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Sample records for net methylation potentials

  1. Waterscape determinants of net mercury methylation in a tropical wetland.

    Science.gov (United States)

    Lázaro, Wilkinson L; Díez, Sergi; da Silva, Carolina J; Ignácio, Áurea R A; Guimarães, Jean R D

    2016-10-01

    The periphyton associated with freshwater macrophyte roots is the main site of Hg methylation in different wetland environments in the world. The aim of this study was to test the use of connectivity metrics of water bodies, in the context of patches, in a tropical waterscape wetland (Guapore River, Amazonia, Brazil) as a predictor of potential net methylmercury (MeHg) production by periphyton communities. We sampled 15 lakes with different patterns of lateral connectivity with the main river channel, performing net mercury methylation potential tests in incubations with local water and Eichhornia crassipes root-periphyton samples, using (203)HgCl2 as a tracer. Physico-chemical variables, landscape data (morphological characteristics, land use, and lateral connection type of water bodies) using GIS resources and field data were analyzed with Generalized Additive Models (GAM). The net Me(203)Hg production (as % of total added (203)Hg) was expressive (6.2-25.6%) showing that periphyton is an important matrix in MeHg production. The model that best explained the variation in the net Me(203)Hg production (76%) was built by the variables: connection type, total phosphorus and dissolved organic carbon (DOC) in water (AICc=48.324, p=0.001). Connection type factor was the best factor to model fit (r(2)=0.32; p=0.008) and temporarily connected lakes had higher rates of net mercury methylation. Both DOC and total phosphorus showed positive significant covariation with the net methylation rates (r(2)=0.26; p=0.008 and r(2)=0.21; p=0.012 respectively). Our study suggests a strong relationship between rates of net MeHg production in this tropical area and the type of water body and its hydrological connectivity within the waterscape. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Net Ecosystem Fluxes of Methyl Halides from a Coastal Salt Marsh with Invasive Pepperweed

    Science.gov (United States)

    Deventer, M. J.; Jiao, Y.; Lewis, J. A.; Weiss, R. F.; Rhew, R. C.; Turnipseed, A. A.

    2016-12-01

    Terrestrial emissions of methyl bromide (CH3Br) and methyl chloride (CH3Cl) are believed to constitute the `missing' source of these compounds to the atmosphere, but the variability of emission rates from natural ecosystems has led to large uncertainties in scaling up. Since April 2016, surface-atmosphere fluxes for methyl halides have been measured at Suisun Marsh, a coastal salt marsh in northern California, USA. Flux measurements are performed in two ways: tower based relaxed eddy accumulation (REA) for net ecosystem fluxes and static flux chamber measurements for plant-scale fluxes. The study site is invaded by perennial pepperweed (Lepidium latifolium), a methyl halide emitting species, covering a significant part of the flux source area. Both, REA and chamber samples are analyzed for methyl chloride (CH3Cl) and methyl bromide (CH3Br) using gas chromatography with electron capture detector (GC-ECD). The analytical precision [ppt] and REA flux detection limits [μmol m-2 d-1] are on the order of 3.9/0.6 for CH3Cl and 0.01/0.2 for CH3Br. Chamber measurements confirmed that methyl halide emissions of pepperweed are large, but that the native alkali heath (Frankenia salina) is a much stronger emitter, when normalized by biomass. REA measurements show that during the summer, the studied marsh is a substantial methyl halide source with net fluxes of 20 μmol m-2 d-1 (CH3Cl) and 1 μmol m-2 d-1 (CH3Br). Notably, these fluxes are comparable with reported chamber based emissions from southern California salt marshes. Furthermore, a positive response to light and temperature was found. The presentation will also expand on the diurnal variability and seasonality of the measured fluxes.

  3. Net global warming potential and greenhouse gas intensity

    Science.gov (United States)

    Various methods exist to calculate global warming potential (GWP) and greenhouse gas intensity (GHG) as measures of net greenhouse gas (GHG) emissions from agroecosystems. Little is, however, known about net GWP and GHGI that account for all sources and sinks of GHG emissions. Sources of GHG include...

  4. Origin of methyl torsional potential barrier–An overview

    Indian Academy of Sciences (India)

    This paper presents the evolution of views on methyl internal rotation potential barrier. Various mechanisms proposed for the origin of torsional barrier in ethane have been reviewed. Inadequacy of one dimensional description of internal rotation has been highlighted in small methyl conjugated molecules in the light of its ...

  5. DNA Methylation and Potential for Epigenetic Regulation in Pygospio elegans

    Science.gov (United States)

    Kesäniemi, Jenni E.; Heikkinen, Liisa; Knott, K. Emily

    2016-01-01

    Transitions in developmental mode are common evolutionarily, but how and why they occur is not understood. Developmental mode describes larval phenotypes, including morphology, ecology and behavior of larvae, which typically are generalized across different species. The polychaete worm Pygospio elegans is one of few species polymorphic in developmental mode, with multiple larval phenotypes, providing a possibility to examine the potential mechanisms allowing transitions in developmental mode. We investigated the presence of DNA methylation in P. elegans, and, since maternal provisioning is a key factor determining eventual larval phenotype, we compared patterns of DNA methylation in females during oogenesis in this species. We demonstrate that intragenic CpG site DNA methylation and many relevant genes necessary for DNA methylation occur in P. elegans. Methylation-sensitive AFLP analysis showed that gravid females with offspring differing in larval developmental mode have significantly different methylation profiles and that the females with benthic larvae and non-reproductive females from the same location also differ in their epigenetic profiles. Analysis of CpG sites in transcriptome data supported our findings of DNA methylation in this species and showed that CpG observed/expected ratios differ among females gravid with embryos destined to different developmental modes. The differences in CpG site DNA methylation patterns seen among the samples suggest a potential for epigenetic regulation of gene expression (through DNA methylation) in this species. PMID:27008314

  6. SIMULATION OF NET INFILTRATION FOR MODERN AND POTENTIAL FUTURE CLIMATES

    Energy Technology Data Exchange (ETDEWEB)

    J.A. Heveal

    2000-06-16

    This Analysis/Model Report (AMR) describes enhancements made to the infiltration model documented in Flint et al. (1996) and documents an analysis using the enhanced model to generate spatial and temporal distributions over a model domain encompassing the Yucca Mountain site, Nevada. Net infiltration is the component of infiltrated precipitation, snowmelt, or surface water run-on that has percolated below the zone of evapotranspiration as defined by the depth of the effective root zone, the average depth below the ground surface (at a given location) from which water is removed by evapotranspiration. The estimates of net infiltration are used for defining the upper boundary condition for the site-scale 3-dimensional Unsaturated-Zone Ground Water Flow and Transport (UZ flow and transport) Model (CRWMS M&O 2000a). The UZ flow and transport model is one of several process models abstracted by the Total System Performance Assessment model to evaluate expected performance of the potential repository at Yucca Mountain, Nevada, in terms of radionuclide transport (CRWMS M&O 1998). The net-infiltration model is important for assessing potential repository-system performance because output from this model provides the upper boundary condition for the UZ flow and transport model that is used to generate flow fields for evaluating potential radionuclide transport through the unsaturated zone. Estimates of net infiltration are provided as raster-based, 2-dimensional grids of spatially distributed, time-averaged rates for three different climate stages estimated as likely conditions for the next 10,000 years beyond the present. Each climate stage is represented using a lower bound, a mean, and an upper bound climate and corresponding net-infiltration scenario for representing uncertainty in the characterization of daily climate conditions for each climate stage, as well as potential climate variability within each climate stage. The set of nine raster grid maps provide spatially

  7. Solar and Net Radiation for Estimating Potential Evaporation from Three Vegetation Canopies

    Science.gov (United States)

    D.M. Amatya; R.W. Skaggs; G.W. Cheschier; G.P. Fernandez

    2000-01-01

    Solar and net radiation data are frequent/y used in estimating potential evaporation (PE) from various vegetative surfaces needed for water balance and hydrologic modeling studies. Weather parameters such as air temperature, relative humidity, wind speed, solar radiation, and net radiation have been continuously monitored using automated sensors to estimate PE for...

  8. China and the Fifth Estate: Net Delusion or Democratic Potential?

    Directory of Open Access Journals (Sweden)

    William H. Dutton

    2015-07-01

    Full Text Available

    Arguably, liberal democratic societies are seeing the emergence of a ‘Fifth Estate’ that is being enabled by the Internet. This new organizational form is comparable to, but potentially more powerful than, the Fourth Estate, which developed as a significant force in an earlier period with an independent press and other mass media. While the significance of the press and the Internet to democratic governance is questioned in all societies, there is particular skepticism of their relevance outside the most liberal democratic regimes, which have a relatively free press and more pluralistic political systems, such as in North America and West Europe. Nevertheless, there have been vivid examples of where networked individuals have appeared to assert greater communicative power in the politics of governance, the media and everyday life, even in non-liberal democratic regimes, such as Hong Kong, and in some cases, China. This potential points to the need for more systematic empirical research in a wider variety of economic and political settings worldwide, particularly in states in which the Internet might offer a potential for more democratic governance and greater accountability of government controlled media. This paper examines cases in which networked individuals in China used the Internet to hold governmental and press institutions more accountable. The cases provide support for the relevance of the Fifth Estate concept in China, and also illuminates the process – showing how the Internet can be used to empower networked individuals in more autocratic regimes.

  9. The potential role of DNA methylation in abdominal aortic aneurysms.

    Science.gov (United States)

    Ryer, Evan J; Ronning, Kaitryn E; Erdman, Robert; Schworer, Charles M; Elmore, James R; Peeler, Thomas C; Nevius, Christopher D; Lillvis, John H; Garvin, Robert P; Franklin, David P; Kuivaniemi, Helena; Tromp, Gerard

    2015-05-18

    Abdominal aortic aneurysm (AAA) is a complex disorder that has a significant impact on the aging population. While both genetic and environmental risk factors have been implicated in AAA formation, the precise genetic markers involved and the factors influencing their expression remain an area of ongoing investigation. DNA methylation has been previously used to study gene silencing in other inflammatory disorders and since AAA has an extensive inflammatory component, we sought to examine the genome-wide DNA methylation profiles in mononuclear blood cells of AAA cases and matched non-AAA controls. To this end, we collected blood samples and isolated mononuclear cells for DNA and RNA extraction from four all male groups: AAA smokers (n = 11), AAA non-smokers (n = 9), control smokers (n = 10) and control non-smokers (n = 11). Methylation data were obtained using the Illumina 450k Human Methylation Bead Chip and analyzed using the R language and multiple Bioconductor packages. Principal component analysis and linear analysis of CpG island subsets identified four regions with significant differences in methylation with respect to AAA: kelch-like family member 35 (KLHL35), calponin 2 (CNN2), serpin peptidase inhibitor clade B (ovalbumin) member 9 (SERPINB9), and adenylate cyclase 10 pseudogene 1 (ADCY10P1). Follow-up studies included RT-PCR and immunostaining for CNN2 and SERPINB9. These findings are novel and suggest DNA methylation may play a role in AAA pathobiology.

  10. Potential Toxicity of α-Cypermethrin-Treated Nets on Tuta absoluta (Lepidoptera: Gelechiidae).

    Science.gov (United States)

    Biondi, A; Zappalà, L; Desneux, N; Aparo, A; Siscaro, G; Rapisarda, C; Martin, T; Tropea Garzia, G

    2015-06-01

    Insect-proof nets are thought to be effective physical barriers to protect tomato crops against several insect pests, including the invasive tomato pest, Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae). However, protected tomato crops are frequently infested by this destructive pest, and there is a higher infestation of plants closer to openings in Mediterranean greenhouses, suggesting that immigrating adults can easily walk on these protective materials and find a way to reach the crop. Laboratory bioassays were carried out to characterize the potential toxicity of α-cypermethrin-treated insect-proof nets (Agronet) against T. absoluta adults. The data showed that the net acts mainly through a variety of chronic sublethal effects rather than acute ones. Reduced longevity and, more markedly, a reduced number of laid eggs were observed after the moths were exposed to the treated net over the duration of their lifetimes. A Y-tube experiment showed that the treated net does not affect the T. absoluta olfaction cues for host location. In contrast, when the moths were given the option to choose either the treated or the untreated net in laboratory cages, they significantly preferred the untreated one. The toxicological significance and the functional implications of these subtle effects for the implementation of integrated T. absoluta management strategies are discussed. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. Thermal Decomposition of Potential Ester Biofuels. Part I: Methyl Acetate and Methyl Butanoate

    Energy Technology Data Exchange (ETDEWEB)

    Porterfield, Jessica P.; Bross, David H.; Ruscic, Branko; Thorpe, James H.; Nguyen, Thanh Lam; Baraban, Joshua H.; Stanton, John F.; Daily, John W.; Ellison, G. Barney

    2017-06-09

    Two methyl esters have been examined as models for the pyrolysis of biofuels. Dilute samples (0.06 - 0.13%) of methyl acetate (CH3COOCH3) and methyl butanoate (CH3CH2CH2COOCH3) were entrained in (He, Ar) carrier gas and decomposed in a set of flash-pyrolysis micro-reactors. The pyrolysis products resulting from the methyl esters were detected and identified by vacuum ultraviolet photoionization mass spectrometry. Complementary product identification was provided by matrix infrared absorption spectroscopy. Pyrolysis pressures in the pulsed micro-reactor were roughly 20 Torr and residence times through the reactors were approximately 25 - 150 µs. Reactor temperatures of 300 – 1600 K were explored. Decomposition of CH3COOCH3 commences at 1000 K and the initial products are (CH2=C=O and CH3OH). As the micro-reactor is heated to 1300 K, a mixture of (CH2=C=O and CH3OH, CH3, CH2=O, H, CO, CO2) appears. The thermal cracking of CH3CH2CH2COOCH3 begins at 800 K with the formation of (CH3CH2CH=C=O, CH3OH). By 1300 K, the pyrolysis of methyl butanoate yields a complex mixture of (CH3CH2CH=C=O, CH3OH, CH3, CH2=O, CO, CO2, CH3CH=CH2, CH2CHCH2, CH2=C=CH2, HCCCH2, CH2=C=C=O, CH2=CH2, HCΞCH, CH2=C=O). Based on the results from the thermal cracking of methyl acetate and methyl butanoate, we predict several important decomposition channels for the pyrolysis of fatty acid methyl esters, R CH2-COOCH3. The lowest energy fragmentation will be a 4-center elimination of methanol to form the ketene, RCH=C=O. At higher temperatures, concerted

  12. Thermal Decomposition of Potential Ester Biofuels. Part I: Methyl Acetate and Methyl Butanoate.

    Science.gov (United States)

    Porterfield, Jessica P; Bross, David H; Ruscic, Branko; Thorpe, James H; Nguyen, Thanh Lam; Baraban, Joshua H; Stanton, John F; Daily, John W; Ellison, G Barney

    2017-06-22

    Two methyl esters were examined as models for the pyrolysis of biofuels. Dilute samples (0.06-0.13%) of methyl acetate (CH3COOCH3) and methyl butanoate (CH3CH2CH2COOCH3) were entrained in (He, Ar) carrier gas and decomposed in a set of flash-pyrolysis microreactors. The pyrolysis products resulting from the methyl esters were detected and identified by vacuum ultraviolet photoionization mass spectrometry. Complementary product identification was provided by matrix infrared absorption spectroscopy. Pyrolysis pressures in the pulsed microreactor were about 20 Torr and residence times through the reactors were roughly 25-150 μs. Reactor temperatures of 300-1600 K were explored. Decomposition of CH3COOCH3 commences at 1000 K, and the initial products are (CH2═C═O and CH3OH). As the microreactor is heated to 1300 K, a mixture of CH2═C═O and CH3OH, CH3, CH2═O, H, CO, and CO2 appears. The thermal cracking of CH3CH2CH2COOCH3 begins at 800 K with the formation of CH3CH2CH═C═O and CH3OH. By 1300 K, the pyrolysis of methyl butanoate yields a complex mixture of CH3CH2CH═C═O, CH3OH, CH3, CH2═O, CO, CO2, CH3CH═CH2, CH2CHCH2, CH2═C═CH2, HCCCH2, CH2═C═C═O, CH2═CH2, HC≡CH, and CH2═C═O. On the basis of the results from the thermal cracking of methyl acetate and methyl butanoate, we predict several important decomposition channels for the pyrolysis of fatty acid methyl esters, R-CH2-COOCH3. The lowest-energy fragmentation will be a 4-center elimination of methanol to form the ketene RCH═C═O. At higher temperatures, concerted fragmentation to radicals will ensue to produce a mixture of species: (RCH2 + CO2 + CH3) and (RCH2 + CO + CH2═O + H). Thermal cracking of the β C-C bond of the methyl ester will generate the radicals (R and H) as well as CH2═C═O + CH2═O. The thermochemistry of methyl acetate and its fragmentation products were obtained via the Active Thermochemical Tables (ATcT) approach, resulting in ΔfH298(CH3COOCH3) = -98

  13. Independent Review of Simulation of Net Infiltration for Present-Day and Potential Future Climates

    Energy Technology Data Exchange (ETDEWEB)

    Review Panel: Soroosh Sorooshian, Ph.D., Panel Chairperson, University of California, Irvine; Jan M. H. Hendrickx, Ph.D., New Mexico Institute of Mining and Technology; Binayak P. Mohanty, Ph.D., Texas A& M University; Scott W. Tyler, Ph.D., University of Nevada, Reno; Tian-Chyi Jim Yeh, Ph.D., University of Arizona -- ORISE Review Facilitators: Robert S. Turner, Ph.D., Technical Review Group Manager, Oak Ridge Institute for Science and Education; Brian R. Herndon, Project Manager, Oak Ridge Institute for Science and Education; Russ Manning, Technical Writer/Editor, Haselwood Enterprises, Inc.

    2008-08-30

    The DOE Office of Civilian Radioactive Waste Management (OCRWM) tasked Oak Ridge Institute for Science and Education (ORISE) with providing an independent expert review of the documented model and prediction results for net infiltration of water into the unsaturated zone at Yucca Mountain. The specific purpose of the model, as documented in the report MDL-NBS-HS-000023, Rev. 01, is “to provide a spatial representation, including epistemic and aleatory uncertainty, of the predicted mean annual net infiltration at the Yucca Mountain site ...” (p. 1-1) The expert review panel assembled by ORISE concluded that the model report does not provide a technically credible spatial representation of net infiltration at Yucca Mountain. Specifically, the ORISE Review Panel found that: • A critical lack of site-specific meteorological, surface, and subsurface information prevents verification of (i) the net infiltration estimates, (ii) the uncertainty estimates of parameters caused by their spatial variability, and (iii) the assumptions used by the modelers (ranges and distributions) for the characterization of parameters. The paucity of site-specific data used by the modeling team for model implementation and validation is a major deficiency in this effort. • The model does not incorporate at least one potentially important hydrologic process. Subsurface lateral flow is not accounted for by the model, and the assumption that the effect of subsurface lateral flow is negligible is not adequately justified. This issue is especially critical for the wetter climate periods. This omission may be one reason the model results appear to underestimate net infiltration beneath wash environments and therefore imprecisely represent the spatial variability of net infiltration. • While the model uses assumptions consistently, such as uniform soil depths and a constant vegetation rooting depth, such assumptions may not be appropriate for this net infiltration simulation because they

  14. Potential Role of Methylation Marker in Glioma Supporting Clinical Decisions

    Directory of Open Access Journals (Sweden)

    Krzysztof Roszkowski

    2016-11-01

    Full Text Available The IDH1/2 gene mutations, ATRX loss/mutation, 1p/19q status, and MGMT promoter methylation are increasingly used as prognostic or predictive biomarkers of gliomas. However, the effect of their combination on radiation therapy outcome is discussable. Previously, we demonstrated that the IDH1 c.G395A; p.R132H mutation was associated with longer survival in grade II astrocytoma and GBM (Glioblastoma. Here we analyzed the MGMT promoter methylation status in patients with a known mutation status in codon 132 of IDH1, followed by clinical and genetic data analysis based on the two statuses. After a subtotal tumor resection, the patients were treated using IMRT (Intensity-Modulated Radiation Therapy with 6 MeV photons. The total dose was: 54 Gy for astrocytoma II, 60 Gy for astrocytoma III, 60 Gy for glioblastoma, 2 Gy per day, with 24 h intervals, five days per week. The patients with MGMT promoter methylation and IDH1 somatic mutation (OS = 40 months had a better prognosis than those with MGMT methylation alone (OS = 18 months. In patients with astrocytoma anaplasticum (n = 7 with the IDH1 p.R132H mutation and hypermethylated MGMT, the prognosis was particularly favorable (median OS = 47 months. In patients with astrocytoma II meeting the above criteria, the prognosis was also better than in those not meeting those criteria. The IDH1 mutation appears more relevant for the prognosis than MGMT methylation. The IDH1 p.R132H mutation combined with MGMT hypermethylation seems to be the most advantageous for treatment success. Patients not meeting those criteria may require more aggressive treatments.

  15. Simulation of Net Infiltration for Present-Day and Potential Future Climates

    Energy Technology Data Exchange (ETDEWEB)

    D. Levitt

    2004-11-09

    The purpose of this model report is to document the infiltration model used to estimate upper-bound, mean, and lower-bound spatially-distributed average annual net infiltration rates for present-day and potential future climates at Yucca Mountain, Nevada. Net infiltration is the component of infiltrated precipitation, snowmelt, or surface water run-on that has percolated below the zone of evapotranspiration as defined by the depth of the effective root zone. The estimates of net infiltration are primarily used for defining the upper boundary condition for the site-scale three-dimensional unsaturated zone (UZ) model. The UZ flow model is one of several process models abstracted by the total system performance assessment (TSPA) model used to evaluate performance of the repository at Yucca Mountain, Nevada. The net-infiltration model is important for assessing repository-system performance because output from this model provides the upper boundary condition for the UZ flow model used to generate flow fields; water percolating downward from the UZ will be the principal means by which radionuclides are potentially released to the saturated zone (SZ). The SZ is the principal pathway to the biosphere where the reasonably maximally exposed individual (RMEI) is exposed to radionuclides.

  16. Validation of methodology for determination of the mercury methylation potential in sediments using radiotracers.

    Science.gov (United States)

    Zizek, Suzana; Ribeiro Guevara, Sergio; Horvat, Milena

    2008-04-01

    Experiments to determine the mercury methylation potential were performed on sediments from two locations on the river Idrijca (Slovenia), differing in ambient mercury concentrations. The tracer used was the radioactive isotope (197)Hg. The benefit of using this tracer is its high specific activity, which enables spikes as low as 0.02 ng Hg(2+) g(-1) of sample to be used. It was therefore possible to compare the efficiency of the methylation potential experiments over a range of spike concentrations from picogram to microgram levels. The first part of the work aimed to validate the experimental blanks and the second part consisted of several series of incubation experiments on two different river sediments using a range of tracer additions. The results showed high variability in the obtained methylation potentials. Increasing Hg(2+) additions gave a decrease in the percentage of the tracer methylated during incubation; in absolute terms, the spikes that spanned four orders of magnitude (0.019-190 pg g(-1) of sediment slurry) resulted in MeHg formation between 0.01 and 0.1 ng MeHg g(-1) in Podroteja and Kozarska Grapa. Higher spikes resulted in slightly elevated MeHg production (up to a maximum of 0.27 ng g(-1)). The values of methylation potential were similar in both sediments. The results imply that the experimental determination of mercury methylation potential strongly depends on the experimental setup itself and the amount of tracer added to the system under study. It is therefore recommended to use different concentrations of tracer and perform the experiments in several replicates. The amount of mercury available for methylation in nature is usually very small. Therefore, adding very low amounts of tracer in the methylation potential studies probably gives results that have a higher environmental relevance. It is also suggested to express the results obtained in absolute amounts of MeHg produced and not just as the percentage of the added tracer.

  17. Mito-methyl coumarin, a novel mitochondria-targeted drug with great antitumor potential was synthesized.

    Science.gov (United States)

    Wang, Huanan; Xu, Wenqing

    2017-07-15

    Due to higher transmembrane potential of tumor cells, enhanced accumulation of cationic drugs in tumor mitochondria has been attributed to a higher (more negative inside) mitochondrial transmembrane potential compared with normal cells, emerging researchers are focus on developing mitochondria-targeted antitumor drugs. Coumarins showed great potential on antitumor, but mitochondria-targeted coumarin derivatives have not been reported. In the present study, we synthesized mitochondria-targeted-methyl coumarin (mito-methyl coumarin) through coupling 6-methyl coumarin to TPP. We confirmed that mito-methyl coumarin inhibited HeLa cells proliferation selectively, induced ROS generation, reduced mitochondrial membrane potential, promoted mitochondria Ca 2+ accumulation, decreased mitochondria mass and induced HeLa cells apoptosis, but methyl coumarin did not. These results demonstrate that we succeed in synthesizing a novel mitochondria-targeted drug, mito-methyl coumarin, which is effective in inhibiting HeLa cells proliferation and inducing HeLa cells apoptosis through promoting ROS generation and mitochondria Ca 2+ accumulation. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Hepatocellular carcinoma displays distinct DNA methylation signatures with potential as clinical predictors.

    Directory of Open Access Journals (Sweden)

    Hector Hernandez-Vargas

    Full Text Available BACKGROUND: Hepatocellular carcinoma (HCC is characterized by late detection and fast progression, and it is believed that epigenetic disruption may be the cause of its molecular and clinicopathological heterogeneity. A better understanding of the global deregulation of methylation states and how they correlate with disease progression will aid in the design of strategies for earlier detection and better therapeutic decisions. METHODS AND FINDINGS: We characterized the changes in promoter methylation in a series of 30 HCC tumors and their respective surrounding tissue and identified methylation signatures associated with major risk factors and clinical correlates. A wide panel of cancer-related gene promoters was analyzed using Illumina bead array technology, and CpG sites were then selected according to their ability to classify clinicopathological parameters. An independent series of HCC tumors and matched surrounding tissue was used for validation of the signatures. We were able to develop and validate a signature of methylation in HCC. This signature distinguished HCC from surrounding tissue and from other tumor types, and was independent of risk factors. However, aberrant methylation of an independent subset of promoters was associated with tumor progression and etiological risk factors (HBV or HCV infection and alcohol consumption. Interestingly, distinct methylation of an independent panel of gene promoters was strongly correlated with survival after cancer therapy. CONCLUSION: Our study shows that HCC tumors exhibit specific DNA methylation signatures associated with major risk factors and tumor progression stage, with potential clinical applications in diagnosis and prognosis.

  19. LINE-1 DNA methylation: A potential forensic marker for discriminating monozygotic twins.

    Science.gov (United States)

    Xu, Jie; Fu, Guangping; Yan, Lina; Craig, Jeffery M; Zhang, Xiaojing; Fu, Lihong; Ma, Chunling; Li, Shujin; Cong, Bin

    2015-11-01

    Discriminating individuals within a pair of monozygotic (MZ) twins using genetic markers remains unresolved. This inability causes problems in criminal or paternity cases involving MZ twins as suspects or alleged fathers. Our previous study showed DNA methylation differences in interspersed repeat sequences such as Alu and LINE-1 within pairs of newborn MZ twins. To further evaluate the possible value of LINE-1 DNA methylation for discriminating MZ twins, this study investigated the LINE-1 DNA methylation of a large number of twins. We collected blood samples and buccal cell samples from 119 pairs of MZ and 57 pairs of dizygotic (DZ) twins. Genomic DNA was extracted and LINE-1 methylation level was detected using bisulfite pyrosequencing. The mean methylation level of the three CpG sites in the blood sample among the 176 unrelated individuals was 76.60% and 70.08% in buccal samples. This difference was significant, indicating the tissue specificity of LINE-1 DNA methylation. Among 119 pairs of MZ twins, 15 pairs could be discriminated according to the difference of CpG methylation level between them, which accounted for 12.61% of total number of MZ pairs. As for DZ twins, 10 pairs had significant differences between two individuals, which accounted for 17.54% of the total 57 DZ pairs. In conclusion, there are global DNA methylation differences within some healthy concordant monozygotic (MZ) twin pairs. LINE-1 DNA methylation might be a potential marker for helping to discriminate individuals within MZ twin pairs, and the tissue specificity must be considered in practice. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Heterogeneity in white blood cells has potential to confound DNA methylation measurements.

    Directory of Open Access Journals (Sweden)

    Bjorn T Adalsteinsson

    Full Text Available Epigenetic studies are commonly conducted on DNA from tissue samples. However, tissues are ensembles of cells that may each have their own epigenetic profile, and therefore inter-individual cellular heterogeneity may compromise these studies. Here, we explore the potential for such confounding on DNA methylation measurement outcomes when using DNA from whole blood. DNA methylation was measured using pyrosequencing-based methodology in whole blood (n = 50-179 and in two white blood cell fractions (n = 20, isolated using density gradient centrifugation, in four CGIs (CpG Islands located in genes HHEX (10 CpG sites assayed, KCNJ11 (8 CpGs, KCNQ1 (4 CpGs and PM20D1 (7 CpGs. Cellular heterogeneity (variation in proportional white blood cell counts of neutrophils, lymphocytes, monocytes, eosinophils and basophils, counted by an automated cell counter explained up to 40% (p<0.0001 of the inter-individual variation in whole blood DNA methylation levels in the HHEX CGI, but not a significant proportion of the variation in the other three CGIs tested. DNA methylation levels in the two cell fractions, polymorphonuclear and mononuclear cells, differed significantly in the HHEX CGI; specifically the average absolute difference ranged between 3.4-15.7 percentage points per CpG site. In the other three CGIs tested, methylation levels in the two fractions did not differ significantly, and/or the difference was more moderate. In the examined CGIs, methylation levels were highly correlated between cell fractions. In summary, our analysis detects region-specific differential DNA methylation between white blood cell subtypes, which can confound the outcome of whole blood DNA methylation measurements. Finally, by demonstrating the high correlation between methylation levels in cell fractions, our results suggest a possibility to use a proportional number of a single white blood cell type to correct for this confounding effect in analyses.

  1. Origin of methyl torsional potential barrier – An overview

    Indian Academy of Sciences (India)

    Unknown

    ~10% above the experimental barrier (see table 1). The potential surface is the adiabatic fully relaxed (FR) pathway with respect to all other coordinates, hence cannot be truly one dimensional. Ozkabak and Goodman8c pointed out that the internal rotation is a multidimensional process and addressed the skeletal flexing of ...

  2. CCNA1 promoter methylation: a potential marker for grading Papanicolaou smear cervical squamous intraepithelial lesions.

    Science.gov (United States)

    Chujan, Suthipong; Kitkumthorn, Nakarin; Siriangkul, Sumalee; Mutirangura, Apiwat

    2014-01-01

    From our previous study, we established that cyclin A1 (CCNA1) promoter methylation is strongly correlated with multistep progression of HPV-associated cervical cancer, suggesting potential use as a diagnostic maker of disease. The purpose of the present study was to assess the prevalence of CCNA1 promoter methylation in residual cervical cells isolated from liquid-based cytology that underwent hrHPV DNA screening for cervical cancer, and then to evaluate this marker for diagnostic accuracy using parameters like sensitivity, specificity, predictive values and likelihood ratio. In this retrospective study, histopathology was used as the gold standard method with specimens separated into the following groups: negative (n=31), low- grade squamous intraepithelial lesions (LSIL, n=34) and high-grade squamous intraepithelial lesions or worse (HSIL+, n=32). The hrHPV was detected by Hybrid Capture 2 (HC2) and CCNA1 promoter methylation was examined by CCNA1 duplex methylation specific PCR. The results showed the frequencies of CCNA1 promoter methylation were 0%, 5.88% and 83.33%, while the percentages of hrHPV were 66.67%, 82.35% and 100% in the negative, LSIL and HSIL+ groups, respectively. Although hrHPV infection showed high frequency in all three groups, it could not differentiate between the different groups and grades of precancerous lesions. In contrast, CCNA1 promoter methylation clearly distinguished between negative/LSIL and HSIL+, with high levels of all statistic parameters. CCNA1 promoter methylation is a potential marker for distinguishing between histologic negative/LSIL and HSIL+using cervical cytology samples.

  3. Validation of methodology for determination of the mercury methylation potential in sediments using radiotracers

    Energy Technology Data Exchange (ETDEWEB)

    Zizek, Suzana; Horvat, Milena [Jozef Stefan Institute, Department of Environmental Sciences, Ljubljana (Slovenia); Ribeiro Guevara, Sergio [Centro Atomico Bariloche, Laboratorio de Analisis por Activacion Neutronica, Bariloche (Argentina)

    2008-04-15

    Experiments to determine the mercury methylation potential were performed on sediments from two locations on the river Idrijca (Slovenia), differing in ambient mercury concentrations. The tracer used was the radioactive isotope {sup 197}Hg. The benefit of using this tracer is its high specific activity, which enables spikes as low as 0.02 ng Hg{sup 2+} g{sup -1} of sample to be used. It was therefore possible to compare the efficiency of the methylation potential experiments over a range of spike concentrations from picogram to microgram levels. The first part of the work aimed to validate the experimental blanks and the second part consisted of several series of incubation experiments on two different river sediments using a range of tracer additions. The results showed high variability in the obtained methylation potentials. Increasing Hg{sup 2+} additions gave a decrease in the percentage of the tracer methylated during incubation; in absolute terms, the spikes that spanned four orders of magnitude (0.019-190 pg g{sup -1} of sediment slurry) resulted in MeHg formation between 0.01 and 0.1 ng MeHg g{sup -1} in Podroteja and Kozarska Grapa. Higher spikes resulted in slightly elevated MeHg production (up to a maximum of 0.27 ng g{sup -1}). The values of methylation potential were similar in both sediments. The results imply that the experimental determination of mercury methylation potential strongly depends on the experimental setup itself and the amount of tracer added to the system under study. It is therefore recommended to use different concentrations of tracer and perform the experiments in several replicates. The amount of mercury available for methylation in nature is usually very small. Therefore, adding very low amounts of tracer in the methylation potential studies probably gives results that have a higher environmental relevance. It is also suggested to express the results obtained in absolute amounts of MeHg produced and not just as the percentage of

  4. Status of Net Metering: Assessing the Potential to Reach Program Caps

    Energy Technology Data Exchange (ETDEWEB)

    Heeter, J.; Gelman, R.; Bird, L.

    2014-09-01

    Several states are addressing the issue of net metering program caps, which limit the total amount of net metered generating capacity that can be installed in a state or utility service territory. In this analysis, we examine net metering caps to gain perspective on how long net metering will be available in various jurisdictions under current policies. We also surveyed state practices and experience to understand important policy design considerations.

  5. Potential role of DNA methylation as a facilitator of target search processes for transcription factors through interplay with methyl-CpG-binding proteins.

    Science.gov (United States)

    Kemme, Catherine A; Marquez, Rolando; Luu, Ross H; Iwahara, Junji

    2017-07-27

    Eukaryotic genomes contain numerous non-functional high-affinity sequences for transcription factors. These sequences potentially serve as natural decoys that sequester transcription factors. We have previously shown that the presence of sequences similar to the target sequence could substantially impede association of the transcription factor Egr-1 with its targets. In this study, using a stopped-flow fluorescence method, we examined the kinetic impact of DNA methylation of decoys on the search process of the Egr-1 zinc-finger protein. We analyzed its association with an unmethylated target site on fluorescence-labeled DNA in the presence of competitor DNA duplexes, including Egr-1 decoys. DNA methylation of decoys alone did not affect target search kinetics. In the presence of the MeCP2 methyl-CpG-binding domain (MBD), however, DNA methylation of decoys substantially (∼10-30-fold) accelerated the target search process of the Egr-1 zinc-finger protein. This acceleration did not occur when the target was also methylated. These results suggest that when decoys are methylated, MBD proteins can block them and thereby allow Egr-1 to avoid sequestration in non-functional locations. This effect may occur in vivo for DNA methylation outside CpG islands (CGIs) and could facilitate localization of some transcription factors within regulatory CGIs, where DNA methylation is rare. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  6. Evaluation of DNA methylation markers and their potential to predict human aging.

    Science.gov (United States)

    Soares Bispo Santos Silva, Deborah; Antunes, Joana; Balamurugan, Kuppareddi; Duncan, George; Sampaio Alho, Clarice; McCord, Bruce

    2015-08-01

    We present epigenetic methylation data for two genetic loci, GRIA2, and NPTX2, which were tested for prediction of age from different donors of biofluids. We analyzed 44 saliva samples and 23 blood samples from volunteers with ages ranging from 5 to 72 years. DNA was extracted and bisulfite modified using commercial kits. Specific primers were used for amplification and methylation profiles were determined by pyrosequencing. Methylation data from both markers and their relationship with age were determined using linear regression analysis, which indicates a positive correlation between methylation and age. Older individuals tend to have increased methylation in both markers compared to younger individuals and this trend was more pronounced in the GRIA2 locus when compared to NPTX2. The epigenetic predicted age, calculated using a GRIA2 regression analysis model, was strongly correlated to chronological age (R(2) = 0.801), with an average difference of 6.9 years between estimated and observed ages. When using a NPTX2 regression model, we observed a lower correlation between predicted and chronological age (R(2) = 0.654), with an average difference of 9.2 years. These data indicate these loci can be used as a novel tool for age prediction with potential applications in many areas, including clinical and forensic investigations. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Variable Methylation Potential in Preterm Placenta: Implication for Epigenetic Programming of the Offspring.

    Science.gov (United States)

    Khot, Vinita V; Chavan-Gautam, Preeti; Mehendale, Savita; Joshi, Sadhana R

    2017-06-01

    Children born preterm are reported to be at increased risk of developing noncommunicable diseases in later life. Altered placental DNA methylation patterns are implicated in fetal programming of adult diseases. Our earlier animal studies focus on micronutrients (folic acid, vitamin B12) and long-chain polyunsaturated fatty acids (LCPUFAs) that interact in the 1 carbon cycle, thereby influencing methylation reactions. Our previous studies in women delivering preterm show altered plasma levels of micronutrients and lower plasma LCPUFA levels. We postulate that alterations in the micronutrient metabolism may affect the regulation of enzymes, methionine adenosyltransferase ( MAT2A), and SAH-hydrolase ( AHCY), involved in the production of methyl donor S-adenosylmethionine (SAM), thereby influencing the methylation potential (MP) in the placenta of women delivering preterm. The present study, therefore, examines the mRNA, protein levels of enzymes ( MAT2A and AHCY), SAM, S-adenosylhomocysteine (SAH) levels, and global DNA methylation levels from preterm (n = 73) and term (n = 73) placentae. The enzyme messenger RNA (mRNA) levels were analyzed by real-time quantitative polymerase chain reaction, protein levels by enzyme-linked immunosorbent assay, and SAM-SAH levels by high-performance liquid chromatography. The mRNA levels for MAT2A and AHCY are higher ( P epigenetic programming of the developing fetus.

  8. Tunneling of coupled methyl quantum rotors in 4-methylpyridine: Single rotor potential versus coupling interaction

    Science.gov (United States)

    Khazaei, Somayeh; Sebastiani, Daniel

    2017-11-01

    We study the influence of rotational coupling between a pair of methyl rotators on the tunneling spectrum in condensed phase. Two interacting adjacent methyl groups are simulated within a coupled-pair model composed of static rotational potential created by the chemical environment and the interaction potential between two methyl groups. We solve the two-dimensional time-independent Schrödinger equation analytically by expanding the wave functions on the basis set of two independent free-rotor functions. We investigate three scenarios which differ with respect to the relative strength of single-rotor and coupling potential. For each scenario, we illustrate the dependence of the energy level scheme on the coupling strength. It is found that the main determinant of splitting energy levels tends to be a function of the ratio of strengths of coupling and single-rotor potential. The tunnel splitting caused by coupling is maximized for the coupled rotors in which their total hindering potential is relatively shallow. Such a weakly hindered methyl rotational potential is predicted for 4-methylpyridine at low temperature. The experimental observation of multiple tunneling peaks arising from a single type of methyl group in 4-methylpyridine in the inelastic neutron scattering spectrum is widely attributed to the rotor-rotor coupling. In this regard, using a set of first-principles calculations combined with the nudged elastic band method, we investigate the rotational potential energy surface (PES) of the coaxial pairs of rotors in 4-methylpyridine. A Numerov-type method is used to numerically solve the two-dimensional time-independent Schrödinger equation for the calculated 2D-density functional theory profile. Our computed energy levels reproduce the observed tunneling transitions well. Moreover, the calculated density distribution of the three methyl protons resembles the experimental nuclear densities obtained from the Fourier difference method. By mapping the

  9. Experimental mitochondria-targeted DNA methylation identifies GpC methylation, not CpG methylation, as potential regulator of mitochondrial gene expression

    OpenAIRE

    van der Wijst, Monique G. P.; van Tilburg, Amanda Y.; Marcel H J Ruiters; Rots, Marianne G

    2017-01-01

    Like the nucleus, mitochondria contain their own DNA and recent reports provide accumulating evidence that also the mitochondrial DNA (mtDNA) is subjective to DNA methylation. This evidence includes the demonstration of mitochondria-localised DNA methyltransferases and demethylases, and the detection of mtDNA methylation as well as hydroxymethylation. Importantly, differential mtDNA methylation has been linked to aging and diseases, including cancer and diabetes. However, functionality of mtD...

