74 research outputs found

    Development and testing of a novel sulfur dioxide sonde

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    A novel technique has been developed to measure sulfur dioxide (SO2) using a modification of the existing electrochemical concentration cell (ECC) ozonesonde technology. The current sonde-based method to measure SO2 (i.e., the dual-sonde approach) involves launching two ozonesondes together, with one of the sondes having a filter to remove SO2 at the inlet. The SO2 profile is determined by taking the difference between the measurements from the two instruments. The dual-sonde method works well in typical tropospheric conditions when [O3]&gt;[SO2] but saturates when [SO2]&gt;[O3] and has large uncertainties in the upper troposphere and lower stratosphere that would limit its effectiveness in measuring SO2 from an explosive volcanic eruption. Due to these limitations, several modifications were made to create a single-sonde system that would directly measure SO2 (i.e., the SO2 sonde). These modifications included (1) a positively biased ECC current, (2) the addition of an O3 removal filter, and (3) the addition of a sample dryer. The SO2 sonde measures SO2 as a reduction in the cell current. There was a strong correlation (r2&gt;0.94) between the SO2 sonde and a Thermo 43c analyzer during controlled laboratory tests and pre-flight tests. Varying humidity levels affected the SO2 sonde's sensitivity (avg =84.6±31.7 ppbv µA−1, 1σ RSD =37 %) during initial field tests, which was resolved by adding a sample dryer upstream of the O3 removal filter and pump inlet. This modification significantly reduced the variability and increased the sensitivity of the SO2 measurements (avg =47±5.8 ppbv µA−1, 1σ RSD =12 %). Field tests included measurements near Kīlauea volcano (before and during the 2018 eruption of the Lower East Rift Zone), Costa Rica's Turrialba volcano, and anthropogenic plumes from the Athabasca oil sands region of Alberta, Canada. This single-SO2-sonde system is an effective, inexpensive instrument for measuring both ground-based and vertical profiles of SO2 from anthropogenic and natural sources (i.e., volcanic eruptions) over a wide range of concentrations.</p

    Modulation of purinergic signaling by NPP-type ectophosphodiesterases

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    Extracellular nucleotides can elicit a wide array of cellular responses by binding to specific purinergic receptors. The level of ectonucleotides is dynamically controlled by their release from cells, synthesis by ectonucleoside diphosphokinases and ectoadenylate kinases, and hydrolysis by ectonucleotidases. One of the four structurally unrelated families of ectonucleotidases is represented by the NPP-type ectophosphodiesterases. Three of the seven members of the NPP family, namely NPP1–3, are known to hydrolyze nucleotides. The enzymatic action of NPP1–3 (in)directly results in the termination of nucleotide signaling, the salvage of nucleotides and/or the generation of new messengers like ADP, adenosine or pyrophosphate. NPP2 is unique in that it hydrolyzes both nucleotides and lysophospholipids and, thereby, generates products that could synergistically promote cell motility. We review here the enzymatic properties of NPPs and analyze current evidence that links their nucleotide-hydrolyzing capability to epithelial and neural functions, the immune response and cell motility

    Nucleophile-Catalyzed Additions to Activated Triple Bonds. Protection of Lactams, Imides, and Nucleosides with MocVinyl and Related Groups

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    Additions of lactams, imides, (S)-4-benzyl-1,3-oxazolidin-2-one, 2-pyridone, pyrimidine-2,4-diones (AZT derivatives), or inosines to the electron-deficient triple bonds of methyl propynoate, tert-butyl propynoate, 3-butyn-2-one, N-propynoylmorpholine, or N-methoxy-N-methylpropynamide in the presence of many potential catalysts were examined. DABCO and, second, DMAP appeared to be the best (highest reaction rates and E/Z ratios), while RuCl3, RuClCp*(PPh3)2, AuCl, AuCl(PPh3), CuI, and Cu2(OTf)2 were incapable of catalyzing such additions. The groups incorporated (for example, the 2-(methoxycarbonyl)ethenyl group that we name MocVinyl) serve as protecting groups for the above-mentioned heterocyclic CONH or CONHCO moieties. Deprotections were accomplished via exchange with good nucleophiles: the 1-dodecanethiolate anion turned out to be the most general and efficient reagent, but in some particular cases other nucleophiles also worked (e.g., MocVinyl-inosines can be cleaved with succinimide anion). Some structural and mechanistic details have been accounted for with the help of DFT and MP2 calculations

