressed and can only decay through neutral mutations, whereas female-specific traits are expressed and subject to negative selection. We present the genome of an asexual parasitoid wasp and compare it to that of a sexual lineage of the same species. We identify a short-list of 16 genes for which the asexual lineage carries deleterious SNP or indel variants, whereas the sexual lineag e does not. Using tissue-specific expression data from other insects, we show that fifteen of these are expressed in male-specific reproductive tissues. Only one deleterious variant was found that is expressed in the female-specific spermathecae, a trait that is heavily degraded and thought to be under negative selection in L. clavipes . Although the phenotypic decay of male-specific sexual traits in asexuals is generally slow compared with the decay of female-specific sexual traits, we show that male-specific traits do indeed accumulate deleterious mutations as expected by theory. Our results provide an excellent starting point for detailed s tudy of the genomics of neutral and selected trait decay