  10. The potential use of DNA methylation biomarkers to identify risk and progression of type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Linn eGillberg

    2015-03-01

    Full Text Available Type 2 diabetes mellitus (T2D is a slowly progressive disease that can be postponed or even avoided through lifestyle changes. Recent data demonstrate highly significant correlations between DNA methylation and the most important risk factors of T2D, including age and BMI, in blood and human tissues relevant to insulin resistance and T2D. Also, T2D patients and individuals with increased risk of the disease display differential DNA methylation profiles and plasticity compared to controls. Accordingly, the novel clues to DNA methylation fingerprints in blood and tissues with deteriorated metabolic capacity indicate that blood-borne epigenetic biomarkers of T2D progression might become a reality. This Mini Review will address the most recent associations between DNA methylation and diabetes-related traits in human tissues and blood. The overall focus is on the potential of future epigenome-wide studies, carried out across tissues and populations with correlations to pre-diabetes and T2D risk factors, to build up a library of epigenetic markers of risk and early progression of T2D. These markers may, tentatively in combination with other predictors of T2D development, increase the possibility of individual-based lifestyle prevention of T2D and associated metabolic diseases.

  11. Discovery of potential DNA methylation markers for forensic tissue identification using bisulphite pyrosequencing.

    Science.gov (United States)

    Vidaki, Athina; Giangasparo, Federica; Syndercombe Court, Denise

    2016-10-01

    The presence of specific body fluids at crime scenes could be linked with particular types of crime, therefore attributing a DNA profile to a specific tissue could increase the evidential significance of a match with a suspect. Current methodologies such as tissue-specific mRNA profiling are useful but drawbacks include low tissue specificity and applicability to degraded samples. In this study, the potential of 11 tissue-specific differentially methylated regions, initially identified following large-scale methylation analysis of whole blood, buccal cells and sperm, was explored in order to identify markers for blood, saliva and semen. Bisulphite pyrosequencing analysis supported previous findings, but tissue-specific differentially methylated regions for blood and buccal cells did not show enough specificity to be proposed as markers for blood and saliva, respectively. For some CpGs, a large inter-individual variation in methylation levels was also observed. Two of the semen markers (cg04382920 and cg11768416) were used for further validation on a large set of stains. These two semen-specific assays showed high sensitivity (as low as 50 pg) and stability. Future experiments will shed light on the usefulness of these markers in forensic casework. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Potentiation of insulin release in response to amino acid methyl esters correlates to activation of islet glutamate dehydrogenase activity

    DEFF Research Database (Denmark)

    Kofod, Hans; Lernmark, A; Hedeskov, C J

    1986-01-01

    Column perifusion of mouse pancreatic islets was used to study the ability of amino acids and their methyl esters to influence insulin release and activate islet glutamate dehydrogenase activity. In the absence of L-glutamine, L-serine and the methyl ester of L-phenylalanine, but neither L...... glutamate dehydrogenase activity showed that only the two methyl esters of L-phenylalanine and L-serine activated the enzyme. It is concluded that the mechanism by which methyl esters of amino acids potentiate insulin release is most likely to be mediated by the activation of pancreatic beta-cell glutamate...

  13. Biogeochemical controls on mercury methylation in the Allequash Creek wetland.

    Science.gov (United States)

    Creswell, Joel E; Shafer, Martin M; Babiarz, Christopher L; Tan, Sue-Zanne; Musinsky, Abbey L; Schott, Trevor H; Roden, Eric E; Armstrong, David E

    2017-06-01

    We measured mercury methylation potentials and a suite of related biogeochemical parameters in sediment cores and porewater from two geochemically distinct sites in the Allequash Creek wetland, northern Wisconsin, USA. We found a high degree of spatial variability in the methylation rate potentials but no significant differences between the two sites. We identified the primary geochemical factors controlling net methylmercury production at this site to be acid-volatile sulfide, dissolved organic carbon, total dissolved iron, and porewater iron(II). Season and demethylation rates also appear to regulate net methylmercury production. Our equilibrium speciation modeling demonstrated that sulfide likely regulated methylation rates by controlling the speciation of inorganic mercury and therefore its bioavailability to methylating bacteria. We found that no individual geochemical parameter could explain a significant amount of the observed variability in mercury methylation rates, but we found significant multivariate relationships, supporting the widely held understanding that net methylmercury production is balance of several simultaneously occurring processes.

  14. MOURA magnetometer for Mars MetNet Precursor Mission. Its potential for an in situ magnetic environment and surface characterization

    Energy Technology Data Exchange (ETDEWEB)

    Diaz Michelena, M.; Sanz, R.; Fernandez, A.B.; Manuel, V. de; Cerdan, M.F.; Apestigue, V.; Arruego, I.; Azcue, J.; Dominguez, J.A.; Gonzalez, M.; Guerrero, H.; Sabau, M.; Kilian, R.; Baeza, O.; Ros, F.; Vazquez, M.; Tordesillas, J.M.; Covisa, P.; Aguado, J.

    2016-07-01

    MOURA magnetometer and gradiometer is part of the scientific instrumentation for Mars MetNet Precursor mission. This work describes the objective of the investigation, summarizes the work done in the design and development of the sensor as well as its calibration, and shows the demonstration campaigns to show the potential of such instrument for planetary landers and rovers. (Author)

  15. Comparison of net global warming potential and greenhouse gas intensity affected by management practices in two dryland cropping sites

    Science.gov (United States)

    Little is known about the effect of management practices on net global warming potential (GWP) and greenhouse gas intensity (GHGI) that account for all sources and sinks of greenhouse gas (GHG) emissions in dryland cropping systems. The objective of this study was to compare the effect of a combinat...

  16. Control of pyrethroid and DDT-resistant Anopheles gambiae by application of indoor residual spraying or mosquito nets treated with a long-lasting organophosphate insecticide, chlorpyrifos-methyl

    Directory of Open Access Journals (Sweden)

    Chabi Joseph

    2010-02-01

    Full Text Available Abstract Background Scaling up of long-lasting insecticidal nets (LLINs and indoor residual spraying (IRS with support from the Global Fund and President's Malaria Initiative is providing increased opportunities for malaria control in Africa. The most cost-effective and longest-lasting residual insecticide DDT is also the most environmentally persistent. Alternative residual insecticides exist, but are too short-lived or too expensive to sustain. Dow Agrosciences have developed a microencapsulated formulation (CS of the organophosphate chlorpyrifos methyl as a cost-effective, long-lasting alternative to DDT. Methods Chlorpyrifos methyl CS was tested as an IRS or ITN treatment in experimental huts in an area of Benin where Anopheles gambiae and Culex quinquefasiactus are resistant to pyrethroids, but susceptible to organophosphates. Efficacy and residual activity was compared to that of DDT and the pyrethroid lambdacyalothrin. Results IRS with chlorpyrifos methyl killed 95% of An. gambiae that entered the hut as compared to 31% with lambdacyhalothrin and 50% with DDT. Control of Cx. quinquefasciatus showed a similar trend; although the level of mortality with chlorpyrifos methyl was lower (66% it was still much higher than for DDT (14% or pyrethroid (15% treatments. Nets impregnated with lambdacyhalothrin were compromized by resistance, killing only 30% of An. gambiae and 8% of Cx. quinquefasciatus. Nets impregnated with chlorpyrifos methyl killed more (45% of An gambiae and 15% of Cx. quinquefasciatus, but its activity on netting was of short duration. Contact bioassays on the sprayed cement-sand walls over the nine months of monitoring showed no loss of activity of chlorpyrifos methyl, whereas lambdacyhalothrin and DDT lost activity within a few months of spraying. Conclusion As an IRS treatment against pyrethroid resistant mosquitoes chlorpyrifos methyl CS outperformed DDT and lambdacyhalothrin. In IRS campaigns, chlorpyrifos methyl CS should

  17. Improvement potential for net energy balance of biodiesel derived from palm oil: A case study from Indonesian practice

    Energy Technology Data Exchange (ETDEWEB)

    Kamahara, Hirotsugu [Research Institute of Science for Safety and Sustainability, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki 305-8569 (Japan); Hasanudin, Udin [Department of Agroindustrial Technology, University of Lampung, Bandar Lampung, Lampung 35145 (Indonesia); Widiyanto, Anugerah [International Cooperation Center for Engineering Education Development, Toyohashi University of Technology, Toyohashi, Aichi 441-8580 (Japan); Tachibana, Ryuichi [Department of Civil and Environmental Engineering, Nagaoka University of Technology, Nagaoka, Niigata 940-2188 (Japan); Atsuta, Yoichi; Goto, Naohiro; Daimon, Hiroyuki [Department of Environmental and Life Sciences, Toyohashi University of Technology, 1-1 Hibarigaoka, Tempaku, Toyohashi, Aichi 441-8580 (Japan); Fujie, Koichi [Graduate School of Environment and Information Sciences, Yokohama National University, Yokohama, Kanagawa 240-8501 (Japan)

    2010-12-15

    Biodiesel derived from palm oil has been recognized as a high-productivity oil crop among the first generation of biofuels. This study evaluated and discussed the net energy balance for biodiesel in Indonesia by calculating the net energy ratio (NER) and net energy production (NEP) form the total energy input and output. The results of the calculation of energy input for the default scenario demonstrated that the primary energy inputs in the biodiesel production lifecycle were the methanol feedstock, energy input during the biodiesel production process, and urea production. These three items amounted to 85% of the total energy input. Next, we considered and evaluated ways to potentially improve the energy balance by utilizing by-products and biogas from wastewater treatment in the palm oil mill. This result emphasized the importance of utilizing the biomass residue and by-products. Finally, we discussed the need to be aware of energy balance issues between countries when biofuels are transported internationally. (author)

  18. NetLand: quantitative modeling and visualization of Waddington's epigenetic landscape using probabilistic potential.

    Science.gov (United States)

    Guo, Jing; Lin, Feng; Zhang, Xiaomeng; Tanavde, Vivek; Zheng, Jie

    2017-05-15

    Waddington's epigenetic landscape is a powerful metaphor for cellular dynamics driven by gene regulatory networks (GRNs). Its quantitative modeling and visualization, however, remains a challenge, especially when there are more than two genes in the network. A software tool for Waddington's landscape has not been available in the literature. We present NetLand, an open-source software tool for modeling and simulating the kinetic dynamics of GRNs, and visualizing the corresponding Waddington's epigenetic landscape in three dimensions without restriction on the number of genes in a GRN. With an interactive and graphical user interface, NetLand can facilitate the knowledge discovery and experimental design in the study of cell fate regulation (e.g. stem cell differentiation and reprogramming). NetLand can run under operating systems including Windows, Linux and OS X. The executive files and source code of NetLand as well as a user manual, example models etc. can be downloaded from http://netland-ntu.github.io/NetLand/ . zhengjie@ntu.edu.sg. Supplementary data are available at Bioinformatics online.

  19. Experimental mitochondria-targeted DNA methylation identifies GpC methylation, not CpG methylation, as potential regulator of mitochondrial gene expression

    NARCIS (Netherlands)

    van der Wijst, Monique G. P.; van Tilburg, Amanda Y.; Ruiters, Marcel H. J.; Rots, Marianne G.

    2017-01-01

    Like the nucleus, mitochondria contain their own DNA and recent reports provide accumulating evidence that also the mitochondrial DNA (mtDNA) is subjective to DNA methylation. This evidence includes the demonstration of mitochondria-localised DNA methyltransferases and demethylases, and the

  20. Methylated TRF2 associates with the nuclear matrix and serves as a potential biomarker for cellular senescence.

    Science.gov (United States)

    Mitchell, Taylor R H; Zhu, Xu-Dong

    2014-04-01

    Methylation of N-terminal arginines of the shelterin component TRF2 is important for cellular proliferation. While TRF2 is found at telomeres, where it plays an essential role in maintaining telomere integrity, little is known about the cellular localization of methylated TRF2. Here we report that the majority of methylated TRF2 is resistant to extraction by high salt buffer and DNase I treatment, indicating that methylated TRF2 is tightly associated with the nuclear matrix. We show that methylated TRF2 drastically alters its nuclear staining as normal human primary fibroblast cells approach and enter replicative senescence. This altered nuclear staining, which is found to be overwhelmingly associated with misshapen nuclei and abnormal nuclear matrix folds, can be suppressed by hTERT and it is barely detectable in transformed and cancer cell lines. We find that dysfunctional telomeres and DNA damage, both of which are potent inducers of cellular senescence, promote the altered nuclear staining of methylated TRF2, which is dependent upon the ATM-mediated DNA damage response. Collectively, these results suggest that the altered nuclear staining of methylated TRF2 may represent ATM-mediated nuclear structural alteration associated with cellular senescence. Our data further imply that methylated TRF2 can serve as a potential biomarker for cellular senescence.

  1. Net sulfur mineralization potential in Swedish arable soils in relation to long-term treatment history and soil properties

    DEFF Research Database (Denmark)

    Boye, Kristin; Nilsson, S Ingvar; Eriksen, Jørgen

    2009-01-01

    The long-term treatment effect (since 1957-1966) of farmyard manure (FYM) application compared with crop residue incorporation was investigated in five soils (sandy loam to silty clay) with regards to the net sulfur (S) mineralization potential. An open incubation technique was used to determine ...... to SAccMin. Conclusively, different treatment histories influenced the quality (e.g., chemical composition) and cycling rate of the organic S pool, rather than its size...

  2. A novel electrochemical membrane bioreactor as a potential net energy producer for sustainable wastewater treatment.

    Science.gov (United States)

    Wang, Yun-Kun; Sheng, Guo-Ping; Shi, Bing-Jing; Li, Wen-Wei; Yu, Han-Qing

    2013-01-01

    One possible way to address both water and energy shortage issues, the two of major global challenges, is to recover energy and water resource from wastewater. Herein, a novel electrochemical membrane bioreactor (EMBR) was developed to recover energy from wastewater and meantime harvest clean water for reuse. With the help of the microorganisms in the biocatalysis and biodegradation process, net electricity could be recovered from a low-strength synthetic wastewater after estimating total energy consumption of this system. In addition, high-quality clean water was obtained for reuse. The results clearly demonstrate that, under the optimized operating conditions, it is possible to recover net energy from wastewater, while at the same time to harvest high-quality effluent for reuse with this novel wastewater treatment system.

  3. Assessing DNA methylation in the developing human intestinal epithelium: potential link to inflammatory bowel disease.

    Science.gov (United States)

    Kraiczy, J; Nayak, K; Ross, A; Raine, T; Mak, T N; Gasparetto, M; Cario, E; Rakyan, V; Heuschkel, R; Zilbauer, M

    2016-05-01

    DNA methylation is one of the major epigenetic mechanisms implicated in regulating cellular development and cell-type-specific gene expression. Here we performed simultaneous genome-wide DNA methylation and gene expression analysis on purified intestinal epithelial cells derived from human fetal gut, healthy pediatric biopsies, and children newly diagnosed with inflammatory bowel disease (IBD). Results were validated using pyrosequencing, real-time PCR, and immunostaining. The functional impact of DNA methylation changes on gene expression was assessed by employing in-vitro assays in intestinal cell lines. DNA methylation analyses allowed identification of 214 genes for which expression is regulated via DNA methylation, i.e. regulatory differentially methylated regions (rDMRs). Pathway and functional analysis of rDMRs suggested a critical role for DNA methylation in regulating gene expression and functional development of the human intestinal epithelium. Moreover, analysis performed on intestinal epithelium of children newly diagnosed with IBD revealed alterations in DNA methylation within genomic loci, which were found to overlap significantly with those undergoing methylation changes during intestinal development. Our study provides novel insights into the physiological role of DNA methylation in regulating functional maturation of the human intestinal epithelium. Moreover, we provide data linking developmentally acquired alterations in the DNA methylation profile to changes seen in pediatric IBD.

  4. Net mineralization of N at deeper soil depths as a potential mechanism for sustained forest production under elevated [CO2

    Energy Technology Data Exchange (ETDEWEB)

    Iversen, Colleen M [ORNL; Hooker, Toby [Utah State University (USU); Classen, Aimee T [University of Tennessee, Knoxville (UTK); Norby, Richard J [ORNL

    2011-01-01

    Elevated atmospheric [CO2] is projected to increase forest production, which could increase ecosystem carbon (C) storage. However, sustained forest production will depend on the nutrient balance of the forested ecosystem. Our aim was to examine the causes and consequences of increased fine-root production and mortality throughout the soil profile under elevated CO2 with respect to potential gross nitrogen (N) cycling rates. Our study was conducted in a CO2-enriched sweetgum (Liquidambar styraciflua L.) plantation in Oak Ridge, TN, USA. We used isotope pool dilution methodology to measure potential gross N cycling rates in laboratory incubations of soil from four depth increments to 60 cm. Our objectives were two-fold: (1) determine whether N is available for root acquisition in deeper soil, and (2) determine whether increased inputs of labile C from greater fine-root mortality at depth under elevated [CO2] had altered N cycling rates. While gross N fluxes declined with soil depth, we found that N is potentially available for roots to access, especially below 15 cm depth where microbial consumption of mineral N was reduced. Overall, up to 60% of potential gross N mineralization, and 100% of potential net N mineralization, occurred below 15-cm depth at this site. This finding was supported by in situ measurements from ion-exchange resins, where total inorganic N availability at 55 cm depth was equal to or greater than N availability at 15 cm depth. While it is likely that trees grown under elevated [CO2] are accessing a larger pool of inorganic N by mining deeper soil, we found no effect of elevated [CO2] on potential gross or net N cycling rates. Thus, increased root exploration of the soil volume under elevated [CO2] may be more important than changes in potential gross N cycling rates in sustaining forest responses to rising atmospheric CO2.

  5. Delayed cognitive and psychiatric symptoms following methyl iodide and manganese poisoning: Potential for misdiagnosis.

    Science.gov (United States)

    Mackenzie Ross, Sarah

    2016-01-01

    This paper describes two patients who were exposed to toxic substances in the workplace, but for whom diagnosis proved difficult, particularly in case 2. Case 1 was exposed to methyl iodide and case 2 to manganese. Poisoning was characterised by delayed onset of symptoms following exposure and symptom progression after cessation of exposure. The clinical consequences of exposure to these substances include cerebellar and Parkinsonian symptoms followed by the development of cognitive impairment and the late appearance of psychiatric disturbances. Both cases were evaluated by physicians with little training in toxicology. Apart from abnormal liver function in case 1 and decreased power, coordination and proprioception in case 2, results of most routine medical investigations were normal. Both cases were referred for MRI brain scan and neuropsychological assessment. Abnormalities were noted on MRI but reported as being absent initially in case 1and of unknown significance in case 2. There was evidence of cognitive impairment in both and personality change in case 1 of sufficient severity to prevent both cases from returning to work and to impact on family life. There is no antidote to methyl iodide or manganese poisoning. Successful treatment requires early diagnosis and cessation of exposure, but neurotoxic syndromes are difficult to diagnose when a time lag exists between exposure and symptom onset and there is no biomarker of exposure. These syndromes may initially be confused with other neurodegenerative conditions, infectious processes, and psychiatric disorders. Clinician's lack of familiarity with the potential toxicity of environmental and industrial chemicals can lead to misdiagnosis and mismanagement, and this lack of recognition can lead to continued exposure. These cases highlight the importance of taking a detailed occupational history in patients who present with atypical neurological symptoms. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. [THE SOMATIC MUTATIONS AND ABERRANT METHYLATION AS POTENTIAL GENETIC MARKERS OF URINARY BLADDER CANCER].

    Science.gov (United States)

    Mikhailenko, D S; Kushlinskii, N E

    2016-02-01

    All around the world, more than 330 thousands cases of bladder cancer are registered annually hence representing actual problem of modern oncology. Still in demand are search and characteristic of new molecular markers of bladder cancer detecting in tumor cells from urinary sediment and having high diagnostic accuracy. The studies of last decade, especially using methods of genome-wide sequencing, permitted to receive a large amount of experimental data concerning development and progression of bladder cancer The review presents systematic analysis of publications available in PubMed data base mainly of last five years. The original studies of molecular genetic disorders under bladder cancer and meta-analyzes were considered This approach permitted to detected the most common local alterations of DNA under bladder cancer which can be detected using routine genetic methods indifferent clinical material and present prospective interest for development of test-systems. The molecular genetic markers of disease can be activating missense mutations in 7 and 10 exons of gene of receptor of growth factor of fibroblasts 3 (FGFR3), 9 and 20 exons of gene of Phosphatidylinositol-4,5-bi-phosphate-3-kinase (PIK3CA) and mutation in -124 and -146 nucleotides in promoter of gene of catalytic subunit telomerase (TERT). The development of test-systems on the basis of aberrant methylation of CpG-islets of genes-suppressors still is seemed as a difficult task because of differences in pattern of methylation of different primary tumors at various stages of clonal evolution of bladder cancer though they can be considered as potential markers.

  7. Biocatalytic potential of lipase from Staphylococcus sp. MS1 for transesterification of jatropha oil into fatty acid methyl esters.

    Science.gov (United States)

    Sharma, Monika; Singh, Shelley Sardul; Maan, Pratibha; Sharma, Rohit

    2014-11-01

    An extracellular lipase producing isolate Staphylococcus sp. MS1 was optimized for lipase production and its biocatalytic potential was assessed. Medium with tributyrin (0.25 %) and without any exogenous inorganic nitrogen source was found to be optimum for lipase production from Staphylococcus sp. MS1. The optimum pH and temperature for lipase production were found to be pH 7 and 37 °C respectively, showing lipase activity of 37.91 U. It showed good lipase production at pH 6-8. The lipase was found to be stable in organic solvents like hexane and petroleum ether, showing 98 and 88 % residual activity respectively. The biotransformation using the concentrated enzyme in petroleum ether resulted in the synthesis of fatty acid methyl esters like methyl oleate, methyl palmitate and methyl stearate. Thus, the lipase under study has got the potential to bring about transesterification of oils into methyl esters which can be exploited for various biotechnological applications.

  8. Thiolated methylated dimethylaminobenzyl chitosan: A novel chitosan derivative as a potential delivery vehicle.

    Science.gov (United States)

    Hakimi, Shirin; Mortazavian, Elaheh; Mohammadi, Zohreh; Samadi, Fatemeh Yazdi; Samadikhah, Hamidreza; Taheritarigh, Sadegh; Tehrani, Niyousha Rafiee; Rafiee-Tehrani, Morteza

    2017-02-01

    Chitosan is a natural mucoadhesive, biodegradable, biocompatible and nontoxic polymer which has been used in pharmaceutical industry for a lot of purposes such as dissolution enhancing, absorption enhancing, sustained releasing and protein, gene or drug delivery. Two major disadvantages of chitosan are poor solubility in physiological pH and low efficiency for protein and gene delivery. In this study thiolated methylated N-(4-N,N-dimethylaminobenzyl) chitosan was prepared for the first time in order to improve the solubility and delivery properties of chitosan. This novel chitosan derivative was characterized using 1H NMR, Ellman test, TGA and Zetasizer. Cell toxicity studies were performed on Human Embryonic Kidney 293 (Hek293) cell line using XTT method, to investigate the potential effect of this new derivative on cell viability. 1H NMR results showed that all substitution reactions were successfully carried out. Zeta potential of new derivative at acidic and physiological pHs was greater than chitosan and it revealed an increase in solubility of the derivative. Furthermore, it had no significant cytotoxicity against Hek293 cell line in comparison to chitosan. These findings confirm that this new derivative can be introduced as a suitable compound for biomedical purposes. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Integrated data analysis reveals potential drivers and pathways disrupted by DNA methylation in papillary thyroid carcinomas

    DEFF Research Database (Denmark)

    Beltrami, Caroline Moraes; Dos Reis, Mariana Bisarro; Barros-Filho, Mateus Camargo

    2017-01-01

    BACKGROUND: Papillary thyroid carcinoma (PTC) is a common endocrine neoplasm with a recent increase in incidence in many countries. Although PTC has been explored by gene expression and DNA methylation studies, the regulatory mechanisms of the methylation on the gene expression was poorly clarified...

  10. The potential of net zero energy buildings (NZEBs) concept at design stage for healthcare buildings towards sustainable development

    Science.gov (United States)

    Hazli Abdellah, Roy; Asrul Nasid Masrom, Md; Chen, Goh Kai; Mohamed, Sulzakimin; Omar, Roshartini

    2017-11-01

    The focus on net-zero energy buildings (NZEBs) has been widely analysed and discussed particularly when European Union Parliament are progressively moving towards regulation that promotes the improvement of energy efficiency (EE). Additionally, it also to reduce energy consumption through the recast of the EU Directive on Energy Performance of Buildings (EPBD) in which all new buildings to be “nearly Zero-Energy” Buildings by 2020. Broadly, there is a growing trend to explore the feasibility of net zero energy in healthcare sector as the level energy consumption for healthcare sector is found significantly high. Besides that, healthcare buildings energy consumption also exceeds of many other nondomestic building types, and this shortcoming is still undetermined yet especially for developing countries. This paper aims to review the potential of NZEBs in healthcare buildings by considering its concept in design features. Data are gathered through a comprehensive energy management literature review from previous studies. The review is vital to encourage construction players to increase their awareness, practices, and implementation of NZEBs in healthcare buildings. It suggests that NZEBs concept has a potential to be adapted in healthcare buildings through emphasizing of passive approach as well as the utilization of energy efficiency systems and renewable energy systems in buildings. This paper will provide a basis knowledge for construction key players mainly architects to promote NZEBs concept at design stage for healthcare buildings development.

  11. TargetNet: a web service for predicting potential drug-target interaction profiling via multi-target SAR models.

    Science.gov (United States)

    Yao, Zhi-Jiang; Dong, Jie; Che, Yu-Jing; Zhu, Min-Feng; Wen, Ming; Wang, Ning-Ning; Wang, Shan; Lu, Ai-Ping; Cao, Dong-Sheng

    2016-05-01

    Drug-target interactions (DTIs) are central to current drug discovery processes and public health fields. Analyzing the DTI profiling of the drugs helps to infer drug indications, adverse drug reactions, drug-drug interactions, and drug mode of actions. Therefore, it is of high importance to reliably and fast predict DTI profiling of the drugs on a genome-scale level. Here, we develop the TargetNet server, which can make real-time DTI predictions based only on molecular structures, following the spirit of multi-target SAR methodology. Naïve Bayes models together with various molecular fingerprints were employed to construct prediction models. Ensemble learning from these fingerprints was also provided to improve the prediction ability. When the user submits a molecule, the server will predict the activity of the user's molecule across 623 human proteins by the established high quality SAR model, thus generating a DTI profiling that can be used as a feature vector of chemicals for wide applications. The 623 SAR models related to 623 human proteins were strictly evaluated and validated by several model validation strategies, resulting in the AUC scores of 75-100 %. We applied the generated DTI profiling to successfully predict potential targets, toxicity classification, drug-drug interactions, and drug mode of action, which sufficiently demonstrated the wide application value of the potential DTI profiling. The TargetNet webserver is designed based on the Django framework in Python, and is freely accessible at http://targetnet.scbdd.com .

  12. Cutaneous and mucosal human papillomaviruses differ in net surface charge, potential impact on tropism

    Directory of Open Access Journals (Sweden)

    Wibom Carl

    2008-10-01

    Full Text Available Abstract Papillomaviruses can roughly be divided into two tropism groups, those infecting the skin, including the genus beta PVs, and those infecting the mucosa, predominantly genus alpha PVs. The L1 capsid protein determines the phylogenetic separation between beta types and alpha types and the L1 protein is most probably responsible for the first interaction with the cell surface. Virus entry is a known determinant for tissue tropism and to study if interactions of the viral capsid with the cell surface could affect HPV tropism, the net surface charge of the HPV L1 capsid proteins was analyzed and HPV-16 (alpha and HPV-5 (beta with a mucosal and cutaneous tropism respectively were used to study heparin inhibition of uptake. The negatively charged L1 proteins were all found among HPVs with cutaneous tropism from the beta- and gamma-PV genus, while all alpha HPVs were positively charged at pH 7.4. The linear sequence of the HPV-5 L1 capsid protein had a predicted isoelectric point (pI of 6.59 and a charge of -2.74 at pH 7.4, while HPV-16 had a pI of 7.95 with a charge of +2.98, suggesting no interaction between HPV-5 and the highly negative charged heparin. Furthermore, 3D-modelling indicated that HPV-5 L1 exposed more negatively charged amino acids than HPV-16. Uptake of HPV-5 (beta and HPV-16 (alpha was studied in vitro by using a pseudovirus (PsV assay. Uptake of HPV-5 PsV was not inhibited by heparin in C33A cells and only minor inhibition was detected in HaCaT cells. HPV-16 PsV uptake was significantly more inhibited by heparin in both cells and completely blocked in C33A cells.

  13. In silico identification of BIM-1 (2-methyl-1H-indol-3-yl) as a potential ...

    African Journals Online (AJOL)

    In silico identification of BIM-1 (2-methyl-1H-indol-3-yl) as a potential therapeutic agent against elevated protein kinase C beta associated diseases. U Saeed, N Nawaz, Y Waheed, N Chaudry, HT Bhatti, S Urooj, H Waheed, M Ashraf, UHK Naizi ...

  14. Potential usefulness of methyl gallate in the treatment of experimental colitis.

    Science.gov (United States)

    Anzoise, María Laura; Basso, Angeles Rodríguez; Del Mauro, Julieta Sofía; Carranza, Andrea; Ordieres, Graciela López; Gorzalczany, Susana

    2017-11-07

    Methyl gallate is a gallotannin widely distributed in nature. Previous studies have demonstrated its antioxidant, anti-inflammatory, antimicrobial and anti-tumor activities. In the present study, the activity of methyl gallate on experimental models of inflammatory bowel disease has been investigated. Experimental colitis was induced in Sprague-Dawley rats through the intracolonic instillation of an acetic acid solution (2 mL, 4% v/v). Methyl gallate (100 and 300 mg/kg, p.o.) and the reference drug mesalazine (100 mg/kg, p.o.) were tested. Methyl gallate induced a significant reduction in the colon weight/length ratio and macroscopic lesion score. Besides, the malondialdehyde content and the GSSG/GSH ratio were remarkably decreased. Furthermore, the administration of methyl gallate reduced the expression of COX 2 , IL-6, TNFα and the severity of microscopic tissue damage induced by acetic acid, while the mean goblet cell density was significantly higher in both the group treated with methyl gallate and the one treated with mesalazine, in comparison with untreated animals. The Na + K + ATPase pump activity was recovered in treated groups (control: 827.2 ± 59.6, colitis: 311.6 ± 54.8, methyl gallate 100 mg/kg: 642.2 ± 175.0, methyl gallate 300 mg/kg: 809.7 ± 100.6, mesalazine: 525.3 ± 81.7). Methyl gallate was also found to induce a significant reduction in the castor oil-induced intestinal motility in Swiss mice, decreasing the peristalsis by 74.5 and 58.82% at 100 and 300 mg/kg p.o., respectively. This compound also antagonized the jejunum contractions induced by Ach and CaCl 2 . This study demonstrates that methyl gallate exerts beneficial effects in a preclinical model of intestinal disorders.

  15. FOXP3 DNA methylation levels as a potential biomarker in the development of periapical lesions.

    Science.gov (United States)

    Campos, Kelma; Franscisconi, Carolina F; Okehie, Valerie; de Souza, Letícia C; Trombone, Ana Paula F; Letra, Ariadne; Garlet, Gustavo P; Gomez, Ricardo S; Silva, Renato M

    2015-02-01

    Epigenetic mechanisms, such as DNA methylation, can modify gene expression patterns without changing the DNA sequence, comprising a tool that cells use to lock genes in the "off" position. Variations in the methylation profile have been correlated to a variety of human diseases. Here, we hypothesize that DNA methylation in immune response-related genes may contribute to the development of periapical lesions. The DNA methylation patterns of 22 immune response-related gene promoters were evaluated in 137 human periapical granulomas, 8 apical cysts, and 31 healthy gingival tissues from 2 independent cohorts using a pathway-specific real-time polymerase chain reaction array (EpiTect Methyl II; Qiagen Inc, Valencia, CA). Messenger RNA expression analysis by qualitative polymerase chain reaction was also performed. SABiosciences's hierarchical clustering and methylation (Qiagen, Valencia, CA) and Prism6 software (GraphPad Software, Inc, La Jolla, CA) were used for data analysis. FOXP3 gene promoter showed the highest level of methylation in both periapical granulomas and apical cysts (P < .001), and methylation levels were inversely correlated with FOXP3 messenger RNA expression in the lesions. Furthermore, FOXP3 expression was prevalent in inactive lesions and was positively correlated with interleukin-10 and transforming growth factor beta levels. Our results suggest that FOXP3 acts as a master switch governing the development and function of T-regulatory cells, whose functions include the inhibition of immune responses and temper inflammation. The observed differential methylation patterns of FOXP3 in periapical lesions may be crucial in determining its suppressive activity and may be involved in periapical lesion development. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  16. Hydrogen peroxide filled poly(methyl methacrylate) microcapsules: potential oxygen delivery materials.

    Science.gov (United States)

    Mallepally, Rajendar R; Parrish, Chance C; Mc Hugh, Mark A M; Ward, Kevin R

    2014-11-20

    This paper describes the synthesis of H₂O₂-H₂O filled poly(methyl methacrylate) (PMMA) microcapsules as potential candidates for controlled O₂ delivery. The microcapsules are prepared by a water-in-oil solvent emulsion and evaporation method. The results of this study describe the effect of process parameters on the characteristics of the microcapsules and on their in vitro performance. The size of the microcapsules, as determined from scanning electron microscopy, ranges from ∼5 to 30 μm and the size distribution is narrow. The microcapsules exhibit an internal morphology with entrapped H₂O₂-H₂O droplets randomly distributed in the PMMA continuous phase. In vitro release studies of 4.5 wt% H₂O₂-loaded microcapsules show that ∼70% of the H₂O₂ releases in 24h. This corresponds to a total O₂ production of ∼12 cc/gram of dry microcapsules. Shelf-life studies show that the microcapsules retain ∼84 wt% of the initially loaded H₂O₂ after nine months storage at 2-8 °C, which is an attractive feature for clinical applications. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. 3-Hydroxybutyrate methyl ester as a potential drug against Alzheimer's disease via mitochondria protection mechanism.

    Science.gov (United States)

    Zhang, Junyu; Cao, Qian; Li, Shaowu; Lu, Xiaoyun; Zhao, Yongxi; Guan, Ji-Song; Chen, Jin-Chun; Wu, Qiong; Chen, Guo-Qiang

    2013-10-01

    Alzheimer's disease (AD) is induced by many reasons, including decreased cellular utilization of glucose and brain cell mitochondrial damages. Degradation product of microbially synthesized polyhydroxybutyrate (PHB), namely, 3-hydroxybutyrate (3HB), can be an alternative to glucose during sustained hypoglycemia. In this study, the derivative of 3HB, 3-hydroxybutyrate methyl ester (HBME), was used by cells as an alternative to glucose. HBME inhibited cell apoptosis under glucose deprivation, rescued activities of mitochondrial respiratory chain complexes that were impaired in AD patients and decreased the generation of ROS. Meanwhile, HBME stabilized the mitochondrial membrane potential. In vivo studies showed that HBME crossed the blood brain barrier easier compared with charged 3HB, resulting in a better bioavailability. AD mice treated with HBME performed significantly better (p memory of mice. A reduced amyloid-β deposition in mouse brains after intragastric administration of HBME was also observed. Combined with the in vitro and in vivo results, HBME was proposed to be a drug candidate against AD, its working mechanism appeared to be mediated by various effects of protecting mitochondrial damages. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Biochar amendment reduces paddy soil nitrogen leaching but increases net global warming potential in Ningxia irrigation, China.

    Science.gov (United States)

    Wang, Yongsheng; Liu, Yansui; Liu, Ruliang; Zhang, Aiping; Yang, Shiqi; Liu, Hongyuan; Zhou, Yang; Yang, Zhengli

    2017-05-09

    The efficacy of biochar as an environmentally friendly agent for non-point source and climate change mitigation remains uncertain. Our goal was to test the impact of biochar amendment on paddy rice nitrogen (N) uptake, soil N leaching, and soil CH 4 and N 2 O fluxes in northwest China. Biochar was applied at four rates (0, 4.5, 9 and13.5 t ha -1 yr -1 ). Biochar amendment significantly increased rice N uptake, soil total N concentration and the abundance of soil ammonia-oxidizing archaea (AOA), but it significantly reduced the soil NO 3 - -N concentration and soil bulk density. Biochar significantly reduced NO 3 - -N and NH 4 + -N leaching. The C2 and C3 treatments significantly increased the soil CH 4 flux and reduced the soil N 2 O flux, leading to significantly increased net global warming potential (GWP). Soil NO 3 - -N rather than NH 4 + -N was the key integrator of the soil CH 4 and N 2 O fluxes. Our results indicate that a shift in abundance of the AOA community and increased rice N uptake are closely linked to the reduced soil NO 3 - -N concentration under biochar amendment. Furthermore, soil NO 3 - -N availability plays an important role in regulating soil inorganic N leaching and net GWP in rice paddies in northwest China.

  19. Prooxidant/Antioxidant Ratio (ProAntidex as a Better Index of Net Free Radical Scavenging Potential

    Directory of Open Access Journals (Sweden)

    Hwee Ming Cheng

    2010-11-01

    Full Text Available The antioxidant activity of several Malaysian plant extracts was analyzed simultaneously with their pro-oxidant capacity. This ratio represents an index (ProAntidex of the net free radical scavenging ability of whole plant extracts. We observed that ethanolic extracts of Nephelium lappaceum peel, Fragaria x ananassa leaf, Lawsonia inermis leaf, Syzygium aqueum leaf and grape seed had a lower Pro-Antidex than the commercially available Emblica™ extract which is an antioxidant agent with very low pro-oxidant activity. Among the aqueous extracts, Lawsonia inermis leaf, Nephelium mutobile leaf and grape seed had lower pro-oxidant activity compared to the Emblica™ extract. Among these extracts, aqueous extract of Nephelium mutobile leaf had a very low index of 0.05 compared to 0.69 for Emblica™. Most of the extracts had a far lower ProAntidex compared to the Vitamin C. The index enables us to identify extracts with high net free radical scavenging activity potential. The ProAntidex is beneficial as a screening parameter to the food industries and healthcare.

  20. Prooxidant/antioxidant ratio (ProAntidex) as a better index of net free radical scavenging potential.

    Science.gov (United States)

    Ling, Lai Teng; Palanisamy, Uma D; Cheng, Hwee Ming

    2010-11-03

    The antioxidant activity of several Malaysian plant extracts was analyzed simultaneously with their pro-oxidant capacity. This ratio represents an index (ProAntidex) of the net free radical scavenging ability of whole plant extracts. We observed that ethanolic extracts of Nephelium lappaceum peel, Fragaria x ananassa leaf, Lawsonia inermis leaf, Syzygium aqueum leaf and grape seed had a lower Pro-Antidex than the commercially available Emblica™ extract which is an antioxidant agent with very low pro-oxidant activity. Among the aqueous extracts, Lawsonia inermis leaf, Nephelium mutobile leaf and grape seed had lower pro-oxidant activity compared to the Emblica™ extract. Among these extracts, aqueous extract of Nephelium mutobile leaf had a very low index of 0.05 compared to 0.69 for Emblica™. Most of the extracts had a far lower ProAntidex compared to the Vitamin C. The index enables us to identify extracts with high net free radical scavenging activity potential. The ProAntidex is beneficial as a screening parameter to the food industries and healthcare.

