673 research outputs found

    Lamp reliability studies for improved satellite rubidium frequency standard

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    In response to the premature failure of Rb lamps used in Rb atomic clocks onboard NAVSTAR GPS satellites experimental and theoretical investigations into their failure mechanism were initiated. The primary goal of these studies is the development of an accelerated life test for future GPS lamps. The primary failure mechanism was identified as consumption of the lamp's Rb charge via direct interaction between Rb and the lamp's glass surface. The most effective parameters to accelerate the interaction between the Rb and the glass are felt to be RF excitation power and lamp temperature. Differential scanning calorimetry is used to monitor the consumption of Rb within a lamp as a function of operation time. This technique yielded base line Rb consumption data for GPS lamps operating under normal conditions

    THE ASSOCIATION BETWEEN THE IL-1 PATHWAY

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    Cutaneous malignant melanoma (CMM) is a potentially lethal malignancy that warrants attention and further research, as it is known to that there is an increasing rate of incidence in theUnited States, and it is also known that exposure to UV light is its most crucial risk factor, and family history of melanoma is also an important risk factor. Melanoma is an aggressive and lethal cancer in humans. There are an estimated new 132,000 melanoma cases annually worldwide, and the trend has doubled in the past 20 years. However, attempts to treat melanoma have encountered considerable resistance and remained ineffective. The 5-year survival rate for metastatic melanoma remains less than 5%. CMM patients may develop an immune response to their tumors, but innate anti-tumor immune responses are insufficient for controlling the development of the tumor. Melanoma is a very immunogenic tumor, sometimes exhibiting spontaneous remissions, making it one of the foremost targets for immunotherapy. Unfortunately, despite the attempts at making tumor-infiltrating lymphocyte treatments, the clinical response has been borderline. The immunosuppressive microenvironment of tumor cells becomes significant and intertwines with the resistance of tumor treatment. Furthermore, IL-1 can hinder the immune response to melanoma. The pathway of MAPK activation leads to the production interleukin(IL)-1α/β. IL-1 conducts immunomodulatory activity through tumor-associated fibroblasts and locks in the turnkey position of the immunosuppression pathway to resist the cytotoxic T lymphocyte function. Hence, IL-1 is a key target of interest in treating melanoma, along with the entire pathway flowing from it. Polymorphisms in genes regulating the immune response could result in increased susceptibility to and/or poorer prognosis in certain individuals. For this study, one of the objectives was to examine if single nucleotide polymorphisms (SNPs) of certain pro- and anti-inflammatory cytokines and growth factors, namely IL-1, IL-6, IL-8, IFN-γ, and TNF-α are associated with melanoma outcome of death, recurrence, or composite, and thus susceptibility. Those genes are the upstream and downstream targets for the greater IL-1 pathway. The greater IL-1 pathway has multiple genes in between those upstream and downstream targets. Those genes are IL-1RI, IL-1RAcP, IL-1RA, MYD88, TOLLIP, IRAKs, MEKK1, MEK3, MEK6, JNK, P38, c-JUN, ECSIT, TRAF6, TAB1, TAK1, RKIP, NIK, IKKα, IKKβ, IκBα, and NF-κB. The individual SNP analysis proved to be interesting though inconclusive. There were some borderline significant results, such as associations of the SNPs rs16944, rs1143627, rs1071676, and rs3136558 with the endpoint of death. The French validation verified a significant association of rs3136558 with death but none of the others. The next objective was to perform a full pathway analysis, incorporating all available SNPs for each gene in the overall IL-1 pathway to determine if any components were significant and if so, to attempt further verification at the protein level if the data were available. By using the SKAT program for pathway analysis, several genes in the IL-1 pathway were found to be significant. They were IL-1, c-JUN, and ECSIT, with borderline significance for TAK1. With the observation of associations of these four genes with melanoma outcomes at the DNA level, the next step was to determine if they were also significantly associated with melanoma outcomes at the expression level. The data for the DNA level studies did not include protein expression studies, so we used data provided by The Cancer Genome Atlas (TCGA). TAK1 data was not available, but RNA expression data were gathered for IL-1, c-JUN, and ECSIT. At the protein level, only c-JUN data was available. At the RNA level, IL1 showed that survival was proportional to IL-1 level, ECSIT showed lower survival for higher level, while c-JUN showed higher survival for higher levels. At the protein level, c-JUN was significant at the protein level, both adjusted and unadjusted via logistic regression. It seems that for developing further therapy against melanoma, c-JUN may be be a crucial target in the IL-1 pathway. IL-1 and ECSIT could also play important roles related to melanoma outcomes but require future studies where protein expression data is available to confirm the DNA- and RNA-based results

