746 research outputs found

    Solid motor diagnostic instrumentation

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    A review of typical surveillance and monitoring practices followed during the flight phases of representative solid-propellant upper stages and apogee motors was conducted to evaluate the need for improved flight diagnostic instrumentation on future spacecraft. The capabilities of the flight instrumentation package were limited to the detection of whether or not the solid motor was the cause of failure and to the identification of probable primary failure modes. Conceptual designs of self-contained flight instrumentation packages capable of meeting these reqirements were generated and their performance, typical cost, and unit characteristics determined. Comparisons of a continuous real time and a thresholded hybrid design were made on the basis of performance, mass, power, cost, and expected life. The results of this analysis substantiated the feasibility of a self-contained independent flight instrumentation module as well as the existence of performance margins by which to exploit growth option applications

    A New Pseudopolymorph of Hexakis-(4-cynaophenyl)benzene

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    The title compound (systematic name: benzene-4,4ā€²,4ā€²ā€²,4ā€²ā€²ā€²,-4ā€²ā€²ā€²ā€²,4ā€²ā€²ā€²ā€²ā€²-hexaylhexabenzonitrile dichloromethane disolvate), C48H24N6ā€¢2CH2Cl2, crystallizes as an inclusion compound during the slow diffusion of methanol into a solution of hexakis(4-cyanophenyl)benzene in CH2Cl2. The hexakis(4- cyanophenyl)benzene molecule lies on an axis of twofold rotation in the space group Pbcn. Weak Cā€”Hā€¢ā€¢ā€¢N interactions between hexakis(4-cyanophenyl)benzene molecules define an open network with space for including guests. The resulting structure is a new pseudopolymorph of hexakis-(4-cyanophenyl)benzene. The eight known pseudopolymorphs have few shared architectural features, in part because none of the intermolecular interactions that are present plays a dominant role or forces neighboring molecules to assume particular relative orientations

    Injustice perceptions about pain: parentā€“child discordance is associated with worse functional outcomes

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    Pain is experienced within and influenced by social environments. For children with chronic pain, the childā€“parent relationship and parental beliefs about pain are particularly important and may influence pain outcomes. Pain-related injustice perceptions have recently been identified as an important cognitiveā€“emotional factor for children with pain. The current study aimed to better understand the pain-related injustice perceptions of children with chronic pain and their parents. The sample consisted of 253 pediatric chronic pain patients (mean age = 14.1 years, 74% female) presenting to a tertiary pain clinic. Patients completed measures of pain intensity, pain-related injustice perceptions, stress, functional disability, and quality of life. Parents completed a measure of pain-related injustice perceptions about their child's pain. Childā€“parent dyads were categorized into 1 of 4 categories based on the degree of concordance or discordance between their scores on the injustice measures. One-way analysis of variances examined differences in pain intensity, stress, functional disability, and quality of life across the 4 dyad categories. Our findings indicated that both the degree (concordant vs discordant) and direction (discordant low childā€“high parent vs discordant high childā€“low parent) of similarity between child and parent injustice perceptions were associated with child-reported pain intensity, stress, functional disability, and quality of life. The poorest outcomes were reported when children considered their pain as highly unjust, but their parents did not. These findings highlight the important role of parents in the context of pain-related injustice perceptions in pediatric chronic pain

    Immuno-PET of epithelial ovarian cancer: Harnessing the potential of CA125 for non-invasive imaging