  1. Along-the-net reconstruction of hydropower potential with consideration of anthropic alterations

    Directory of Open Access Journals (Sweden)

    A. Masoero

    2014-09-01

    Full Text Available Even in regions with mature hydropower development, requirements for stable renewable power sources suggest revision of plans of exploitation of water resources, while taking care of the environmental regulations. Mean Annual Flow (MAF is a key parameter when trying to represent water availability for hydropower purposes. MAF is usually determined in ungauged basins by means of regional statistical analysis. For this study a regional estimation method consistent along-the-river network has been developed for MAF estimation; the method uses a multi-regressive approach based on geomorphoclimatic descriptors, and it is applied on 100 gauged basins located in NW Italy. The method has been designed to keep the estimates of mean annual flow congruent at the confluences, by considering only raster-summable explanatory variables. Also, the influence of human alterations in the regional analysis of MAF has been studied: impact due to the presence of existing hydropower plants has been taken into account, restoring the "natural" value of runoff through analytical corrections. To exemplify the representation of the assessment of residual hydropower potential, the model has been applied extensively to two specific mountain watersheds by mapping the estimated mean flow for the basins draining into each pixel of a the DEM-derived river network. Spatial algorithms were developed using the OpenSource Software GRASS GIS and PostgreSQL/PostGIS. Spatial representation of the hydropower potential was obtained using different mean flow vs hydraulic-head relations for each pixel. Final potential indices have been represented and mapped through the Google Earth platform, providing a complete and interactive picture of the available potential, useful for planning and regulation purposes.

  2. Assessment of the Technical Potential for Achieving Net Zero-Energy Buildings in the Commercial Sector

    Energy Technology Data Exchange (ETDEWEB)

    Griffith, B.; Long, N.; Torcellini, P.; Judkoff, R.; Crawley, D.; Ryan, J.

    2007-12-01

    This report summarizes the findings from research conducted at NREL to assess the technical potential for zero-energy building technologies and practices to reduce the impact of commercial buildings on the U.S. energy system. Commercial buildings currently account for 18% of annual U.S. energy consumption, and energy use is growing along with overall floor area. Reducing the energy use of this sector will require aggressive research goals and rapid implementation of the research results.

  3. On the potential of models for location and scale for genome-wide DNA methylation data.

    Science.gov (United States)

    Wahl, Simone; Fenske, Nora; Zeilinger, Sonja; Suhre, Karsten; Gieger, Christian; Waldenberger, Melanie; Grallert, Harald; Schmid, Matthias

    2014-07-03

    With the help of epigenome-wide association studies (EWAS), increasing knowledge on the role of epigenetic mechanisms such as DNA methylation in disease processes is obtained. In addition, EWAS aid the understanding of behavioral and environmental effects on DNA methylation. In terms of statistical analysis, specific challenges arise from the characteristics of methylation data. First, methylation β-values represent proportions with skewed and heteroscedastic distributions. Thus, traditional modeling strategies assuming a normally distributed response might not be appropriate. Second, recent evidence suggests that not only mean differences but also variability in site-specific DNA methylation associates with diseases, including cancer. The purpose of this study was to compare different modeling strategies for methylation data in terms of model performance and performance of downstream hypothesis tests. Specifically, we used the generalized additive models for location, scale and shape (GAMLSS) framework to compare beta regression with Gaussian regression on raw, binary logit and arcsine square root transformed methylation data, with and without modeling a covariate effect on the scale parameter. Using simulated and real data from a large population-based study and an independent sample of cancer patients and healthy controls, we show that beta regression does not outperform competing strategies in terms of model performance. In addition, Gaussian models for location and scale showed an improved performance as compared to models for location only. The best performance was observed for the Gaussian model on binary logit transformed β-values, referred to as M-values. Our results further suggest that models for location and scale are specifically sensitive towards violations of the distribution assumption and towards outliers in the methylation data. Therefore, a resampling procedure is proposed as a mode of inference and shown to diminish type I error rate in

  4. Aberrant Promoter Methylation of Protocadherin8 (PCDH8) in Serum is a Potential Prognostic Marker for Low Gleason Score Prostate Cancer.

    Science.gov (United States)

    Lin, Ying-Li; Li, Yan-Li; Ma, Jian-Guo

    2017-10-13

    BACKGROUND PCDH8 is a newly-discovered suppressor gene that is frequently inactivated by aberrant methylation in several human cancers, including prostate cancer. The identification of PCDH8 methylation can be used as a potential predictive biomarker. Prostate cancer patients with high Gleason score are considered as being at high risk for tumor recurrence and progression, and adjuvant therapy is often routinely performed in clinical practice. In the present study, we did not measure the methylation of PCDH8 in these patients. The main purpose of the present study was to evaluate the clinical significance of PCDH8 methylation in serum of prostate cancer patients with low Gleason score. MATERIAL AND METHODS PCDH8 methylation in serum samples of 117 patients and 47 controls was checked by methylation-specific PCR (MSP). Then, we correlated PCDH8 methylation status with the clinicopathological parameters of prostate cancer patients with low Gleason score and patient outcomes. RESULTS We found that PCDH8 was more frequently methylated in serum samples of patients with prostate cancer than in controls. PCDH8 methylation was correlated with advanced clinical stage (P=0.021), higher level of preoperative PSA (P=0.008), and positive lymph node metastasis (P=0.010). Moreover, patients with PCDH8 methylation had worse biochemical recurrence (BCR)-free survival (PGleason score were: PCDH8 methylation in serum (Exp (B)=3.147, 95% CI: 1.152-7.961, P=0.007), clinical stage (Exp (B)=2.53, 95% CI: 1.032-4.763, P=0.025) and lymph node status (Exp (B)=1.476, 95% CI: 1.107-4.572, P=0.042). CONCLUSIONS Our study indicated that PCDH8 methylation in serum occurred frequently in prostate cancer patients and was correlated with risk factors for poor outcome. The methylation of PCDH8 in serum is a potential predictive marker for prostate cancer patients with low Gleason score after surgery.

  5. Entamoeba histolytica: protein arginine transferase 1a methylates arginine residues and potentially modify the H4 histone.

    Science.gov (United States)

    Borbolla-Vázquez, Jessica; Orozco, Esther; Betanzos, Abigail; Rodríguez, Mario A

    2015-04-10

    In eukaryotes, histone arginine methylation associates with both active and repressed chromatin states depending on the residues involved and the status of methylation. Even when the amino-terminus of Entamoeba histolytica histones diverge from metazoan sequences, these regions contain arginine residues that are potential targets for methylation. However, histone arginine methylation as well as the activity of arginine methyltransferases (PRMTs) has not been studied in this parasite. The aim of this work was to examine the dimethylation of arginine 3 of H4 histone (H4R3me2) and to identify the parasite PRMT that could be responsible for this modification (EhPRMT1). To examine the presence of H4R3me2 in E histolytica, we performed Western blot and immunofluorescence assays on trophozoites using an antibody against this epigenetic mark. To recognize the PRMT1 enzyme of this parasite that possibly perform that modification, we first performed a phylogenetic analysis of E. histolytica and human PRMTs. RT-PCR assays were carried out to analyze the expression of the putative PRMT1 genes. One of these genes was cloned and expressed in Escherichia coli. The recombinant protein was tested by its recognition by an antibody against human PRMT1 and in its ability to form homodimers and to methylate commercial histones. The arginine 3 of human H4, which is subjected to post translational methylation, was aligned with the arginine 8 of E. histolytica H4, suggesting that this residue could be methylated. The recognition of an 18 kDa nuclear protein of E. histolytica by an antibody against H4R3me2 confirmed this assumption. We found that this parasite expresses three phylogenetic and structural proteins related to PRMT1. Antibodies against the human PRMT1 detected E. histolytica proteins in cytoplasm and nuclei and recognized a recombinant PRMT1 of this parasite. The recombinant protein was able to form homodimers and homotetramers and displayed methyltransferase activity on

  6. Characterization of a novel and potentially lethal designer drug, (±)-cis-para-methyl-4-methylaminorex (4,4'-DMAR, or “Serotoni”)

    Science.gov (United States)

    Brandt, Simon D.; Baumann, Michael H.; Partilla, John S.; Kavanagh, Pierce V.; Power, John D.; Talbot, Brian; Twamley, Brendan; Mahony, Olivia; O’Brien, John; Elliott, Simon P.; Archer, Roland P.; Patrick, Julian; Singh, Kuldip; Dempster, Nicola M.; Cosbey, Simon H.

    2014-01-01

    During the second half of 2013, a total of 26 deaths involving para-methyl-4-methylaminorex (4,4’-DMAR) were reported to the European Monitoring Centre for Drugs and Drug Addiction. While aminorex and 4-methylaminorex (4-MAR) are known psychostimulants, nothing is known about the comparatively new para-methyl analogue. Analytical characterization of two independent samples obtained from online vendors confirmed the presence of the (±)-cis isomer that also appeared to be involved in at least 18 of the 26 deaths. Extensive characterizations included crystal structure analysis, single, tandem and high-resolution mass spectrometry, liquid and gas chromatography and nuclear magnetic resonance spectroscopy. For the work described here, both the (±)-cis and (±)-trans racemates were also synthesized, confirming that the differentiation between these two forms was straight-forward. Monoamine transporter activity was studied using rat brain synaptosomes. (±)-cis-4,4'-DMAR was a potent, efficacious substrate-type releaser at transporters for dopamine, norepinephrine and serotonin with EC50 values of 8.6 ± 1.1 nM (DAT), 26.9 ± 5.9 nM (NET) and 18.5 ± 2.8 nM (SERT), respectively. A comparison with d-amphetamine, aminorex and (±)-cis-4-MAR revealed that activity at SERT varied more than 100-fold across the four drugs, with (±)-cis-4,4’-DMAR exhibiting the highest potency for releasing 5-HT. The potent releasing activity of (±)-cis-4,4’-DMAR at all three monoamine transporters predicts a potential for serious side-effects such as psychotic symptoms, agitation, hyperthermia and cardiovascular stimulation, especially after high-dose exposure or following combination with other psychostimulants. PMID:24841869

  7. Integrated data analysis reveals potential drivers and pathways disrupted by DNA methylation in papillary thyroid carcinomas

    DEFF Research Database (Denmark)

    Beltrami, Caroline Moraes; Dos Reis, Mariana Bisarro; Barros-Filho, Mateus Camargo

    2017-01-01

    and positive correlation, respectively. Genes showing negative correlation underlined FGF and retinoic acid signaling as critical canonical pathways disrupted by DNA methylation in PTC. BRAF mutation was detected in 68% (28 of 41) of the tumors, which presented a higher level of demethylation (95...

  8. Methyl isonicotinate - A non-pheromone thrips semiochemical - And its potential for pest management

    NARCIS (Netherlands)

    Teulon, D.A.J.; Davidson, M.M.; Perry, N.B.; Nielsen, M.C.; Castañé, C.; Bosch, D.; Riudavets, J.; Tol, Van R.W.H.M.; Kogel, de W.J.

    2017-01-01

    Methyl isonicotinate is one of several patented 4-pyridyl carbonyl compounds being investigated for a variety of uses in thrips pest management. It is probably the most extensively studied thrips non-pheromone semiochemical, with field and glasshouse trapping experiments, and wind tunnel and

  9. Growth of human cells on a non-woven silk fibroin net: a potential for use in tissue engineering.

    Science.gov (United States)

    Unger, Ronald E; Wolf, Michael; Peters, Kirsten; Motta, Antonella; Migliaresi, Claudio; James Kirkpatrick, C

    2004-03-01

    We have examined a novel biomaterial consisting of a non-woven fibroin net produced from silk (Bombyx mori) cocoons for its ability to support the growth of human cells. Various human cells of different tissue and cell types (endothelial, epithelial, fibroblast, glial, keratinocyte, osteoblast) were examined for adherence and growth on the nets by confocal laser microscopy after staining of the cells with calcein-AM and by electron microscopy. All the cells readily adhered and spread over the individual fibers of the nets. Most of the cells were able to grow and survive on the nets for at least 7 weeks and growth not only covered the individual fibers of the net but generally bridged the gaps between individual fibers forming tissue-like structures. Scanning electron microscopic examination of the nets demonstrated a tight association of individual cells with the fibers and nets examined after removal of cells showed no evidence that the growth of cells in any way changed the structure of the fibers. Thus, silk fibroin nets are highly human cell-compatible and should be a useful new scaffolding biomaterial applicable for a wide range of target tissues in addition to supporting endothelial cells required for the vascularization of the newly formed tissue.

  10. DNA methylation as a potential mediator of environmental risks in the development of childhood acute lymphoblastic leukemia

    Science.gov (United States)

    Timms, Jessica A; Relton, Caroline L; Rankin, Judith; Strathdee, Gordon; McKay, Jill A

    2016-01-01

    5-year survival rate for childhood acute lymphoblastic leukemia (ALL) has risen to approximately 90%, yet the causal disease pathway is still poorly understood. Evidence suggests multiple ‘hits’ are required for disease progression; an initial genetic abnormality followed by additional secondary ‘hits’. It is plausible that environmental influences may trigger these secondary hits, and with the peak incidence of diagnosis between 2 and 5 years of age, early life exposures are likely to be key. DNA methylation can be modified by many environmental exposures and is dramatically altered in cancers, including childhood ALL. Here we explore the potential that DNA methylation may be involved in the causal pathway toward disease by acting as a mediator between established environmental factors and childhood ALL development. PMID:27035209

  11. Genetic and epigenetic drivers of neuroendocrine tumours (NET).

    Science.gov (United States)

    Di Domenico, Annunziata; Wiedmer, Tabea; Marinoni, Ilaria; Perren, Aurel

    2017-09-01

    Neuroendocrine tumours (NET) of the gastrointestinal tract and the lung are a rare and heterogeneous group of tumours. The molecular characterization and the clinical classification of these tumours have been evolving slowly and show differences according to organs of origin. Novel technologies such as next-generation sequencing revealed new molecular aspects of NET over the last years. Notably, whole-exome/genome sequencing (WES/WGS) approaches underlined the very low mutation rate of well-differentiated NET of all organs compared to other malignancies, while the engagement of epigenetic changes in driving NET evolution is emerging. Indeed, mutations in genes encoding for proteins directly involved in chromatin remodelling, such as DAXX and ATRX are a frequent event in NET. Epigenetic changes are reversible and targetable; therefore, an attractive target for treatment. The discovery of the mechanisms underlying the epigenetic changes and the implication on gene and miRNA expression in the different subgroups of NET may represent a crucial change in the diagnosis of this disease, reveal new therapy targets and identify predictive markers. Molecular profiles derived from omics data including DNA mutation, methylation, gene and miRNA expression have already shown promising results in distinguishing clinically and molecularly different subtypes of NET. In this review, we recapitulate the major genetic and epigenetic characteristics of pancreatic, lung and small intestinal NET and the affected pathways. We also discuss potential epigenetic mechanisms leading to NET development. © 2017 Society for Endocrinology.

  12. Differences in net global warming potential and greenhouse gas intensity between major rice-based cropping systems in China.

    Science.gov (United States)

    Xiong, Zhengqin; Liu, Yinglie; Wu, Zhen; Zhang, Xiaolin; Liu, Pingli; Huang, Taiqing

    2015-12-02

    Double rice (DR) and upland crop-single rice (UR) systems are the major rice-based cropping systems in China, yet differences in net global warming potential (NGWP) and greenhouse gas intensity (GHGI) between the two systems are poorly documented. Accordingly, a 3-year field experiment was conducted to simultaneously measure methane (CH4) and nitrous oxide (N2O) emissions and changes in soil organic carbon (SOC) in oil rape-rice-rice and wheat-rice (representing DR and UR, respectively) systems with straw incorporation (0, 3 and 6 t/ha) during the rice-growing seasons. Compared with the UR system, the annual CH4, N2O, grain yield and NGWP were significantly increased in the DR system, though little effect on SOC sequestration or GHGI was observed without straw incorporation. Straw incorporation increased CH4 emission and SOC sequestration but had no significant effect on N2O emission in both systems. Averaged over the three study years, straw incorporation had no significant effect on NGWP and GHGI in the UR system, whereas these parameters were greatly increased in the DR system, i.e., by 108% (3 t/ha) and 180% (6 t/ha) for NGWP and 103% (3 t/ha) and 168% (6 t/ha) for GHGI.

  13. A global meta-analysis on the impact of management practices on net global warming potential and greenhouse gas intensity from cropland soils

    Science.gov (United States)

    Agricultural practices contribute significant amount of greenhouse gas (GHG) emissions, but little is known about their effects on net global warming potential (GWP) and greenhouse gas intensity (GHGI) that account for all sources and sinks of carbon dioxide emissions per unit area or crop yield. Se...

  14. Effects of organic fertilizer on net global warming potential under an intensively managed vegetable field in southeastern China: A three-year field study

    Science.gov (United States)

    Zhang, M.; Li, B.; Xiong, Z. Q.

    2016-11-01

    Organic fertilizer may not only improve soil quality but may also contribute to climate protection by increasing carbon sequestration in agricultural ecosystems. A 3-yr study was conducted with ten consecutive vegetable crops in intensively managed vegetable cropping systems in southeastern China to examine the effects of organic fertilizer application (ORGA) on net global warming potential (net GWP) after accounting for carbon dioxide equivalent emissions from all sources including methane (CH4) and nitrous oxide (N2O) emissions, agrochemical inputs and farm operations and sinks (i.e., soil organic carbon (SOC) sequestration derived from the net ecosystem carbon budget). Results indicated that ORGA significantly increased ecosystem respiration by 13.9% without obvious effects on CH4 and N2O emissions as compared to local conventional chemical fertilization (CHEM). The SOC sequestration rates during the 3-year observation period were estimated at -0.52 t C ha-1 for the control, -0.42 t C ha-1 for the CHEM plot and 0.27 t C ha-1 for the ORGA plot, respectively, and thus contributed significantly to the net GWP. Overall, compared with CHEM, the ORGA significantly decreased net GWP and greenhouse gas intensity by 15.3% and 27.4%, respectively. Our findings suggest that higher yields and lower greenhouse gas intensities and carbon costs can be achieved by substituting chemical nitrogen fertilizers with organic fertilization strategies.

  15. Cardiac and renal function in patients with type 2 diabetes who have chronic kidney disease: potential effects of bardoxolone methyl

    Directory of Open Access Journals (Sweden)

    McCullough PA

    2012-06-01

    Full Text Available Peter A McCullough, Sajid AliSt John Hospital and Medical Center, Providence Hospital and Medical Centers, Departments of Medicine, St John Providence Health System, Detroit, MI, USAAbstract: The intracellular and tissue balance of oxidant and antioxidant forces is a potential therapeutic target for a variety of agents in the treatment of complications due to chronic disease including diabetes mellitus and hypertension. There are a myriad of processes controlled at the level of genes, transcription factors, and protein messages that work to control the normal use of oxidative reactions within cells. Loss of control of these processes may lead to reversible dysfunction in many cell lines including the podocyte, renal tubular cells, and cardiac myocytes. Bardoxolone methyl is a novel nuclear regulator factor (Nrf-2 activator which works to tip the balance of effects towards antioxidation and as an observation made serendipitously, improves renal filtration function in humans after approximately 12 weeks of therapy. The improvement in estimated glomerular filtration can be up to 30% in those with stage 3 and 4 chronic kidney disease. However, experimental evidence suggests there may be a consequence of relative hyperfiltration in diseased kidneys as well as potential adverse effects on skeletal and cardiac myocytes. Only large, prospective randomized trials with carefully collected and adjudicated clinical outcomes will inform the research community on the therapeutic risks and benefits of this important new agent.Keywords: bardoxolone methyl, chronic kidney disease, diabetes mellitus, glomerular filtration, cardiomyocyte, oxidative stress

  16. Methylated TRF2 associates with the nuclear matrix and serves as a potential biomarker for cellular senescence

    OpenAIRE

    Mitchell, Taylor R. H.; Zhu, Xu-Dong

    2014-01-01

    Methylation of N-terminal arginines of the shelterin component TRF2 is important for cellular proliferation. While TRF2 is found at telomeres, where it plays an essential role in maintaining telomere integrity, little is known about the cellular localization of methylated TRF2. Here we report that the majority of methylated TRF2 is resistant to extraction by high salt buffer and DNase I treatment, indicating that methylated TRF2 is tightly associated with the nuclear matrix. We show that meth...

  17. Gene transcription profiles, global DNA methylation and potential transgenerational epigenetic effects related to Zn exposure history in Daphnia magna

    Energy Technology Data Exchange (ETDEWEB)

    Vandegehuchte, Michiel B., E-mail: michiel.vandegehuchte@ugent.b [Laboratory of Environmental Toxicology and Aquatic Ecology, Ghent University, J. Plateaustraat 22, B-9000 Ghent (Belgium); De Coninck, Dieter [Laboratory of Environmental Toxicology and Aquatic Ecology, Ghent University, J. Plateaustraat 22, B-9000 Ghent (Belgium); Vandenbrouck, Tine; De Coen, Wim M. [Laboratory for Ecophysiology, Biochemistry and Toxicology, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp (Belgium); Janssen, Colin R. [Laboratory of Environmental Toxicology and Aquatic Ecology, Ghent University, J. Plateaustraat 22, B-9000 Ghent (Belgium)

    2010-10-15

    A reduced level of DNA methylation has recently been described in both Zn-exposed and non-exposed offspring of Daphnia magna exposed to Zn. The hypothesis examined in this study is that DNA hypomethylation has an effect on gene transcription. A second hypothesis is that accumulative epigenetic effects can affect gene transcription in non-exposed offspring from parents with an exposure history of more than one generation. Transcriptional gene regulation was studied with a cDNA microarray. In the exposed and non-exposed hypomethylated daphnids, a large proportion of common genes were similarly up- or down-regulated, indicating a possible effect of the DNA hypomethylation. Two of these genes can be mechanistically involved in DNA methylation reduction. The similar transcriptional regulation of two and three genes in the F{sub 0} and F{sub 1} exposed daphnids on one hand and their non-exposed offspring on the other hand, could be the result of a one-generation temporary transgenerational epigenetic effect, which was not accumulative. - Zn-induced DNA hypomethylation is related to gene transcription in Daphnia magna and Zn exposure potentially induced limited temporary transgenerational effects on gene transcription.

  18. Net Locality

    DEFF Research Database (Denmark)

    de Souza e Silva, Adriana Araujo; Gordon, Eric

    Provides an introduction to the new theory of Net Locality and the profound effect on individuals and societies when everything is located or locatable. Describes net locality as an emerging form of location awareness central to all aspects of digital media, from mobile phones, to Google Maps...... of emerging technologies, from GeoCities to GPS, Wi-Fi, Wiki Me, and Google Android....

  19. Net Neutrality

    DEFF Research Database (Denmark)

    Savin, Andrej

    2017-01-01

    Repealing “net neutrality” in the US will have no bearing on Internet freedom or security there or anywhere else.......Repealing “net neutrality” in the US will have no bearing on Internet freedom or security there or anywhere else....

  20. DNA methylation

    DEFF Research Database (Denmark)

    Williams, Kristine; Christensen, Jesper; Helin, Kristian

    2012-01-01

    DNA methylation is involved in key cellular processes, including X-chromosome inactivation, imprinting and transcriptional silencing of specific genes and repetitive elements. DNA methylation patterns are frequently perturbed in human diseases such as imprinting disorders and cancer. The recent...... discovery that the three members of the TET protein family can convert 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) has provided a potential mechanism leading to DNA demethylation. Moreover, the demonstration that TET2 is frequently mutated in haematopoietic tumours suggests that the TET...... proteins are important regulators of cellular identity. Here, we review the current knowledge regarding the function of the TET proteins, and discuss various mechanisms by which they contribute to transcriptional control. We propose that the TET proteins have an important role in regulating DNA methylation...

  1. Simulation of net infiltration and potential recharge using a distributed-parameter watershed model of the Death Valley region, Nevada and California

    Science.gov (United States)

    Hevesi, Joseph A.; Flint, Alan L.; Flint, Lorraine E.

    2003-01-01

    This report presents the development and application of the distributed-parameter watershed model, INFILv3, for estimating the temporal and spatial distribution of net infiltration and potential recharge in the Death Valley region, Nevada and California. The estimates of net infiltration quantify the downward drainage of water across the lower boundary of the root zone and are used to indicate potential recharge under variable climate conditions and drainage basin characteristics. Spatial variability in recharge in the Death Valley region likely is high owing to large differences in precipitation, potential evapotranspiration, bedrock permeability, soil thickness, vegetation characteristics, and contributions to recharge along active stream channels. The quantity and spatial distribution of recharge representing the effects of variable climatic conditions and drainage basin characteristics on recharge are needed to reduce uncertainty in modeling ground-water flow. The U.S. Geological Survey, in cooperation with the Department of Energy, developed a regional saturated-zone ground-water flow model of the Death Valley regional ground-water flow system to help evaluate the current hydrogeologic system and the potential effects of natural or human-induced changes. Although previous estimates of recharge have been made for most areas of the Death Valley region, including the area defined by the boundary of the Death Valley regional ground-water flow system, the uncertainty of these estimates is high, and the spatial and temporal variability of the recharge in these basins has not been quantified. To estimate the magnitude and distribution of potential recharge in response to variable climate and spatially varying drainage basin characteristics, the INFILv3 model uses a daily water-balance model of the root zone with a primarily deterministic representation of the processes controlling net infiltration and potential recharge. The daily water balance includes precipitation

  2. Simultaneous Analysis of SEPT9 Promoter Methylation Status, Micronuclei Frequency, and Folate-Related Gene Polymorphisms: The Potential for a Novel Blood-Based Colorectal Cancer Biomarker

    Directory of Open Access Journals (Sweden)

    Gloria Ravegnini

    2015-12-01

    Full Text Available One challenge in colorectal cancer (CRC is identifying novel biomarkers to be introduced in screening programs. The present study investigated the promoter methylation status of the SEPT9 gene in peripheral blood samples of subjects’ positive fecal occult blood test (FOBT. In order to add new insights, we investigated the association between SEPT9 promoter methylation and micronuclei frequency, and polymorphisms in the folate-related pathway genes. SEPT9 promoter methylation, micronuclei frequency, and genotypes were evaluated on 74 individuals’ FOBT positive. Individuals were subjected to a colonoscopy that provided written informed consent for study participation. SEPT9 promoter methylation status was significantly lower in the CRC group than controls (p = 0.0006. In contrast, the CaCo2 cell-line, analyzed as a tissue specific model of colon adenocarcinoma, showed a significantly higher percentage of SEPT9 promoter methylation compared to the CRC group (p < 0.0001. Linear regression analysis showed an inverse correlation between micronuclei frequency and the decrease in the methylation levels of SEPT9 promoter region among CRC patients (β = −0.926, p = 0.0001. With regard to genotype analysis, we showed the involvement of the DHFR polymorphism (rs70991108 in SEPT9 promoter methylation level in CRC patients only. In particular, the presence of at least one 19 bp del allele significantly correlates with decreased SEPT9 promoter methylation, compared to the 19 bp ins/ins genotype (p = 0.007. While remaining aware of the strengths and limitations of the study, this represents the first evidence of a novel approach for the early detection of CRC, using SEPT9 promoter methylation, micronuclei frequency and genotypes, with the potential to improve CRC risk assessment.

  3. Prospects and potential of fatty acid methyl esters of some non-traditional seed oils for use as biodiesel in India

    Energy Technology Data Exchange (ETDEWEB)

    Mohibbe Azam, M.; Waris, Amtul; Nahar, N.M. [Central Arid Zone Research Institute, Jodhpur 342003 (India)

    2005-10-01

    Fatty acid profiles of seed oils of 75 plant species having 30% or more fixed oil in their seed/kernel were examined. Saponification number (SN), iodine value (IV) and cetane number (CN) of fatty acid methyl esters of oils were empirically determined and they varied from 169.2 to 312.5, 4.8 to 212 and 20.56 to 67.47, respectively. Fatty acid compositions, IV and CN were used to predict the quality of fatty acid methyl esters of oil for use as biodiesel. Fatty acid methyl ester of oils of 26 species including Azadirachta indica, Calophyllum inophyllum, Jatropha curcas and Pongamia pinnata were found most suitable for use as biodiesel and they meet the major specification of biodiesel standards of USA, Germany and European Standard Organization. The fatty acid methyl esters of another 11 species meet the specification of biodiesel standard of USA only. These selected plants have great potential for biodiesel. (author)

  4. NET23/STING Promotes Chromatin Compaction from the Nuclear Envelope

    Science.gov (United States)

    de las Heras, Jose I.; Saiz-Ros, Natalia; Makarov, Alexandr A.; Lazou, Vassiliki; Meinke, Peter; Waterfall, Martin; Kelly, David A.; Schirmer, Eric C.

    2014-01-01

    Changes in the peripheral distribution and amount of condensed chromatin are observed in a number of diseases linked to mutations in the lamin A protein of the nuclear envelope. We postulated that lamin A interactions with nuclear envelope transmembrane proteins (NETs) that affect chromatin structure might be altered in these diseases and so screened thirty-one NETs for those that promote chromatin compaction as determined by an increase in the number of chromatin clusters of high pixel intensity. One of these, NET23 (also called STING, MITA, MPYS, ERIS, Tmem173), strongly promoted chromatin compaction. A correlation between chromatin compaction and endogenous levels of NET23/STING was observed for a number of human cell lines, suggesting that NET23/STING may contribute generally to chromatin condensation. NET23/STING has separately been found to be involved in innate immune response signaling. Upon infection cells make a choice to either apoptose or to alter chromatin architecture to support focused expression of interferon genes and other response factors. We postulate that the chromatin compaction induced by NET23/STING may contribute to this choice because the cells expressing NET23/STING eventually apoptose, but the chromatin compaction effect is separate from this as the condensation was still observed when cells were treated with Z-VAD to block apoptosis. NET23/STING-induced compacted chromatin revealed changes in epigenetic marks including changes in histone methylation and acetylation. This indicates a previously uncharacterized nuclear role for NET23/STING potentially in both innate immune signaling and general chromatin architecture. PMID:25386906

  5. Hydrologic indicators of hot spots and hot moments of mercury methylation potential along river corridors

    Science.gov (United States)

    Singer, Michael B.; Harrison, Lee R.; Donovan, Patrick M.; Blum, Joel D.; Marvin-DiPasquale, Mark C.

    2016-01-01

    The biogeochemical cycling of metals and other contaminants in river-floodplain corridors is controlled by microbial activity responding to dynamic redox conditions. Riverine flooding thus has the potential to affect speciation of redox-sensitive metals such as mercury (Hg). Therefore, inundation history over a period of decades potentially holds information on past production of bioavailable Hg. We investigate this within a Northern California river system with a legacy of landscape-scale 19th century hydraulic gold mining. We combine hydraulic modeling, Hg measurements in sediment and biota, and first-order calculations of mercury transformation to assess the potential role of river floodplains in producing monomethylmercury (MMHg), a neurotoxin which accumulates in local and migratory food webs. We identify frequently inundated floodplain areas, as well as floodplain areas inundated for long periods. We quantify the probability of MMHg production potential (MPP) associated with hydrology in each sector of the river system as a function of the spatial patterns of overbank inundation and drainage, which affect long-term redox history of contaminated sediments. Our findings identify river floodplains as periodic, temporary, yet potentially important, loci of biogeochemical transformation in which contaminants may undergo change during limited periods of the hydrologic record. We suggest that inundation is an important driver of MPP in river corridors and that the entire flow history must be analyzed retrospectively in terms of inundation magnitude and frequency in order to accurately assess biogeochemical risks, rather than merely highlighting the largest floods or low-flow periods. MMHg bioaccumulation within the aquatic food web in this system may pose a major risk to humans and waterfowl that eat migratory salmonids, which are being encouraged to come up these rivers to spawn. There is a long-term pattern of MPP under the current flow regime that is likely to be

  6. Partial dissolution of ACQ-treated wood in lithium chloride/N-methyl-2-pyrrolidinone: Separation of copper from potential lignocellulosic feedstocks

    Science.gov (United States)

    Thomas L. Eberhardt; Stan Lebow; Karen G. Reed

    2012-01-01

    A cellulose solvent system based on lithium chloride (LiCl) in N-methyl-2-pyrrolidinone (NMP) was used to assess the merits of partial dissolutions of coarsely ground wood samples. Alkaline Copper Quaternary (ACQ)-treated pine wood was of particular interest for treatment given the potential to generate a copper- rich stream apart from solid and/or liquid...

  7. Transcriptome-wide N 6 -methyladenosine methylome profiling of porcine muscle and adipose tissues reveals a potential mechanism for transcriptional regulation and differential methylation pattern.

    Science.gov (United States)

    Tao, Xuelian; Chen, Jianning; Jiang, Yanzhi; Wei, Yingying; Chen, Yan; Xu, Huaming; Zhu, Li; Tang, Guoqing; Li, Mingzhou; Jiang, Anan; Shuai, Surong; Bai, Lin; Liu, Haifeng; Ma, Jideng; Jin, Long; Wen, Anxiang; Wang, Qin; Zhu, Guangxiang; Xie, Meng; Wu, Jiayun; He, Tao; Huang, Chunyu; Gao, Xiang; Li, Xuewei

    2017-04-28

    N 6 -methyladenosine (m6A) is the most prevalent internal form of modification in messenger RNA in higher eukaryotes and potential regulatory functions of reversible m6A methylation on mRNA have been revealed by mapping of m6A methylomes in several species. m6A modification in active gene regulation manifests itself as altered methylation profiles in a tissue-specific manner or in response to changing cellular or species living environment. However, up to date, there has no data on m6A porcine transcriptome-wide map and its potential biological roles in adipose deposition and muscle growth. In this work, we used methylated RNA immunoprecipitation with next-generation sequencing (MeRIP-Seq) technique to acquire the first ever m6A porcine transcriptome-wide map. Transcriptomes of muscle and adipose tissues from three different pig breeds, the wild boar, Landrace, and Rongchang pig, were used to generate these maps. Our findings show that there were 5,872 and 2,826 m6A peaks respectively, in the porcine muscle and adipose tissue transcriptomes. Stop codons, 3'-untranslated regions, and coding regions were found to be mainly enriched for m6A peaks. Gene ontology analysis revealed that common m6A peaks in nuclear genes are associated with transcriptional factors, suggestive of a relationship between m6A mRNA methylation and nuclear genome transcription. Some genes showed tissue- and breed-differential methylation, and have novel biological functions. We also found a relationship between the m6A methylation extent and the transcript level, suggesting a regulatory role for m6A in gene expression. This comprehensive map provides a solid basis for the determination of potential functional roles for RNA m6A modification in adipose deposition and muscle growth.

  8. RESTful NET

    CERN Document Server

    Flanders, Jon

    2008-01-01

    RESTful .NET is the first book that teaches Windows developers to build RESTful web services using the latest Microsoft tools. Written by Windows Communication Foundation (WFC) expert Jon Flanders, this hands-on tutorial demonstrates how you can use WCF and other components of the .NET 3.5 Framework to build, deploy and use REST-based web services in a variety of application scenarios. RESTful architecture offers a simpler approach to building web services than SOAP, SOA, and the cumbersome WS- stack. And WCF has proven to be a flexible technology for building distributed systems not necessa

  9. NetSig

    DEFF Research Database (Denmark)

    Horn, Heiko; Lawrence, Michael S; Chouinard, Candace R

    2018-01-01

    Methods that integrate molecular network information and tumor genome data could complement gene-based statistical tests to identify likely new cancer genes; but such approaches are challenging to validate at scale, and their predictive value remains unclear. We developed a robust statistic (Net......Sig) that integrates protein interaction networks with data from 4,742 tumor exomes. NetSig can accurately classify known driver genes in 60% of tested tumor types and predicts 62 new driver candidates. Using a quantitative experimental framework to determine in vivo tumorigenic potential in mice, we found that Net......Sig candidates induce tumors at rates that are comparable to those of known oncogenes and are ten-fold higher than those of random genes. By reanalyzing nine tumor-inducing NetSig candidates in 242 patients with oncogene-negative lung adenocarcinomas, we find that two (AKT2 and TFDP2) are significantly amplified...

  10. Petri Nets

    Indian Academy of Sciences (India)

    Associate Professor of. Computer Science and. Automation at the Indian. Institute of Science,. Bangalore. His research interests are broadly in the areas of stochastic modeling and scheduling methodologies for future factories; and object oriented modeling. GENERAL I ARTICLE. Petri Nets. 1. Overview and Foundations.

  11. Petri Nets

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 4; Issue 8. Petri Nets - Overview and Foundations. Y Narahari. General Article Volume 4 Issue 8 August 1999 pp ... Author Affiliations. Y Narahari1. Department ot Computer Science and Automation, Indian Institute of Science, Bangalore 560 012, India.

  12. Regions of common inter-individual DNA methylation differences in human monocytes: genetic basis and potential function.

    Science.gov (United States)

    Schröder, Christopher; Leitão, Elsa; Wallner, Stefan; Schmitz, Gerd; Klein-Hitpass, Ludger; Sinha, Anupam; Jöckel, Karl-Heinz; Heilmann-Heimbach, Stefanie; Hoffmann, Per; Nöthen, Markus M; Steffens, Michael; Ebert, Peter; Rahmann, Sven; Horsthemke, Bernhard

    2017-07-26

    There is increasing evidence for inter-individual methylation differences at CpG dinucleotides in the human genome, but the regional extent and function of these differences have not yet been studied in detail. For identifying regions of common methylation differences, we used whole genome bisulfite sequencing data of monocytes from five donors and a novel bioinformatic strategy. We identified 157 differentially methylated regions (DMRs) with four or more CpGs, almost none of which has been described before. The DMRs fall into different chromatin states, where methylation is inversely correlated with active, but not repressive histone marks. However, methylation is not correlated with the expression of associated genes. High-resolution single nucleotide polymorphism (SNP) genotyping of the five donors revealed evidence for a role of cis-acting genetic variation in establishing methylation patterns. To validate this finding in a larger cohort, we performed genome-wide association studies (GWAS) using SNP genotypes and 450k array methylation data from blood samples of 1128 individuals. Only 30/157 (19%) DMRs include at least one 450k CpG, which shows that these arrays miss a large proportion of DNA methylation variation. In most cases, the GWAS peak overlapped the CpG position, and these regions are enriched for CREB group, NF-1, Sp100 and CTCF binding motifs. In two cases, there was tentative evidence for a trans-effect by KRAB zinc finger proteins. Allele-specific DNA methylation occurs in discrete chromosomal regions and is driven by genetic variation in cis and trans, but in general has little effect on gene expression.

  13. A study of production and characterization of Manketti (Ricinodendron rautonemii methyl ester and its blends as a potential biodiesel feedstock

    Directory of Open Access Journals (Sweden)

    A.E. Atabani

    2014-12-01

    Full Text Available Globally, more than 350 oil-bearing crops are known as potential biodiesel feedstocks. This study reports on production and characterization of Manketti (Ricinodendron rautonemii methyl ester and its blends with diesel. The effect of Manketti biodiesel (B5 on engine and emissions performance was also investigated. The cloud, pour and cold filter plugging points of the produced biodiesel were measured at 1, 3 and 5 °C, respectively. However, the kinematic viscosity of the biodiesel generated was found to be 8.34 mm2/s which was higher than the limit described by ASTM D6751 and EN 14214. This can be attributed to the high kinematic viscosity of the parent oil (132.75 mm2/s. Nevertheless, blending with diesel improved this attribute. Moreover, it is observed that at all engine speeds, B5 produced lower brake power (1.18% and higher brake specific fuel consumption (2.26% compared to B0 (neat diesel. B5 increased the CO and HC emissions by 32.27% and 37.5%, respectively, compared to B0. However, B0 produced 5.26% higher NO emissions than B5.

  14. GATA5 CpG island methylation in renal cell cancer: a potential biomarker for metastasis and disease progression.

    Science.gov (United States)

    Peters, Inga; Eggers, Hendrik; Atschekzei, Faranaz; Hennenlotter, Jörg; Waalkes, Sandra; Tränkenschuh, Wolfgang; Grosshennig, Anika; Merseburger, Axel S; Stenzl, Arnulf; Kuczyk, Markus A; Serth, Jürgen

    2012-07-01

    GATA5 CpG island (CGI) methylation and transcriptional inactivation is involved in colorectal and gastric cancer. Whether DNA methylation of GATA5 affects clinical pathology is still unclear. In the present study, we analysed, for the first time, CGI methylation in RCC and its association with clinicopathological parameters and progression-free survival of patients. We show for the first time GATA5 CGI hypermethylation in RCC. Moreover, we found out that increased methylation is statistically associated with status of metastasis, progressive disease and shortened progression-free survival. The present study underline the necessity for further functional investigations as well as prospective survival analyses to clarify whether GATA5 promoter methylation can provide independent information for future clinical management of patients with RCC. To investigate whether GATA5 CpG island (CGI) methylation occurs in renal cell carcinoma (RCC) and is associated with clinical, histopathological characteristics or progression-free survival of patients. Methylation was quantified in 117 RCC samples and 89 paired adjacent normal tissues using quantitative combined bisulphite restriction analysis (COBRA). COBRA was evaluated in advance by pyrosequencing analyses of control RCC cell lines (coefficient of correlation, R = 0.95). Statistical analyses were carried out using the paired t-test for matched tumour tissue (TU) and adjacent normal tissue (adN) samples, logistic regression for comparisons of independent sample groups and Cox regression for analysis of progression-free survival. In the present study, we found a significant higher mean relative methylation in TU (20.4%) than in adN (7.9%, P methylation in tumours was associated with metastasis (P = 0.005) and decreased progression-free survival (P = 0.005, HR = 4.59) in the clear-cell RCC (ccRCC) group. CGI methylation in advanced ccRCCs (pT ≥3 and/or N1, M1 or G2-3/G3) exceeds those detected in localized tumours (pT ≤2

  15. Aberrant methylation of MUC1 and MUC4 promoters are potential prognostic biomarkers for pancreatic ductal adenocarcinomas

    Science.gov (United States)

    Yokoyama, Seiya; Higashi, Michiyo; Kitamoto, Sho; Oeldorf, Monika; Knippschild, Uwe; Kornmann, Marko; Maemura, Kosei; Kurahara, Hiroshi; Wiest, Edwin; Hamada, Tomofumi; Kitazono, Ikumi; Goto, Yuko; Tasaki, Takashi; Hiraki, Tsubasa; Hatanaka, Kazuhito; Mataki, Yuko; Taguchi, Hiroki; Hashimoto, Shinichi; Batra, Surinder K.; Tanimoto, Akihide; Yonezawa, Suguru; Hollingsworth, Michael A.