    Increase in ACC Oxidase Levels and Activities During Paradormancy Release of Leafy Spurge (Euphorbia Esula) Buds

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    The plant hormone ethylene is known to affect various developmental processes including dormancy and growth. Yet, little information is available about the role of ethylene during paradormancy release in underground adventitious buds of leafy spurge. In this study, we examined changes in ethylene evolution and the ethylene biosynthetic enzyme ACC oxidase following paradormancy release (growth induction). Our results did not show an obvious increase in ethylene during bud growth. However, when buds were incubated with 1 mM ACC, ethylene levels were higher in growing than non-growing buds, suggesting that the levels of ACC oxidase increased in growing buds. Real-time qPCR indicated that the transcript of a Euphorbia esula ACC oxidase (Ee-ACO) increased up to threefold following growth induction. In addition, a 2.5- to 4-fold increase in ACO activity was observed 4 days after decapitation, and the Ee-ACO accounted for 40 % of the total ACO activity. Immunoblot analyses identified a 36-kD Ee-ACO protein that increased in expression during bud growth. This protein was highly expressed in leaves, moderately expressed in crown buds, stems and meristems, and weakly expressed in roots and flowers. Immunolocalization of Ee-ACO on growing bud sections revealed strong labeling of the nucleus and cytoplasm in cells at the shoot apical meristem and leaf primordia. An exception to this pattern occurred in cells undergoing mitosis, where labeling of Ee-ACO was negligible. Taken together, our results indicated an increase in the levels of Ee-ACO during paradormancy release of leafy spurge that was not correlated with an increase in ethylene synthesis

    Transcriptome analysis identifies novel responses and potential regulatory genes involved in seasonal dormancy transitions of leafy spurge (Euphorbia esula L.)

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    <p>Abstract</p> <p>Background</p> <p>Dormancy of buds is a critical developmental process that allows perennial plants to survive extreme seasonal variations in climate. Dormancy transitions in underground crown buds of the model herbaceous perennial weed leafy spurge were investigated using a 23 K element cDNA microarray. These data represent the first large-scale transcriptome analysis of dormancy in underground buds of an herbaceous perennial species. Crown buds collected monthly from August through December, over a five year period, were used to monitor the changes in the transcriptome during dormancy transitions.</p> <p>Results</p> <p>Nearly 1,000 genes were differentially-expressed through seasonal dormancy transitions. Expected patterns of gene expression were observed for previously characterized genes and physiological processes indicated that resolution in our analysis was sufficient for identifying shifts in global gene expression.</p> <p>Conclusion</p> <p>Gene ontology of differentially-expressed genes suggests dormancy transitions require specific alterations in transport functions (including induction of a series of mitochondrial substrate carriers, and sugar transporters), ethylene, jasmonic acid, auxin, gibberellic acid, and abscisic acid responses, and responses to stress (primarily oxidative and cold/drought). Comparison to other dormancy microarray studies indicated that nearly half of the genes identified in our study were also differentially expressed in at least two other plant species during dormancy transitions. This comparison allowed us to identify a particular MADS-box transcription factor related to the <it>DORMANCY ASSOCIATED MADS-BOX </it>genes from peach and hypothesize that it may play a direct role in dormancy induction and maintenance through regulation of <it>FLOWERING LOCUS T</it>.</p