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    BACKGROUND: Epithelial ovarian cancer (EOC) is characterized by the overexpression of cancer antigen 125 (CA125), a mucinous glycoprotein that serves as a tumor biomarker. Early diagnosis of EOC is plagued by its asymptomatic nature of progression and the limitations of currently used immunoassay techniques that detect CA125 as a shed antigen in serum samples. Presently, there is no technique available for the in vivo evaluation of CA125 expression in malignant tissues. Moreover, there could be an unexplored pathophysiological time window for the detection of CA125 in EOC, during which it is expressed on tumor cells prior to being shed into the bloodstream. A method for the in vivo evaluation of CA125 expression on ovarian neoplasms earlier along disease progression and/or recurrence can potentially contribute to better disease management. To this end, the present work utilizes an anti-CA125 monoclonal antibody (MAb) and a single-chain variable fragment (scFv) labeled with the positron-emitting radionuclide (64)Cu for preclinical molecular imaging of CA125 expression in vivo. METHODS: Anti-CA125 MAb and scFv were prepared and functionally characterized for target binding prior to being tested as radiotracers in a preclinical setting. RESULTS: Immunoblotting, immunofluorescence, and flow cytometry revealed specific binding of CA125-targeting vectors to NIH:OVCAR-3 cells and no binding to antigen-negative SKOV3 cells. (64)Cu-labeled anti-CA125 MAb and scFv were obtained in specific activities of 296 and 122 MBq/mg, respectively. Both radioimmunoconjugate vectors demonstrated highly selective binding to NIH:OVCAR-3 cells and virtually no binding to SKOV3 cells. In vivo radiopharmacological evaluation using xenograft mouse models injected with (64)Cu-labeled anti-CA125 MAb provided a standardized uptake value (SUV) of 5.76 (29.70 %ID/g) in OVCAR3 tumors 24 h post-injection (p.i.) versus 1.80 (5.91 %ID/g) in SKOV3 tumors. (64)Cu-labeled anti-CA125 scFv provided an SUV of 0.64 (3.21 %ID/g) in OVCAR3 tumors 24 h p.i. versus 0.25 (1.49 %ID/g) in SKOV3 tumors. Results from small-animal PET imaging were confirmed by ex vivo autoradiography and immunohistochemistry. CONCLUSIONS: Radiolabeling of anti-CA125 MAb and scFv with (64)Cu did not compromise their immunoreactivity. Both radioimmunoconjugates presented specific tumor uptake and expected biological clearance profiles. This renders them as potential immuno-PET probes for targeted in vivo molecular imaging of CA125 in EOC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13550-014-0060-4) contains supplementary material, which is available to authorized users

    Model for predicting the UHPFRC tensile hardening response

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    Ultra High Performances Fibre Reinforced Concretes (UHPFRC) are characterised by an ex-tremely low permeability and outstanding mechanical properties. These characteristics make UHPFRC suitable for locally ā€œhardenā€ reinforced concrete structures subjected to aggressive environments and/or mechanical stresses. Results from uni-axial tensile tests on different UHPFRC materials and cast in different directions have shown a variety of mechanical behav-iour. In particular, the hardening behaviour ranges from 0.1-0.4 % but is, in some cases, not existent. A meso-mechanical model is developed to predict the UHPFRC tensile response as a function of the volume, aspect-ratio, distribution and orientation of the fibres and the mechanical properties of the matrix. The model allows determining the effect of two parameters, the coeffi-cient of orientation and the volume of fibre, on the hardening behaviour

    A plant biodiversity effect resolved to a single chromosomal region

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    Despite extensive evidence that biodiversity promotes plant community productivity, progress towards understanding the mechanistic basis of this effect remains slow, impeding the development of predictive ecological theory and agricultural applications. Here, we analysed non-additive interactions between genetically divergent Arabidopsis accessions in experimental plant communities. By combining methods from ecology and quantitative genetics, we identify a major effect locus at which allelic differences between individuals increase the above-ground productivity of communities. In experiments with near-isogenic lines, we show that this diversity effect acts independently of other genomic regions and can be resolved to a single region representing less than 0.3% of the genome. Using plantā€“soil feedback experiments, we also demonstrate that allelic diversity causes genotype-specific soil legacy responses in a consecutive growing period, even after the original community has disappeared. Our work thus suggests that positive diversity effects can be linked to single Mendelian factors, and that a range of complex community properties can have a simple cause. This may pave the way to novel breeding strategies, focusing on phenotypic properties that manifest themselves beyond isolated individuals; that is, at a higher level of biological organization

    Increasing plant group productivity through latent genetic variation for cooperation

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    Historic yield advances in the major crops have, to a large extent, been achieved by selection for improved productivity of groups of plant individuals such as high-density stands. Research suggests that such improved group productivity depends on ā€œcooperativeā€ traits (e.g., erect leaves, short stems) thatā€”while beneficial to the groupā€”decrease individual fitness under competition. This poses a problem for some traditional breeding approaches, especially when selection occurs at the level of individuals, because ā€œselfishā€ traits will be selected for and reduce yield in high-density monocultures. One approach, therefore, has been to select individuals based on ideotypes with traits expected to promote group productivity. However, this approach is limited to architectural and physiological traits whose effects on growth and competition are relatively easy to anticipate. Here, we developed a general and simple method for the discovery of alleles promoting cooperation in plant stands. Our method is based on the game-theoretical premise that alleles increasing cooperation benefit the monoculture group but are disadvantageous to the individual when facing noncooperative neighbors. Testing the approach using the model plant Arabidopsis thaliana, we found a major effect locus where the rarer allele was associated with increased cooperation and productivity in high-density stands. The allele likely affects a pleiotropic gene, since we find that it is also associated with reduced root competition but higher resistance against disease. Thus, even though cooperation is considered evolutionarily unstable except under special circumstances, conflicting selective forces acting on a pleiotropic gene might maintain latent genetic variation for cooperation in nature. Such variation, once identified in a crop, could rapidly be leveraged in modern breeding programs and provide efficient routes to increase yields