    2016-01-01

    Pancreatic cancer is still a disease of high mortality despite availability of diagnostic techniques. Mucins (MUC) play crucial roles in carcinogenesis and tumor invasion in pancreatic neoplasms. MUC1 and MUC4 are high molecular weight transmembrane mucins. These are overexpressed in many carcinomas, and high expression of these molecules is a risk factor associated with poor prognosis. We evaluated the methylation status of MUC1 and MUC4 promoter regions in pancreatic tissue samples from 169 patients with various pancreatic lesions by the methylation specific electrophoresis (MSE) method. These results were compared with expression of MUC1 and MUC4, several DNA methylation/demethylation factors (e.g. ten-eleven translocation or TET, and activation-induced cytidine deaminase or AID) and CAIX (carbonic anhydrase IX, as a hypoxia biomarker). These results were also analyzed with clinicopathological features including time of overall survival of PDAC patients. We show that the DNA methylation status of the promoters of MUC1 and MUC4 in pancreatic tissue correlates with the expression of MUC1 and MUC4 mRNA. In addition, the expression of several DNA methylation/demethylation factors show a significant correlation with MUC1 and MUC4 methylation status. Furthermore, CAIX expression significantly correlates with the expression of MUC1 and MUC4. Interestingly, our results indicate that low methylation of MUC1 and/or MUC4 promoters correlates with decreased overall survival. This is the first report to show a relationship between MUC1 and/or MUC4 methylation status and prognosis. Analysis of epigenetic changes in mucin genes may be of diagnostic utility and one of the prognostic predictors for patients with PDAC. PMID:27283771

  16. Modeling impacts of alternative practices on net global warming potential and greenhouse gas intensity from rice-wheat annual rotation in China.

    Directory of Open Access Journals (Sweden)

    Jinyang Wang

    Full Text Available BACKGROUND: Evaluating the net exchange of greenhouse gas (GHG emissions in conjunction with soil carbon sequestration may give a comprehensive insight on the role of agricultural production in global warming. MATERIALS AND METHODS: Measured data of methane (CH(4 and nitrous oxide (N(2O were utilized to test the applicability of the Denitrification and Decomposition (DNDC model to a winter wheat - single rice rotation system in southern China. Six alternative scenarios were simulated against the baseline scenario to evaluate their long-term (45-year impacts on net global warming potential (GWP and greenhouse gas intensity (GHGI. PRINCIPAL RESULTS: The simulated cumulative CH(4 emissions fell within the statistical deviation ranges of the field data, with the exception of N(2O emissions during rice-growing season and both gases from the control treatment. Sensitivity tests showed that both CH(4 and N(2O emissions were significantly affected by changes in both environmental factors and management practices. Compared with the baseline scenario, the long-term simulation had the following results: (1 high straw return and manure amendment scenarios greatly increased CH(4 emissions, while other scenarios had similar CH(4 emissions, (2 high inorganic N fertilizer increased N(2O emissions while manure amendment and reduced inorganic N fertilizer scenarios decreased N(2O emissions, (3 the mean annual soil organic carbon sequestration rates (SOCSR under manure amendment, high straw return, and no-tillage scenarios averaged 0.20 t C ha(-1 yr(-1, being greater than other scenarios, and (4 the reduced inorganic N fertilizer scenario produced the least N loss from the system, while all the scenarios produced comparable grain yields. CONCLUSIONS: In terms of net GWP and GHGI for the comprehensive assessment of climate change and crop production, reduced inorganic N fertilizer scenario followed by no-tillage scenario would be advocated for this specified

  17. Modeling Impacts of Alternative Practices on Net Global Warming Potential and Greenhouse Gas Intensity from Rice–Wheat Annual Rotation in China

    Science.gov (United States)

    Wang, Jinyang; Zhang, Xiaolin; Liu, Yinglie; Pan, Xiaojian; Liu, Pingli; Chen, Zhaozhi; Huang, Taiqing; Xiong, Zhengqin

    2012-01-01

    Background Evaluating the net exchange of greenhouse gas (GHG) emissions in conjunction with soil carbon sequestration may give a comprehensive insight on the role of agricultural production in global warming. Materials and Methods Measured data of methane (CH4) and nitrous oxide (N2O) were utilized to test the applicability of the Denitrification and Decomposition (DNDC) model to a winter wheat – single rice rotation system in southern China. Six alternative scenarios were simulated against the baseline scenario to evaluate their long-term (45-year) impacts on net global warming potential (GWP) and greenhouse gas intensity (GHGI). Principal Results The simulated cumulative CH4 emissions fell within the statistical deviation ranges of the field data, with the exception of N2O emissions during rice-growing season and both gases from the control treatment. Sensitivity tests showed that both CH4 and N2O emissions were significantly affected by changes in both environmental factors and management practices. Compared with the baseline scenario, the long-term simulation had the following results: (1) high straw return and manure amendment scenarios greatly increased CH4 emissions, while other scenarios had similar CH4 emissions, (2) high inorganic N fertilizer increased N2O emissions while manure amendment and reduced inorganic N fertilizer scenarios decreased N2O emissions, (3) the mean annual soil organic carbon sequestration rates (SOCSR) under manure amendment, high straw return, and no-tillage scenarios averaged 0.20 t C ha−1 yr−1, being greater than other scenarios, and (4) the reduced inorganic N fertilizer scenario produced the least N loss from the system, while all the scenarios produced comparable grain yields. Conclusions In terms of net GWP and GHGI for the comprehensive assessment of climate change and crop production, reduced inorganic N fertilizer scenario followed by no-tillage scenario would be advocated for this specified cropping system. PMID

  18. The potential of identification of a malignancy-associated biomarker in breast cancer diagnosis and research: hTERT gene DNA methylation.

    Science.gov (United States)

    Masood, Shahla; El-Gabry, Ehab; Zhang, Chuhua; Wang, Zhiqianq

    2016-08-01

    DNA hypermethylation has been documented to be prominent at a CpG island rich region about 600 bp upstream the transcription start site of the hTERT gene using qualitative methylation specific PCR on DNA isolated from tumor cell lines. In order to assess the potential significance of this biomarker in breast cancer research and diagnosis, we explored if such findings are reproducible on surgically resected fresh breast tumor cells. Using quantitative pyrosequencing technology, we investigated and present methylation status of four CpG islands of this region in a cohort of 77 invasive breast carcinomas using normal breast tissue as controls. Globally, a significant hypermethylation in tumor cells was observed in the four CpG islands as a sum, in comparison to methylation of the normal breast tissue. Individually, certain CpG islands displayed methylation greater than 50% in about 3/4 of the 77 breast cancers, but in none of the normal breast tissue. Our results highlight the value of DNA hypermethylation in the -600 bp region of the hTERT gene as a potential marker for breast cancer diagnosis. We believe that integration of this novel, malignancy-associated molecular testing with morphology is of significant value in the accurate interpretation of small tumor sample size obtained via fine needle aspiration biopsy, ductal lavage, and nipple fluid aspirates both in clinical practice and in breast cancer research. Diagn. Cytopathol. 2016;44:670-675. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  19. A Global Meta-Analysis on the Impact of Management Practices on Net Global Warming Potential and Greenhouse Gas Intensity from Cropland Soils

    Science.gov (United States)

    Sainju, Upendra M.

    2016-01-01

    Management practices, such as tillage, crop rotation, and N fertilization, may affect net global warming potential (GWP) and greenhouse gas intensity (GHGI), but their global impact on cropland soils under different soil and climatic conditions need further evaluation. Available global data from 57 experiments and 225 treatments were evaluated for individual and combined effects of tillage, cropping systems, and N fertilization rates on GWP and GHGI which accounted for CO2 equivalents from N2O and CH4 emissions with or without equivalents from soil C sequestration rate (ΔSOC), farm operations, and N fertilization. The GWP and GHGI were 66 to 71% lower with no-till than conventional till and 168 to 215% lower with perennial than annual cropping systems, but 41 to 46% greater with crop rotation than monocroppping. With no-till vs. conventional till, GWP and GHGI were 2.6- to 7.4-fold lower when partial than full accounting of all sources and sinks of greenhouse gases (GHGs) were considered. With 100 kg N ha-1, GWP and GHGI were 3.2 to 11.4 times greater with partial than full accounting. Both GWP and GHGI increased curvilinearly with increased N fertilization rate. Net GWP and GHGI were 70 to 87% lower in the improved combined management that included no-till, crop rotation/perennial crop, and reduced N rate than the traditional combined management that included conventional till, monocopping/annual crop, and recommended N rate. An alternative soil respiration method, which replaces ΔSOC by soil respiration and crop residue returned to soil in the previous year, similarly reduced GWP and GHGI by 133 to 158% in the improved vs. the traditional combined management. Changes in GWP and GHGI due to improved vs. traditional management varied with the duration of the experiment and inclusion of soil and climatic factors in multiple linear regressions improved their relationships. Improved management practices reduced GWP and GHGI compared with traditional management

  20. A Global Meta-Analysis on the Impact of Management Practices on Net Global Warming Potential and Greenhouse Gas Intensity from Cropland Soils.

    Science.gov (United States)

    Sainju, Upendra M

    2016-01-01

    Management practices, such as tillage, crop rotation, and N fertilization, may affect net global warming potential (GWP) and greenhouse gas intensity (GHGI), but their global impact on cropland soils under different soil and climatic conditions need further evaluation. Available global data from 57 experiments and 225 treatments were evaluated for individual and combined effects of tillage, cropping systems, and N fertilization rates on GWP and GHGI which accounted for CO2 equivalents from N2O and CH4 emissions with or without equivalents from soil C sequestration rate (ΔSOC), farm operations, and N fertilization. The GWP and GHGI were 66 to 71% lower with no-till than conventional till and 168 to 215% lower with perennial than annual cropping systems, but 41 to 46% greater with crop rotation than monocroppping. With no-till vs. conventional till, GWP and GHGI were 2.6- to 7.4-fold lower when partial than full accounting of all sources and sinks of greenhouse gases (GHGs) were considered. With 100 kg N ha-1, GWP and GHGI were 3.2 to 11.4 times greater with partial than full accounting. Both GWP and GHGI increased curvilinearly with increased N fertilization rate. Net GWP and GHGI were 70 to 87% lower in the improved combined management that included no-till, crop rotation/perennial crop, and reduced N rate than the traditional combined management that included conventional till, monocopping/annual crop, and recommended N rate. An alternative soil respiration method, which replaces ΔSOC by soil respiration and crop residue returned to soil in the previous year, similarly reduced GWP and GHGI by 133 to 158% in the improved vs. the traditional combined management. Changes in GWP and GHGI due to improved vs. traditional management varied with the duration of the experiment and inclusion of soil and climatic factors in multiple linear regressions improved their relationships. Improved management practices reduced GWP and GHGI compared with traditional management

  1. The Effects of Rape Residue Mulching on Net Global Warming Potential and Greenhouse Gas Intensity from No-Tillage Paddy Fields

    Science.gov (United States)

    Zhang, Zhi-Sheng; Cao, Cou-Gui; Guo, Li-Jin; Li, Cheng-Fang

    2014-01-01

    A field experiment was conducted to provide a complete greenhouse gas (GHG) accounting for global warming potential (GWP), net GWP, and greenhouse gas intensity (GHGI) from no-tillage (NT) paddy fields with different amounts of oilseed rape residue mulch (0, 3000, 4000, and 6000 kg dry matter (DM) ha−1) during a rice-growing season after 3 years of oilseed rape-rice cultivation. Residue mulching treatments showed significantly more organic carbon (C) density for the 0–20 cm soil layer at harvesting than no residue treatment. During a rice-growing season, residue mulching treatments sequestered significantly more organic C from 687 kg C ha−1 season−1 to 1654 kg C ha−1 season−1 than no residue treatment. Residue mulching significantly increased emissions of CO2 and N2O but decreased CH4 emissions. Residue mulching treatments significantly increased GWP by 9–30% but significantly decreased net GWP by 33–71% and GHGI by 35–72% relative to no residue treatment. These results suggest that agricultural economic viability and GHG mitigation can be achieved simultaneously by residue mulching on NT paddy fields in central China. PMID:25140329

  2. Accurate and reliable quantification of total microalgal fuel potential as fatty acid methyl esters by in situ transesterification

    Energy Technology Data Exchange (ETDEWEB)

    Laurens, Lieve M.L.; Quinn, Matthew; Wychen, Stefanie van; Templeton, David W.; Wolfrum, Edward J. [National Bioenergy Center, National Renewable Energy Laboratory, Golden, CO (United States)

    2012-04-15

    In the context of algal biofuels, lipids, or better aliphatic chains of the fatty acids, are perhaps the most important constituents of algal biomass. Accurate quantification of lipids and their respective fuel yield is crucial for comparison of algal strains and growth conditions and for process monitoring. As an alternative to traditional solvent-based lipid extraction procedures, we have developed a robust whole-biomass in situ transesterification procedure for quantification of algal lipids (as fatty acid methyl esters, FAMEs) that (a) can be carried out on a small scale (using 4-7 mg of biomass), (b) is applicable to a range of different species, (c) consists of a single-step reaction, (d) is robust over a range of different temperature and time combinations, and (e) tolerant to at least 50% water in the biomass. Unlike gravimetric lipid quantification, which can over- or underestimate the lipid content, whole biomass transesterification reflects the true potential fuel yield of algal biomass. We report here on the comparison of the yield of FAMEs by using different catalysts and catalyst combinations, with the acid catalyst HCl providing a consistently high level of conversion of fatty acids with a precision of 1.9% relative standard deviation. We investigate the influence of reaction time, temperature, and biomass water content on the measured FAME content and profile for 4 different samples of algae (replete and deplete Chlorella vulgaris, replete Phaeodactylum tricornutum, and replete Nannochloropsis sp.). We conclude by demonstrating a full mass balance closure of all fatty acids around a traditional lipid extraction process. (orig.)

  3. Accurate and Reliable Quantification of Total Microalgal Fuel Potential as Fatty Acid Methyl Esters by in situ Transesterfication

    Energy Technology Data Exchange (ETDEWEB)

    Laurens, L. M. L.; Quinn, M.; Van Wychen, S.; Templeton, D. W.; Wolfrum, E. J.

    2012-04-01

    In the context of algal biofuels, lipids, or better aliphatic chains of the fatty acids, are perhaps the most important constituents of algal biomass. Accurate quantification of lipids and their respective fuel yield is crucial for comparison of algal strains and growth conditions and for process monitoring. As an alternative to traditional solvent-based lipid extraction procedures, we have developed a robust whole-biomass in situ transesterification procedure for quantification of algal lipids (as fatty acid methyl esters, FAMEs) that (a) can be carried out on a small scale (using 4-7 mg of biomass), (b) is applicable to a range of different species, (c) consists of a single-step reaction, (d) is robust over a range of different temperature and time combinations, and (e) tolerant to at least 50% water in the biomass. Unlike gravimetric lipid quantification, which can over- or underestimate the lipid content, whole biomass transesterification reflects the true potential fuel yield of algal biomass. We report here on the comparison of the yield of FAMEs by using different catalysts and catalyst combinations, with the acid catalyst HCl providing a consistently high level of conversion of fatty acids with a precision of 1.9% relative standard deviation. We investigate the influence of reaction time, temperature, and biomass water content on the measured FAME content and profile for 4 different samples of algae (replete and deplete Chlorella vulgaris, replete Phaeodactylum tricornutum, and replete Nannochloropsis sp.). We conclude by demonstrating a full mass balance closure of all fatty acids around a traditional lipid extraction process.

  4. Investigation of a potential scintigraphic marker of apoptosis: radioiodinated Z-Val-Ala-DL-Asp(O-methyl)-fluoromethyl ketone

    Energy Technology Data Exchange (ETDEWEB)

    Haberkorn, Uwe E-mail: uwe_haberkorn@med.uni-heidelberg.de; Kinscherf, Ralf; Krammer, Peter H.; Mier, Walter; Eisenhut, Michael

    2001-10-01

    The imaging of apoptosis represents an attractive diagnostic goal in the area of tumor therapy, degenerative diseases and organ transplantation. Since caspases play a key role during the early period of the intracellular signal cascade of cells undergoing apoptosis we considered benzyloxycarbonyl-Val-Ala-DL-Asp(O-methyl)-fluoromethyl ketone [Z-VAD-fmk], a pan-caspase inhibitor, as a potential apoptosis imaging agent. Applying the Tl(TFA){sub 3}/[{sup 131}I]iodide method Z-VAD-fmk was successfully labeled at the benzyloxycarbonyl protecting group. The success of radioiodination, however, depended on the presence of carrier iodide resulting in specific radioactivities of 2.6 GBq/{mu}mol and the formation of a mixture of the 2- and 4-iodophenyl derivative (61%) which could not be separated by HPLC. Uptake measurements were performed with Morris hepatoma cells (MH3924Atk8) which showed expression of the Herpes Simplex Virus thymidine kinase (HSVtk) gene. Apoptosis was induced by treatment of the cells with 25 {mu}M ganciclovir. The TUNEL assay revealed 1.3{+-}0.3 and 23{+-}1.1% apoptotic cells immediately and 24 h after therapy, respectively. A two-fold increase of [{sup 131}I]IZ-VAD-fmk uptake was found at the end of treatment with the HSVtk/suicide system which constantly remained elevated for the following 4 hours. The slow cellular influx and lack of uptake saturation of [{sup 131}I]IZ-VAD-fmk are evidence for simple diffusion as transport mechanism. In addition, the absolute cellular uptake of [{sup 131}I]IZ-VAD-fmk was found to be low. This quality was related to the rather high lipophilicity of [{sup 131}I]IZ-VAD-fmk causing unspecific binding to macromolecules in the medium. Instead of using an inhibitor, synthetic caspase substrates are currently investigated which may accumulate in the apoptotic cell by metabolic trapping thereby enhancing the imaging signal.

  5. Accurate and reliable quantification of total microalgal fuel potential as fatty acid methyl esters by in situ transesterification.

    Science.gov (United States)

    Laurens, Lieve M L; Quinn, Matthew; Van Wychen, Stefanie; Templeton, David W; Wolfrum, Edward J

    2012-04-01

    In the context of algal biofuels, lipids, or better aliphatic chains of the fatty acids, are perhaps the most important constituents of algal biomass. Accurate quantification of lipids and their respective fuel yield is crucial for comparison of algal strains and growth conditions and for process monitoring. As an alternative to traditional solvent-based lipid extraction procedures, we have developed a robust whole-biomass in situ transesterification procedure for quantification of algal lipids (as fatty acid methyl esters, FAMEs) that (a) can be carried out on a small scale (using 4-7 mg of biomass), (b) is applicable to a range of different species, (c) consists of a single-step reaction, (d) is robust over a range of different temperature and time combinations, and (e) tolerant to at least 50% water in the biomass. Unlike gravimetric lipid quantification, which can over- or underestimate the lipid content, whole biomass transesterification reflects the true potential fuel yield of algal biomass. We report here on the comparison of the yield of FAMEs by using different catalysts and catalyst combinations, with the acid catalyst HCl providing a consistently high level of conversion of fatty acids with a precision of 1.9% relative standard deviation. We investigate the influence of reaction time, temperature, and biomass water content on the measured FAME content and profile for 4 different samples of algae (replete and deplete Chlorella vulgaris, replete Phaeodactylum tricornutum, and replete Nannochloropsis sp.). We conclude by demonstrating a full mass balance closure of all fatty acids around a traditional lipid extraction process.

  6. Sirt1 Regulates DNA Methylation and Differentiation Potential of Embryonic Stem Cells by Antagonizing Dnmt3l

    Directory of Open Access Journals (Sweden)

    Jinbeom Heo

    2017-02-01

    Full Text Available Embryonic stem cell (ESC abnormalities in genome methylation hamper the utility of their therapeutic derivatives; however, the underlying mechanisms are unknown. Here, we show that the nicotinamide adenine dinucleotide (NAD-dependent deacetylase, Sirt1, selectively prevents abnormal DNA methylation of some developmental genes in murine ESCs by antagonizing Dnmt3l. Transcriptome and DNA methylome analyses demonstrated that Sirt1-null (Sirt1−/− ESCs repress expression of a subset of imprinted and germline genes concomitant with increased DNA methylation of regulatory elements. Dnmt3l was highly expressed in Sirt1−/− ESCs, and knockdown partially rescued abnormal DNA methylation of the Sirt1 target genes. The Sirt1 protein suppressed transcription of Dnmt3l and physically interacted with the Dnmt3l protein, deacetylating and destabilizing Dnmt3l protein. Sirt1 deficiency delayed neurogenesis and spermatogenesis. These differentiation delays were significantly or partially abolished by reintroduction of Sirt1 cDNA or Dnmt3l knockdown. This study sheds light on mechanisms that restrain DNA methylation of developmentally vital genes operating in ESCs.

  7. Genome-wide DNA methylation analysis reveals a potential mechanism for the pathogenesis and development of uterine leiomyomas.

    Directory of Open Access Journals (Sweden)

    Ryo Maekawa

    Full Text Available BACKGROUND: The pathogenesis of uterine leiomyomas, the most common benign tumor in women, remains unclear. Since acquired factors such as obesity, hypertension and early menarche place women at greater risk for uterine leiomyomas, uterine leiomyomas may be associated with epigenetic abnormalities that are caused by unfavorable environmental exposures. PRINCIPAL FINDINGS: Profiles of genome-wide DNA methylation and mRNA expression were investigated in leiomyomas and in myometrium with and without leiomyomas. Profiles of DNA methylation and mRNA expression in the myometrium with and without leiomyomas were quite similar while those in leiomyomas were distinct. We identified 120 genes whose DNA methylation and mRNA expression patterns differed between leiomyomas and the adjacent myometrium. The biological relevance of the aberrantly methylated and expressed genes was cancer process, including IRS1 that is related to transformation, and collagen-related genes such as COL4A1, COL4A2 and COL6A3. We also detected 22 target genes of estrogen receptor (ER alpha, including apoptosis-related genes, that have aberrant DNA methylation in the promoter, suggesting that the aberrant epigenetic regulation of ER alpha-target genes contributes to the aberrant response to estrogen. CONCLUSIONS: Aberrant DNA methylation and its related transcriptional aberration were associated with cancer processes, which may represent a critical initial mechanism that triggers transformation of a single tumor stem cell that will eventually develop into a monoclonal leiomyoma tumor. The aberrant epigenetic regulation of ER alpha-target genes also may contribute to the aberrant response to estrogen, which is involved in the development of uterine leiomyomas after menarche.

  8. Mercury methylation rates of biofilm and plankton microorganisms from a hydroelectric reservoir in French Guiana.

    Science.gov (United States)

    Huguet, L; Castelle, S; Schäfer, J; Blanc, G; Maury-Brachet, R; Reynouard, C; Jorand, F

    2010-02-15

    The Petit-Saut ecosystem is a hydroelectric reservoir covering 365km(2) of flooded tropical forest. This reservoir and the Sinnamary Estuary downstream of the dam are subject to significant mercury methylation. The mercury methylation potential of plankton and biofilm microorganisms/components from different depths in the anoxic reservoir water column and from two different sites along the estuary was assessed. For this, reservoir water and samples of epiphytic biofilms from the trunk of a submerged tree in the anoxic water column and from submerged branches in the estuary were batch-incubated from 1h to 3 months with a nominal 1000ng/L spike of Hg(II) chloride enriched in (199)Hg. Methylation rates were determined for different reservoir and estuarine communities under natural nutrient (reservoir water, estuary freshwater) and artificial nutrient (culture medium) conditions. Methylation rates in reservoir water incubations were the highest with plankton microorganisms sampled at -9.5m depth (0.5%/d) without addition of biofilm components. Mercury methylation rates of incubated biofilm components were strongly enhanced by nutrient addition. The results suggested that plankton microorganisms strongly contribute to the total Hg methylation in the Petit-Saut reservoir and in the Sinnamary Estuary. Moreover, specific methylation efficiencies (%Me(199)Hg(net)/cell) suggested that plankton microorganisms could be more efficient methylating actors than biofilm consortia and that their methylation efficiency may be reduced in the presence of biofilm components. Extrapolation to the reservoir scale of the experimentally determined preliminary methylation efficiencies suggested that plankton microorganisms in the anoxic water column could produce up to 27mol MeHg/year. Taking into account that (i) demethylation probably occurs in the reservoir and (ii) that the presence of biofilm components may limit the methylation efficiency of plankton microorganisms, this result is

  9. Efficacy of insect-proof nets used in Tunisian tomato greenhouses against Tuta absoluta (Meyrick (Lepidoptera: Gelechiidae and potential impact on plant growth and fruit quality

    Directory of Open Access Journals (Sweden)

    A. Harbi

    2015-12-01

    Full Text Available Insect-proof screens constitute efficient physical means of protecting horticultural crops against insect pests and their use has become widespread. However, they may have a negative impact on plant growth and fruit quality by modifying climatic parameters of greenhouses. In case of tomato crops, they are used mainly against white flies and the tomato leaf miner Tuta absoluta (Meyrick. In Tunisia, tomato plastic tunnels are often netted following two modalities: i complete netting of the greenhouse under the plastic screen (total netting; or ii netting only doors and lateral aeration windows (partial netting. Weekly monitoring of T. absoluta in two tomato greenhouses with different netting setups using pheromone traps and sampling of leaves and fruits showed no differences in the levels of infestation by the pest with a maximum average values of 6.66 eggs/leaf, 4.16 larvae/leaf and 4.16 mines/leaf. The maximum infestation rate of leaves was 86.66% and that of fruits was 10.83%. No effects of the netting setup used on plant growth parameters were detected. However, the study of fruit quality parameters revealed significant decrease in sugar contents in tomato fruits when using total netting setup (4.26°Brix versus 3.68°Brix. Recommendations regarding the combined use of pheromones traps and insect-proof nets are given and possibilities to enhance the efficiency of nets as physical barrier against T. absoluta are explored.

  10. Genome-wide identification of mononuclear cell DNA methylation sites potentially affected by fish oil supplementation in young infants

    DEFF Research Database (Denmark)

    Lind, Mads Vendelbo; Martino, D; Harsløf, Laurine Bente Schram

    2015-01-01

    Recent evidence suggests that the effects of n-3LCPUFA might be mediated through epigenetic mechanisms, especially DNA-methylation, during pregnancy and early life. A randomized trial was conducted in 133 9-mo-old, infants who received 3.8g/day of fish oil (FO) or sunflower oil (SO) for 9 mo...

  11. Genome-Wide DNA Methylation Analysis Identifies Novel Hypomethylated Non-Pericentromeric Genes with Potential Clinical Implications in ICF Syndrome.

    Directory of Open Access Journals (Sweden)

    L Simo-Riudalbas

    Full Text Available Immunodeficiency, centromeric instability and facial anomalies syndrome (ICF is a rare autosomal recessive disease, characterized by severe hypomethylation in pericentromeric regions of chromosomes (1, 16 and 9, marked immunodeficiency and facial anomalies. The majority of ICF patients present mutations in the DNMT3B gene, affecting the DNA methyltransferase activity of the protein. In the present study, we have used the Infinium 450K DNA methylation array to evaluate the methylation level of 450,000 CpGs in lymphoblastoid cell lines and untrasformed fibroblasts derived from ICF patients and healthy donors. Our results demonstrate that ICF-specific DNMT3B variants A603T/STP807ins and V699G/R54X cause global DNA hypomethylation compared to wild-type protein. We identified 181 novel differentially methylated positions (DMPs including subtelomeric and intrachromosomic regions, outside the classical ICF-related pericentromeric hypomethylated positions. Interestingly, these sites were mainly located in intergenic regions and inside the CpG islands. Among the identified hypomethylated CpG-island associated genes, we confirmed the overexpression of three selected genes, BOLL, SYCP2 and NCRNA00221, in ICF compared to healthy controls, which are supposed to be expressed in germ line and silenced in somatic tissues.In conclusion, this study contributes in clarifying the direct relationship between DNA methylation defect and gene expression impairment in ICF syndrome, identifying novel direct target genes of DNMT3B. A high percentage of the DMPs are located in the subtelomeric regions, indicating a specific role of DNMT3B in methylating these chromosomal sites. Therefore, we provide further evidence that hypomethylation in specific non-pericentromeric regions of chromosomes might be involved in the molecular pathogenesis of ICF syndrome. The detection of DNA hypomethylation at BOLL, SYCP2 and NCRNA00221 may pave the way for the development of specific

  12. Modulation of DL-. alpha. -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/quisqualate receptors by phospholipase A sub 2 : A necessary step in long-term potentiation

    Energy Technology Data Exchange (ETDEWEB)

    Massicotte, G.; Baudry, M. (Univ. of Southern California, Los Angeles (United States)); Vanderklish, P.; Lynch, G. (Univ. of California, Irvine (United States))

    1991-03-01

    The effects of kainate (KA)-induced epileptic seizures on the binding properites of hippocampal glutamate receptors, on the modulation of DL-{alpha}-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/quisqualate receptor by phospholipase A{sub 2} (PLA{sub 2}), and on the formation of long-term potentiation (LTP) were studied in hippocampal membranes and hippocampal slices. Systemic administration of KA produced specific changes in the binding properties of the AMPA/quisqualate receptors and its regulation. Whereas the binding of various ligands to the N-methyl-D-aspartate receptors was not modified by KA treatment, there was a singificant decrease in the maximal number of binding sites for ({sup 3}H)AMPA. The loss of LTP was not due to changes in postsynaptic responses elicited by the bursts that trigger the potentiation effect, thus suggesting that KA treatment disrupts processes that follow N-methyl-D-aspartate receptor activation. Systemic administration of KA was associated with calpain activation as the amount of spectrin breakdown products was increased severalfold in hippocampus but not in cerebellum. Pretreatment of telencephalic membranes with calpain greatly reduced the PLA{sub 2}-induced increase in ({sup 3}H)AMPA binding. The results provide evidence in favor of an essential role of PLA{sub 2} in the development of LTP and suggest that the order of activation of different calcium-dependent processes is critical for producing the final changes underlying LTP.

  13. Co-polymerization of methyl methacrylate and styrene via surfactant-free emulsion polymerization, as a potential material for photonic crystal application

    Science.gov (United States)

    Kassim, Syara; Zahari, Siti Balqis; Tahrin, Rabiatul Addawiyah Azwa; Harun, Noor Aniza

    2017-09-01

    Photonic crystals are being the great interest of researcher to studies due to a variety of potential application for the interaction of light including the solar cells, optical sensors and paints. In order to evaluate the fabrication of photonic crystals thin film, a free-emulsifier emulsion copolymerization of styrene and methyl methacrylate was carried out. By using the self -assembly approach, this method offers the opportunity to produce crystalline polymer sphere in more ease operation, low cost and environmental friendly. The influences of the mixing ratio of monomer and amount of initiators were studied. In advance, the presence of styrene as co-monomer had improved the thermal degradation of polymer methyl methacrylate. While in changing the mixing ratio of styrene and methyl methacrylate resulted in particle size of the sphere. The size of polymer particles slightly increased on increasing volume of styrene monomer ratio. This occurred because the properties of styrene in water where it sparingly soluble and lead to coagulation of particles. This simple, yet effective method for preparing functional complex 3D structures has the potential to be used generically to fabricate a variety of functional porous 3D structures that could find application not only in new or improved photonic crystal (PC) devices but also in areas such as catalysis, solar cell, separation, fuel cells technology, microelectronics and optoelectronics.

  14. Hydrogen atoms in acetylsalicylic acid (Aspirin): the librating methyl group and probing the potential well in the hydrogen-bonded dimer

    Science.gov (United States)

    Wilson, Chick C.

    2001-02-01

    The structure of acetylsalicylic acid (2-(acetoyloxy)benzoic acid; Aspirin) has been studied by variable temperature single crystal neutron diffraction. The usual large torsional librational motion of the terminal methyl group is observed and its temperature dependence analysed using a simple model for the potential, yielding the force constant and barrier height for this motion. In addition, asymmetry of the scattering density of the proton involved in the hydrogen bond forming the carboxylic acid dimer motif is observed at temperatures above 200 K. This asymmetry is discussed in terms of its possible implications for the shape of the hydrogen bonding potential well.

  15. Methyl Methacrylate and Alpha-Methyl Styrene: New Strategy for Synthesis of Bloc Copolymers for Use in Potential Biomedical Applications Generated by an Ecologic Catalyst Called Maghnite (Algerian MMT

    Directory of Open Access Journals (Sweden)

    Moulkheir Ayat

    2016-10-01

    Full Text Available A new model for synthesis of the plastics, block copolymers were prepared from methyl methacrylate (MMA and alpha-methyl styrene (α-MS by cationic copolymerization in the presence of a new and efficient catalyst of “Maghnite-Na” at 0 °C in bulk. In this paper, the copolymerization of α-MS and MMA was induced in heterogeneous phase catalyzed by Maghnite-Na was investigated under suitable conditions. The “Maghnite-Na” is a montmorillonite sheet silicate clay, with exchanged sodium cations to produce Na-Montmorillonite (Na+-MMT obtained from Tlemcen, Algeria, was investigated to remove heavy metal ion from wastewater as an efficient catalyst for cationic polymerization of many vinylic and heterocyclic monomers. The synthesized copolymer were characterized by Nuclear Magnetic Resonance (NMR-1H, NMR-13C, FT-IR spectroscopy, Differential Scanning Calorimetry (DSC, and Gel Permeation Chromatography (GPC to elucidate structural characteristics and thermal properties of the resulting copolymers. The structure compositions of “MMT”, “H+-MMT” and “Na+-MMT” have been developed. The effect of the MMA/α-MS molar ratio on the rate of copolymerization, the amount of catalyst, temperature and time of copolymerization on yield of copolymers was studied. The yield of copolymerization depends on the amount of Na+-MMT used and the reaction time. The kinetic studies indicated that the polymerization rate is first order with respect to monomer concentration. A possible mechanism of this cationic polymerization is discussed based on the results of the 1H-NMR Spectroscopic analysis of these model reactions. A cationic mechanism for the reaction studies showed that monomer was inserted into the growing chains. Copyright © 2016 BCREC GROUP. All rights reserved Received: 2nd May 2015; Revised: 24th February 2016; Accepted: 15th March 2016 How to Cite: Ayat, M., Belbachir, M., Rahmouni, A. (2016. Methyl Methacrylate and Alpha-Methyl Styrene: New

  16. Experimental and computational approaches of a novel methyl (2E)-2-{[N-(2-formylphenyl)(4-methylbenzene)sulfonamido]methyl}-3-(4-chlorophenyl)prop-2-enoate: A potential antimicrobial agent and an inhibition of penicillin-binding protein

    Science.gov (United States)

    Murugavel, S.; Vetri velan, V.; Kannan, Damodharan; Bakthadoss, Manickam

    2016-07-01

    The title compound methyl(2E)-2-{[N-(2-formylphenyl) (4-methylbenzene)sulfonamido]methyl}-3-(4-chlorophenyl) prop-2-enoate (MFMSC) has been synthesized and single crystals were grown by slow evaporation solution growth technique at room temperature. Structural and vibrational spectroscopic studies were carried out by using single crystal X-ray diffraction, FT-IR and NMR spectral analysis together with DFT method using GAUSSIAN'03 software. The detailed interpretation of the vibrational spectra has been carried out by VEDA program. NBO analysis, Mulliken charge analysis, HOMO-LUMO, MEP, Global chemical reactivity descriptors and thermodynamic properties have been analyzed. The hyperpolarisability calculation reveals the present material has a reasonably good propensity for nonlinear optical activity. The obtained antimicrobial activity results indicate that the compound shows good to moderate activity against all tested bacterial and fungal pathogens. A computational study was also carried out to predict the drug-likeness and ADMET properties of the title compound. Due to the different potential biological activity of the title compound, molecular docking study is also reported and the compound might exhibit inhibitory activity against penicillin-binding protein PBP-2X.

  17. DNA methylation alterations in iPSC- and hESC-derived neurons: potential implications for neurological disease modeling.

    Science.gov (United States)

    de Boni, Laura; Gasparoni, Gilles; Haubenreich, Carolin; Tierling, Sascha; Schmitt, Ina; Peitz, Michael; Koch, Philipp; Walter, Jörn; Wüllner, Ullrich; Brüstle, Oliver

    2018-01-01

    Genetic predisposition and epigenetic alterations are both considered to contribute to sporadic neurodegenerative diseases (NDDs) such as Parkinson's disease (PD). Since cell reprogramming and the generation of induced pluripotent stem cells (iPSCs) are themselves associated with major epigenetic remodeling, it remains unclear to what extent iPSC-derived neurons lend themselves to model epigenetic disease-associated changes. A key question to be addressed in this context is whether iPSC-derived neurons exhibit epigenetic signatures typically observed in neurons derived from non-reprogrammed human embryonic stem cells (hESCs). Here, we compare mature neurons derived from hESC and isogenic human iPSC generated from hESC-derived neural stem cells. Genome-wide 450 K-based DNA methylation and HT12v4 gene array expression analyses were complemented by a deep analysis of selected genes known to be involved in NDD. Our studies show that DNA methylation and gene expression patterns of isogenic hESC- and iPSC-derived neurons are markedly preserved on a genome-wide and single gene level. Overall, iPSC-derived neurons exhibit similar DNA methylation patterns compared to isogenic hESC-derived neurons. Further studies will be required to explore whether the epigenetic patterns observed in iPSC-derived neurons correspond to those detectable in native brain neurons.