    SafeWeb: A Middleware for Securing Ruby-Based Web Applications

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    Web applications in many domains such as healthcare and finance must process sensitive data, while complying with legal policies regarding the release of different classes of data to different parties. Currently, software bugs may lead to irreversible disclosure of confidential data in multi-tier web applications. An open challenge is how developers can guarantee these web applications only ever release sensitive data to authorised users without costly, recurring security audits. Our solution is to provide a trusted middleware that acts as a “safety net” to event-based enterprise web applications by preventing harmful data disclosure before it happens. We describe the design and implementation of SafeWeb, a Ruby-based middleware that associates data with security labels and transparently tracks their propagation at different granularities across a multi-tier web architecture with storage and complex event processing. For efficiency, maintainability and ease-of-use, SafeWeb exploits the dynamic features of the Ruby programming language to achieve label propagation and data flow enforcement. We evaluate SafeWeb by reporting our experience of implementing a web-based cancer treatment application and deploying it as part of the UK National Health Service (NHS)

    Characterization of soluble microbial products (SMPs) in a membrane bioreactor (MBR) treating municipal wastewater containing pharmaceutical compounds

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    This study investigated the behaviour and characteristics of soluble microbial products (SMP) in two anoxic-aerobic membrane bioreactors (MBRs): MBRcontrol and MBRpharma, for treating municipal wastewater. Both protein and polysaccharides measured exhibited higher concentrations in the MBRpharma than the MBRcontrol. Molecular weight (MW) distribution analysis revealed that the presence of pharmaceuticals enhanced the accumulation of SMPs with macro- (13,091 kDa and 1,587 kDa) and intermediate-MW (189 kDa) compounds in the anoxic MBRpharma, while a substantial decrease was observed in both MBR effluents. Excitation emission matrix (EEM) fluorescence contours indicated that the exposure to pharmaceuticals seemed to stimulate the production of aromatic proteins containing tyrosine (10.1-32.6%) and tryptophan (14.7-43.1%), compared to MBRcontrol (9.9-29.1% for tyrosine; 11.8-42.5% for tryptophan). Gas chromatography - mass spectrometry (GC-MS) analysis revealed aromatics, long-chain alkanes and esters were the predominant SMPs in the MBRs. More peaks were present in the aerobic MBRpharma (196) than anoxic MBRpharma (133). The SMPs identified exhibited both biodegradability and recalcitrance in the MBR treatment processes. Only 8 compounds in the MBRpharma were the same as in the MBRcontrol. Alkanes were the most dominant SMPs (51%) in the MBRcontrol, while aromatics were dominant (40%) in the MBRpharma. A significant decrease in aromatics (from 16 to 7) in the MBRpharma permeate was observed, compared to the aerobic MBRpharma. Approximately 21% of compounds in the aerobic MBRcontrol were rejected by membrane filtration, while this increased to 28% in the MBRpharma

    Repeated Small Perturbation Approach Reveals Transcriptomic Steady States

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    The study of biological systems dynamics requires elucidation of the transitions of steady states. A “small perturbation” approach can provide important information on the “steady state” of a biological system. In our experiments, small perturbations were generated by applying a series of repeating small doses of ultraviolet radiation to a human keratinocyte cell line, HaCaT. The biological response was assessed by monitoring the gene expression profiles using cDNA microarrays. Repeated small doses (10 J/m2) of ultraviolet B (UVB) exposure modulated the expression profiles of two groups of genes in opposite directions. The genes that were up-regulated have functions mainly associated with anti-proliferation/anti-mitogenesis/apoptosis, and the genes that were down-regulated were mainly related to proliferation/mitogenesis/anti-apoptosis. For both groups of genes, repetition of the small doses of UVB caused an immediate response followed by relaxation between successive small perturbations. This cyclic pattern was suppressed when large doses (233 or 582.5 J/m2) of UVB were applied. Our method and results contribute to a foundation for computational systems biology, which implicitly uses the concept of steady state
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