    Synthesis, complex stability and small animal PET imaging of a novel 64Cu-labelled cryptand molecule

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    The radiosynthesis and radiopharmacological evaluation including small animal PET imaging of a novel 64Cu-labelled cryptand molecule ([64Cu]CryptTM) possessing a tris-pyridyl/tris-amido set of donor atoms is described

    The muscarinic receptor antagonist propiverine exhibits Ī±1-adrenoceptor antagonism in human prostate and porcine trigonum

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    Combination therapy of male lower urinary tract symptoms with Ī±(1)-adrenoceptor and muscarinic receptor antagonists attracts increasing interest. Propiverine is a muscarinic receptor antagonist possessing additional properties, i.e., block of L-type Ca(2+) channels. Here, we have investigated whether propiverine and its metabolites can additionally antagonize Ī±(1)-adrenoceptors. Human prostate and porcine trigone muscle strips were used to explore inhibition of Ī±(1)-adrenoceptor-mediated contractile responses. Chinese hamster ovary (CHO) cells expressing cloned human Ī±(1)-adrenoceptors were used to determine direct interactions with the receptor in radioligand binding and intracellular Ca(2+) elevation assays. Propiverine concentration-dependently reversed contraction of human prostate pre-contracted with 10 Ī¼M phenylephrine (-log IC(50) [M] 4.43 Ā± 0.08). Similar inhibition was observed in porcine trigone (-log IC(50) 5.01 Ā± 0.05), and in additional experiments consisted mainly of reduced maximum phenylephrine responses. At concentrations ā‰„1 Ī¼M, the propiverine metabolite M-14 also relaxed phenylephrine pre-contracted trigone strips, whereas metabolites M-5 and M-6 were ineffective. In radioligand binding experiments, propiverine and M-14 exhibited similar affinity for the three Ī±(1)-adrenoceptor subtypes with -log K (i) [M] values ranging from 4.72 to 4.94, whereas the M-5 and M-6 did not affect [(3)H]-prazosin binding. In CHO cells, propiverine inhibited Ī±(1)-adrenoceptor-mediated Ca(2+) elevations with similar potency as radioligand binding, again mainly by reducing maximum responses. In contrast to other muscarinic receptor antagonists, propiverine exerts additional L-type Ca(2+)-channel blocking and Ī±(1)-adrenoceptor antagonist effects. It remains to be determined clinically, how these additional properties contribute to the clinical effects of propiverine, particularly in male voiding dysfunctio

    The cortisol awakening response predicts same morning executive function: results from a 50-day case study

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    A relationship between individual differences in trait estimates of the cortisol-awakening response (CAR) and indices of executive function (EF) has been reported. However, it is difficult to determine causality from such studies. The aim of the present study was to capitalise upon state variation in both variables to seek stronger support for causality by examining daily co-variation. A 50 days researcherā€“participant case study was employed, ensuring careful adherence to the sampling protocol. A 24-year-old healthy male collected saliva samples and completed an attention-switching index of EF on the morning of each study day. Subsidiary control measures included wake time, sleep duration, morning fatigue, and amount of prior day exercise and alcohol consumption. As the CAR preceded daily measurement of EF, we hypothesised that, over time, a greater than average CAR would predict better than average EF. This was confirmed by mixed regression modelling of variation in cortisol concentrations, which indicated that the greater the increase in cortisol concentrations from 0 to 30ā€‰min post-awakening (CAR) the better was subsequent EF performance at 45ā€‰min post-awakening (tā€‰=ā€‰2.29, pā€‰=ā€‰0.024). This effect was independent of all potential confounding measures. Results are discussed in terms of implications for the understanding of the relationship between the CAR and the cognitive function, and the previously suggested role of the CAR in ā€œboostingā€ an individualā€™s performance for the day ahead
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