  18. Mathematical evaluation of community level impact of combining bed nets and indoor residual spraying upon malaria transmission in areas where the main vectors are Anopheles arabiensis mosquitoes

    Directory of Open Access Journals (Sweden)

    Okumu Fredros O

    2013-01-01

    Full Text Available Abstract Background Indoor residual insecticide spraying (IRS and long-lasting insecticide treated nets (LLINs are commonly used together even though evidence that such combinations confer greater protection against malaria than either method alone is inconsistent. Methods A deterministic model of mosquito life cycle processes was adapted to allow parameterization with results from experimental hut trials of various combinations of untreated nets or LLINs (Olyset®, PermaNet 2.0®, Icon Life® nets with IRS (pirimiphos methyl, lambda cyhalothrin, DDT, in a setting where vector populations are dominated by Anopheles arabiensis, so that community level impact upon malaria transmission at high coverage could be predicted. Results Intact untreated nets alone provide equivalent personal protection to all three LLINs. Relative to IRS plus untreated nets, community level protection is slightly higher when Olyset® or PermaNet 2.0® nets are added onto IRS with pirimiphos methyl or lambda cyhalothrin but not DDT, and when Icon Life® nets supplement any of the IRS insecticides. Adding IRS onto any net modestly enhances communal protection when pirimiphos methyl is sprayed, while spraying lambda cyhalothrin enhances protection for untreated nets but not LLINs. Addition of DDT reduces communal protection when added to LLINs. Conclusions Where transmission is mediated primarily by An. arabiensis, adding IRS to high LLIN coverage provides only modest incremental benefit (e.g. when an organophosphate like pirimiphos methyl is used, but can be redundant (e.g. when a pyrethroid like lambda cyhalothin is used or even regressive (e.g. when DDT is used for the IRS. Relative to IRS plus untreated nets, supplementing IRS with LLINs will only modestly improve community protection. Beyond the physical protection that intact nets provide, additional protection against transmission by An. arabiensis conferred by insecticides will be remarkably small, regardless of

  19. Methodological considerations regarding the use of inorganic {sup 197}Hg(II) radiotracer to assess mercury methylation potential rates in lake sediment

    Energy Technology Data Exchange (ETDEWEB)

    Perez Catan, Soledad [Laboratorio de Analisis por Activacion Neutronica, Comision Nacional de Energia Atomica, Centro Atomico Bariloche, 8400 Bariloche (Argentina); Guevara, Sergio Ribeiro [Laboratorio de Analisis por Activacion Neutronica, Comision Nacional de Energia Atomica, Centro Atomico Bariloche, 8400 Bariloche (Argentina)], E-mail: ribeiro@cab.cnea.gov.ar; Marvin-DiPasquale, Mark [US Geological Survey, 345 Middlefield Rd./MS 480, Menlo Park, CA 94025 (United States); Magnavacca, Cecilia [Centro Atomico Ezeiza, Comision Nacional de Energia Atomica, Presbitero Gonzalez y Aragon No. 15, B1802AYA, Ezeiza, Buenos Aires (Argentina); Cohen, Isaac Marcos [Departamento de Ingenieria Quimica, Facultad Regional Buenos Aires, Universidad Tecnologica Nacional, Medrano 951 (C1179AAQ) Buenos Aires (Argentina); Arribere, Maria [Laboratorio de Analisis por Activacion Neutronica, Comision Nacional de Energia Atomica, Centro Atomico Bariloche, 8400 Bariloche (Argentina)

    2007-09-15

    Methodological considerations on the determination of benthic methyl-mercury (CH{sub 3}Hg) production potentials were investigated on lake sediment, using {sup 197}Hg radiotracer. Three methods to arrest bacterial activity were compared: flash freezing, thermal sterilization, and {gamma}-irradiation. Flash freezing showed similar CH{sub 3}Hg recoveries as thermal sterilization, which was both 50% higher than the recoveries obtained with {gamma}-ray irradiation. No additional radiolabel was recovered in kill-control samples after an additional 24 or 65 h of incubation, suggesting that all treatments were effective at arresting Hg(II)-methylating bacterial activity, and that the initial recoveries are likely due to non-methylated {sup 197}Hg(II) carry-over in the organic extraction and/or [{sup 197}Hg]CH{sub 3}Hg produced via abiotic reactions. Two CH{sub 3}Hg extraction methods from sediment were compared: (a) direct extraction into toluene after sediment leaching with CuSO{sub 4} and HCl and (b) the same extraction with an additional back-extraction step to thiosulphate. Similar information was obtained with both methods, but the low efficiency observed and the extra work associated with the back-extraction procedure represent significant disadvantages, even tough the direct extraction involves higher Hg(II) carry over.

  20. Pro asynchronous programming with .NET

    CERN Document Server

    Blewett, Richard; Ltd, Rock Solid Knowledge

    2014-01-01

    Pro Asynchronous Programming with .NET teaches the essential skill of asynchronous programming in .NET. It answers critical questions in .NET application development, such as: how do I keep my program responding at all times to keep my users happy how do I make the most of the available hardware how can I improve performanceIn the modern world, users expect more and more from their applications and devices, and multi-core hardware has the potential to provide it. But it takes carefully crafted code to turn that potential into responsive, scalable applications.With Pro Asynchronous Programming

  1. POTENTIAL APPLICATION OF A LOCALLY SOURCED PHOTOCATALYST FOR THE PHOTOCATALYTIC DECOLOURISATION OF METHYL ORANGE IN AQUEOUS SOLUTION

    Directory of Open Access Journals (Sweden)

    F. A. AISIEN

    2015-12-01

    Full Text Available Periwinkle shell ash (PSA was investigated for its photocatalytic properties in decolourising methyl orange in aqueous solution. The effects of irradiation time, initial dye concentration and PSA dosage on the decolourisation process were investigated. The optimum values of the process variables were: irradiation time, 50 minutes; initial dye concentration, 20 mg/L and PSA dosage, 3 g/L. The kinetics of the process was well described by the pseudo first order and Langmuir-Hinshelwood kinetic models while the adsorption equilibrium was well elucidated by both the Langmuir isotherm and Freundlich isotherm equations with high R2 values.

  2. Effects of nitrogen application rates on net annual global warming potential and greenhouse gas intensity in double-rice cropping systems of the Southern China.

    Science.gov (United States)

    Chen, Zhongdu; Chen, Fu; Zhang, Hailin; Liu, Shengli

    2016-12-01

    The net global warming potential (NGWP) and net greenhouse gas intensity (NGHGI) of double-rice cropping systems are not well documented. We measured the NGWP and NGHGI including soil organic carbon (SOC) change and indirect emissions (IE) from double-crop rice fields with fertilizing systems in Southern China. These experiments with three different nitrogen (N) application rates since 2012 are as follows: 165 kgN ha -1 for early rice and 225 kgN ha -1 for late rice (N1), which was the local N application rates as the control; 135 kgN ha -1 for early rice and 180 kgN ha -1 for late rice (N2, 20 % reduction); and 105 kgN ha -1 for early rice and 135 kgN ha -1 for late rice (N3, 40 % reduction). Results showed that yields increased with the increase of N application rate, but without significant difference between N1 and N2 plots. Annual SOC sequestration rate under N1 was estimated to be 1.15 MgC ha -1  year -1 , which was higher than those under other fertilizing systems. Higher N application tended to increase CH 4 emissions during the flooded rice season and significantly increased N 2 O emissions from drained soils during the nonrice season, ranking as N1 > N2 > N3 with significant difference (P < 0.05). Two-year average IE has a huge contribution to GHG emissions mainly coming from the higher N inputs in the double-rice cropping system. Reducing N fertilizer usage can effectively decrease the NGWP and NGHGI in the double-rice cropping system, with the lowest NGHGI obtained in the N2 plot (0.99 kg CO 2 -eq kg -1 yield year -1 ). The results suggested that agricultural economic viability and GHG mitigation can be simultaneously achieved by properly reducing N fertilizer application in double-rice cropping systems.

  3. Net global warming potential and greenhouse gas intensity in a double-cropping cereal rotation as affected by nitrogen and straw management

    Science.gov (United States)

    Huang, T.; Gao, B.; Christie, P.; Ju, X.

    2013-12-01

    The effects of nitrogen and straw management on global warming potential (GWP) and greenhouse gas intensity (GHGI) in a winter wheat-summer maize double-cropping system on the North China Plain were investigated. We measured nitrous oxide (N2O) emissions and studied net GWP (NGWP) and GHGI by calculating the net exchange of CO2 equivalent (CO2-eq) from greenhouse gas emissions, agricultural inputs and management practices, as well as changes in soil organic carbon (SOC), based on a long-term field experiment established in 2006. The field experiment includes six treatments with three fertilizer N levels (zero N (control), optimum and conventional N) and straw removal (i.e. N0, Nopt and Ncon) or return (i.e. SN0, SNopt and SNcon). Optimum N management (Nopt, SNopt) saved roughly half of the fertilizer N compared to conventional agricultural practice (Ncon, SNcon), with no significant effect on grain yields. Annual mean N2O emissions reached 3.90 kg N2O-N ha-1 in Ncon and SNcon, and N2O emissions were reduced by 46.9% by optimizing N management of Nopt and SNopt. Straw return increased annual mean N2O emissions by 27.9%. Annual SOC sequestration was 0.40-1.44 Mg C ha-1 yr-1 in plots with N application and/or straw return. Compared to the conventional N treatments the optimum N treatments reduced NGWP by 51%, comprising 25% from decreasing N2O emissions and 75% from reducing N fertilizer application rates. Straw return treatments reduced NGWP by 30% compared to no straw return because the GWP from increments of SOC offset the GWP from higher emissions of N2O, N fertilizer and fuel after straw return. The GHGI trends from the different nitrogen and straw management practices were similar to the NGWP. In conclusion, optimum N and straw return significantly reduced NGWP and GHGI and concomitantly achieved relatively high grain yields in this important winter wheat-summer maize double-cropping system.

  4. Net global warming potential and greenhouse gas intensity in a double cropping cereal rotation as affected by nitrogen and straw management

    Science.gov (United States)

    Huang, T.; Gao, B.; Christie, P.; Ju, X.

    2013-08-01

    The effects of nitrogen and straw management on global warming potential (GWP) and greenhouse gas intensity (GHGI) in a winter wheat-summer maize double-cropping system on the North China Plain were investigated. We measured nitrous oxide (N2O) emissions and studied net GWP (NGWP) and GHGI by calculating the net exchange of CO2 equivalent (CO2-eq) from greenhouse gas emissions, agricultural inputs and management practices, and changes in soil organic carbon (SOC), based on a long-term field experiment established in 2006. The field experiment includes six treatments with three fertilizer N levels (zero-N control, optimum and conventional N) and straw removal (i.e. N0, Nopt and Ncon) or return (i.e. N0, Nopt and SNcon). Optimum N management (Nopt, SNopt) saved roughly half of the fertilizer N compared to conventional agricultural practice (Ncon, SNcon) with no significant effect on grain yields. Annual mean N2O emissions reached 3.90 kg N2O-N ha-1 in Ncon and SNcon, and N2O emissions were reduced by 46.9% by optimizing N management of Nopt and SNopt. Straw return increased annual mean N2O emissions by 27.9%. Annual SOC sequestration was 0.40-1.44 Mg C ha-1 yr-1 in plots with N application and/or straw return. Compared to the conventional N treatments the optimum N treatments reduced NGWP by 51%, comprising 25% from decreasing N2O emissions and 75% from reducing N fertilizer application rates. Straw return treatments reduced NGWP by 30% compared to no straw return because the GWP from increments of SOC offset the GWP from higher emissions of N2O, N fertilizer and fuel after straw return. The GHGI trends from the different nitrogen and straw management practices were similar to the NGWP. In conclusion, optimum N and straw return significantly reduced NGWP and GHGI and concomitantly achieved relatively high grain yields in this important winter wheat-summer maize double-cropping system.

  5. Energy potential, energy ratios, and the amount of net energy in Finnish field crop production; Peltobioenergian tuotanto Suomessa. Potentiaali, energiasuhteet ja nettoenergia

    Energy Technology Data Exchange (ETDEWEB)

    Mikkola, H.

    2012-11-01

    Energy potential, energy ratios, and the amount of net energy in Finnish field crop production were studied in this thesis. Special attention was paid to indirect energy inputs and how to treat them in energy analysis. Manufacturing of machines and agrochemicals and production of seeds are examples of indirect energy inputs.The bioenergy potential of the Finnish field crop production could be as large as 12 - 22 TWh, or 3 - 5% of the total energy consumption in Finland in 2008. The major part of this energy would originate from straw and biomass like reed canary grass cultivated for energy use. However, only 0.5 TWh of the potential is utilized. The output/input energy ratios of the studied field crops varied from 3 to 18, being highest (18) for reed canary grass and second highest (7) for sugar beet and grass cultivated for silage. The energy ratio of cereals and oil seed crops varied from 3 to 5 if only the yield of seeds was considered. If the yield of straw and stems was also taken into account the energy ratios would have been almost twofold. The energy ratios for Finnish wheat and barley were as high as those gained in Italian and Spanish conditions, respectively. However, the energy ratios of maize, elephant grass and giant reed were even over 50 in Central and Southern Europe. Plants that use the C4 photosynthesis pathway and produce high biomass yields thrive best in warm and sunny climate conditions. They use nitrogen and water more sparingly than C3 plants typically thriving in the cooler part of the temperate zone. When evaluating energy ratios for field crops it should be kept in mind that the maximal energy potential of the energy crop is the heating value of the dry matter at the field gate. Transportation of the crop and production of liquid fuels and electricity from biomass lowers the energy ratio. A comparison of field energy crops to a reforested field suggested that fast growing trees, as hybrid aspen and silver birch, would yield almost as

  6. A Potential Synergy between Incomplete Arsenic Methylation Capacity and Demographic Characteristics on the Risk of Hypertension: Findings from a Cross-Sectional Study in an Arsenic-Endemic Area of Inner Mongolia, China

    Directory of Open Access Journals (Sweden)

    Yongfang Li

    2015-03-01

    Full Text Available Inefficient arsenic methylation capacity has been associated with various health hazards induced by arsenic. In this study, we aimed to explore the interaction effect of lower arsenic methylation capacity with demographic characteristics on hypertension risk. A total of 512 adult participants (126 hypertension subjects and 386 non-hypertension subjects residing in an arsenic-endemic area in Inner Mongolia, China were included. Urinary levels of inorganic arsenic (iAs, monomethylarsonic acid (MMA, and dimethylarsinic acid (DMA were measured for all subjects. The percentage of urinary arsenic metabolites (iAs%, MMA%, and DMA%, primary methylation index (PMI and secondary methylation index (SMI were calculated to assess arsenic methylation capacity of individuals. Results showed that participants carrying a lower methylation capacity, which is characterized by lower DMA% and SMI, have a higher risk of hypertension compared to their corresponding references after adjusting for multiple confounders. A potential synergy between poor arsenic methylation capacity (higher MMA%, lower DMA% and SMI and older age or higher BMI were detected. The joint effects of higher MMA% and lower SMI with cigarette smoking also suggest some evidence of synergism. The findings of present study indicated that inefficient arsenic methylation capacity was associated with hypertension and the effect might be enhanced by certain demographic factors.

  7. Methyl parathion inhibits the nuclear maturation, decreases the cytoplasmic quality in oocytes and alters the developmental potential of embryos of Swiss albino mice

    Energy Technology Data Exchange (ETDEWEB)

    Nair, Ramya; Singh, Vikram Jeet; Salian, Sujith Raj [Division of Clinical Embryology, Department of Obstetrics and Gynecology, Kasturba Medical College, Manipal University, Manipal 576 104 (India); Kalthur, Sneha Guruprasad; D' Souza, Antony Sylvan [Department of Anatomy, Kasturba Medical College, Manipal University, Manipal 576 104 (India); Shetty, Pallavi K.; Mutalik, Srinivas [Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal 576 104 (India); Kalthur, Guruprasad, E-mail: guru.kalthur@manipal.edu [Division of Clinical Embryology, Department of Obstetrics and Gynecology, Kasturba Medical College, Manipal University, Manipal 576 104 (India); Adiga, Satish Kumar [Division of Clinical Embryology, Department of Obstetrics and Gynecology, Kasturba Medical College, Manipal University, Manipal 576 104 (India)

    2014-09-15

    Methyl parathion (MP) is one of the most commonly used and extremely toxic organophosphorous group of pesticide. A large number of studies in the literature suggest that it has adverse effects on the male reproductive system. However, there is limited information about its toxicity to the female reproductive system. In the present study we report the toxic effects of methyl parathion on the female reproductive system using Swiss albino mice as the experimental model. The female mice were administered orally with 5, 10 and 20 mg/kg of MP. One week later, the mice were superovulated with pregnant mare serum gonadotrophin (PMSG) and human chorionic gonadotrophin (hCG) to study the quality of the oocytes, spindle organization, developmental potential of early embryos and the DNA integrity in blastocysts. MP exposure resulted in a non-significant decrease in the number of primordial follicles and increased DNA damage in granulosa cells. Though MP did not have any effect on the ovulation it had a significant inhibitory effect on the nuclear maturity of oocytes which was associated with spindle deformity. In addition, the oocytes had higher cytoplasmic abnormalities with depleted glutathione level. Even though it did not have any effect on the fertilization and blastocyst rate at lower doses, at 20 mg/kg MP it resulted in a significant decrease in blastocyst hatching, decrease in cell number and high DNA damage. While low body weight gain was observed in F1 generation from 5 mg/kg group, at higher dose, the body weight in F1 generation was marginally higher than control. Post-natal death in F1 generation was observed only in mice treated with 20 mg/kg MP. In conclusion, we report that MP has adverse effects on the oocyte quality, developmental potential of the embryo and reproductive outcome. - Highlights: • Methyl parathion induces severe cytoplasmic abnormalities in oocytes. • Inhibits nuclear maturation and spindle damage • Poor blastocyst quality and high DNA

  8. Phorbol 12-myristate 13-acetate potentiation of N-methyl-D-aspartate-induced currents in primary cultured cerebellar granule cells is mediated by protein kinase C alpha.

    Science.gov (United States)

    Reneau, Jason C; Reyland, Mary E; Phillips, Jonathan; Kindy, Carissa; Popp, R Lisa

    2009-08-01

    We have previously reported that activation of protein kinase C (PKC) by phorbol 12-myristate 13-acetate (PMA) results in potentiation of N-methyl-D-aspartate-induced currents (I(NMDA))of receptors contained in primary cultured cerebellar granule cells (CGCs). The purpose of this study was to identify which PKC isoform(s) was responsible for this effect by using the whole-cell patch-clamp technique. Experiments were conducted on CGCs that expressed both the NR2A and NR2B NMDA receptor subunits as well as the PMA-sensitive PKC isoforms alpha, betaI, betaII, delta, epsilon, gamma, and . As observed previously, N-methyl-D-aspartate-induced peak currents (I(Pk)) were enhanced by a 12.5-min, 100 nM PMA exposure at 37 degrees C under normal recording conditions. Potentiation of receptor function was not observed when extracellular Ca(2+) was removed and 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid was present inside the cell. PMA-induced potentiation of I(Pk) did not occur when PKCalpha-specific antibody was introduced into the cell via the recording electrode. However, in similar experiments with antibodies specific for PKCbetaII, delta, epsilon, gamma, and , PMA potentiation of I(Pk) was observed. Down-regulation of PMA-sensitive PKC isoforms by an overnight exposure of 100 nM PMA resulted in lack of potentiation by PMA that was rescued when catalytically active PKCalpha was introduced into the cell via the patch electrode. PMA potentiation of I(Pk) was not recovered when catalytically active PKCbetaI, PKCbetaII, or PKCgamma was introduced into the cell via the patch electrode. Collectively, our data provide strong evidence that PMA-enhanced function of native NMDA receptors expressed in primary cultured CGCs is mediated by activation of PKCalpha.

  9. Synthesis, crystal structures, quantum chemical studies and corrosion inhibition potentials of 4-(((4-ethylphenyl)imino)methyl)phenol and (E)-4-((naphthalen-2-ylimino) methyl) phenol Schiff bases

    Science.gov (United States)

    Elemike, Elias E.; Nwankwo, Henry U.; Onwudiwe, Damian C.; Hosten, Eric C.

    2017-11-01

    Two Schiff base ligands, 4-(((4-ethylphenyl)imino)methyl)phenol (4EMP) and (E)-4-((naphthalen-2-ylimino) methyl) phenol (4NMP) were synthesized by the reaction of 4-hydroxybenzaldehyde with 4-ethylaniline, 4EMP, or naphthalene-2-amine, 4NMP. The compounds were characterized using NMR (1H and 13C), Fourier transform infra-red (FTIR) and mass spectroscopic techniques. The proton NMR identified the OH peaks at 9.73 and 9.77 ppm for 4EMP and 4NMP respectively, while the 13C NMR showed the imine carbons at 172.57 ppm for 4EMP and at 160.89 ppm for 4NMP. The FTIR spectra showed characteristic peaks at 1605 cm-1 (4EMP) and 1600 cm-1 (4NMP) typical of the azomethine group, and the mass spectra results gave molecular ion peaks of 226.12 and 248.10 respectively. The structures of the compounds were further established by single crystal X-ray analysis. The corrosion inhibition potential of the compounds were studied on mild steel surface in a 1 M hydrochloric acid (HCl) solution, and was analysed using potentiodynamic polarization (PDP) and electrochemical impedance spectroscopy (EIS). The results of the electrochemical methods showed that the studied molecules imparted high resistance in allowing flow of electrons across the metal-electrolyte platform and behaved as mixed type inhibitors with 4EMP showing better inhibition properties than 4NMP. Scanning electron microscopy (SEM) showed the formation of film on the mild steel surface. Quantum chemical calculations achieved by density functional theory (DFT) was further applied to explain the adsorption as well as inhibition abilities of the molecules on the mild steel surface. Thermodynamics studies showed that the two compounds obeyed the Langmuir isotherm with 4EMP conforming to chemisorption mechanism while 4NMP involved competitive physisorption and chemisorption mechanism.

  10. Rhodotorulaglutinis phenylalanine/tyrosine ammonia lyase enzyme catalyzed synthesis of the methyl ester of para-hydroxycinnamic acid and its potential antibacterial activity

    Directory of Open Access Journals (Sweden)

    Marybeth C MacDonald

    2016-03-01

    Full Text Available Biotransformation of L-tyrosine methyl ester (L-TM to the methyl ester of para- hydroxycinnamic acid (p-HCAM using Rhodotorula glutinis yeast phenylalanine/tyrosine ammonia lyase (PTAL; EC 4.3.1.26 enzyme was successfully demonstrated for the first time; progress of the reaction was followed by spectrophotometric determination at 315 nm. The following conditions were optimized for maximal formation of p-HCAM: pH (8.5, temperature (37 C, speed of agitation (50 rpm, enzyme concentration (0.080 µM, and substrate concentration (0.50 mM. Under these conditions, the yield of the reaction was ~15% in 1 h incubation period and ~63% after an overnight (~18 h incubation period. The product (p-HCAM of the reaction of PTAL with L-TM was confirmed using Nuclear Magnetic Resonance spectroscopy (NMR. Fourier Transform Infra-Red spectroscopy (FTIR was carried out to rule out potential hydrolysis of p-HCAM during overnight incubation. Potential antibacterial activity of p-HCAM was tested against several strains of Gram positive and Gram negative bacteria. This study describes a synthetically useful transformation, and could have future clinical and industrial applications.

  11. Rhodotorula glutinis Phenylalanine/Tyrosine Ammonia Lyase Enzyme Catalyzed Synthesis of the Methyl Ester of para-Hydroxycinnamic Acid and its Potential Antibacterial Activity.

    Science.gov (United States)

    MacDonald, Marybeth C; Arivalagan, Pugazhendhi; Barre, Douglas E; MacInnis, Judith A; D'Cunha, Godwin B

    2016-01-01

    Biotransformation of L-tyrosine methyl ester (L-TM) to the methyl ester of para- hydroxycinnamic acid (p-HCAM) using Rhodotorula glutinis yeast phenylalanine/tyrosine ammonia lyase (PTAL; EC 4.3.1.26) enzyme was successfully demonstrated for the first time; progress of the reaction was followed by spectrophotometric determination at 315 nm. The following conditions were optimized for maximal formation of p-HCAM: pH (8.5), temperature (37°C), speed of agitation (50 rpm), enzyme concentration (0.080 μM), and substrate concentration (0.50 mM). Under these conditions, the yield of the reaction was ∼15% in 1 h incubation period and ∼63% after an overnight (∼18 h) incubation period. The product (p-HCAM) of the reaction of PTAL with L-TM was confirmed using Nuclear Magnetic Resonance spectroscopy (NMR). Fourier Transform Infra-Red spectroscopy (FTIR) was carried out to rule out potential hydrolysis of p-HCAM during overnight incubation. Potential antibacterial activity of p-HCAM was tested against several strains of Gram-positive and Gram-negative bacteria. This study describes a synthetically useful transformation, and could have future clinical and industrial applications.

  12. From intervention to impact: modelling the potential mortality impact achievable by different long-lasting, insecticide-treated net delivery strategies

    Directory of Open Access Journals (Sweden)

    Okell Lucy C

    2012-09-01

    Full Text Available Abstract Background The current target of universal access to long-lasting, insecticide-treated nets (LLIN is 80% coverage to reduce malaria deaths by 75% by 2015. So far, campaigns have been the main channel for large-scale delivery of LLINs, however the World Health Organization has recommended that equal priority should be given to delivery via routine antenatal care (ANC and immunization systems (EPI to target pregnant women and children from birth. These various channels of LLIN delivery are targeted to children of different ages. Since risk of mortality varies with child age and LLIN effectiveness declines with net age, it was hypothesized that the age at which a child receives a new LLIN, and therefore the delivery channel, is important in optimizing the health impact of a net. Methods A simple dynamic mathematical model was developed of delivery and impact of LLINs among children under five years of age and their household members, incorporating data on age-specific malaria death rates, net use by household structure, and net efficacy over time. Results The presented analysis finds that supplementing a universal mass campaign with extra ANC delivery would achieve a 1.4 times higher mortality reduction than campaign delivery alone, reflecting that children born in the years between campaigns would otherwise have access to old nets or no nets at an age of high risk. The relative advantage of supplementary ANC delivery is still present though smaller if malaria transmission levels are lower or if there is a strong mass effect achieved by mass campaigns. Conclusion These results indicate that LLIN delivery policies must take into account the age of greatest malaria risk. Emphasis should be placed on supporting routine delivery of LLINs to young children as well as campaigns.

  13. Higher-order organisation of extremely amplified, potentially functional and massively methylated 5S rDNA in European pikes (Esox sp.).

    Science.gov (United States)

    Symonová, Radka; Ocalewicz, Konrad; Kirtiklis, Lech; Delmastro, Giovanni Battista; Pelikánová, Šárka; Garcia, Sonia; Kovařík, Aleš

    2017-05-18

    Pikes represent an important genus (Esox) harbouring a pre-duplication karyotype (2n = 2x = 50) of economically important salmonid pseudopolyploids. Here, we have characterized the 5S ribosomal RNA genes (rDNA) in Esox lucius and its closely related E. cisalpinus using cytogenetic, molecular and genomic approaches. Intragenomic homogeneity and copy number estimation was carried out using Illumina reads. The higher-order structure of rDNA arrays was investigated by the analysis of long PacBio reads. Position of loci on chromosomes was determined by FISH. DNA methylation was analysed by methylation-sensitive restriction enzymes. The 5S rDNA loci occupy exclusively (peri)centromeric regions on 30-38 acrocentric chromosomes in both E. lucius and E. cisalpinus. The large number of loci is accompanied by extreme amplification of genes (>20,000 copies), which is to the best of our knowledge one of the highest copy number of rRNA genes in animals ever reported. Conserved secondary structures of predicted 5S rRNAs indicate that most of the amplified genes are potentially functional. Only few SNPs were found in genic regions indicating their high homogeneity while intergenic spacers were more heterogeneous and several families were identified. Analysis of 10-30 kb-long molecules sequenced by the PacBio technology (containing about 40% of total 5S rDNA) revealed that the vast majority (96%) of genes are organised in large several kilobase-long blocks. Dispersed genes or short tandems were less common (4%). The adjacent 5S blocks were directly linked, separated by intervening DNA and even inverted. The 5S units differing in the intergenic spacers formed both homogeneous and heterogeneous (mixed) blocks indicating variable degree of homogenisation between the loci. Both E. lucius and E. cisalpinus 5S rDNA was heavily methylated at CG dinucleotides. Extreme amplification of 5S rRNA genes in the Esox genome occurred in the absence of significant pseudogenisation

  14. Synthesis and characterization of methyl 4-(4-aminostyryl) benzoate as a potential precursor in the synthesis of Schiff base derivatives

    Science.gov (United States)

    Mohamad, Fatin Izwani; Hassan, Nor Hafiefa; Yusoff H., M.

    2017-09-01

    Methyl 4-(4-aminostyryl) benzoate was successfully prepared and characterized. The compound was characterized via Fourier transform infrared (FT-IR), 1H and 13C nuclear magnetic resonance (NMR) and UV-Visible analysis (UV-Vis). From the FT-IR result, it can be concluded that there is absorption of interest in carbon-carbon bond formation at 1624 cm-1 and it is assigned as C=C. While 1H NMR result showed the presence of methoxy resonance as singlet and the resonance of carbon-carbon bond formation at the expected regions. 13C showed the most deshielded regions appeared at carbons of carbonyl which is at δC 166.01 ppm and the carbons for methyl group at 50.97 ppm. In UV-Vis analysis, there are two important peaks that can be observed which is attributed in the presence of n-π* and π-π* electronic transition of C=O chromophores. The result suggested that the synthesized compound has great potential to act as precursor for formation of Schiff base derivatives. However, this study is still under preliminary stages on synthesizing Schiff base derivatives.

  15. Engineering of Corynebacterium glutamicum to utilize methyl acetate, a potential feedstock derived by carbonylation of methanol with CO.

    Science.gov (United States)

    Choo, Seungjung; Um, Youngsoon; Han, Sung Ok; Woo, Han Min

    2016-04-20

    The possibilities to utilize one-carbon substrates (C1) like CO, methane and methanol have been explored as a cheap alternative feedstock in the biotechnology. For the first time, methyl acetate (MeOAc), which can be formed from carbonylation of methanol with CO, was demonstrated to be an alternative carbon source for the cell growth of Corynebacterium glutamicum as a model microbial cell factory. To do so, a carboxyl esterase activity was necessary to hydrolyze MeOAc to methanol and acetate. Although the wild-type has an unknown esterase activity to MeOAc, the activity was not high enough to grow from 270mM MeOAc as sole carbon source, reaching OD600 of 5.28±0.2 in 32h. Based on the literatures studied for the esterase, we chose three esterases (MekB of Pseudomonas veronii MEK700, AcmB of Gordonia sp. Strain TY-5, and Est of Pyrobaculum calidifontis VA1) and cloned into the wild-type. As a result, the recombinant C. glutamicum expressing the highly active MekB esterase (28.6±0.77U/mg protein) showed complete degradation of MeOAc and utilization of acetate, resulting in OD600 of 16.5±0.02at 24h. In addition, the recombinant strain exhibited the rapid degradation of MeOAc to methanol and acetate in 2h under anaerobic condition. Therefore, MeOAc can be used as another C1-derived carbon source in the biotechnology. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Novel characteristics of horseradish peroxidase immobilized onto the polyvinyl alcohol-alginate beads and its methyl orange degradation potential.

    Science.gov (United States)

    Bilal, Muhammad; Rasheed, Tahir; Iqbal, Hafiz M N; Hu, Hongbo; Wang, Wei; Zhang, Xuehong

    2017-12-01

    Herein, we report the immobilization of in-house isolated horseradish peroxidase (HRP) from Armoracia rusticana with novel characteristics. The HRP was immobilized onto the self-fabricated polyvinyl alcohol-alginate (PVA-alginate) beads using sodium nitrate as a cross-linker. The PVA-alginate beads (2.0mm size) developed using 10% PVA and 1.5% sodium alginate showed maximal immobilization yield. The surface morphologies of the PVA-alginate (control) and immobilized-HRP were characterized by scanning electron microscopy (SEM). The immobilized-HRP retained 64.14% of its initial activity after 10 consecutive substrate-oxidation cycles as compared to the free counterpart. Simultaneously, the thermal stability of the immobilized-HRP was significantly enhanced as compared to the free HRP. The enzyme leakage (E L ) assay was performed by storing the immobilized-HRP in phosphate buffer solution for 30days. Evidently, the leakage of immobilized-HRP was recorded to be 6.98% and 14.82% after 15 and 30days of incubation, respectively. Finally, the immobilized-HRP was used for methyl orange (MO) dye degradation in a batch mode. A noticeable decline in spectral shift accompanied by no appearance of a new peak demonstrated the complete degradation of MO. The degraded fragments of MO were scrutinized by ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS). A plausible degradation pathway for MO was proposed based on the identified intermediates. In conclusion, the study portrays the PVA-alginate-immobilized-HRP as a cost-effective and industrially desirable green catalyst, for biotechnological at large and industrial in particular, especially for the treatment of textile dyes or dye-containing industrial waste effluents. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Evaluation of wetland methyl mercury export as a function of experimental manipulations.

    Science.gov (United States)

    Gustin, Mae Sexauer; Chavan, Prithviraj V; Dennett, Keith E; Marchand, Eric A; Donaldson, Susan

    2006-01-01

    Mercury associated with natural enrichment, historic mining, and ore processing is a contaminant of concern in watersheds of the western USA. In this region, water is a highly managed resource and wetlands, known to be important sites of methyl mercury production, are often an integral component of watersheds. This study applied controlled manipulations of four replicated experimental wetland designs with different water and soil mercury concentrations to determine the potential impacts on methyl mercury export. Wetlands were manipulated by drying and wetting, changing hydraulic retention time, and adding sulfate and nitrate to influent waters. In a summer drying and wetting manipulation, an immediate increase in total methyl mercury release was observed with rewetting, however, concentrations decreased quickly. Drying all wetlands over the winter and rewetting in the spring resulted in high net methyl mercury output relative to that observed before drying. Net methyl mercury output was not influenced by changes in hydraulic retention time from 4 to 8 h or to 30 min, or by increasing the nitrate concentration from 0.1 to 10 mg L(-1). The addition of sulfate to the inlet waters of two mesocosms to increase concentrations from approximately 100 to 250 mg L(-1) did not result in a clear effect on methyl mercury output, most likely due to sulfate concentrations being higher than optimal for methyl mercury production. Despite the lack of response to sulfate amendments, the change in sulfate concentration between the inlet and outlet of the mesocosms and temperature were the parameters best correlated with methyl mercury outputs.

  18. Laboratory study on heterogeneous decomposition of methyl chloroform on various standard aluminosilica clay minerals as a potential tropospheric sink

    Directory of Open Access Journals (Sweden)

    S. Kutsuna

    2003-01-01

    Full Text Available Methyl chloroform (1,1,1-trichloroethane, CH3CCl3 was found to decompose heterogeneously on seven types of standard clay minerals (23 materials in dry air at 313 K in the laboratory. All reactions proceeded through the elimination of HCl; CH3CCl3 was converted quantitatively to CH2=CCl2. The activities of the clay minerals were compared via their pseudo-first-order reaction rate constants (k1. A positive correlation was observed between the k1 value and the specific surface area (S of clay minerals, where the S value was determined by means of the general Brunauer-Emmett-Teller (BET equation. The k1 value was anti-correlated with the value of n, which was a parameter of the general BET equation and related to the average pore size of the clay minerals, and correlated with the water content that can be removed easily from the clay minerals. The reaction required no special pretreatment of clay minerals, such as heating at high temperatures; hence, the reaction can be expected to occur in the environment. Photoillumination by wavelengths present in the troposphere did not accelerate the decomposition of CH3CCl3, but it induced heterogeneous photodecomposition of CH2=CCl2. The temperature dependence of k1, the adsorption equilibrium coefficient of CH3CCl3 and CH2=CCl2, and the surface reaction rate constant of CH3CCl3 were determined for an illite sample. The k1 value increased with increasing temperature. The amount of CH3CCl3 adsorbed on the illite during the reaction was proportional to the partial pressure of CH3CCl3. The reaction was sensitive to relative humidity and the k1 value decreased with increasing relative humidity. However, the reaction was found to proceed at a relative humidity of 22% at 313 K, although the k1 value was about one-twentieth of the value in non-humidified air. The conditions required for the reaction may be present in major desert regions of the world. A simple estimation indicates that the possible heterogeneous

  19. NA-NET numerical analysis net

    Energy Technology Data Exchange (ETDEWEB)

    Dongarra, J. [Tennessee Univ., Knoxville, TN (United States). Dept. of Computer Science]|[Oak Ridge National Lab., TN (United States); Rosener, B. [Tennessee Univ., Knoxville, TN (United States). Dept. of Computer Science

    1991-12-01

    This report describes a facility called NA-NET created to allow numerical analysts (na) an easy method of communicating with one another. The main advantage of the NA-NET is uniformity of addressing. All mail is addressed to the Internet host ``na-net.ornl.gov`` at Oak Ridge National Laboratory. Hence, members of the NA-NET do not need to remember complicated addresses or even where a member is currently located. As long as moving members change their e-mail address in the NA-NET everything works smoothly. The NA-NET system is currently located at Oak Ridge National Laboratory. It is running on the same machine that serves netlib. Netlib is a separate facility that distributes mathematical software via electronic mail. For more information on netlib consult, or send the one-line message ``send index`` to netlib{at}ornl.gov. The following report describes the current NA-NET system from both a user`s perspective and from an implementation perspective. Currently, there are over 2100 members in the NA-NET. An average of 110 mail messages pass through this facility daily.

  20. NA-NET numerical analysis net

    Energy Technology Data Exchange (ETDEWEB)

    Dongarra, J. (Tennessee Univ., Knoxville, TN (United States). Dept. of Computer Science Oak Ridge National Lab., TN (United States)); Rosener, B. (Tennessee Univ., Knoxville, TN (United States). Dept. of Computer Science)

    1991-12-01

    This report describes a facility called NA-NET created to allow numerical analysts (na) an easy method of communicating with one another. The main advantage of the NA-NET is uniformity of addressing. All mail is addressed to the Internet host na-net.ornl.gov'' at Oak Ridge National Laboratory. Hence, members of the NA-NET do not need to remember complicated addresses or even where a member is currently located. As long as moving members change their e-mail address in the NA-NET everything works smoothly. The NA-NET system is currently located at Oak Ridge National Laboratory. It is running on the same machine that serves netlib. Netlib is a separate facility that distributes mathematical software via electronic mail. For more information on netlib consult, or send the one-line message send index'' to netlib{at}ornl.gov. The following report describes the current NA-NET system from both a user's perspective and from an implementation perspective. Currently, there are over 2100 members in the NA-NET. An average of 110 mail messages pass through this facility daily.

  1. Bisulfite Conversion of DNA: Performance Comparison of Different Kits and Methylation Quantitation of Epigenetic Biomarkers that Have the Potential to Be Used in Non-Invasive Prenatal Testing

    Science.gov (United States)

    Leontiou, Chrysanthia A.; Hadjidaniel, Michael D.; Mina, Petros; Antoniou, Pavlos; Ioannides, Marios; Patsalis, Philippos C.

    2015-01-01

    Introduction Epigenetic alterations, including DNA methylation, play an important role in the regulation of gene expression. Several methods exist for evaluating DNA methylation, but bisulfite sequencing remains the gold standard by which base-pair resolution of CpG methylation is achieved. The challenge of the method is that the desired outcome (conversion of unmethylated cytosines) positively correlates with the undesired side effects (DNA degradation and inappropriate conversion), thus several commercial kits try to adjust a balance between the two. The aim of this study was to compare the performance of four bisulfite conversion kits [Premium Bisulfite kit (Diagenode), EpiTect Bisulfite kit (Qiagen), MethylEdge Bisulfite Conversion System (Promega) and BisulFlash DNA Modification kit (Epigentek)] regarding conversion efficiency, DNA degradation and conversion specificity. Methods Performance was tested by combining fully methylated and fully unmethylated λ-DNA controls in a series of spikes by means of Sanger sequencing (0%, 25%, 50% and 100% methylated spikes) and Next-Generation Sequencing (0%, 3%, 5%, 7%, 10%, 25%, 50% and 100% methylated spikes). We also studied the methylation status of two of our previously published differentially methylated regions (DMRs) at base resolution by using spikes of chorionic villus sample in whole blood. Results The kits studied showed different but comparable results regarding DNA degradation, conversion efficiency and conversion specificity. However, the best performance was observed with the MethylEdge Bisulfite Conversion System (Promega) followed by the Premium Bisulfite kit (Diagenode). The DMRs, EP6 and EP10, were confirmed to be hypermethylated in the CVS and hypomethylated in whole blood. Conclusion Our findings indicate that the MethylEdge Bisulfite Conversion System (Promega) was shown to have the best performance among the kits. In addition, the methylation level of two of our DMRs, EP6 and EP10, was confirmed

  2. Negative cross resistance mediated by co-treated bed nets: a potential means of restoring pyrethroid-susceptibility to malaria vectors.

    Directory of Open Access Journals (Sweden)

    Michael T White

    Full Text Available Insecticide-treated nets and indoor residual spray programs for malaria control are entirely dependent on pyrethroid insecticides. The ubiquitous exposure of Anopheles mosquitoes to this chemistry has selected for resistance in a number of populations. This threatens the sustainability of our most effective interventions but no operationally practicable way of resolving the problem currently exists. One innovative solution involves the co-application of a powerful chemosterilant (pyriproxyfen or PPF to bed nets that are usually treated only with pyrethroids. Resistant mosquitoes that are unaffected by the pyrethroid component of a PPF/pyrethroid co-treatment remain vulnerable to PPF. There is a differential impact of PPF on pyrethroid-resistant and susceptible mosquitoes that is modulated by the mosquito's behavioural response at co-treated surfaces. This imposes a specific fitness cost on pyrethroid-resistant phenotypes and can reverse selection. The concept is demonstrated using a mathematical model.

  3. Net Ecosystem Carbon Flux

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — Net Ecosystem Carbon Flux is defined as the year-over-year change in Total Ecosystem Carbon Stock, or the net rate of carbon exchange between an ecosystem and the...

  4. Human Papillomavirus DNA methylation as a biomarker for cervical precancer: Consistency across 12 genotypes and potential impact on management of HPV-positive women.

