516 research outputs found

    Supersonic Engine Inlet Tone Noise Radiation

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    A computational and experimental acoustic analysis was conducted on a supersonic engine inlet geometry with a spike center body and an auxiliary inlet. Simulations performed using two different commercial acoustics software packages were compared to a scale model experiment conducted using an ultrasonic fan noise simulator. Both the experiment and simulations were run at discrete circumferential mode and frequency combinations to identify strengths and weaknesses of each method. For cases where a single azimuthal mode was well cut on throughout the length of the duct, reasonable agreement was found between the three methods. In cases with more complicated acoustic effects, the experimental results became intractable when considered alone and the simulations were needed for interpreting the results. The peak sound level and the peak angle of the far field radiation vary widely when changing modes and frequencies. The objective of the study is to develop a validated workflow for simulation of fan tone noise through supersonic inlet geometries for community noise predictions

    Frustrations of fur-farmed mink

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    Captive animals may suffer if strongly motivated to perform activities that their housing does not allow. We investigated this experimentally for caged mink, and found that they would pay high costs to perform a range of natural behaviours, and release cortisol if their most preferred activity, swimming, was prevented. Investigates the effect of limitations on caged mink. Popularity of fur farming; Research into the possible deprivation of mink, which result in their frustration; Details of the experiment; Impact of an access to water; Results which indicate that fur-farmed mink are still motivated to perform the same activities as their wild counterpart

    Fluorescence: A Novel Method for Determining Manuka Honey Floral Purity

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    Manuka honey, harvested from Leptospermum scoparium, is New Zealand\u27s most recognised honey type and commands a premium due to health‐related benefits. However, the plant\u27s distribution, relative to other species flowering simultaneously, allows honeybees to incorporate alternative nectars into the honey. Melissopalynological analysis in New Zealand is often unrepresentative due to the presence of many pollen‐bearing sources; consequently, alternative means of categorising manuka honey were examined. RP‐HPLC revealed that manuka honey contains distinct compounds, of which were relatively enriched and not present in the other New Zealand monofloral honeys. These main candidate compounds were isolated and have been described by mass spectrometry and nuclear magnetic resonance, synthesised to confirm structure, and as standards. These compounds, Leptosperin and Lepteridine, are a methyl syringate glycoside and pteridine derivative, respectively. Examination of these compounds revealed unique fluorescence signatures, this fluorescence could be detected in manuka honey samples the signal used to confirm that a honey was solely or predominantly consisted of L. scoparium nectar. Commercial manuka honeys were assessed by traditional analytical techniques, and comparisons were made with fluorescence signature; the fluorescence technique determined the authenticity of the honeys accurately

    WholePathwayScope: a comprehensive pathway-based analysis tool for high-throughput data

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    BACKGROUND: Analysis of High Throughput (HTP) Data such as microarray and proteomics data has provided a powerful methodology to study patterns of gene regulation at genome scale. A major unresolved problem in the post-genomic era is to assemble the large amounts of data generated into a meaningful biological context. We have developed a comprehensive software tool, WholePathwayScope (WPS), for deriving biological insights from analysis of HTP data. RESULT: WPS extracts gene lists with shared biological themes through color cue templates. WPS statistically evaluates global functional category enrichment of gene lists and pathway-level pattern enrichment of data. WPS incorporates well-known biological pathways from KEGG (Kyoto Encyclopedia of Genes and Genomes) and Biocarta, GO (Gene Ontology) terms as well as user-defined pathways or relevant gene clusters or groups, and explores gene-term relationships within the derived gene-term association networks (GTANs). WPS simultaneously compares multiple datasets within biological contexts either as pathways or as association networks. WPS also integrates Genetic Association Database and Partial MedGene Database for disease-association information. We have used this program to analyze and compare microarray and proteomics datasets derived from a variety of biological systems. Application examples demonstrated the capacity of WPS to significantly facilitate the analysis of HTP data for integrative discovery. CONCLUSION: This tool represents a pathway-based platform for discovery integration to maximize analysis power. The tool is freely available at

    a4-Containing GABA <sub>A</sub> Receptors on DRD2 Neurons of the Nucleus Accumbens Mediate Instrumental Responding for Conditioned Reinforcers and Its Potentiation by Cocaine