    Analyzing the regulation of metabolic pathways in human breast cancer

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    <p>Abstract</p> <p>Background</p> <p>Tumor therapy mainly attacks the metabolism to interfere the tumor's anabolism and signaling of proliferative second messengers. However, the metabolic demands of different cancers are very heterogeneous and depend on their origin of tissue, age, gender and other clinical parameters. We investigated tumor specific regulation in the metabolism of breast cancer.</p> <p>Methods</p> <p>For this, we mapped gene expression data from microarrays onto the corresponding enzymes and their metabolic reaction network. We used Haar Wavelet transforms on optimally arranged grid representations of metabolic pathways as a pattern recognition method to detect orchestrated regulation of neighboring enzymes in the network. Significant combined expression patterns were used to select metabolic pathways showing shifted regulation of the aggressive tumors.</p> <p>Results</p> <p>Besides up-regulation for energy production and nucleotide anabolism, we found an interesting cellular switch in the interplay of biosynthesis of steroids and bile acids. The biosynthesis of steroids was up-regulated for estrogen synthesis which is needed for proliferative signaling in breast cancer. In turn, the decomposition of steroid precursors was blocked by down-regulation of the bile acid pathway.</p> <p>Conclusion</p> <p>We applied an intelligent pattern recognition method for analyzing the regulation of metabolism and elucidated substantial regulation of human breast cancer at the interplay of cholesterol biosynthesis and bile acid metabolism pointing to specific breast cancer treatment.</p

    Genome-Wide Mutagenesis of Xanthomonas axonopodis pv. citri Reveals Novel Genetic Determinants and Regulation Mechanisms of Biofilm Formation

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    Xanthomonas axonopodis pv. citri (Xac) causes citrus canker disease, a major threat to citrus production worldwide. Accumulating evidence suggests that the formation of biofilms on citrus leaves plays an important role in the epiphytic survival of this pathogen prior to the development of canker disease. However, the process of Xac biofilm formation is poorly understood. Here, we report a genome-scale study of Xac biofilm formation in which we identified 92 genes, including 33 novel genes involved in biofilm formation and 7 previously characterized genes, colR, fhaB, fliC, galU, gumD, wxacO, and rbfC, known to be important for Xac biofilm formation. In addition, 52 other genes with defined or putative functions in biofilm formation were identified, even though they had not previously reported been to be associated with biofilm formation. The 92 genes were isolated from 292 biofilm-defective mutants following a screen of a transposon insertion library containing 22,000 Xac strain 306 mutants. Further analyses indicated that 16 of the novel genes are involved in the production of extracellular polysaccharide (EPS) and/or lipopolysaccharide (LPS), 7 genes are involved in signaling and regulatory pathways, and 5 genes have unknown roles in biofilm formation. Furthermore, two novel genes, XAC0482, encoding a haloacid dehalogenase-like phosphatase, and XAC0494 (designated as rbfS), encoding a two-component sensor protein, were confirmed to be biofilm-related genes through complementation assays. Our data demonstrate that the formation of mature biofilm requires EPS, LPS, both flagellum-dependent and flagellum-independent cell motility, secreted proteins and extracellular DNA. Additionally, multiple signaling pathways are involved in Xac biofilm formation. This work is the first report on a genome-wide scale of the genetic processes of biofilm formation in plant pathogenic bacteria. The report provides significant new information about the genetic determinants and regulatory mechanism of biofilm formation

    A fate worse than death: apoptosis as an oncogenic process

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    Outbreak of Klebsiella pneumoniae Carbapenemase-Producing Citrobacter freundii at a Tertiary Acute Care Facility in Miami, Florida

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    OBJECTIVE To describe the investigation and control of a rare cluster of Klebsiella pneumoniae carbapenemase-producing Citrobacter freundii in a hospital in southern Florida. METHODS An epidemiologic investigation, review of infection prevention procedures, and molecular studies including whole genome sequencing were conducted. RESULTS An outbreak of K. pneumoniae carbapenemase-3-producing C. freundii was identified at a tertiary hospital in Florida in 2014. Of the 6 cases identified, 3 occurred in the same intensive care unit and were caused by the same clone. For 2 of the 3 remaining cases, the isolates had low carbapenem minimum inhibitory concentrations and were unrelated by whole genome sequencing. As a response to the outbreak, supplementary environmental cleaning was implemented, including closure and terminal cleaning of the unit where the 3 cases clustered, in addition to the infection control bundle already in place at the time. No further cases were identified after these additional interventions. CONCLUSIONS Although C. freundii is not a species that commonly demonstrates carbapenem resistance, our findings suggest that carbapenemase-producing C. freundii may be underdetected even when active surveillance is in place and has a potential to cause hospital outbreak. Infect Control Hosp Epidemiol 2017;38:320-326

    Nucleotidases and Nucleoside Analog Cytotoxicity

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