    Science.gov (United States)

    Clarke, Megan A; Gradíssimo, Ana; Schiffman, Mark; Lam, Jessica; Sollecito, Christopher C; Fetterman, Barbara; Lorey, Thomas; Poitras, Nancy E; Raine-Bennett, Tina; Castle, Philip E; Wentzensen, Nicolas; Burk, Robert D

    2018-02-02

    Human papillomavirus (HPV) DNA methylation testing is a promising triage option for women testing HPV-positive during cervical cancer screening. However, the extent to which methylation indicates precancer for all 12 carcinogenic HPV types has not been evaluated. In this nested case-control study, we tested up to 30 cases of precancer (CIN3/AIS) and 30 normal controls for each carcinogenic type (single infections with 16/18/31/33/35/39/45/51/52/56/58/59). Next-generation bisulfite sequencing was performed on CpG sites within the L1 and L2 genes. We calculated differences in methylation, odds ratios, and areas under the curve (AUC). Using a fixed sensitivity of 80%, we evaluated the specificity and the risk of CIN3/AIS for best performing CpG sites, and compared the performance of an explorative multi-type methylation assay with current triage strategies. Methylation was positively associated with CIN3/AIS across all 12 types. AUCs for the top sites ranged from 0.71 (HPV51 and HPV56) to 0.86 (HPV18). A combined 12-type methylation assay had the highest Youden's index (0.46), compared with cytology (0.31) and a 5-type methylation assay including only previously described types (0.26).  The 12-type methylation assay had higher sensitivity (80% vs. 76.6%) and lower test positivity compared to cytology (38.5% vs. 48.7%). The risk of CIN3/AIS was highest for methylation positives and lowest for cytology- or HPV16/18-positives. HPV DNA methylation is a general phenomenon marking the transition from HPV infection to precancer for all 12 carcinogenic types. Development of a combined multi-type methylation assay may serve as a triage test for HPV-positive women. Copyright ©2018, American Association for Cancer Research.

  5. Nanoliposomes for encapsulation and delivery of the potential antitumoral methyl 6-methoxy-3-(4-methoxyphenyl)-1 H-indole-2-carboxylate

    Science.gov (United States)

    Abreu, Ana S.; Castanheira, Elisabete Ms; Queiroz, Maria-João Rp; Ferreira, Paula Mt; Vale-Silva, Luís A.; Pinto, Eugénia

    2011-08-01

    A potential antitumoral fluorescent indole derivative, methyl 6-methoxy-3-(4-methoxyphenyl)-1 H-indole-2-carboxylate, was evaluated for the in vitro cell growth inhibition on three human tumor cell lines, MCF-7 (breast adenocarcinoma), A375-C5 (melanoma), and NCI-H460 (non-small cell lung cancer), after a continuous exposure of 48 h, exhibiting very low GI50 values for all the cell lines tested (0.25 to 0.33 μM). This compound was encapsulated in different nanosized liposome formulations, containing egg lecithin (Egg-PC), dipalmitoyl phosphatidylcholine (DPPC), dipalmitoyl phosphatidylglycerol (DPPG), DSPC, cholesterol, dihexadecyl phosphate, and DSPE-PEG. Dynamic light scattering measurements showed that nanoliposomes with the encapsulated compound are generally monodisperse and with hydrodynamic diameters lower than 120 nm, good stability and zeta potential values lower than -18 mV. Dialysis experiments allowed to monitor compound diffusion through the lipid membrane, from DPPC/DPPG donor liposomes to NBD-labelled lipid/DPPC/DPPG acceptor liposomes.

  6. Enhanced phytoremediation potential of polychlorinated biphenyl contaminated soil from e-waste recycling area in the presence of randomly methylated-{beta}-cyclodextrins

    Energy Technology Data Exchange (ETDEWEB)

    Shen Chaofeng [Institute of Environmental Science and Technology, Zhejiang University, Hangzhou 310029 (China); MOE Key Lab of Environmental Remediation and Ecosystem Health, College of Environmental and Resources Science, Zhejiang University, Hangzhou 310029 (China); Tang Xianjin; Cheema, Sardar Alam; Zhang Congkai; Khan, Muhammad Imran; Liang Fang; Chen Xincai; Zhu Youfeng [Institute of Environmental Science and Technology, Zhejiang University, Hangzhou 310029 (China); Lin Qi, E-mail: linqi@zju.edu.cn [Institute of Environmental Science and Technology, Zhejiang University, Hangzhou 310029 (China); Chen, Yingxu [Institute of Environmental Science and Technology, Zhejiang University, Hangzhou 310029 (China)

    2009-12-30

    The crude recycling of electronic and electric waste (e-waste) is now creating soil pollution problems with organic compounds such as polychlorinated biphenyls (PCBs). The present study aimed to compare the phytoremediation potential of four plant species (rice, alfalfa, ryegrass and tall fescue) for PCBs contaminated soil from Taizhou city, one of the largest e-waste recycling centers in China. In addition, the enhanced effects of randomly methylated-{beta}-cyclodextrins (RAMEB) on PCBs phytoremediation potential were evaluated. Higher PCBs removal percentages of 25.6-28.5% in rhizosphere soil were observed after 120 days, compared with those of the non-rhizosphere (10.4-16.9%) and unplanted controls (7.3%). The average PCBs removal percentages of four plant species increased from 26.9% to 37.1% in the rhizosphere soil with addition of RAMEB. Meanwhile, relatively high microbial counts and dehydrogenase activity were detected in planted soils and a stimulatory effect by RAMEB addition was found. The present study indicated that all the plant candidates were feasible for phytoremediation of PCBs contaminated soil from the e-waste recycling area, and tall fescue with RAMEB amendment seemed as a promising remediation strategy. High PCBs removal percentage was due to the increased PCBs bioavailability as well as biostimulation of microbial communities after plantation and RAMEB addition.

  7. Concentrations and potential health risks of methyl tertiary-butyl ether (MTBE) in air and drinking water from Nanning, South China.

    Science.gov (United States)

    Zhang, Li'e; Qin, Jian; Zhang, Zhiyong; Li, Qin; Huang, Jiongli; Peng, Xiaowu; Qing, Li; Liang, Guiqiang; Liang, Linhan; Huang, Yuman; Yang, Xiaobo; Zou, Yunfeng

    2016-01-15

    Levels of methyl tertiary-butyl ether (MTBE) in occupational air, ambient air, and drinking water in Nanning, South China, were investigated, and then their potential health risks to occupational workers and the general public were evaluated. Results show that the MTBE concentration in occupational air from 13 service stations was significantly higher than that in ambient air from residential areas (pwater samples from household taps yielded detectable MTBE in the range of 0.04-0.33 μg/L, which is below the US drinking water standard of 20-40 μg/L. The non-carcinogenic risk of MTBE from air inhalation may be negligible because the calculated hazard quotient was less than 1. The mean MTBE lifetime cancer risk was within the acceptable limit of 1 × 10(-6) to 1 × 10(-4), but the lifetime cancer risk of refueling workers in the urban service station at the 95th percentile slightly exceeded the maximum acceptable carcinogen risk (1 × 10(-4)), indicating the potential carcinogenic health effects on the population highly exposed to MTBE in this region. The hazard index and carcinogenic risk of MTBE in drinking water were significantly lower than the safe limit of US Environmental Protection Agency, suggesting that drinking water unlikely poses significant health risks to the residents in Nanning. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Atmospheric lifetimes and ozone depletion potentials of methyl bromide (CH3Br) and dibromomethane (CH2Br2)

    Energy Technology Data Exchange (ETDEWEB)

    Mellouki, A.; Talukdar, R.K.; Schmoltner, A.; Gierczak, T.; Mills, M.J.; Solomon, S.; Ravishankara, A.R. (NOAA, Boulder, CO (United States))

    1992-10-01

    The rate coefficients for the reactions of OH radical with CH3Br and CH2Br2 were measured as functions of temperature using the laser photolysis - laser induced fluorescence method. This data was incorporated into a semiempirical model (Solomon et al., 1992) and a 2D model to calculate the steady-state ozone depletion potentials (ODP) and atmospheri lifetimes, tau, with greatly improved accuracy as compared to earlier studies. The calculated ODPs and tau are 0.65 and 1.7 years and 0.17 and 0.41 years for CH3Br and CH2Br2, respectively, using the semiempirical model. These lifetimes agree well with those calculated using a 2D model. This study better quantifies the ODPs and tau of these species which are needed inputs for discussion of possible regulation of human emissions currently under international considerations. 29 refs.

  9. Professional Enterprise NET

    CERN Document Server

    Arking, Jon

    2010-01-01

    Comprehensive coverage to help experienced .NET developers create flexible, extensible enterprise application code If you're an experienced Microsoft .NET developer, you'll find in this book a road map to the latest enterprise development methodologies. It covers the tools you will use in addition to Visual Studio, including Spring.NET and nUnit, and applies to development with ASP.NET, C#, VB, Office (VBA), and database. You will find comprehensive coverage of the tools and practices that professional .NET developers need to master in order to build enterprise more flexible, testable, and ext

  10. Synthesis and preliminary in vitro evaluation of a new memantine derivative 1-amino-3-[{sup 18}F]fluoromethyl-5-methyl-adamantane: a potential ligand for mapping the N-methyl-D-aspartate receptor complex

    Energy Technology Data Exchange (ETDEWEB)

    Samnick, S.; Ametamey, S.; Schubiger, P.A. [Paul Scherrer Institute, Villigen (Switzerland); Gold, M.R. [Merz and Co., GmbH, Reinheim (Germany)

    1997-03-01

    The new memantine derivative 1-amino-3-[{sup 18}F]fluoromethyl-5-methyl-adamantane ({sup 18}F-MEM) was prepared in a two-step reaction sequence for evaluation as a PET tracer. This involves the no-carrier-added nucleophilic radiofluorination of 1-[N-(tert-butyloxy)-carbamoyl]-3-(toluenesulfonyl)methyl-5-methyl -adamantane with K{sup 18}F/Kryptofix 2.2.2 in DMSO and the subsequent deprotection of the resulting {sup 18}F-BOC-MEM by addition of aqueous HCl. {sup 18}F-MEM was obtained after purification by reversed phase HPLC in 22{+-}7% radiochemical yield (decay corrected to EOB) with a radiochemical purity > 99% and a total synthesis time of 100 min. {sup 18}F-MEM is stable up to 6 h in aqueous solution at room temperature and revealed appropriate lipophilicity for good diffusion through the blood-brain-barrier. In vitro studies with the non-radioactive analog, 1-amino-3-fluoromethyl-5-methyl-adamantane ({sup 18}F-MEM) indicated that this compound binds selectively to the phencyclidine (PCP) binding site within the NMDA receptor complex. (author).

  11. Facile synthesis of fluoro, methoxy, and methyl substituted ferrocene-based urea complexes as potential therapeutic agents.

    Science.gov (United States)

    Asghar, Faiza; Badshah, Amin; Lal, Bhajan; Zubair, Shumaila; Fatima, Saira; Butler, Ian S

    2017-06-01

    In the present work, the synthesis, characterization (FT-IR, multinuclear ((1)H and (13)C) NMR, AAS, Raman, and elemental analysis), DNA binding (cyclic voltammetry, UV-Vis spectroscopy and viscometry), and in vitro biological assessment of nine new ferrocene-based ureas are reported. The desulphurization of ferrocenyl thioureas to the corresponding oxo analogues using aqueous sodium hydroxide and mercuric chloride led to the ferrocenyl ureas (F1-F9) in high yields. The DNA binding studies performed by cyclic voltammetry and UV-Vis spectroscopy produced results that are in close agreement with one another for the binding constants (K) and an electrostatic mode of interaction was observed. The nature and the extent of interaction with DNA was further investigated by viscometry. The DFT/B3LYP method was used to determine the charge distribution and HOMO/LUMO energies of the optimized structure. The DFT calculated HOMO and LUMO energies correlate well with the experimentally determined redox potential values. The synthesized ferrocenyl derivatives exhibited good scavenging activity against 1,1-diphenyl-2-picrylhydrazyl radical (DPPH). These complexes were also scanned for their in vitro cytotoxicity against human carcinoma cell line THP-1 (leukemia cells). The results showed a moderate level of cytotoxicity against the subjected cancer cell line as compared with the standard chemotherapeutic drug (cisplatin). Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Evolution of DNA Methylation across Insects

    Science.gov (United States)

    Vogel, Kevin J.; Moore, Allen J.; Schmitz, Robert J.

    2017-01-01

    DNA methylation contributes to gene and transcriptional regulation in eukaryotes, and therefore has been hypothesized to facilitate the evolution of plastic traits such as sociality in insects. However, DNA methylation is sparsely studied in insects. Therefore, we documented patterns of DNA methylation across a wide diversity of insects. We predicted that underlying enzymatic machinery is concordant with patterns of DNA methylation. Finally, given the suggestion that DNA methylation facilitated social evolution in Hymenoptera, we tested the hypothesis that the DNA methylation system will be associated with presence/absence of sociality among other insect orders. We found DNA methylation to be widespread, detected in all orders examined except Diptera (flies). Whole genome bisulfite sequencing showed that orders differed in levels of DNA methylation. Hymenopteran (ants, bees, wasps and sawflies) had some of the lowest levels, including several potential losses. Blattodea (cockroaches and termites) show all possible patterns, including a potential loss of DNA methylation in a eusocial species whereas solitary species had the highest levels. Species with DNA methylation do not always possess the typical enzymatic machinery. We identified a gene duplication event in the maintenance DNA methyltransferase 1 (DNMT1) that is shared by some Hymenoptera, and paralogs have experienced divergent, nonneutral evolution. This diversity and nonneutral evolution of underlying machinery suggests alternative DNA methylation pathways may exist. Phylogenetically corrected comparisons revealed no evidence that supports evolutionary association between sociality and DNA methylation. Future functional studies will be required to advance our understanding of DNA methylation in insects. PMID:28025279

  13. Electronic transport in methylated fragments of DNA

    Science.gov (United States)

    de Almeida, M. L.; Oliveira, J. I. N.; Lima Neto, J. X.; Gomes, C. E. M.; Fulco, U. L.; Albuquerque, E. L.; Freire, V. N.; Caetano, E. W. S.; de Moura, F. A. B. F.; Lyra, M. L.

    2015-11-01

    We investigate the electronic transport properties of methylated deoxyribonucleic-acid (DNA) strands, a biological system in which methyl groups are added to DNA (a major epigenetic modification in gene expression), sandwiched between two metallic platinum electrodes. Our theoretical simulations apply an effective Hamiltonian based on a tight-binding model to obtain current-voltage curves related to the non-methylated/methylated DNA strands. The results suggest potential applications in the development of novel biosensors for molecular diagnostics.

  14. Electronic transport in methylated fragments of DNA

    Energy Technology Data Exchange (ETDEWEB)

    Almeida, M. L. de; Oliveira, J. I. N.; Lima Neto, J. X.; Gomes, C. E. M.; Fulco, U. L., E-mail: umbertofulco@gmail.com; Albuquerque, E. L. [Departamento de Biofísica e Farmacologia, Universidade Federal do Rio Grande do Norte, 59072-970 Natal-RN (Brazil); Freire, V. N. [Departamento de Física, Universidade Federal do Ceará, 60455-760 Fortaleza, CE (Brazil); Caetano, E. W. S. [Instituto Federal de Educação, Ciência e Tecnologia do Ceará, 60040-531 Fortaleza, CE (Brazil); Moura, F. A. B. F. de; Lyra, M. L. [Instituto de Física, Universidade Federal de Alagoas, 57072-900 Maceió-AL (Brazil)

    2015-11-16

    We investigate the electronic transport properties of methylated deoxyribonucleic-acid (DNA) strands, a biological system in which methyl groups are added to DNA (a major epigenetic modification in gene expression), sandwiched between two metallic platinum electrodes. Our theoretical simulations apply an effective Hamiltonian based on a tight-binding model to obtain current-voltage curves related to the non-methylated/methylated DNA strands. The results suggest potential applications in the development of novel biosensors for molecular diagnostics.

  15. Hydroxy-directed diastereoselective installation of a methyl group on indalone models and spiroketal potential precursors for the bafilomycin A(1) C15-C25 subunit.

    Science.gov (United States)

    Poupon, Jean-Christophe; Lopez, Roman; Prunet, Joëlle; Férézou, Jean-Pierre

    2002-04-05

    Current efforts devoted to the synthesis of Bafilomycin A(1) led us to investigate a synthetic route through a spiroketal intermediate for the construction of the C15-C25 subunit. Preliminary studies for the diastereoselective installation of the methyl-16 cis with respect to the vicinal OH-15 group through radical opening of either siloxafuran intermediate 7 or cyclopropyl compounds 9 and 13 have been carried out using model compounds derived from commercial Indalone 6. In each case the expected "cis" diastereoisomer was obtained in good to excellent yield. Application of these results to Bafilomycin A(1) synthon led to the opposite "trans" stereoselectivity when alpha-carboxy- or alpha-keto-substituted spiroketals 4 or 19 were used. However, the expected potential intermediate has been obtained from the alpha-hydroxymethyl cyclopropanated synthon 21. A Barton-Motherwell xanthate radical deoxygenation-cylopropane opening methodology, followed by a hydroboration-oxidation of the exovinylic intermediate, delivered the expected product 22cis in high yield and excellent stereoselectivity.

  16. Modulation of the activity of N-methyl-d-aspartate receptors as a novel treatment option for depression: current clinical evidence and therapeutic potential of rapastinel (GLYX-13).

    Science.gov (United States)

    Vasilescu, Andrei-Nicolae; Schweinfurth, Nina; Borgwardt, Stefan; Gass, Peter; Lang, Undine E; Inta, Dragos; Eckart, Sarah

    2017-01-01

    Classical monoaminergic antidepressants show several disadvantages, such as protracted onset of therapeutic action. Conversely, the fast and sustained antidepressant effect of the N-methyl-d-aspartate receptor (NMDAR) antagonist ketamine raises vast interest in understanding the role of the glutamate system in mood disorders. Indeed, numerous data support the existence of glutamatergic dysfunction in major depressive disorder (MDD). Drawback to this short-latency therapy is its side effect profile, especially the psychotomimetic action, which seriously hampers the common and widespread clinical use of ketamine. Therefore, there is a substantial need for alternative glutamatergic antidepressants with milder side effects. In this article, we review evidence that implicates NMDARs in the prospective treatment of MDD with focus on rapastinel (formerly known as GLYX-13), a novel synthetic NMDAR modulator with fast antidepressant effect, which acts by enhancing NMDAR function as opposed to blocking it. We summarize and discuss current clinical and animal studies regarding the therapeutic potential of rapastinel not only in MDD but also in other psychiatric disorders, such as obsessive-compulsive disorder and posttraumatic stress disorder. Additionally, we discuss current data concerning the molecular mechanisms underlying the antidepressant effect of rapastinel, highlighting common aspects as well as differences to ketamine. In 2016, rapastinel received the Breakthrough Therapy designation for the treatment of MDD from the US Food and Drug Administration, representing one of the most promising alternative antidepressants under current investigation.

  17. Continuous hydrogenation of ethyl levulinate to γ-valerolactone and 2-methyl tetrahydrofuran over alumina doped Cu/SiO2 catalyst: the potential of commercialization

    Science.gov (United States)

    Zheng, Junlin; Zhu, Junhua; Xu, Xuan; Wang, Wanmin; Li, Jiwen; Zhao, Yan; Tang, Kangjian; Song, Qi; Qi, Xiaolan; Kong, Dejin; Tang, Yi

    2016-01-01

    Hydrogenation of levulinic acid (LA) and its esters to produce γ-valerolactone (GVL) and 2-methyl tetrahydrofuran (2-MTHF) is a key step for the utilization of cellulose derived LA. Aiming to develop a commercially feasible base metal catalyst for the production of GVL from LA, with satisfactory activity, selectivity, and stability, Al2O3 doped Cu/SiO2 and Cu/SiO2 catalysts were fabricated by co-precipitation routes in parallel. The diverse physio-chemical properties of these two catalysts were characterized by XRD, TEM, dissociative N2O chemisorptions, and Py-IR methods. The catalytic properties of these two catalysts were systematically assessed in the continuous hydrogenation of ethyl levulinate (EL) in a fixed-bed reactor. The effect of acidic property of the SiO2 substrate on the catalytic properties was investigated. To justify the potential of its commercialization, significant attention was paid on the initial activity, proper operation window, by-products control, selectivity, and stability of the catalyst. The effect of reaction conditions, such as temperature and pressure, on the performance of the catalyst was also thoroughly studied. The development of alumina doped Cu/SiO2 catalyst strengthened the value-chain from cellulose to industrially important chemicals via LA and GVL. PMID:27377401

  18. Evaluation of the potential of volatile organic compound (di-methyl benzene) removal using adsorption on natural minerals compared to commercial oxides

    Energy Technology Data Exchange (ETDEWEB)

    Zaitan, Hicham, E-mail: hicham.zaitan@usmba.ac.ma [Laboratory LCMC, Faculty of Sciences and Techniques, University Sidi Mohamed BenAbdellah, B.P. 2202, Fez (Morocco); Korrir, Abdelhamid; Chafik, Tarik [Laboratory LGCVR, Faculty of Sciences and Techniques, University Abdelmalek Essaadi, B.P. 416, Tangier (Morocco); Bianchi, Daniel [Institut de Recherche sur la Catalyse et l’Environnement de Lyon (IRCELYON), UMR 5256 CNRS, University Claude Bernard Lyon I, Bat. Chevreul, 43 Boulevard du 11 Novembre 1918, 69622 Villeurbanne (France)

    2013-11-15

    Highlights: • The adsorption of dMB on natural minerals and commercial oxides was evaluated. • The adsorption capacities were discussed considering the adsorbents cost and the bed size. • The adsorption capacity of bentonite is higher than other adsorbents. • Langmuir model provide best correlation of the experimental data. • The isotherms data allow determination of isosteric heat of adsorption. -- Abstract: This study is dedicated to the investigation of the potential of volatile organic compounds (VOC) adsorption over low cost natural minerals (bentonite and diatomite). The performances of these solids, in terms of adsorption/desorption properties, were compared to commercial adsorbents, such as silica, alumina and titanium dioxide. The solids were first characterized by different physico-chemical methods and di-methyl benzene (dMB) was selected as model VOC pollutant for the investigation of adsorptive characteristics. The experiments were carried out with a fixed bed reactor under dynamic conditions using Fourier Transform InfraRed spectrometer to measure the evolution of dMB concentrations in the gaseous stream at the outlet of the reactor. The measured breakthrough curves yields to adsorbed amounts at saturation that has been used to obtain adsorption isotherms. The latters were used for determination of the heat involved in the adsorption process and estimation of its values using the isosteric method. Furthermore, the performances of the studied materials were compared considering the adsorption efficiency/cost ratio.

  19. Roles of N-methyl-d-aspartate receptors during the sensory stimulation-evoked field potential responses in mouse cerebellar cortical molecular layer.

    Science.gov (United States)

    Xu, Yin-Hua; Zhang, Guang-Jian; Zhao, Jing-Tong; Chu, Chun-Ping; Li, Yu-Zi; Qiu, De-Lai

    2017-11-01

    The functions of N-methyl-d-aspartate receptors (NMDARs) in cerebellar cortex have been widely studied under in vitro condition, but their roles during the sensory stimulation-evoked responses in the cerebellar cortical molecular layer in living animals are currently unclear. We here investigated the roles of NMDARs during the air-puff stimulation on ipsilateral whisker pad-evoked field potential responses in cerebellar cortical molecular layer in urethane-anesthetized mice by electrophysiological recording and pharmacological methods. Our results showed that cerebellar surface administration of NMDA induced a dose-dependent decrease in amplitude of the facial stimulation-evoked inhibitory responses (P1) in the molecular layer, accompanied with decreases in decay time, half-width and area under curve (AUC) of P1. The IC50 of NMDA induced inhibition in amplitude of P1 was 46.5μM. In addition, application of NMDA induced significant increases in the decay time, half-width and AUC values of the facial stimulation-evoked excitatory responses (N1) in the molecular layer. Application of an NMDAR blocker, D-APV (250μM) abolished the facial stimulation-evoked P1 in the molecular layer. These results suggested that NMDARs play a critical role during the sensory information processing in cerebellar cortical molecular layer in vivo in mice. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Atmospheric Chemistry of Six Methyl-perfluoroheptene-ethers Used as Heat Transfer Fluid Replacement Compounds: Measured OH Radical Reaction Rate Coefficients, Atmospheric Lifetimes, and Global Warming Potentials

    Science.gov (United States)

    Jubb, A. M.; Gierczak, T.; Baasandorj, M.; Waterland, R. L.; Burkholder, J. B.

    2013-12-01

    Mixtures of methyl-perfluoroheptene-ethers (C7F13OCH3, MPHEs) are currently in use as a replacement for perfluorinated alkane (PFC) and polyether mixtures (both persistent greenhouse gases with atmospheric lifetimes >1000 years) used as heat transfer fluids. Currently, the atmospheric fate of the MPHE isomers are not well characterized, however, reaction with the OH radical is expected to be a dominant tropospheric loss process for these compounds. In order to assess the atmospheric lifetimes and environmental implications of MPHE use, rate coefficients for MPHE isomers' reaction with OH radicals are desired. In the work presented here, rate coefficients, k, for the gas-phase reaction of the OH radical with six MPHEs commonly used in commercial mixtures (isomers and stereoisomers) and their deuterated analogs (d3-MPHE) were determined at 296 K using a relative rate method with combined gas-chromatography/IR spectroscopy detection. A range of OH rate coefficient values was observed, up to a factor of 20× different, between the MPHE isomers with the (E)-stereoisomers exhibiting the greatest reactivity. The measured OH reaction rate coefficients for the d3-MPHE isomers were lower than the observed MPHE values although a large range of k values between isomers was still observed. The reduction in reactivity with deuteration signifies that the MPHE + OH reaction proceeds via both addition to the olefinic C=C bond and H-abstraction from the methyl ester group. OH addition to the C=C bond was determined to be the primary reaction channel. Atmospheric lifetimes with respect to the OH reaction for the six MPHE isomers were found to be in the range of days to months. The short lifetimes indicate that MPHE use will primarily impact tropospheric local and regional air quality. A MPHE atmospheric degradation mechanism will be presented. As part of this work, radiative efficiencies and global warming potentials (GWPs) for the MPHE isomers were estimated based on measured

  1. WaveNet

    Science.gov (United States)

    2015-10-30

    Coastal Inlets Research Program WaveNet WaveNet is a web-based, Graphical-User-Interface ( GUI ) data management tool developed for Corps coastal...generates tabular and graphical information for project planning and design documents. The WaveNet is a web-based GUI designed to provide users with a...data from different sources, and employs a combination of Fortran, Python and Matlab codes to process and analyze data for USACE applications

  2. Coloured Petri Nets

    DEFF Research Database (Denmark)

    Jensen, Kurt

    1991-01-01

    This paper describes how Coloured Petri Nets (CP-nets) have been developed — from being a promising theoretical model to being a full-fledged language for the design, specification, simulation, validation and implementation of large software systems (and other systems in which human beings and...... use of CP-nets — because it means that the function representation and the translations (which are a bit mathematically complex) no longer are parts of the basic definition of CP-nets. Instead they are parts of the invariant method (which anyway demands considerable mathematical skills...

  3. Game Coloured Petri Nets

    DEFF Research Database (Denmark)

    Westergaard, Michael

    2006-01-01

    This paper introduces the notion of game coloured Petri nets. This allows the modeler to explicitly model what parts of the model comprise the modeled system and what parts are the environment of the modeled system. We give the formal definition of game coloured Petri nets, a means of reachability...... analysis of this net class, and an application of game coloured Petri nets to automatically generate easy-to-understand visualizations of the model by exploiting the knowledge that some parts of the model are not interesting from a visualization perspective (i.e. they are part of the environment...

  4. Programming NET Web Services

    CERN Document Server

    Ferrara, Alex

    2007-01-01

    Web services are poised to become a key technology for a wide range of Internet-enabled applications, spanning everything from straight B2B systems to mobile devices and proprietary in-house software. While there are several tools and platforms that can be used for building web services, developers are finding a powerful tool in Microsoft's .NET Framework and Visual Studio .NET. Designed from scratch to support the development of web services, the .NET Framework simplifies the process--programmers find that tasks that took an hour using the SOAP Toolkit take just minutes. Programming .NET

  5. Annotating Coloured Petri Nets

    DEFF Research Database (Denmark)

    Lindstrøm, Bo; Wells, Lisa Marie

    2002-01-01

    -net. An example of such auxiliary information is a counter which is associated with a token to be able to do performance analysis. Modifying colour sets and arc inscriptions in a CP-net to support a specific use may lead to creation of several slightly different CP-nets – only to support the different uses...... a method which makes it possible to associate auxiliary information, called annotations, with tokens without modifying the colour sets of the CP-net. Annotations are pieces of information that are not essential for determining the behaviour of the system being modelled, but are rather added to support...

  6. Potential roles of DNA methylation in the initiation and establishment of replicative senescence revealed by array-based methylome and transcriptome analyses.

    Directory of Open Access Journals (Sweden)

    Mizuho Sakaki

    Full Text Available Cellular senescence is classified into two groups: replicative and premature senescence. Gene expression and epigenetic changes are reported to differ between these two groups and cell types. Normal human diploid fibroblast TIG-3 cells have often been used in cellular senescence research; however, their epigenetic profiles are still not fully understood. To elucidate how cellular senescence is epigenetically regulated in TIG-3 cells, we analyzed the gene expression and DNA methylation profiles of three types of senescent cells, namely, replicatively senescent, ras-induced senescent (RIS, and non-permissive temperature-induced senescent SVts8 cells, using gene expression and DNA methylation microarrays. The expression of genes involved in the cell cycle and immune response was commonly either down- or up-regulated in the three types of senescent cells, respectively. The altered DNA methylation patterns were observed in replicatively senescent cells, but not in prematurely senescent cells. Interestingly, hypomethylated CpG sites detected on non-CpG island regions ("open sea" were enriched in immune response-related genes that had non-CpG island promoters. The integrated analysis of gene expression and methylation in replicatively senescent cells demonstrated that differentially expressed 867 genes, including cell cycle- and immune response-related genes, were associated with DNA methylation changes in CpG sites close to the transcription start sites (TSSs. Furthermore, several miRNAs regulated in part through DNA methylation were found to affect the expression of their targeted genes. Taken together, these results indicate that the epigenetic changes of DNA methylation regulate the expression of a certain portion of genes and partly contribute to the introduction and establishment of replicative senescence.

  7. Net zero water

    CSIR Research Space (South Africa)

    Lindeque, M

    2013-01-01

    Full Text Available Is it possible to develop a building that uses a net zero amount of water? In recent years it has become evident that it is possible to have buildings that use a net zero amount of electricity. This is possible when the building is taken off...

  8. SolNet

    DEFF Research Database (Denmark)

    Jordan, Ulrike; Vajen, Klaus; Bales, Chris

    2014-01-01

    SolNet, founded in 2006, is the first coordinated International PhD education program on Solar Thermal Engineering. The SolNet network is coordinated by the Institute of Thermal Engineering at Kassel University, Germany. The network offers PhD courses on solar heating and cooling, conference...

  9. Kunstige neurale net

    DEFF Research Database (Denmark)

    Hørning, Annette

    1994-01-01

    Artiklen beskæftiger sig med muligheden for at anvende kunstige neurale net i forbindelse med datamatisk procession af naturligt sprog, specielt automatisk talegenkendelse.......Artiklen beskæftiger sig med muligheden for at anvende kunstige neurale net i forbindelse med datamatisk procession af naturligt sprog, specielt automatisk talegenkendelse....

  10. Modulation of the activity of N-methyl-D-aspartate receptors as a novel treatment option for depression: current clinical evidence and therapeutic potential of rapastinel (GLYX-13

    Directory of Open Access Journals (Sweden)

    Vasilescu AN

    2017-03-01

    Full Text Available Andrei-Nicolae Vasilescu,1,* Nina Schweinfurth,2,* Stefan Borgwardt,2,* Peter Gass,1 Undine E Lang,2,* Dragos Inta,1,2,* Sarah Eckart2,* 1Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany; 2Department of Psychiatry (Universitäre Psychiatrische Kliniken, University of Basel, Basel, Switzerland *These authors contributed equally to this work Abstract: Classical monoaminergic antidepressants show several disadvantages, such as protracted onset of therapeutic action. Conversely, the fast and sustained antidepressant effect of the N-methyl-d-aspartate receptor (NMDAR antagonist ketamine raises vast interest in understanding the role of the glutamate system in mood disorders. Indeed, numerous data support the existence of glutamatergic dysfunction in major depressive disorder (MDD. Drawback to this short-latency therapy is its side effect profile, especially the psychotomimetic action, which seriously hampers the common and widespread clinical use of ketamine. Therefore, there is a substantial need for alternative glutamatergic antidepressants with milder side effects. In this article, we review evidence that implicates NMDARs in the prospective treatment of MDD with focus on rapastinel (formerly known as GLYX-13, a novel synthetic NMDAR modulator with fast antidepressant effect, which acts by enhancing NMDAR function as opposed to blocking it. We summarize and discuss current clinical and animal studies regarding the therapeutic potential of rapastinel not only in MDD but also in other psychiatric disorders, such as obsessive–compulsive disorder and posttraumatic stress disorder. Additionally, we discuss current data concerning the molecular mechanisms underlying the antidepressant effect of rapastinel, highlighting common aspects as well as differences to ketamine. In 2016, rapastinel received the Breakthrough Therapy designation for the treatment

  11. Low temperature kinetics and theoretical studies of the reaction CN + CH3NH2: a potential source of cyanamide and methyl cyanamide in the interstellar medium.

    Science.gov (United States)

    Sleiman, Chantal; El Dib, Gisèle; Rosi, Marzio; Skouteris, Dimitrios; Balucani, Nadia; Canosa, André

    2017-10-30

    The reaction between cyano radicals (which are ubiquitous in interstellar clouds) and methylamine (a molecule detected in various interstellar sources) has been investigated in a synergistic experimental and theoretical study. The reaction has been found to be very fast in the entire range of temperatures investigated (23-297 K) by using a CRESU apparatus coupled to pulsed laser photolysis - laser induced fluorescence. The global experimental rate coefficient is given by In addition, dedicated electronic structure calculations of the underlying potential energy surface have been performed, together with capture theory and RRKM calculations. The experimental data have been interpreted in the light of the theoretical calculations and the product branching ratio has been established. According to the present study, in the range of temperatures investigated the title reaction is an efficient interstellar route of formation of cyanamide, NH2CN, another interstellar species. The second most important channel is the one leading to methyl cyanamide, CH3NHCN (an isomer of aminoacetonitrile), via a CN/H exchange mechanism with a yield of 12% of the global reaction in the entire range of temperatures explored. For a possible inclusion in future astrochemical models we suggest, by referring to the usual expression the following values: α = 3.68 × 10(-12) cm(3) molec(-1) s(-1), β = -1.80, γ = 7.79 K for the channel leading to NH2CN + CH3; α = 5.05 × 10(-13) cm(3) molec(-1) s(-1), β = -1.82, γ = 7.93 K for the channel leading to CH3NHCN + H.

  12. 1-Methyl-D-tryptophan potentiates TGF-β-induced epithelial-mesenchymal transition in T24 human bladder cancer cells.

    Science.gov (United States)

    Brito, Rodrigo Barbosa Oliveira; Malta, Camila Soares; Souza, Diego Mota; Matheus, Luiz Henrique Gomes; Matos, Yves Silva Teles; Silva, Chrisna Souza; Ferreira, Janaína Mendes; Nunes, Valeria Sutti; França, Cristiane Miranda; Dellê, Humberto

    2015-01-01

    Immune escape and metastasis are the hallmarks of several types of cancer including bladder cancer. One of the mechanisms involved in these processes has been linked to indoleamine 2,3-dioxygenase (IDO). Although IDO is classically recognized for its immunomodulatory property, it has presented nonimmunological effects in some tumors. TGF-β1 is believed to contribute to carcinoma development by modulating immunossupressive molecules, including IDO. In addition, TGF-β1 induces the epithelial-mesenchymal transition (EMT), which is a critical step in the tumor invasiveness and metastasis. We investigated the role of MT and IDO modulation in the induction of EMT by TGF-β1 in T24 human bladder carcinoma cells. When T24 cells were incubated with the IDO inhibitor (MT, 1-methyl-D-tryptophan), with TGF-β1, and with MT+TGF-β1, a significant decrease of IDO expression and activity was observed. In addition, downregulation of e-cadherin and upregulation of n-cadherin and EMT transcription factors were induced by the treatments, confirming the induction of EMT. siRNA-mediated knockdown of IDO decreased e-cadherin expression, but had no effect on EMT transcription factors. In the scratch-wound assay, the heightened migration process was intensified when the cells were incubated with MT+TGF-β1. These effects were associated with a robust inhibition of Akt activation. After inoculation of T24 cells under the kidney capsule of Balb/c nude, the cells were positive for IDO in the center of the cell infiltrate, being negative in the periphery, where EMT is high. In conclusion, inhibition of IDO by TGF-β1 and MT is associated with EMT in T24 human bladder carcinoma cells. MT has potentiating effect in TGF-β1-induced EMT, independently of IDO. This nonimmunological effect of MT should be considered if IDO is the target to avoid immune escape in bladder cancer.

  13. 1-Methyl-D-tryptophan potentiates TGF-β-induced epithelial-mesenchymal transition in T24 human bladder cancer cells.

    Directory of Open Access Journals (Sweden)

    Rodrigo Barbosa Oliveira Brito

    Full Text Available Immune escape and metastasis are the hallmarks of several types of cancer including bladder cancer. One of the mechanisms involved in these processes has been linked to indoleamine 2,3-dioxygenase (IDO. Although IDO is classically recognized for its immunomodulatory property, it has presented nonimmunological effects in some tumors. TGF-β1 is believed to contribute to carcinoma development by modulating immunossupressive molecules, including IDO. In addition, TGF-β1 induces the epithelial-mesenchymal transition (EMT, which is a critical step in the tumor invasiveness and metastasis. We investigated the role of MT and IDO modulation in the induction of EMT by TGF-β1 in T24 human bladder carcinoma cells. When T24 cells were incubated with the IDO inhibitor (MT, 1-methyl-D-tryptophan, with TGF-β1, and with MT+TGF-β1, a significant decrease of IDO expression and activity was observed. In addition, downregulation of e-cadherin and upregulation of n-cadherin and EMT transcription factors were induced by the treatments, confirming the induction of EMT. siRNA-mediated knockdown of IDO decreased e-cadherin expression, but had no effect on EMT transcription factors. In the scratch-wound assay, the heightened migration process was intensified when the cells were incubated with MT+TGF-β1. These effects were associated with a robust inhibition of Akt activation. After inoculation of T24 cells under the kidney capsule of Balb/c nude, the cells were positive for IDO in the center of the cell infiltrate, being negative in the periphery, where EMT is high. In conclusion, inhibition of IDO by TGF-β1 and MT is associated with EMT in T24 human bladder carcinoma cells. MT has potentiating effect in TGF-β1-induced EMT, independently of IDO. This nonimmunological effect of MT should be considered if IDO is the target to avoid immune escape in bladder cancer.