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    Extrasynaptic GABA A receptors (GABA ARs) composed of a4, b, and d subunits mediate GABAergic tonic inhibition and are potential molecular targets in the modulation of behavioral responses to natural and drug rewards. These GABA ARs are highly expressed within the nucleus accumbens (NAc), where they influence the excitability of the medium spiny neurons. Here, we explore their role in modulating behavioral responses to food-conditioned cues and the behavior-potentiating effects of cocaine. a4-Subunit constitutive knock-out mice (a4 /) showed higher rates of instrumental responding for reward-paired stimuli in a test of conditioned reinforcement (CRf). A similar effect was seen fol-lowing viral knockdown of GABA AR a4 subunits within the NAc. Local infusion of the a4b d-GABA AR-preferring agonist THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol; Gaboxadol) into the NAc had no effect on responding when given alone but reduced cocaine potentiation of responding for conditioned reinforcers in wild-type, but not a4 / mice. Finally, specific deletion of a4-subunits from dopamine D2, but not D1, receptor-expressing neurons (DRD2 and DRD1 neurons), mimicked the phenotype of the constitutive knockout, potentiating CRf responding, and blocking intra-accumbal THIP attenuation of cocaine-potentiated CRf responding. These data demonstrate that a4-GABA AR-mediated inhibition of DRD2 neurons reduces instrumental responding for a conditioned reinforcer and its po-tentiation by cocaine and emphasize the importance of GABAergic signaling within the NAc in mediating the effects of cocaine.</p

    Genomic Profiling of T-Cell Neoplasms Reveals Frequent

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    Purpose: The promise of precision oncology is that identification of genomic alterations will direct the rational use of molecularly targeted therapy. This approach is particularly applicable to neoplasms that are resistant to standard cytotoxic chemotherapy, like T-cell leukemias and lymphomas. In this study, we tested the feasibility of targeted next-generation sequencing in profiles of diverse T-cell neoplasms and focused on the therapeutic utility of targeting activated JAK1 and JAK3 in an index case. Patients and Methods: Using Foundation One and Foundation One Heme assays, we performed genomic profiling on 91 consecutive T-cell neoplasms for alterations in 405 genes. The samples were sequenced to high uniform coverage with an Illumina HiSeq and averaged a coverage depth of greater than 500× for DNA and more than 8M total pairs for RNA. An index case of T-cell prolymphocytic leukemia (T-PLL), which was analyzed by targeted next-generation sequencing, is presented. T-PLL cells were analyzed by RNA-seq, in vitro drug testing, mass cytometry, and phospho-flow. Results: One third of the samples had genomic aberrations in the JAK-STAT pathway, most often composed of Conclusion: These results underscore the utility of profiling occurrences of resistance to standard regimens and support JAK enzymes as rational therapeutic targets for T-cell leukemias and lymphomas

    Genomic Profiling of T-Cell Neoplasms Reveals Frequent JAK1 and JAK3 Mutations With Clonal Evasion From Targeted Therapies

