899 research outputs found
Aqueous Cleaning and Validation for Space Shuttle Propulsion Hardware at the White Sands Test Facility
The NASA White Sands Test Facility (WSTF) has developed an entirely aqueous final cleaning and verification process to replace the current chlorofluorocarbon (CFC) 113 based process. This process has been accepted for final cleaning and cleanliness verification of WSTF ground support equipment. The aqueous process relies on ultrapure water at 50 C (323 K) and ultrasonic agitation for removal of organic compounds and particulate. The cleanliness is verified bv determining the total organic carbon (TOC) content and filtration with particulate counting. The effectiveness of the aqueous methods for detecting hydrocarbon contamination and particulate was compared to the accepted CFC 113 sampling procedures. Testing with known contaminants, such as hydraulic fluid and cutting and lubricating oils, to establish a correlation between aqueous TOC and CFC 113 nonvolatile residue (NVR) was performed. Particulate sampling on cleaned batches of hardware that were randomly separated and sampled by the two methods was performed. This paper presents the approach and results, and discusses the issues in establishing the equivalence of aqueous sampling to CFC 113 sampling, while describing the approach for implementing aqueous techniques on Space Shuttle Propulsion hardware
A Scalable, Correct Time-stamped Stack
Concurrent data-structures, such as stacks, queues, and deques, often implicitly enforce a total order over elements in their underlying memory layout. However, much of this order is unnecessary: linearizability only requires that elements are ordered if the insert methods ran in sequence. We propose a new approach which uses timestamping to avoid unnecessary ordering. Pairs of elements can be left unordered if their associated insert operations ran concurrently, and order imposed as necessary at the eventual removal. We realise our approach in a new non-blocking datastructure, the TS (timestamped) stack. Using the same approach, we can define corresponding queue and deque datastructures. In experiments on x86, the TS stack outperforms and outscales all its competitors – for example, it outperforms the elimination-backoff stack by factor of two. In our approach, more concurrency translates into less ordering, giving less-contended removal and thus higher performance and scalability. Despite this, the TS stack is linearizable with respect to stack semantics. The weak internal ordering in the TS stack presents a challenge when establishing linearizability: standard techniques such as linearization points work well when there exists a total internal order. We present a new stack theorem, mechanised in Isabelle, which characterises the orderings sufficient to establish stack semantics. By applying our stack theorem, we show that the TS stack is indeed linearizable. Our theorem constitutes a new, generic proof technique for concurrent stacks, and it paves the way for future weakly ordered data-structure designs
The NeMo real-time fMRI neurofeedback study: protocol of a randomised controlled clinical intervention trial in the neural foundations of mother-infant bonding
Identification of a Putative Crf Splice Variant and Generation of Recombinant Antibodies for the Specific Detection of Aspergillus fumigatus
BACKGROUND: Aspergillus fumigatus is a common airborne fungal pathogen for humans. It frequently causes an invasive aspergillosis (IA) in immunocompromised patients with poor prognosis. Potent antifungal drugs are very expensive and cause serious adverse effects. Their correct application requires an early and specific diagnosis of IA, which is still not properly achievable. This work aims to a specific detection of A. fumigatus by immunofluorescence and the generation of recombinant antibodies for the detection of A. fumigatus by ELISA. RESULTS: The A. fumigatus antigen Crf2 was isolated from a human patient with proven IA. It is a novel variant of a group of surface proteins (Crf1, Asp f9, Asp f16) which belong to the glycosylhydrolase family. Single chain fragment variables (scFvs) were obtained by phage display from a human naive antibody gene library and an immune antibody gene library generated from a macaque immunized with recombinant Crf2. Two different selection strategies were performed and shown to influence the selection of scFvs recognizing the Crf2 antigen in its native conformation. Using these antibodies, Crf2 was localized in growing hyphae of A. fumigatus but not in spores. In addition, the antibodies allowed differentiation between A. fumigatus and related Aspergillus species or Candida albicans by immunofluorescence microscopy. The scFv antibody clones were further characterized for their affinity, the nature of their epitope, their serum stability and their detection limit of Crf2 in human serum. CONCLUSION: Crf2 and the corresponding recombinant antibodies offer a novel approach for the early diagnostics of IA caused by A. fumigatus
Off-Target Effects of Psychoactive Drugs Revealed by Genome-Wide Assays in Yeast