  14. A genome-wide methylation study on obesity Differential variability and differential methylation

    NARCIS (Netherlands)

    Xu, Xiaojing; Su, Shaoyong; Barnes, Vernon A.; De Miguel, Carmen; Pollock, Jennifer; Ownby, Dennis; Shi, Huidong; Zhu, Haidong; Snieder, Harold; Wang, Xiaoling

    2013-01-01

    Besides differential methylation, DNA methylation variation has recently been proposed and demonstrated to be a potential contributing factor to cancer risk. Here we aim to examine whether differential variability in methylation is also an important feature of obesity, a typical non-malignant common

  15. Planning long lasting insecticide treated net campaigns: should households' existing nets be taken into account?

    Science.gov (United States)

    Yukich, Joshua; Bennett, Adam; Keating, Joseph; Yukich, Rudy K; Lynch, Matt; Eisele, Thomas P; Kolaczinski, Kate

    2013-06-14

    Mass distribution of long-lasting insecticide treated bed nets (LLINs) has led to large increases in LLIN coverage in many African countries. As LLIN ownership levels increase, planners of future mass distributions face the challenge of deciding whether to ignore the nets already owned by households or to take these into account and attempt to target individuals or households without nets. Taking existing nets into account would reduce commodity costs but require more sophisticated, and potentially more costly, distribution procedures. The decision may also have implications for the average age of nets in use and therefore on the maintenance of universal LLIN coverage over time. A stochastic simulation model based on the NetCALC algorithm was used to determine the scenarios under which it would be cost saving to take existing nets into account, and the potential effects of doing so on the age profile of LLINs owned. The model accounted for variability in timing of distributions, concomitant use of continuous distribution systems, population growth, sampling error in pre-campaign coverage surveys, variable net 'decay' parameters and other factors including the feasibility and accuracy of identifying existing nets in the field. Results indicate that (i) where pre-campaign coverage is around 40% (of households owning at least 1 LLIN), accounting for existing nets in the campaign will have little effect on the mean age of the net population and (ii) even at pre-campaign coverage levels above 40%, an approach that reduces LLIN distribution requirements by taking existing nets into account may have only a small chance of being cost-saving overall, depending largely on the feasibility of identifying nets in the field. Based on existing literature the epidemiological implications of such a strategy is likely to vary by transmission setting, and the risks of leaving older nets in the field when accounting for existing nets must be considered. Where pre-campaign coverage

  16. Planning long lasting insecticide treated net campaigns: should households’ existing nets be taken into account?

    Science.gov (United States)

    2013-01-01

    Background Mass distribution of long-lasting insecticide treated bed nets (LLINs) has led to large increases in LLIN coverage in many African countries. As LLIN ownership levels increase, planners of future mass distributions face the challenge of deciding whether to ignore the nets already owned by households or to take these into account and attempt to target individuals or households without nets. Taking existing nets into account would reduce commodity costs but require more sophisticated, and potentially more costly, distribution procedures. The decision may also have implications for the average age of nets in use and therefore on the maintenance of universal LLIN coverage over time. Methods A stochastic simulation model based on the NetCALC algorithm was used to determine the scenarios under which it would be cost saving to take existing nets into account, and the potential effects of doing so on the age profile of LLINs owned. The model accounted for variability in timing of distributions, concomitant use of continuous distribution systems, population growth, sampling error in pre-campaign coverage surveys, variable net ‘decay’ parameters and other factors including the feasibility and accuracy of identifying existing nets in the field. Results Results indicate that (i) where pre-campaign coverage is around 40% (of households owning at least 1 LLIN), accounting for existing nets in the campaign will have little effect on the mean age of the net population and (ii) even at pre-campaign coverage levels above 40%, an approach that reduces LLIN distribution requirements by taking existing nets into account may have only a small chance of being cost-saving overall, depending largely on the feasibility of identifying nets in the field. Based on existing literature the epidemiological implications of such a strategy is likely to vary by transmission setting, and the risks of leaving older nets in the field when accounting for existing nets must be considered

  17. Pro NET Best Practices

    CERN Document Server

    Ritchie, Stephen D

    2011-01-01

    Pro .NET Best Practices is a practical reference to the best practices that you can apply to your .NET projects today. You will learn standards, techniques, and conventions that are sharply focused, realistic and helpful for achieving results, steering clear of unproven, idealistic, and impractical recommendations. Pro .NET Best Practices covers a broad range of practices and principles that development experts agree are the right ways to develop software, which includes continuous integration, automated testing, automated deployment, and code analysis. Whether the solution is from a free and

  18. Getting to Net Zero

    Energy Technology Data Exchange (ETDEWEB)

    2016-09-01

    The technology necessary to build net zero energy buildings (NZEBs) is ready and available today, however, building to net zero energy performance levels can be challenging. Energy efficiency measures, onsite energy generation resources, load matching and grid interaction, climatic factors, and local policies vary from location to location and require unique methods of constructing NZEBs. It is recommended that Components start looking into how to construct and operate NZEBs now as there is a learning curve to net zero construction and FY 2020 is just around the corner.

  19. Instant Lucene.NET

    CERN Document Server

    Heydt, Michael

    2013-01-01

    Filled with practical, step-by-step instructions and clear explanations for the most important and useful tasks. A step-by-step guide that helps you to index, search, and retrieve unstructured data with the help of Lucene.NET.Instant Lucene.NET How-to is essential for developers new to Lucene and Lucene.NET who are looking to get an immediate foundational understanding of how to use the library in their application. It's assumed you have programming experience in C# already, but not that you have experience with search techniques such as information retrieval theory (although there will be a l

  20. Development of inhibitors of the 2C-methyl-D-erythritol 4-phosphate (MEP) pathway enzymes as potential anti-infective agents

    NARCIS (Netherlands)

    Masini, Tiziana; Hirsch, Anna K H

    2014-01-01

    Important pathogens such as Mycobacterium tuberculosis and Plasmodium falciparum, the causative agents of tuberculosis and malaria, respectively, and plants, utilize the 2C-methyl-D-erythritol 4-phosphate (MEP, 5) pathway for the biosynthesis of isopentenyl diphosphate (1) and dimethylallyl

  1. Net Zero Energy Buildings

    DEFF Research Database (Denmark)

    Marszal, Anna Joanna; Bourrelle, Julien S.; Musall, Eike

    2010-01-01

    and identify possible renewable energy supply options which may be considered in calculations. Finally, the gap between the methodology proposed by each organisation and their respective national building code is assessed; providing an overview of the possible changes building codes will need to undergo......The international cooperation project IEA SHC Task 40 / ECBCS Annex 52 “Towards Net Zero Energy Solar Buildings”, attempts to develop a common understanding and to set up the basis for an international definition framework of Net Zero Energy Buildings (Net ZEBs). The understanding of such buildings...... parameters used in the calculations are discussed and the various renewable supply options considered in the methodologies are summarised graphically. Thus, the paper helps to understand different existing approaches to calculate energy balance in Net ZEBs, highlights the importance of variables selection...

  2. PhysioNet

    Data.gov (United States)

    U.S. Department of Health & Human Services — The PhysioNet Resource is intended to stimulate current research and new investigations in the study of complex biomedical and physiologic signals. It offers free...

  3. Methylated genes as new cancer biomarkers.

    LENUS (Irish Health Repository)

    Duffy, M J

    2012-02-01

    Aberrant hypermethylation of promoter regions in specific genes is a key event in the formation and progression of cancer. In at least some situations, these aberrant alterations occur early in the formation of malignancy and appear to be tumour specific. Multiple reports have suggested that measurement of the methylation status of the promoter regions of specific genes can aid early detection of cancer, determine prognosis and predict therapy responses. Promising DNA methylation biomarkers include the use of methylated GSTP1 for aiding the early diagnosis of prostate cancer, methylated PITX2 for predicting outcome in lymph node-negative breast cancer patients and methylated MGMT in predicting benefit from alkylating agents in patients with glioblastomas. However, prior to clinical utilisation, these findings require validation in prospective clinical studies. Furthermore, assays for measuring gene methylation need to be standardised, simplified and evaluated in external quality assurance programmes. It is concluded that methylated genes have the potential to provide a new generation of cancer biomarkers.

  4. TideNet

    Science.gov (United States)

    2015-10-30

    query tide data sources in a desired geographic region of USA and its territories (Figure 1). Users can select a tide data source through the Google Map ...select data sources according to the desired geographic region. It uses the Google Map interface to display data from different sources. Recent...Coastal Inlets Research Program TideNet The TideNet is a web-based Graphical User Interface (GUI) that provides users with GIS mapping tools to

  5. Building Neural Net Software

    OpenAIRE

    Neto, João Pedro; Costa, José Félix

    1999-01-01

    In a recent paper [Neto et al. 97] we showed that programming languages can be translated on recurrent (analog, rational weighted) neural nets. The goal was not efficiency but simplicity. Indeed we used a number-theoretic approach to machine programming, where (integer) numbers were coded in a unary fashion, introducing a exponential slow down in the computations, with respect to a two-symbol tape Turing machine. Implementation of programming languages in neural nets turns to be not only theo...

  6. Interaction Nets in Russian

    OpenAIRE

    Salikhmetov, Anton

    2013-01-01

    Draft translation to Russian of Chapter 7, Interaction-Based Models of Computation, from Models of Computation: An Introduction to Computability Theory by Maribel Fernandez. "In this chapter, we study interaction nets, a model of computation that can be seen as a representative of a class of models based on the notion of 'computation as interaction'. Interaction nets are a graphical model of computation devised by Yves Lafont in 1990 as a generalisation of the proof structures of linear logic...

  7. Programming NET 35

    CERN Document Server

    Liberty, Jesse

    2009-01-01

    Bestselling author Jesse Liberty and industry expert Alex Horovitz uncover the common threads that unite the .NET 3.5 technologies, so you can benefit from the best practices and architectural patterns baked into the new Microsoft frameworks. The book offers a Grand Tour" of .NET 3.5 that describes how the principal technologies can be used together, with Ajax, to build modern n-tier and service-oriented applications. "

  8. Drug discovery targeting epigenetic codes: the great potential of UHRF1, which links DNA methylation and histone modifications, as a drug target in cancers and toxoplasmosis.

    Science.gov (United States)

    Unoki, Motoko; Brunet, Julie; Mousli, Marc

    2009-11-15

    UHRF1 plays a central role in transferring methylation status from mother cells to daughter cells. Its SRA domain recognizes hemi-methylated DNA that appears in daughter DNA strands during duplication of DNA. UHRF1 recruits DNMT1 to the site and methylates both strands. UHRF1 also binds to HDAC1 and di- and tri-methyl K9 histone H3, ubiquitinates histone H3, and associates with heterochromatin formation, indicating that UHRF1 links histone modifications, DNA methylation, and chromatin structure. UHRF1 is a direct target of E2F1 and promotes G1/S transition. The tumor suppressor p53, which is deficient in 50% of cancers, down-regulates UHRF1 through up-regulation of p21/WAF1 and subsequent deactivation of E2F1. The expression levels of UHRF1 are up-regulated in many cancers, probably partially because of the absence of wild type p53, but it is probably regulated by several other factors. Knockdown of UHRF1 expression in cancer cells suppressed cell growth, suggesting that UHRF1 can be a useful anticancer drug target. Recently, it was revealed that UHRF1 plays important roles not only in carcinogenesis, but also in toxoplasmosis, which is occasionally fatal to people with a weakened immune system, and can cause blindness in the major pathology of ocular toxoplasmosis. Toxoplasma gondii, which causes toxoplasmosis, utilizes UHRF1 to control the cell cycle phase and enhance its proliferation. Thus, knockdown of UHRF1 can be effective at stopping the proliferation of the parasites in infected cells. In this review, we discuss several possible methods that can inhibit the multiple unique functions of UHRF1, which can be utilized for treating cancers and toxoplasmosis.

  9. Effects of low-dose rate γ-irradiation combined with simulated microgravity on markers of oxidative stress, DNA methylation potential, and remodeling in the mouse heart.

    Directory of Open Access Journals (Sweden)

    John W Seawright

    Full Text Available Space travel is associated with an exposure to low-dose rate ionizing radiation and the microgravity environment, both of which may lead to impairments in cardiac function. We used a mouse model to determine short- and long-term cardiac effects to simulated microgravity (hindlimb unloading; HU, continuous low-dose rate γ-irradiation, or a combination of HU and low-dose rate γ-irradiation.Cardiac tissue was obtained from female, C57BL/6J mice 7 days, 1 month, 4 months, and 9 months following the completion of a 21 day exposure to HU or a 21 day exposure to low-dose rate γ-irradiation (average dose rate of 0.01 cGy/h to a total of 0.04 Gy, or a 21 day simultaneous exposure to HU and low-dose rate γ-irradiation. Immunoblot analysis, rt-PCR, high-performance liquid chromatography, and histology were used to assess inflammatory cell infiltration, cardiac remodeling, oxidative stress, and the methylation potential of cardiac tissue in 3 to 6 animals per group.The combination of HU and γ-irradiation demonstrated the strongest increase in reduced to oxidized glutathione ratios 7 days and 1 month after treatment, but a difference was no longer apparent after 9 months. On the other hand, no significant changes in 4-hydroxynonenal adducts was seen in any of the groups, at the measured endpoints. While manganese superoxide dismutase protein levels decreased 9 months after low-dose γ-radiation, no changes were observed in expression of catalase or Nrf2, a transcription factor that determines the expression of several antioxidant enzymes, at the measured endpoints. Inflammatory marker, CD-2 protein content was significantly decreased in all groups 4 months after treatment. No significant differences were observed in α-smooth muscle cell actin protein content, collagen type III protein content or % total collagen.This study has provided the first and relatively broad analysis of small molecule and protein markers of oxidative stress, T

  10. Effects of low-dose rate γ-irradiation combined with simulated microgravity on markers of oxidative stress, DNA methylation potential, and remodeling in the mouse heart.

    Science.gov (United States)

    Seawright, John W; Samman, Yusra; Sridharan, Vijayalakshmi; Mao, Xiao Wen; Cao, Maohua; Singh, Preeti; Melnyk, Stepan; Koturbash, Igor; Nelson, Gregory A; Hauer-Jensen, Martin; Boerma, Marjan

    2017-01-01

    Space travel is associated with an exposure to low-dose rate ionizing radiation and the microgravity environment, both of which may lead to impairments in cardiac function. We used a mouse model to determine short- and long-term cardiac effects to simulated microgravity (hindlimb unloading; HU), continuous low-dose rate γ-irradiation, or a combination of HU and low-dose rate γ-irradiation. Cardiac tissue was obtained from female, C57BL/6J mice 7 days, 1 month, 4 months, and 9 months following the completion of a 21 day exposure to HU or a 21 day exposure to low-dose rate γ-irradiation (average dose rate of 0.01 cGy/h to a total of 0.04 Gy), or a 21 day simultaneous exposure to HU and low-dose rate γ-irradiation. Immunoblot analysis, rt-PCR, high-performance liquid chromatography, and histology were used to assess inflammatory cell infiltration, cardiac remodeling, oxidative stress, and the methylation potential of cardiac tissue in 3 to 6 animals per group. The combination of HU and γ-irradiation demonstrated the strongest increase in reduced to oxidized glutathione ratios 7 days and 1 month after treatment, but a difference was no longer apparent after 9 months. On the other hand, no significant changes in 4-hydroxynonenal adducts was seen in any of the groups, at the measured endpoints. While manganese superoxide dismutase protein levels decreased 9 months after low-dose γ-radiation, no changes were observed in expression of catalase or Nrf2, a transcription factor that determines the expression of several antioxidant enzymes, at the measured endpoints. Inflammatory marker, CD-2 protein content was significantly decreased in all groups 4 months after treatment. No significant differences were observed in α-smooth muscle cell actin protein content, collagen type III protein content or % total collagen. This study has provided the first and relatively broad analysis of small molecule and protein markers of oxidative stress, T-lymphocyte infiltration, and

  11. Structure, bioactivity, and synthesis of methylated flavonoids.

    Science.gov (United States)

    Wen, Lingrong; Jiang, Yueming; Yang, Jiali; Zhao, Yupeng; Tian, Miaomiao; Yang, Bao

    2017-06-01

    Methylated flavonoids are an important type of natural flavonoid derivative with potentially multiple health benefits; among other things, they have improved bioavailability compared with flavonoid precursors. Flavonoids have been documented to have broad bioactivities, such as anticancer, immunomodulation, and antioxidant activities, that can be elevated, to a certain extent, by methylation. Understanding the structure, bioactivity, and bioavailability of methylated flavonoids, therefore, is an interesting topic with broad potential applications. Though methylated flavonoids are widely present in plants, their levels are usually low. Because developing efficient techniques to produce these chemicals would likely be beneficial, we provide an overview of their chemical and biological synthesis. © 2017 New York Academy of Sciences.

  12. The potential effects of concurrent increases in temperature, CO sub 2 and O sub 3 on net photosynthesis, as mediated by rubisCO

    Energy Technology Data Exchange (ETDEWEB)

    Long, S. (Brookhaven National Lab., Upton, NY (United States) Essex Univ., Colchester (United Kingdom). Dept. of Biology)

    1992-07-01

    At the leaf level, under light saturating and light limiting conditions, it is shown that elevated atmospheric CO{sub 2} concentration not only alters the scale of the response of carbon gain to rising temperature, but can alter the direction of response. These points bring into serious question the value of any predictions of plant production which ignore not only the direct effect Of C0{sub 2} on carbon gain, but also the basic interactions of temperature, C0{sub 2} and 0{sub 3}. Whilst many factors may potentially diminish the enhancement of lightsaturated leaf photosynthetic rates with increase in atmospheric CO{sub 2} concentrations, no mechanism has so far been identified which could remove the parallel stimulation of light-limited photosynthesis.

  13. The potential effects of concurrent increases in temperature, CO{sub 2} and O{sub 3} on net photosynthesis, as mediated by rubisCO

    Energy Technology Data Exchange (ETDEWEB)

    Long, S. [Brookhaven National Lab., Upton, NY (United States)]|[Essex Univ., Colchester (United Kingdom). Dept. of Biology

    1992-07-01

    At the leaf level, under light saturating and light limiting conditions, it is shown that elevated atmospheric CO{sub 2} concentration not only alters the scale of the response of carbon gain to rising temperature, but can alter the direction of response. These points bring into serious question the value of any predictions of plant production which ignore not only the direct effect Of C0{sub 2} on carbon gain, but also the basic interactions of temperature, C0{sub 2} and 0{sub 3}. Whilst many factors may potentially diminish the enhancement of lightsaturated leaf photosynthetic rates with increase in atmospheric CO{sub 2} concentrations, no mechanism has so far been identified which could remove the parallel stimulation of light-limited photosynthesis.

  14. Systematic analysis of O-methyltransferase gene family and identification of potential members involved in the formation of O-methylated flavonoids in Citrus.

    Science.gov (United States)

    Liu, Xiaogang; Luo, Yan; Wu, Hongkun; Xi, Wanpeng; Yu, Jie; Zhang, Qiuyun; Zhou, Zhiqin

    2016-01-10

    The O-methylation of various secondary metabolites is mainly catalyzed by S-adenosyl-l-methionine (SAM)-dependent O-methyltransferase (OMT) proteins that are encoded by the O-methyltransferase gene family. Citrus fruits are a rich source of O-methylated flavonoids that have a broad spectrum of biological activities, including anti-inflammatory, anticarcinogenic, and antiatherogenic properties. However, little is known about this gene family and its members that are involved in the O-methylation of flavonoids and their regulation in Citrus. In this study, 58 OMT genes were identified from the entire Citrus sinensis genome and compared with those from 3 other representative dicot plants. A comprehensive analysis was performed, including functional/substrate predictions, identification of chromosomal locations, phylogenetic relationships, gene structures, and conserved motifs. Distribution mapping revealed that the 58 OMT genes were unevenly distributed on the 9 citrus chromosomes. Phylogenetic analysis of 164 OMT proteins from C.sinensis, Arabidopsis thaliana, Populus trichocarpa, and Vitis vinifera showed that these proteins were categorized into group I (COMT subfamily) and group II (CCoAOMT subfamily), which were further divided into 10 and 2 subgroups, respectively. Finally, digital gene expression and quantitative real-time polymerase chain reaction analyses revealed that citrus OMT genes had distinct temporal and spatial expression patterns in different tissues and developmental stages. Interestingly, 18 and 11 of the 27 genes predicted to be involved in O-methylation of flavonoids had higher expression in the peel and pulp during fruit development, respectively. The citrus OMT gene family identified in this study might help in the selection of appropriate candidate genes and facilitate functional studies in Citrus. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. DNA Methylation Patterns in Crassostrea gigas

    OpenAIRE

    Olson, Claire; Roberts, Steven; Gavery, Mackenzie

    2013-01-01

    Poster presented at the NSA conference in Nashville in 2013.  This research uses the Pacific Oyster as a model organism to characterize the distribution and identify potential functions of DNA methylation.  We examined genome-wide methylation patterns to elucidate the mechanisms by which DNA methylation impacts transcriptional processes. ___________________________________________ This material is based upon work supported by the National Science Foundation under Grant Number 1158119. ...

  16. Effects of damming on the distribution and methylation of mercury in Wujiang River, Southwest China.

    Science.gov (United States)

    Zhao, Lei; Guo, Yanna; Meng, Bo; Yao, Heng; Feng, Xinbin

    2017-10-01

    Newly built reservoirs are regarded as sensitive ecosystem for mercury (Hg) methylation. A comprehensive study was conducted to understand the influence of damming on the distribution and methylation of Hg within a river-reservoir ecosystem in Wujiang River Basin (WRB), Southwest China. Hg species in inflow-outflow rivers of six cascade reservoirs were analyzed each month during 2006. Mean concentrations of total Hg (THg) and methylmercury (MeHg) in river water in WRB were 3.41 ± 1.98 ng L-1 and 0.15 ± 0.06 ng L-1, respectively. THg and particulate Hg (PHg) concentrations in outflow rivers of reservoirs significantly decreased after dam construction, suggesting that a considerable amount of PHg was intercepted by way of sedimentation. However, the influence of damming on the distributions of dissolved Hg (DHg) and reactive Hg (RHg) in rivers was less pronounced. MeHg concentrations in outflow rivers of the older reservoirs significantly increased compared to inflow rivers with the maximum increasing factor of 92%, indicating the active net Hg methylation in the reservoirs. However, the difference between MeHg in inflow rivers and outflow rivers were less pronounced in the newly constructed reservoirs, indicating that these reservoirs were not active sites of Hg methylation. The construction of the cascade reservoirs resulted in the elevation of MeHg in several sections of the Wujiang River, which attributed to the net Hg methylation in reservoirs and discharge of MeHg from hypolimnion. MeHg-enriched water in outflow rivers from hypolimnetic water could be transported to downstream, posing potential threat to the aquatic food web and human health. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Net Neutrality: Media Discourses and Public Perception

    Directory of Open Access Journals (Sweden)

    Christine Quail

    2010-01-01

    Full Text Available This paper analyzes media and public discourses surrounding net neutrality, with particular attention to public utility philosophy, from a critical perspective. The article suggests that further public education about net neutrality would be beneficial. The first portion of this paper provides a survey of the existing literature surrounding net neutrality, highlighting the contentious debate between market-based and public interest perspectives. In order to contextualize the debate, an overview of public utility philosophy is provided, shedding light on how the Internet can be conceptualized as a public good. Following this discussion, an analysis of mainstream media is presented, exploring how the media represents the issue of net neutrality and whether or not the Internet is discussed through the lens of public utility. To further examine how the net neutrality debate is being addressed, and to see the potential impacts of media discourses on the general public, the results of a focus group are reported and analyzed. Finally, a discussion assesses the implications of the net neutrality debate as presented through media discourses, highlighting the future of net neutrality as an important policy issue.

  18. Evolution of DNA Methylation across Insects.

    Science.gov (United States)

    Bewick, Adam J; Vogel, Kevin J; Moore, Allen J; Schmitz, Robert J

    2017-03-01

    DNA methylation contributes to gene and transcriptional regulation in eukaryotes, and therefore has been hypothesized to facilitate the evolution of plastic traits such as sociality in insects. However, DNA methylation is sparsely studied in insects. Therefore, we documented patterns of DNA methylation across a wide diversity of insects. We predicted that underlying enzymatic machinery is concordant with patterns of DNA methylation. Finally, given the suggestion that DNA methylation facilitated social evolution in Hymenoptera, we tested the hypothesis that the DNA methylation system will be associated with presence/absence of sociality among other insect orders. We found DNA methylation to be widespread, detected in all orders examined except Diptera (flies). Whole genome bisulfite sequencing showed that orders differed in levels of DNA methylation. Hymenopteran (ants, bees, wasps and sawflies) had some of the lowest levels, including several potential losses. Blattodea (cockroaches and termites) show all possible patterns, including a potential loss of DNA methylation in a eusocial species whereas solitary species had the highest levels. Species with DNA methylation do not always possess the typical enzymatic machinery. We identified a gene duplication event in the maintenance DNA methyltransferase 1 (DNMT1) that is shared by some Hymenoptera, and paralogs have experienced divergent, nonneutral evolution. This diversity and nonneutral evolution of underlying machinery suggests alternative DNA methylation pathways may exist. Phylogenetically corrected comparisons revealed no evidence that supports evolutionary association between sociality and DNA methylation. Future functional studies will be required to advance our understanding of DNA methylation in insects. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  19. Cigarette smoking and DNA methylation

    Directory of Open Access Journals (Sweden)

    Ken W.K Lee

    2013-07-01

    Full Text Available DNA methylation is the most studied epigenetic modification, capable of controlling gene expression in the contexts of normal traits or diseases. It is highly dynamic during early embryogenesis and remains relatively stable throughout life, and such patterns are intricately related to human development. DNA methylation is a quantitative trait determined by a complex interplay of genetic and environmental factors. Genetic variants at a specific locus can influence both regional and distant DNA methylation. The environment can have varying effects on DNA methylation depending on when the exposure occurs, such as during prenatal life or during adulthood. In particular, cigarette smoking in the context of both current smoking and prenatal exposure is a strong modifier of DNA methylation. Epigenome-wide association studies have uncovered candidate genes associated with cigarette smoking that have biologically relevant functions in the etiology of smoking-related diseases. As such, DNA methylation is a potential mechanistic link between current smoking and cancer, as well as prenatal cigarette-smoke exposure and the development of adult chronic diseases.

  20. La plataforma .NET

    OpenAIRE

    Fornas Estrada, Miquel

    2008-01-01

    L'aparició de la plataforma .NET Framework ha suposat un canvi molt important en la forma de crear i distribuir aplicacions, degut a que incorpora una sèrie d'innovacions tècniques i productives que simplifiquen molt les tasques necessàries per desenvolupar un projecte. La aparición de la plataforma. NET Framework ha supuesto un cambio muy importante en la forma de crear y distribuir aplicaciones, debido a que incorpora una serie de innovaciones técnicas y productivas que simplifican mucho...

  1. Biological Petri Nets

    CERN Document Server

    Wingender, E

    2011-01-01

    It was suggested some years ago that Petri nets might be well suited to modeling metabolic networks, overcoming some of the limitations encountered by the use of systems employing ODEs (ordinary differential equations). Much work has been done since then which confirms this and demonstrates the usefulness of this concept for systems biology. Petri net technology is not only intuitively understood by scientists trained in the life sciences, it also has a robust mathematical foundation and provides the required degree of flexibility. As a result it appears to be a very promising approach to mode

  2. Antibodies against the mono-methylated arginine-glycine repeat (MMA-RG) of the Epstein-Barr virus nuclear antigen 2 (EBNA2) identify potential cellular proteins targeted in viral transformation.

    Science.gov (United States)

    Ayoubian, Hiresh; Fröhlich, Thomas; Pogodski, Dagmar; Flatley, Andrew; Kremmer, Elisabeth; Schepers, Aloys; Feederle, Regina; Arnold, Georg J; Grässer, Friedrich A

    2017-08-01

    The Epstein-Barr virus is a human herpes virus with oncogenic potential. The virus-encoded nuclear antigen 2 (EBNA2) is a key mediator of viral tumorigenesis. EBNA2 features an arginine-glycine (RG) repeat at amino acids (aa)339-354 that is essential for the transformation of lymphocytes and contains symmetrically (SDMA) and asymmetrically (ADMA) di-methylated arginine residues. The SDMA-modified EBNA2 binds the survival motor neuron protein (SMN), thus mimicking SMD3, a cellular SDMA-containing protein that interacts with SMN. Accordingly, a monoclonal antibody (mAb) specific for the SDMA-modified RG repeat of EBNA2 also binds to SMD3. With the novel mAb 19D4 we now show that EBNA2 contains mono-methylated arginine (MMA) residues within the RG repeat. Using 19D4, we immune-precipitated and analysed by mass spectrometry cellular proteins in EBV-transformed B-cells that feature MMA motifs that are similar to the one in EBNA2. Among the cellular proteins identified, we confirmed by immunoprecipitation and/or Western blot analyses Aly/REF, Coilin, DDX5, FXR1, HNRNPK, LSM4, MRE11, NRIP, nucleolin, PRPF8, RBM26, SMD1 (SNRDP1) and THRAP3 proteins that are either known to contain MMA residues or feature RG repeat sequences that probably serve as methylation substrates. The identified proteins are involved in splicing, tumorigenesis, transcriptional activation, DNA stability and RNA processing or export. Furthermore, we found that several proteins involved in energy metabolism are associated with MMA-modified proteins. Interestingly, the viral EBNA1 protein that features methylated RG repeat motifs also reacted with the antibodies. Our results indicate that the region between aa 34-52 of EBNA1 contains ADMA or SDMA residues, while the region between aa 328-377 mainly contains MMA residues.

  3. Approximation methods for stochastic petri nets

    Science.gov (United States)

    Jungnitz, Hauke Joerg

    1992-01-01

    Stochastic Marked Graphs are a concurrent decision free formalism provided with a powerful synchronization mechanism generalizing conventional Fork Join Queueing Networks. In some particular cases the analysis of the throughput can be done analytically. Otherwise the analysis suffers from the classical state explosion problem. Embedded in the divide and conquer paradigm, approximation techniques are introduced for the analysis of stochastic marked graphs and Macroplace/Macrotransition-nets (MPMT-nets), a new subclass introduced herein. MPMT-nets are a subclass of Petri nets that allow limited choice, concurrency and sharing of resources. The modeling power of MPMT is much larger than that of marked graphs, e.g., MPMT-nets can model manufacturing flow lines with unreliable machines and dataflow graphs where choice and synchronization occur. The basic idea leads to the notion of a cut to split the original net system into two subnets. The cuts lead to two aggregated net systems where one of the subnets is reduced to a single transition. A further reduction leads to a basic skeleton. The generalization of the idea leads to multiple cuts, where single cuts can be applied recursively leading to a hierarchical decomposition. Based on the decomposition, a response time approximation technique for the performance analysis is introduced. Also, delay equivalence, which has previously been introduced in the context of marked graphs by Woodside et al., Marie's method and flow equivalent aggregation are applied to the aggregated net systems. The experimental results show that response time approximation converges quickly and shows reasonable accuracy in most cases. The convergence of Marie's method and flow equivalent aggregation are applied to the aggregated net systems. The experimental results show that response time approximation converges quickly and shows reasonable accuracy in most cases. The convergence of Marie's is slower, but the accuracy is generally better. Delay

  4. Petri Nets-Applications

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 4; Issue 9. Petri Nets - Applications. Y Narahari. General Article Volume 4 Issue 9 September 1999 pp 44-52. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/004/09/0044-0052. Author Affiliations. Y Narahari ...

  5. Safety nets or straitjackets?

    DEFF Research Database (Denmark)

    Ilsøe, Anna

    2012-01-01

    Does regulation of working hours at national and sector level impose straitjackets, or offer safety nets to employees seeking working time flexibility? This article compares legislation and collective agreements in the metal industries of Denmark, Germany and the USA. The industry has historically...

  6. Coloured Petri Nets

    CERN Document Server

    Jensen, Kurt

    2009-01-01

    Coloured Petri Nets (CPN) is a graphical language for modelling and validating concurrent and distributed systems, and other systems in which concurrency plays a major role. This book introduces the constructs of the CPN modelling language and presents the related analysis methods. It provides a comprehensive road map for the practical use of CPN.

  7. Boom Booom Net Radio

    DEFF Research Database (Denmark)

    Grimshaw, Mark Nicholas; Yong, Louisa; Dobie, Ian

    1999-01-01

    of an existing Internet radio station; Boom Booom Net Radio. Whilst necessity dictates some use of technology-related terminology, wherever possible we have endeavoured to keep such jargon to a minimum and to either explain it in the text or to provide further explanation in the appended glossary....

  8. Game Theory .net.

    Science.gov (United States)

    Shor, Mikhael

    2003-01-01

    States making game theory relevant and accessible to students is challenging. Describes the primary goal of GameTheory.net is to provide interactive teaching tools. Indicates the site strives to unite educators from economics, political and computer science, and ecology by providing a repository of lecture notes and tests for courses using…

  9. Coloured Petri Nets

    DEFF Research Database (Denmark)

    Jensen, Kurt; Kristensen, Lars Michael

    Coloured Petri Nets (CPN) is a graphical language for modelling and validating concurrent and distributed systems, and other systems in which concurrency plays a major role. The development of such systems is particularly challenging because of inherent intricacies like possible nondeterminism...

  10. Effect of chemical carcinogens on hematopoietic stem cells: temporal correlation between methyl methane sulfonate induced depression of CFU-S and potentiation of Friend viral leukemogenesis in vivo. [Mice

    Energy Technology Data Exchange (ETDEWEB)

    Raikow, R.B.; OKunewick, J.P.; Meredith, R.F.; Brozovich, B.J.; Seeman, P.R.

    1979-05-01

    Methyl methane sulfonate (MMS) was shown to reduce the number of transplantable pluripotent hematopoietic stem cells (CFU-S) in the mouse spleen. A mild depression in CFU-S numbers was seen as early as 1 hr after injection of the chemical carcinogen. Maximal depression was found to be at 5 hrs, followed by a recovery of up to 75% of normal levels by 24 hrs. Comparison of the data with earlier reslts which demonstrated a potentiating effect of MMS on viral leukemogenesis in vivo revealed a good temporal correlation, suggesting a possible relationship between the two effects.

  11. Adiponectin as a potential tumor suppressor inhibiting epithelial-to-mesenchymal transition but frequently silenced in prostate cancer by promoter methylation.

    Science.gov (United States)

    Tan, Weiwei; Wang, Lin; Ma, Quanping; Qi, Mei; Lu, Ning; Zhang, Lili; Han, Bo

    2015-08-01

    Recent evidence suggests a particular role for obesity in prostate cancer (PCa) progression. Adiponectin (ADN) is a hormone secreted by adipose tissue and has a variety of functions including the inhibition of PCa cell proliferation. Although serum ADN levels have been identified to be related with carcinogenesis in a tissue-specific context, the exact role of endogenous ADN in PCa cells remains largely unknown. Two tissue microarrays were constructed and immunohistochemistry (IHC) was utilized to detect ADN's expression in a cohort of 96 Chinese PCa patients with radical prostatectomy as well as 15 cases with Benign Prostatic Hyperplasia (BPH). MTS and transwell assays were applied to validate the effects of ADN on proliferation and invasive capacity of PCa cells. Real-time PCR and Western blot were performed to evaluate the expression at transcript and protein levels. Epigenetic modifications of ADN's promoter after TGF-β1 treatment in 22RV1 cells was monitored by chromatin immunoprecipitation (ChIP). Methylation-Specific PCR (MSP) was performed to determine the methylation status of ADN's promoter. IHC showed decreased levels of ADN in 1 of 15 (6.7%) BPH cases, 6 of 27 (22.2%) PCa cases with low Gleason score (7). Silencing endogenous ADN could promote proliferation and invasion of 22RV1 cells via orchestrating Epithelial-to-mesenchymal Transition (EMT) process. TGF-β1, a potent EMT inducer, could decrease levels of chromatin markers associated with active genes (H3K4me3, H4acetylK16), and increase levels of repressive marker (H3K27me3) at ADN promoter in 22RV1 cells. Additionally, 5-aza and TSA treatment restored ADN expression in LNCaP cells in which the ADN expression was almost absent. MSP analysis revealed that methylation in the promoter might be involved in decreased expression of ADN in PCa tissues. Our findings indicated that endogenous ADN may function as a tumor suppressor gene through inhibiting EMT of PCa cells but is down-regulated in PCa via

  12. Food Safety Nets:

    OpenAIRE

    Haggblade, Steven; Diallo, Boubacar; Staatz, John; Theriault, Veronique; Traoré, Abdramane

    2013-01-01

    Food and social safety nets have a history as long as human civilization. In hunter gatherer societies, food sharing is pervasive. Group members who prove unlucky in the short run, hunting or foraging, receive food from other households in anticipation of reciprocal consideration at a later time (Smith 1988). With the emergence of the first large sedentary civilizations in the Middle East, administrative systems developed specifically around food storage and distribution. The ancient Egyptian...

  13. Net technical assessment

    OpenAIRE

    Wegmann, David G.

    1989-01-01

    Approved for public release; distribution is unlimited. The present and near term military balance of power between the U.S. and the Soviet Union can be expressed in a variety of net assessments. One can examine the strategic nuclear balance, the conventional balance in Europe, the maritime balance, and many others. Such assessments are essential not only for policy making but for arms control purposes and future force structure planning. However, to project the future military balance, on...

  14. Laboratory and Field Studies of Poly(2,5-bis(N-methyl-N-hexylaminophenylene vinylene (BAM-PPV: A Potential Wash Primer Replacement for Army Military Vehicles

    Directory of Open Access Journals (Sweden)

    Peter Zarras

    2014-09-01

    Full Text Available In this study, an electroactive polymer (EAP, poly(2,5-bis(N-methyl-N- hexylaminophenylene vinylene (BAM-PPV, was tested as an alternative to current hexavalent chromium (Cr(VI-based Army wash primers. BAM-PPV was tested in both laboratory and field studies to determine its adhesive and corrosion-inhibiting properties when applied to steel and aluminum alloys. The Army Research Laboratory (ARL tests showed that BAM-PPV combined with an epoxy primer and the Army chemical agent-resistant coating (CARC topcoat met Army performance requirements for military coatings. After successful laboratory testing, the BAM-PPV was then field tested for one year at the Aberdeen Test Center (ATC. This field testing showed that BAM-PPV incorporated into the Army military coating survived with no delamination of the coating and only minor corrosion on the chip sites.

  15. Development of inhibitors of the 2C-methyl-D-erythritol 4-phosphate (MEP) pathway enzymes as potential anti-infective agents.

    Science.gov (United States)

    Masini, Tiziana; Hirsch, Anna K H

    2014-12-11

    Important pathogens such as Mycobacterium tuberculosis and Plasmodium falciparum, the causative agents of tuberculosis and malaria, respectively, and plants, utilize the 2C-methyl-D-erythritol 4-phosphate (MEP, 5) pathway for the biosynthesis of isopentenyl diphosphate (1) and dimethylallyl diphosphate (2), the universal precursors of isoprenoids, while humans exclusively utilize the alternative mevalonate pathway for the synthesis of 1 and 2. This distinct distribution, together with the fact that the MEP pathway is essential in numerous organisms, makes the enzymes of the MEP pathway attractive drug targets for the development of anti-infective agents and herbicides. Herein, we review the inhibitors reported over the past 2 years, in the context of the most important older developments and with a particular focus on the results obtained against enzymes of pathogenic organisms. We will also discuss new discoveries in terms of structural and mechanistic features, which can help to guide a rational development of inhibitors.

  16. Synthesis, radiolabeling and evaluation of novel amine guanidine derivatives as potential positron emission tomography tracers for the ion channel of the N-methyl-d-aspartate receptor.

    Science.gov (United States)

    Klein, Pieter J; Chomet, Marion; Metaxas, Athanasios; Christiaans, Johannes A M; Kooijman, Esther; Schuit, Robert C; Lammertsma, Adriaan A; van Berckel, Bart N M; Windhorst, Albert D

    2016-08-08

    The N-Methyl-d-Aspartate receptor (NMDAR) is involved in many neurological and psychiatric disorders including Alzheimer's disease and schizophrenia. The aim of this study was to develop a positron emission tomography (PET) ligand to assess the bio-availability of the NMDAR ion channel in vivo. A series of tri-N-substituted diarylguanidines was synthesized and their in vitro binding affinities for the NMDAR ion channel assessed in rat forebrain membrane fractions. Compounds 21, 23 and 26 were radiolabeled with either carbon-11 or fluorine-18 and ex vivo biodistribution and metabolite studies were performed in Wistar rats. Biodistribution studies showed high uptake especially in prefrontal cortex and lowest uptake in cerebellum. Pre-treatment with MK-801, however, did not decrease uptake of the radiolabeled ligands. In addition, all three ligands showed fast metabolism. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  17. Using WordNet for Building WordNets

    CERN Document Server

    Farreres, X; Farreres, Xavier; Rodriguez, Horacio; Rigau, German

    1998-01-01

    This paper summarises a set of methodologies and techniques for the fast construction of multilingual WordNets. The English WordNet is used in this approach as a backbone for Catalan and Spanish WordNets and as a lexical knowledge resource for several subtasks.

  18. Water-soluble antioxidant derivative poly(triethylene glycol methyl acrylate-co-α-tocopheryl acrylate) as a potential prodrug to enable localized neuroprotection.

    Science.gov (United States)

    Cao, Y; He, W

    2013-01-01

    Implantable microelectrode arrays (MEA) hold enormous hope for individuals with sensory or motor deficits. However, long-term function of MEA remains a critical hurdle. The objective of this study was to synthesize an antioxidant prodrug that can be delivered to the neural tissue around the implant and present a pharmacological depot to combat the injurious oxidative stress around the MEA. In this report, monomers of triethylene glycol methyl acrylate and α-tocopheryl acrylate, a synthetic derivative of the antioxidant α-tocopherol (vitamin E, Ve), were copolymerized to obtain poly(triethylene glycol methyl acrylate-co-α-tocopheryl acrylate) (PVT) with different compositions. In contrast to the poor water solubility of Ve, solubility of the PVT prodrug in water can reach as high as 3.1 mg ml(-1) (equivalent to 500 μM Ve) by tuning the copolymer composition. To demonstrate the applicability of the prodrug for MEA implants, PVT was successfully deposited on silicon substrates with poly(acrylic acid) (PAA) or tannic acid (TA) using the layer-by-layer technique mediated by hydrogen bonding. Ellipsometry and quartz crystal microbalance data showed that the multilayers of PAA/PVT were destructible at physiological pH. In contrast, multilayers of TA/PVT were stable. The PVT prodrug was non-cytotoxic toward A172 human astrocytes. Furthermore, PVT was able to protect astrocytes against oxidative stress exerted by H(2)O(2) in vitro. Using a free radical scavenging assay, the protection mechanism was attributed to the hydrolysis of the labile ester linkage and release of the active Ve. Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  19. Dissociation dynamics of methylal

    Energy Technology Data Exchange (ETDEWEB)

    Beaud, P.; Frey, H.-M.; Gerber, T.; Mischler, B.; Radi, P.P.; Tzannis, A.-P. [Paul Scherrer Inst. (PSI), Villigen (Switzerland)

    1999-08-01

    The dissociation of methylal is investigated using mass spectrometry, combined with a pyrolytic radical source and femtosecond pump probe experiments. Based on preliminary results two reaction paths of methylal dissociation are proposed and discussed. (author) 4 fig., 3 refs.