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    Purpose: The promise of precision oncology is that identification of genomic alterations will direct the rational use of molecularly targeted therapy. This approach is particularly applicable to neoplasms that are resistant to standard cytotoxic chemotherapy, like T-cell leukemias and lymphomas. In this study, we tested the feasibility of targeted next-generation sequencing in profiles of diverse T-cell neoplasms and focused on the therapeutic utility of targeting activated JAK1 and JAK3 in an index case. Patients and Methods: Using Foundation One and Foundation One Heme assays, we performed genomic profiling on 91 consecutive T-cell neoplasms for alterations in 405 genes. The samples were sequenced to high uniform coverage with an Illumina HiSeq and averaged a coverage depth of greater than 500× for DNA and more than 8M total pairs for RNA. An index case of T-cell prolymphocytic leukemia (T-PLL), which was analyzed by targeted next-generation sequencing, is presented. T-PLL cells were analyzed by RNA-seq, in vitro drug testing, mass cytometry, and phospho-flow. Results: One third of the samples had genomic aberrations in the JAK-STAT pathway, most often composed of JAK1 and JAK3 gain-of-function mutations. We present an index case of a patient with T-PLL with a clonal JAK1 V658F mutation that responded to ruxolitinib therapy. After relapse developed, an expanded clone that harbored mutant JAK3 M511I and downregulation of the phosphatase, CD45, was identified. We demonstrate that the JAK missense mutations were activating, caused pathway hyperactivation, and conferred cytokine hypersensitivity. Conclusion: These results underscore the utility of profiling occurrences of resistance to standard regimens and support JAK enzymes as rational therapeutic targets for T-cell leukemias and lymphomas

    Investigation into Cryogenic Tank Insulation Systems for the Mars Surface Environment

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    In order to use oxygen that is produced on the surface of Mars from In-Situ production processes in a chemical propulsion system, the oxygen must first be converted from vapor phase to liquid phase and then stored within the propellant tanks of the propulsion system. The oxygen must then be stored in the liquid phase for several years between when the liquefaction operations are initiated and when the ascent stage lifts off the Martian surface. Since the Space Exploration Initiative, NASA has been investing small sums of money into soft vacuum systems for Mars Applications. A study was done into these various insulation systems for soft vacuum insulation, to determine what types of systems might be best to further pursue. Five different architectures or cycles were considered: Aerogel-based multilayer Insulation (MLAI), Space Evacuated Mars Vacuum Jacket (SEMOV) (also known as lightweight vacuum jacket), Load Responsive-Multilayer Insulation, Spray on Foam with MLI, and MLAI in SEMOV. Models of each architecture were developed to give insight into the performance and losses of each of the options. The results were then compared across six categories: Insulation System Mass, Active System Power (both input and heat rejection), Insulation System Cost, Manufacturability, Reliability, and Operational Flexibility. The result was that a trade between reliability and mass was clearly identified. Systems with high mass, also had high perceived reliability; whereas, systems with lower mass and power had a much lower perceived reliability. In the end, the numerical trades of these systems showed nominally identical rankings. As a result it is recommended that NASA focus its Martian insulation development activities on demonstrating and improving the reliability of the lightweight identified systems

    Changes in plasma levels of N-arachidonoyl ethanolamine and N-palmitoylethanolamine following bariatric surgery in morbidly obese females with impaired glucose homeostasis

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    Aim: We examined endocannabinoids (ECs) in relation to bariatric surgery and the association between plasma ECs and markers of insulin resistance. Methods: A study of 20 participants undergoing bariatric surgery. Fasting and 2-hour plasma glucose, lipids, insulin, and C-peptide were recorded preoperatively and 6 months postoperatively with plasma ECs (AEA, 2-AG) and endocannabinoid-related lipids (PEA, OEA). Results: Gender-specific analysis showed differences in AEA, OEA, and PEA preoperatively with reductions in AEA and PEA in females postoperatively. Preoperatively, AEA was correlated with 2-hour glucose (r = 0.55, P = 0.01), HOMA-IR (r = 0.61, P = 0.009), and HOMA %S (r = -0.71, P = 0.002). OEA was correlated with weight (r = 0.49, P = 0.03), waist circumference (r = 0.52, P = 0.02), fasting insulin (r = 0.49, P = 0.04), and HOMA-IR (r = 0.48, P = 0.05). PEA was correlated with fasting insulin (r = 0.49, P = 0.04). 2-AG had a negative correlation with fasting glucose (r = -0.59, P = 0.04). Conclusion: Gender differences exist in circulating ECs in obese subjects. Females show changes in AEA and PEA after bariatric surgery. Specific correlations exist between different ECs and markers of obesity and insulin and glucose homeostasis
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