To better understand off-target effects of widely prescribed psychoactive drugs, we performed a comprehensive series of chemogenomic screens using the budding yeast Saccharomyces cerevisiae as a model system. Because the known human targets of these drugs do not exist in yeast, we could employ the yeast gene deletion collections and parallel fitness profiling to explore potential off-target effects in a genome-wide manner. Among 214 tested, documented psychoactive drugs, we identified 81 compounds that inhibited wild-type yeast growth and were thus selected for genome-wide fitness profiling. Many of these drugs had a propensity to affect multiple cellular functions. The sensitivity profiles of half of the analyzed drugs were enriched for core cellular processes such as secretion, protein folding, RNA processing, and chromatin structure. Interestingly, fluoxetine (Prozac) interfered with establishment of cell polarity, cyproheptadine (Periactin) targeted essential genes with chromatin-remodeling roles, while paroxetine (Paxil) interfered with essential RNA metabolism genes, suggesting potential secondary drug targets. We also found that the more recently developed atypical antipsychotic clozapine (Clozaril) had no fewer off-target effects in yeast than the typical antipsychotics haloperidol (Haldol) and pimozide (Orap). Our results suggest that model organism pharmacogenetic studies provide a rational foundation for understanding the off-target effects of clinically important psychoactive agents and suggest a rational means both for devising compound derivatives with fewer side effects and for tailoring drug treatment to individual patient genotypes
Differential regulation of nuclear and mitochondrial Bcl-2 in T cell apoptosis
Activated T cells require anti-apoptotic cytokines for their survival. The anti-apoptotic effects of these factors are mediated by their influence on the balance of expression and localisation of pro- and anti-apoptotic members of the Bcl-2 family. Among the anti-apoptotic Bcl-2 family members, the expression level of Bcl-2 itself and its interaction with the pro-apoptotic protein Bim are now regarded as crucial for the regulation of survival in activated T cells. We studied the changes in Bcl-2 levels and its subcellular distribution in relation to mitochondrial depolarisation and caspase activation in survival factor deprived T cells. Intriguingly, the total Bcl-2 level appeared to remain stable, even after caspase 3 activation indicated entry into the execution phase of apoptosis. However, cell fractionation experiments showed that while the dominant nuclear pool of Bcl-2 remained stable during apoptosis, the level of the smaller mitochondrial pool was rapidly downregulated. Signals induced by anti-apoptotic cytokines continuously replenish the mitochondrial pool, but nuclear Bcl-2 is independent of such signals. Mitochondrial Bcl-2 is lost rapidly by a caspase independent mechanism in the absence of survival factors, in contrast only a small proportion of the nuclear pool of Bcl-2 is lost during the execution phase and this loss is a caspase dependent process. We conclude that these two intracellular pools of Bcl-2 are regulated through different mechanisms and only the cytokine-mediated regulation of the mitochondrial pool is relevant to the control of the initiation of apoptosis
Production of He-4 and (4) in Pb-Pb collisions at root(NN)-N-S=2.76 TeV at the LHC
Results on the production of He-4 and (4) nuclei in Pb-Pb collisions at root(NN)-N-S = 2.76 TeV in the rapidity range vertical bar y vertical bar <1, using the ALICE detector, are presented in this paper. The rapidity densities corresponding to 0-10% central events are found to be dN/dy4(He) = (0.8 +/- 0.4 (stat) +/- 0.3 (syst)) x 10(-6) and dN/dy4 = (1.1 +/- 0.4 (stat) +/- 0.2 (syst)) x 10(-6), respectively. This is in agreement with the statistical thermal model expectation assuming the same chemical freeze-out temperature (T-chem = 156 MeV) as for light hadrons. The measured ratio of (4)/He-4 is 1.4 +/- 0.8 (stat) +/- 0.5 (syst). (C) 2018 Published by Elsevier B.V.Peer reviewe
Direct photon elliptic flow in Pb-Pb collisions at root s(NN)=2.76 TeV
The elliptic flow of inclusive and direct photons was measured at mid-rapidity in two centrality classes 0-20% and 20-40% in Pb-Pb collisions at root s(NN) = 2.76 TeV by ALICE. Photons were detected with the highly segmented electromagnetic calorimeter PHOS and via conversions in the detector material with the e(broken vertical bar)e pairs reconstructed in the central tracking system. The results of the two methods were combined and the direct-photon elliptic flow was extracted in the transverse momentum range 0.9 < p(T) < 6.2 GeV/c. A comparison to RHIC data shows a similar magnitude of the measured direct-photon elliptic flow. Hydrodynamic and transport model calculations are systematically lower than the data, but are found to be compatible. (C) 2018 The Author. Published by Elsevier B.V.Peer reviewe
Cognitive behavioural therapy for the treatment of depression in people with multiple sclerosis: a systematic review and meta-analysis
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