  20. swDMR: A Sliding Window Approach to Identify Differentially Methylated Regions Based on Whole Genome Bisulfite Sequencing.

    Directory of Open Access Journals (Sweden)

    Zhen Wang

    Full Text Available DNA methylation is a widespread epigenetic modification that plays an essential role in gene expression through transcriptional regulation and chromatin remodeling. The emergence of whole genome bisulfite sequencing (WGBS represents an important milestone in the detection of DNA methylation. Characterization of differential methylated regions (DMRs is fundamental as well for further functional analysis. In this study, we present swDMR (http://sourceforge.net/projects/swDMR/ for the comprehensive analysis of DMRs from whole genome methylation profiles by a sliding window approach. It is an integrated tool designed for WGBS data, which not only implements accessible statistical methods to perform hypothesis test adapted to two or more samples without replicates, but false discovery rate was also controlled by multiple test correction. Downstream analysis tools were also provided, including cluster, annotation and visualization modules. In summary, based on WGBS data, swDMR can produce abundant information of differential methylated regions. As a convenient and flexible tool, we believe swDMR will bring us closer to unveil the potential functional regions involved in epigenetic regulation.

  1. Proof nets for lingusitic analysis

    NARCIS (Netherlands)

    Moot, R.C.A.

    2002-01-01

    This book investigates the possible linguistic applications of proof nets, redundancy free representations of proofs, which were introduced by Girard for linear logic. We will adapt the notion of proof net to allow the formulation of a proof net calculus which is soundand complete for the

  2. Teaching Tennis for Net Success.

    Science.gov (United States)

    Young, Bryce

    1989-01-01

    A program for teaching tennis to beginners, NET (Net Easy Teaching) is described. The program addresses three common needs shared by tennis students: active involvement in hitting the ball, clearing the net, and positive reinforcement. A sample lesson plan is included. (IAH)

  3. Net4Care Ecosystem Website

    DEFF Research Database (Denmark)

    Christensen, Henrik Bærbak; Hansen, Klaus Marius; Rasmussen, Morten

    2012-01-01

    is a tele-monitoring scenario in which Net4Care clients are deployed in a gateway in private homes. Medical devices then connect to these gateways and transmit their observations to a Net4Care server. In turn the Net4Care server creates valid clinical HL7 documents, stores them in a national XDS repository...

  4. A novel method to quantify local CpG methylation density by regional methylation elongation assay on microarray

    Directory of Open Access Journals (Sweden)

    Qiao Yingjuan

    2008-01-01

    Full Text Available Abstract Background DNA methylation based techniques are important tools in both clinical diagnostics and therapeutics. But most of these methods only analyze a few CpG sites in a target region. Indeed, difference of site-specific methylation may also lead to a change of methylation density in many cases, and it has been found that the density of methylation is more important than methylation of single CpG site for gene silencing. Results We have developed a novel approach for quantitative analysis of CpG methylation density on the basis of microarray-based hybridization and incorporation of Cy5-dCTP into the Cy3 labeled target DNA by using Taq DNA Polymerase on microarray. The quantification is achieved by measuring Cy5/Cy3 signal ratio which is proportional to methylation density. This methylation-sensitive technique, termed RMEAM (regional methylation elongation assay on microarray, provides several advantages over existing methods used for methylation analysis. It can determine an exact methylation density of the given region, and has potential of high throughput. We demonstrate a use of this method in determining the methylation density of the promoter region of the tumor-related gene MLH1, TERT and MGMT in colorectal carcinoma patients. Conclusion This technique allows for quantitative analysis of regional methylation density, which is the representative of all allelic methylation patterns in the sample. The results show that this technique has the characteristics of simplicity, rapidness, specificity and high-throughput.

  5. Master Robotic Net

    Directory of Open Access Journals (Sweden)

    Vladimir Lipunov

    2010-01-01

    Full Text Available The main goal of the MASTER-Net project is to produce a unique fast sky survey with all sky observed over a single night down to a limiting magnitude of 19-20. Such a survey will make it possible to address a number of fundamental problems: search for dark energy via the discovery and photometry of supernovae (including SNIa, search for exoplanets, microlensing effects, discovery of minor bodies in the Solar System, and space-junk monitoring. All MASTER telescopes can be guided by alerts, and we plan to observe prompt optical emission from gamma-ray bursts synchronously in several filters and in several polarization planes.

  6. Art/Net/Work

    DEFF Research Database (Denmark)

    Andersen, Christian Ulrik; Lindstrøm, Hanne

    2006-01-01

    The seminar Art|Net|Work deals with two important changes in our culture. On one side, the network has become essential in the latest technological development. The Internet has entered a new phase, Web 2.0, including the occurrence of as ‘Wiki’s’, ‘Peer-2-Peer’ distribution, user controlled...... the praxis of the artist. We see different kinds of interventions and activism (including ‘hacktivism’) using the network as a way of questioning the invisible rules that govern public and semi-public spaces. Who ‘owns’ them? What kind of social relationships do they generate? On what principle...

  7. Evaluation of radioiodinated (R)-N-methyl-3-(2-iodophenoxy)-3-phenylpropanamine as a ligand for brain norepinephrine transporter imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kiyono, Yasushi; Kanegawa, Naoki; Kawashima, Hidekazu; Kitamura, Yoji; Iida, Yasuhiko; Saji, Hideo E-mail: hsaji@pharm.kyoto-u.ac.jp

    2004-02-01

    (R)-N-methyl-3-(2-iodophenoxy)-3-phenylpropanamine (MIPP) was evaluated as a radiopharmaceutical for investigating brain norepinephrine transporters (NET) by single photon emission computed tomography (SPECT). (R)-[{sup 125}I]MIPP was synthesized with high radiochemical yield (60%) and high radiochemical purity (> 98%). In biodistribution experiments, (R)-[{sup 125}I]MIPP indicated that the brain uptake of (R)-[{sup 125}I]MIPP was rapid and retained, and that the regional cerebral distribution was consistent with the density of NET. Moreover, the administration of desipramine decreased the accumulation of (R)-[{sup 125}I]MIPP in the brain. HPLC analysis of brain radioactivity showed that more than 90% was intact (R)-MIPP. These results suggested that (R)-[{sup 123}I]MIPP is a potential radiopharmaceutical for imaging brain NET.

  8. Polypyrrole-Grafted Coconut Shell Biological Carbon as a Potential Adsorbent for Methyl Tert-Butyl Ether Removal: Characterization and Adsorption Capability

    Directory of Open Access Journals (Sweden)

    Shanshan Li

    2017-01-01

    Full Text Available Methyl tert-butyl ether (MTBE has been used as a common gasoline additive worldwide since the late twentieth century, and it has become the most frequently detected groundwater pollutant in many countries. This study aimed to synthesize a novel microbial carrier to improve its adsorptive capacity for MTBE and biofilm formation, compared to the traditional granular activated carbon (GAC. A polypyrrole (PPy-modified GAC composite (PPy/GAC was synthesized, and characterized by Fourier transform infrared spectroscopy (FT-IR and Brunauer-Emmett-Teller (BET surface area analysis. The adsorption behaviors of MTBE were well described by the pseudo-second-order and Langmuir isotherm models. Furthermore, three biofilm reactors were established with PPy/GAC, PPy, and GAC as the carriers, respectively, and the degradation of MTBE under continuous flow was investigated. Compared to the biofilm reactors with PPy or GAC (which both broke after a period of operation, the PPy/GAC biofilm column produced stable effluents under variable treatment conditions with a long-term effluent MTBE concentration <20 μg/L. Pseudomonas aeruginosa and Acinetobacter pittii may be the predominant bacteria responsible for MTBE degradation in these biofilm reactors.

  9. Polypyrrole-Grafted Coconut Shell Biological Carbon as a Potential Adsorbent for Methyl Tert-Butyl Ether Removal: Characterization and Adsorption Capability.

    Science.gov (United States)

    Li, Shanshan; Qian, Keke; Wang, Shan; Liang, Kaiqiang; Yan, Wei

    2017-01-24

    Methyl tert-butyl ether (MTBE) has been used as a common gasoline additive worldwide since the late twentieth century, and it has become the most frequently detected groundwater pollutant in many countries. This study aimed to synthesize a novel microbial carrier to improve its adsorptive capacity for MTBE and biofilm formation, compared to the traditional granular activated carbon (GAC). A polypyrrole (PPy)-modified GAC composite (PPy/GAC) was synthesized, and characterized by Fourier transform infrared spectroscopy (FT-IR) and Brunauer-Emmett-Teller (BET) surface area analysis. The adsorption behaviors of MTBE were well described by the pseudo-second-order and Langmuir isotherm models. Furthermore, three biofilm reactors were established with PPy/GAC, PPy, and GAC as the carriers, respectively, and the degradation of MTBE under continuous flow was investigated. Compared to the biofilm reactors with PPy or GAC (which both broke after a period of operation), the PPy/GAC biofilm column produced stable effluents under variable treatment conditions with a long-term effluent MTBE concentration MTBE degradation in these biofilm reactors.

  10. Helminth.net: expansions to Nematode.net and an introduction to Trematode.net

    Science.gov (United States)

    Martin, John; Rosa, Bruce A.; Ozersky, Philip; Hallsworth-Pepin, Kymberlie; Zhang, Xu; Bhonagiri-Palsikar, Veena; Tyagi, Rahul; Wang, Qi; Choi, Young-Jun; Gao, Xin; McNulty, Samantha N.; Brindley, Paul J.; Mitreva, Makedonka

    2015-01-01

    Helminth.net (http://www.helminth.net) is the new moniker for a collection of databases: Nematode.net and Trematode.net. Within this collection we provide services and resources for parasitic roundworms (nematodes) and flatworms (trematodes), collectively known as helminths. For over a decade we have provided resources for studying nematodes via our veteran site Nematode.net (http://nematode.net). In this article, (i) we provide an update on the expansions of Nematode.net that hosts omics data from 84 species and provides advanced search tools to the broad scientific community so that data can be mined in a useful and user-friendly manner and (ii) we introduce Trematode.net, a site dedicated to the dissemination of data from flukes, flatworm parasites of the class Trematoda, phylum Platyhelminthes. Trematode.net is an independent component of Helminth.net and currently hosts data from 16 species, with information ranging from genomic, functional genomic data, enzymatic pathway utilization to microbiome changes associated with helminth infections. The databases’ interface, with a sophisticated query engine as a backbone, is intended to allow users to search for multi-factorial combinations of species’ omics properties. This report describes updates to Nematode.net since its last description in NAR, 2012, and also introduces and presents its new sibling site, Trematode.net. PMID:25392426

  11. NETS FOR PEACH PROTECTED CULTIVATION

    Directory of Open Access Journals (Sweden)

    Evelia Schettini

    2012-06-01

    Full Text Available The aim of this paper was to investigate the radiometric properties of coloured nets used to protect a peach cultivation. The modifications of the solar spectral distribution, mainly in the R and FR wavelength band, influence plant photomorphogenesis by means of the phytochrome and cryptochrome. The phytochrome response is characterized in terms of radiation rate in the red wavelengths (R, 600-700 nm to that in the farred radiation (FR, 700-800 nm, i.e. the R/FR ratio. The effects of the blue radiation (B, 400-500 nm is investigated by the ratio between the blue radiation and the far-red radiation, i.e. the B/FR ratio. A BLUE net, a RED net, a YELLOW net, a PEARL net, a GREY net and a NEUTRAL net were tested in Bari (Italy, latitude 41° 05’ N. Peach trees were located in pots inside the greenhouses and in open field. The growth of the trees cultivated in open field was lower in comparison to the growth of the trees grown under the nets. The RED, PEARL, YELLOW and GREY nets increased the growth of the trees more than the other nets. The nets positively influenced the fruit characteristics, such as fruit weight and flesh firmness.

  12. Automating Ontological Annotation with WordNet

    Energy Technology Data Exchange (ETDEWEB)

    Sanfilippo, Antonio P.; Tratz, Stephen C.; Gregory, Michelle L.; Chappell, Alan R.; Whitney, Paul D.; Posse, Christian; Paulson, Patrick R.; Baddeley, Bob L.; Hohimer, Ryan E.; White, Amanda M.

    2006-01-22

    Semantic Web applications require robust and accurate annotation tools that are capable of automating the assignment of ontological classes to words in naturally occurring text (ontological annotation). Most current ontologies do not include rich lexical databases and are therefore not easily integrated with word sense disambiguation algorithms that are needed to automate ontological annotation. WordNet provides a potentially ideal solution to this problem as it offers a highly structured lexical conceptual representation that has been extensively used to develop word sense disambiguation algorithms. However, WordNet has not been designed as an ontology, and while it can be easily turned into one, the result of doing this would present users with serious practical limitations due to the great number of concepts (synonym sets) it contains. Moreover, mapping WordNet to an existing ontology may be difficult and requires substantial labor. We propose to overcome these limitations by developing an analytical platform that (1) provides a WordNet-based ontology offering a manageable and yet comprehensive set of concept classes, (2) leverages the lexical richness of WordNet to give an extensive characterization of concept class in terms of lexical instances, and (3) integrates a class recognition algorithm that automates the assignment of concept classes to words in naturally occurring text. The ensuing framework makes available an ontological annotation platform that can be effectively integrated with intelligence analysis systems to facilitate evidence marshaling and sustain the creation and validation of inference models.

  13. Ontological Annotation with WordNet

    Energy Technology Data Exchange (ETDEWEB)

    Sanfilippo, Antonio P.; Tratz, Stephen C.; Gregory, Michelle L.; Chappell, Alan R.; Whitney, Paul D.; Posse, Christian; Paulson, Patrick R.; Baddeley, Bob; Hohimer, Ryan E.; White, Amanda M.

    2006-06-06

    Semantic Web applications require robust and accurate annotation tools that are capable of automating the assignment of ontological classes to words in naturally occurring text (ontological annotation). Most current ontologies do not include rich lexical databases and are therefore not easily integrated with word sense disambiguation algorithms that are needed to automate ontological annotation. WordNet provides a potentially ideal solution to this problem as it offers a highly structured lexical conceptual representation that has been extensively used to develop word sense disambiguation algorithms. However, WordNet has not been designed as an ontology, and while it can be easily turned into one, the result of doing this would present users with serious practical limitations due to the great number of concepts (synonym sets) it contains. Moreover, mapping WordNet to an existing ontology may be difficult and requires substantial labor. We propose to overcome these limitations by developing an analytical platform that (1) provides a WordNet-based ontology offering a manageable and yet comprehensive set of concept classes, (2) leverages the lexical richness of WordNet to give an extensive characterization of concept class in terms of lexical instances, and (3) integrates a class recognition algorithm that automates the assignment of concept classes to words in naturally occurring text. The ensuing framework makes available an ontological annotation platform that can be effectively integrated with intelligence analysis systems to facilitate evidence marshaling and sustain the creation and validation of inference models.

  14. Synthesis, characterization and metal coordination of a potential β-lactamase inhibitor: 5-Methyl-2-phenoxymethyl-3-H-imidazole-4-carboxylic acid (PIMA

    Directory of Open Access Journals (Sweden)

    Chiara Romagnoli

    2017-12-01

    Full Text Available Among relevant metal ions in biological systems, zinc and iron play a key role as active partners of the catalytic machinery. In particular, the inhibition of metal enzymes that are involved in physiological and pathological processes has been deeply investigated for the rational design of selective and efficient drugs based on chelators. Since imidazole histidine residue is one of the most versatile sites in proteins, especially in enzymes acting in the presence of metal ions as cofactors, in this work the synthesis and characterization of a new imidazole derivative, namely 5-methyl-2-phenoxymethyl-3-H-imidazole-4-carboxylic acid (PIMA is reported. PIMA was designed as metallo-β-lactamase inhibitor thanks to its similarity with penicillin V, a β-lactam antibiotic inactivated by metallo-β-lactamase, for which there are no commercially available inhibitors. The evaluation of PIMA coordinating ability toward iron, zinc, and gallium, these latter selected as a non-paramagnetic probe for iron, is performed by theoretical DFT calculations and in solution by experimental techniques, i.e. potentiometry, UV–vis and NMR spectroscopy. PIMA exhibits an efficient metal chelating ability; the prevailing species in physiological condition are ML3 for Fe3+ and Ga3+ and ML2 for Zn2+, in which chelation is due to deprotonated carboxylic oxygen and imidazole nitrogen in the N,O donor set. The demonstrated ability of PIMA to chelate zinc ion, combined with its structure similarity with penicillin V, supports further exploration of this imidazole-4-carboxylate as metallo-β-lactamase inhibitor.

  15. Characterization of mammary adenocarcinomas in male rats after N-methyl-N-nitrosourea exposure--Potential for human male breast cancer model.

    Science.gov (United States)

    Yoshizawa, Katsuhiko; Yuki, Michiko; Kinoshita, Yuichi; Emoto, Yuko; Yuri, Takashi; Shikata, Nobuaki; Elmore, Susan A; Tsubura, Airo

    2016-05-01

    The frequency of breast cancer in men is extremely rare, reported to be less than 1% and there is currently no available animal model for male mammary tumors. We compared the characteristics of various immunohistochemical markers in N-methyl-N-nitrosourea (MNU)-induced mammary adenocarcinomas in male and female Crj:CD(SD)IGS rats including: estrogen receptor α (ER), progesterone receptor (PgR), androgen receptor (AR), receptor tyrosine-protein kinase erbB-2 (HER2), GATA binding protein 3 (GATA3), and proliferating cell nuclear antigen (PCNA). Female mammary adenocarcinomas were strongly positive in the nuclei of tumor cells for PCNA and ER (100%) with only 60% and 53% expressing PgR and GATA3, respectively. 100% of male adenocarcinomas also exhibited strongly positive expression in the nuclei of tumor cells for PCNA, with 25% expressing AR and only 8% showing positivity for ER. Male carcinomas did not express PgR or GATA3 and none of the tumors, male or female, were positive for HER2. Based on the observed ER and PgR positivity and HER2 negativity within these tumors, MNU-induced mammary adenocarcinomas in female rats appear to be hormonally dependent, similar to human luminal A type breast cancer. In contrast, MNU-induced mammary adenocarcinomas in male rats showed no reactivity for ER, PgR, HER2 or GATA3, suggesting no hormonal dependency. Both male and female adenocarcinomas showed high proliferating activity by PCNA immunohistochemistry. Based on our literature review, human male breast cancers are mainly dependent on ER and/or PgR, therefore the biological pathogenesis of MNU-induced male mammary cancer in rats may differ from that of male breast cancer in humans. Copyright © 2016 Elsevier GmbH. All rights reserved.

  16. Impact of folate supplementation on the efficacy of sulfadoxine/pyrimethamine in preventing malaria in pregnancy: the potential of 5-methyl-tetrahydrofolate.

    Science.gov (United States)

    Nzila, Alexis; Okombo, John; Molloy, Anne M

    2014-02-01

    Malaria remains the leading cause of mortality and morbidity in children under the age of 5 years and pregnant women. To counterbalance the malaria burden in pregnancy, an intermittent preventive treatment strategy has been developed. This is based on the use of the antifolate sulfadoxine/pyrimethamine, taken at specified intervals during pregnancy, and reports show that this approach reduces the malaria burden in pregnancy. Pregnancy is also associated with the risk of neural tube defects (NTDs), especially in women with low folate status, and folic acid supplementation is recommended in pregnancy to lower the risk of NTDs. Thus, in malaria-endemic areas, pregnant women have to take both antifolate medication to prevent malaria and folic acid to lower the risk of NTDs. However, the concomitant use of folate and antifolate is associated with a decrease in antifolate efficacy, exposing pregnant women to malaria. Thus, there is genuine concern that this strategy may not be appropriate. We have reviewed work carried out on malaria folate metabolism and antifolate efficacy in the context of folate supplementation. This review shows that: (i) the folate supplementation effect on antifolate efficacy is dose-dependent, and folic acid doses required to protect pregnant women from NTDs will not decrease antifolate activity; and (ii) 5-methyl-tetrahydrofolate, the predominant form of folate in the blood circulation, could be administered (even at high dose) concomitantly with antifolate without affecting antifolate efficacy. Thus, strategies exist to protect pregnant women from malaria while maintaining adequate folate levels in the body to reduce the occurrence of NTDs.

  17. Reconciling catch differences from multiple fishery independent gill net surveys

    Science.gov (United States)

    Kraus, Richard T.; Vandergoot, Christopher; Kocovsky, Patrick M.; Rogers, Mark W.; Cook, H. Andrew; Brenden, Travis O.

    2017-01-01

    Fishery independent gill net surveys provide valuable demographic information for population assessment and resource management, but relative to net construction, the effects of ancillary species, and environmental variables on focal species catch rates are poorly understood. In response, we conducted comparative deployments with three unique, inter-agency, survey gill nets used to assess walleye Sander vitreus in Lake Erie. We used an information-theoretic approach with Akaike’s second-order information criterion (AICc) to evaluate linear mixed models of walleye catch as a function of net type (multifilament and two types of monofilament netting), mesh size (categorical), Secchi depth, temperature, water depth, catch of ancillary species, and interactions among selected variables. The model with the greatest weight of evidence showed that walleye catches were positively associated with potential prey and intra-guild predators and negatively associated with water depth and temperature. In addition, the multifilament net had higher average walleye catches than either of the two monofilament nets. Results from this study both help inform decisions about proposed gear changes to stock assessment surveys in Lake Erie, and advance our understanding of how multispecies associations explain variation in gill net catches. Of broader interest to fishery-independent gill net studies, effects of abiotic variables and ancillary species on focal specie’s catch rates were small in comparison with net characteristics of mesh size or twine type.

  18. The equivalency between logic Petri workflow nets and workflow nets.

    Science.gov (United States)

    Wang, Jing; Yu, ShuXia; Du, YuYue

    2015-01-01

    Logic Petri nets (LPNs) can describe and analyze batch processing functions and passing value indeterminacy in cooperative systems. Logic Petri workflow nets (LPWNs) are proposed based on LPNs in this paper. Process mining is regarded as an important bridge between modeling and analysis of data mining and business process. Workflow nets (WF-nets) are the extension to Petri nets (PNs), and have successfully been used to process mining. Some shortcomings cannot be avoided in process mining, such as duplicate tasks, invisible tasks, and the noise of logs. The online shop in electronic commerce in this paper is modeled to prove the equivalence between LPWNs and WF-nets, and advantages of LPWNs are presented.

  19. Electrochemical biosensing strategies for DNA methylation analysis.

    Science.gov (United States)

    Hossain, Tanvir; Mahmudunnabi, Golam; Masud, Mostafa Kamal; Islam, Md Nazmul; Ooi, Lezanne; Konstantinov, Konstantin; Hossain, Md Shahriar Al; Martinac, Boris; Alici, Gursel; Nguyen, Nam-Trung; Shiddiky, Muhammad J A

    2017-08-15

    DNA methylation is one of the key epigenetic modifications of DNA that results from the enzymatic addition of a methyl group at the fifth carbon of the cytosine base. It plays a crucial role in cellular development, genomic stability and gene expression. Aberrant DNA methylation is responsible for the pathogenesis of many diseases including cancers. Over the past several decades, many methodologies have been developed to detect DNA methylation. These methodologies range from classical molecular biology and optical approaches, such as bisulfite sequencing, microarrays, quantitative real-time PCR, colorimetry, Raman spectroscopy to the more recent electrochemical approaches. Among these, electrochemical approaches offer sensitive, simple, specific, rapid, and cost-effective analysis of DNA methylation. Additionally, electrochemical methods are highly amenable to miniaturization and possess the potential to be multiplexed. In recent years, several reviews have provided information on the detection strategies of DNA methylation. However, to date, there is no comprehensive evaluation of electrochemical DNA methylation detection strategies. Herein, we address the recent developments of electrochemical DNA methylation detection approaches. Furthermore, we highlight the major technical and biological challenges involved in these strategies and provide suggestions for the future direction of this important field. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Exploring the Potential use of Photo-Selective Nets for Fruit Growth Regulation in Apple Explorando el uso Potencial de Mallas Foto-Selectivas para la Regulación del Crecimiento de Fruto en Manzano

    Directory of Open Access Journals (Sweden)

    Richard M Bastías

    2012-06-01

    Full Text Available The effect of shading (i.e. reduction of sunlight availability on fruit growth physiology has been widely studied in apple (Malus domestica Borkh., but little knowledge exist about fruit growth responses to changes in the light spectrum. The aim of the present research was to study the effect of use of colored nets with differential sunlight transmission in the blue (B, 400-500 nm, red (R, 600-700 nm and far-red (FR, 700-800 nm spectra on apple fruit growth and physiological associated responses. Three year old 'Fuji' apple trees were covered with 40% photo-selective blue and red shade nets, 40% neutral grey shade net, and 20% neutral white net as control. Red and blue net reduced in the same proportion (27% the photosynthetically active radiation with respect to control. However, blue net increased by 30% and reduced by 10% the B:R and R:FR the light relations, respectively. Maximal fruit growth rate under blue and grey nets was 15-20% greater than control. Fruit weight under blue net was 17% greater than control, but no significant differences in fruit weight were found among red net and control. Leaf photosynthesis and total leaf area under blue net were 28% and 30% higher than control, respectively; with ensuing positive effect on tree net C assimilation rate and total dry matter production. Results suggest that shifting the B, R, and FR light composition with photo-selective nets could be a useful tool to manipulate the photosynthetic and morphogenetic process regulating the carbohydrate availability for apple fruit growth.El efecto del sombreado (i.e. reducción de la cantidad de luz solar sobre la fisiología de crecimiento de fruto ha sido ampliamente estudiado en manzano (Malus domestica Borkh., pero existe poco conocimiento sobre respuestas de crecimiento del fruto a cambios en el espectro de la luz. El objetivo de la presente investigación fue estudiar el efecto del uso de mallas de color con transmisión diferencial de la luz en el

  1. A Novel Schiff Base of 3-acetyl-4-hydroxy-6-methyl-(2Hpyran-2-one and 2,2'-(ethylenedioxydiethylamine as Potential Corrosion Inhibitor for Mild Steel in Acidic Medium

    Directory of Open Access Journals (Sweden)

    Jonnie N. Asegbeloyin

    2015-05-01

    Full Text Available The corrosion inhibition activity of a newly synthesized Schiff base (SB from 3-acetyl-4-hydroxy-6-methyl-(2H-pyran-2-one and 2,2'-(ethylenedioxydiethylamine was investigated on the corrosion of mild steel in 1 M HCl solution using potentiodynamic polarization and electrochemical impedance spectroscopic techniques. Ultraviolet-visible (UV-vis and Raman spectroscopic techniques were used to study the chemical interactions between SB and mild steel surface. SB was found to be a relatively good inhibitor of mild steel corrosion in 1 M HCl. The inhibition efficiency increases with increase in concentration of SB. The inhibition activity of SB was ascribed to its adsorption onto mild steel surface, through physisorption and chemisorption, and described by the Langmuir adsorption model. Quantum chemical calculations indicated the presence of atomic sites with potential nucleophilic and electrophilic characteristics with which SB can establish electronic interactions with the charged mild steel surface.

  2. Coloured Petri Nets

    DEFF Research Database (Denmark)

    Jensen, Kurt; Kristensen, Lars Michael

    studies that illustrate the practical use of CPN modelling and validation for design, specification, simulation, verification and implementation in various application domains. Their presentation primarily aims at readers interested in the practical use of CPN. Thus all concepts and constructs are first......Coloured Petri Nets (CPN) is a graphical language for modelling and validating concurrent and distributed systems, and other systems in which concurrency plays a major role. The development of such systems is particularly challenging because of inherent intricacies like possible nondeterminism...... and the immense number of possible execution sequences. In this textbook, Jensen and Kristensen introduce the constructs of the CPN modelling language and present the related analysis methods in detail. They also provide a comprehensive road map for the practical use of CPN by showcasing selected industrial case...

  3. Total- and methyl-mercury concentrations and methylation rates across the freshwater to hypersaline continuum of the Great Salt Lake, Utah, USA

    Science.gov (United States)

    Johnson, William P.; Swanson, Neil; Black, Brooks; Rudd, Abigail; Carling, Gregory; Fernandez, Diego P.; Luft, John; Van Leeuwen, Jim; Marvin-DiPasquale, Mark C.

    2015-01-01

    We examined mercury (Hg) speciation in water and sediment of the Great Salt Lake and surrounding wetlands, a locale spanning fresh to hypersaline and oxic to anoxic conditions, in order to test the hypothesis that spatial and temporal variations in Hg concentration and methylation rates correspond to observed spatial and temporal trends in Hg burdens previously reported in biota. Water column, sediment, and pore water concentrations of methylmercury (MeHg) and total mercury (THg), as well as related aquatic chemical parameters were examined. Inorganic Hg(II)-methylation rates were determined in selected water column and sediment subsamples spiked with inorganic divalent mercury (204Hg(II)). Net production of Me204Hg was expressed as apparent first-order rate constants for methylation (kmeth), which were also expanded to MeHg production potential (MPP) rates via combination with tin reducible ‘reactive’ Hg(II) (Hg(II)R) as a proxy for bioavailable Hg(II). Notable findings include: 1) elevated Hg concentrations previously reported in birds and brine flies were spatially proximal to the measured highest MeHg concentrations, the latter occurring in the anoxic deep brine layer (DBL) of the Great Salt Lake; 2) timing of reduced Hg(II)-methylation rates in the DBL (according to both kmeth and MPP) coincides with reduced Hg burdens among aquatic invertebrates (brine shrimp and brine flies) that act as potential vectors of Hg propagation to the terrestrial ecosystem; 3) values ofkmeth were found to fall within the range reported by other studies; and 4) MPP rates were on the lower end of the range reported in methodologically comparable studies, suggesting the possibility that elevated MeHg in the anoxic deep brine layer results from its accumulation and persistence in this quasi-isolated environment, due to the absence of light (restricting abiotic photo demethylation) and/or minimal microbiological demethylation.

  4. Total- and methyl-mercury concentrations and methylation rates across the freshwater to hypersaline continuum of the Great Salt Lake, Utah, USA.

    Science.gov (United States)

    Johnson, William P; Swanson, Neil; Black, Brooks; Rudd, Abigail; Carling, Greg; Fernandez, Diego P; Luft, John; Van Leeuwen, Jim; Marvin-DiPasquale, Mark

    2015-04-01

    We examined mercury (Hg) speciation in water and sediment of the Great Salt Lake and surrounding wetlands, a locale spanning fresh to hypersaline and oxic to anoxic conditions, in order to test the hypothesis that spatial and temporal variations in Hg concentration and methylation rates correspond to observed spatial and temporal trends in Hg burdens previously reported in biota. Water column, sediment, and pore water concentrations of methylmercury (MeHg) and total mercury (THg), as well as related aquatic chemical parameters were examined. Inorganic Hg(II)-methylation rates were determined in selected water column and sediment subsamples spiked with inorganic divalent mercury (204Hg(II)). Net production of Me204Hg was expressed as apparent first-order rate constants for methylation (kmeth), which were also expanded to MeHg production potential (MPP) rates via combination with tin reducible 'reactive' Hg(II) (Hg(II)R) as a proxy for bioavailable Hg(II). Notable findings include: 1) elevated Hg concentrations previously reported in birds and brine flies were spatially proximal to the measured highest MeHg concentrations, the latter occurring in the anoxic deep brine layer (DBL) of the Great Salt Lake; 2) timing of reduced Hg(II)-methylation rates in the DBL (according to both kmeth and MPP) coincides with reduced Hg burdens among aquatic invertebrates (brine shrimp and brine flies) that act as potential vectors of Hg propagation to the terrestrial ecosystem; 3) values of kmeth were found to fall within the range reported by other studies; and 4) MPP rates were on the lower end of the range reported in methodologically comparable studies, suggesting the possibility that elevated MeHg in the anoxic deep brine layer results from its accumulation and persistence in this quasi-isolated environment, due to the absence of light (restricting abiotic photo demethylation) and/or minimal microbiological demethylation. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Design and Synthesis of Analogues of Marine Natural Product Galaxamide, an N-methylated Cyclic Pentapeptide, as Potential Anti-Tumor Agent in Vitro.

    Science.gov (United States)

    Lunagariya, Jignesh; Zhong, Shenghui; Chen, Jianwei; Bai, Defa; Bhadja, Poonam; Long, Weili; Liao, Xiaojian; Tang, Xiaoli; Xu, Shihai

    2016-09-03

    Herein, we report design and synthesis of novel 26 galaxamide analogues with N-methylated cyclo-pentapeptide, and their in vitro anti-tumor activity towards the panel of human tumor cell line, such as, A549, A549/DPP, HepG2 and SMMC-7721 using MTT assay. We have also investigated the effect of galaxamide and its representative analogues on growth, cell-cycle phases, and induction of apoptosis in SMMC-7721 cells in vitro. Reckon with the significance of conformational space and N-Me aminoacid (aa) comprising this compound template, we designed the analogues with modification in N-Me-aa position, change in aa configuration from l to d aa and substitute one Leu-aa to d/l Phe-aa residue with respective to the parent structure. The efficient solid phase parallel synthesis approach is employed for the linear pentapeptide residue containing N-Me aa, followed by solution phase macrocyclisation to afford target cyclo pentapeptide compounds. In the present study, all galaxamide analogues exhibited growth inhibition in A549, A549/DPP, SMMC-7721 and HepG2 cell lines. Compounds 6, 18, and 22 exhibited interesting activities towards all cell line tested, while Compounds 1, 4, 15, and 22 showed strong activity towards SMMC-7221 cell line in the range of 1-2 μg/mL IC50. Flow cytometry experiment revealed that galaxamide analogues namely Compounds 6, 18, and 22 induced concentration dependent SMMC-7721 cell apoptosis after 48 h. These compounds induced G0/G1 phase cell-cycle arrest and morphological changes indicating induction of apoptosis. Thus, findings of our study suggest that the galaxamide and its analogues 6, 18 and 22 exerted growth inhibitory effect on SMMC-7721 cells by arresting the cell cycle in the G0/G1 phase and inducing apoptosis. Compound 1 showed promising anti-tumor activity towards SMMC-7721 cancer cell line, which is 9 and 10 fold higher than galaxamide and reference DPP (cisplatin), respectively.

  6. NETS - Danish participation. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Alsen, S. (Grontmij - Carl Bro, Glostrup (Denmark)); Theel, C. (Baltic Sea Solutions, Holeby (Denmark))

    2008-12-15

    Within the NICe-funded project 'Nordic Environmental Technology Solutions (NETS)' a new type of networking at the Nordic level was organized in order to jointly exploit the rapidly growing market potential in the environmental technology sector. The project aimed at increased and professionalized commercialization of Nordic Cleantech in energy and water business segments through 1) closer cooperation and joint marketing activities, 2) a website, 3) cleantech product information via brochures and publications 4) and participating in relevant trade fairs and other industry events. Facilitating business-to-business activities was another core task for the NETS project partners from Norway, Sweden, Finland and Denmark with the aim to encourage total solutions for combined Cleantech system offers. The project has achieved to establish a Cleantech register of 600 Nordic Cleantech companies, a network of 86 member enterprises, produced several publications and brochures for direct technology promotion and a website for direct access to company profiles and contact data. The project partners have attended 14 relevant international Cleantech trade fairs and conferences and facilitated business-to-business contacts added by capacity building offers through two company workshops. The future challenge for the project partners and Nordic Cleantech will be to coordinate the numerous efforts within the Nordic countries in order to reach concerted action and binding of member companies for reliable services, an improved visibility and knowledge exchange. With Cleantech's growing market influence and public awareness, the need to develop total solutions is increasing likewise. Marketing efforts should be encouraged cross-sectional and cross-border among the various levels of involved actors from both the public and the private sector. (au)

  7. Methylation of the SLC6a2 gene promoter in major depression and panic disorder.

    Directory of Open Access Journals (Sweden)

    Richard Bayles

    Full Text Available Reduced function of the noradrenaline transporter (NET has been demonstrated in patients with major depressive disorder (MDD and panic disorder. Attempts to explain NET dysfunction in MDD and panic disorder by genetic variation in the NET gene SLC6a2 have been inconclusive. Transcriptional silencing of the SLC6a2 gene may be an alternative mechanism which can lead to NET dysfunction independent of DNA sequence. The objective of this study was to characterise the DNA methylation state of the SLC6a2 gene promoter in patients with MDD and panic disorder. SLC6a2 promoter methylation was also analysed before and after antidepressant treatment. This study was performed with DNA from blood, using bisulphite sequencing and EpiTYPER methylation analyses. Patients with MDD or panic disorder were not found to differ significantly from healthy controls in the pattern of methylation of the SLC6a2 gene promotor. While significant correlations between methylation levels at some CpG sites and physiological measures were identified, overall the variation in DNA methylation between patients was small, and the significance of this variation remains equivocal. No significant changes in SLC6a2 promoter methylation were observed in response to antidepressant treatment. Further in-depth analysis of alternative mechanisms of transcriptional regulation of the SLC6a2 gene in human health and disease would be of value.

  8. A High Molar Extinction Coefficient Ru(II Complex Functionalized with cis-Dithiocyanato-bis-(9-anthracenyl-10-(2-methyl-2-butenoic acid-1,10-phenanthroline: Potential Sensitizer for Stable Dye-Sensitized Solar Cells

    Directory of Open Access Journals (Sweden)

    Adewale O. Adeloye

    2014-01-01

    Full Text Available New heteroleptic ruthenium(II complex was formulated as [Ru(L12(NCS2], where L1 = 9-anthracenyl-10-(2-methyl-2-butenoic acid-1,10-phenanthroline was synthesized and its photophysical properties were studied and compared to previously reported analogue complex containing no anthracene moiety [Ru(L22(NCS2], L2 = (2-methyl-2-butenoic acid-1,10-phenanthroline. The two complexes though exhibit very strong molar extinction coefficient values; however, [Ru(L12(NCS2] shows better characteristic broad and intense metal-to-ligand charge transfer (MLCT absorption band and higher molar absorptivity coefficient at (λmax=522 nm, ε=6.60×104 M−1 cm−1 than that of [Ru(L22(NCS2] complex, (λmax=446 nm, ε=4.82×104 M−1 cm−1. At room temperature, long wavelength emissions with strong intensity ratio centered at 660 nm were recorded for [Ru(L12(NCS2] complex with a bathochromic shift (λem=700 nm for [Ru(L22(NCS2] complex. It was shown that the luminescence wavelength characteristic of the complexes may be a function relating to the increasing length of π-conjugation and/or molecular weight. A preliminary cyclic voltammetry of [Ru(L12(NCS2] complex also exhibits good electroredox activity with oxidation potential of about 1.04 V, significantly better than other Ru(II polypyridine complexes containing bidentate ligands.

  9. Linear Logic on Petri Nets

    DEFF Research Database (Denmark)

    Engberg, Uffe Henrik; Winskel, Glynn

    This article shows how individual Petri nets form models of Girard's intuitionistic linear logic. It explores questions of expressiveness and completeness of linear logic with respect to this interpretation. An aim is to use Petri nets to give an understanding of linear logic and give some apprai...

  10. Reference Guide Microsoft.NET

    NARCIS (Netherlands)

    Zee M van der; Verspaij GJ; Rosbergen S; IMP; NMD

    2003-01-01

    Developers, administrators and managers can get more understanding of the .NET technology with this report. They can also make better choices how to use this technology. The report describes the results and conclusions of a study of the usability for the RIVM of this new generation .NET development

  11. Net neutrality and audiovisual services

    NARCIS (Netherlands)

    van Eijk, N.; Nikoltchev, S.

    2011-01-01

    Net neutrality is high on the European agenda. New regulations for the communication sector provide a legal framework for net neutrality and need to be implemented on both a European and a national level. The key element is not just about blocking or slowing down traffic across communication

  12. A Small Universal Petri Net

    Directory of Open Access Journals (Sweden)

    Dmitry A. Zaitsev

    2013-09-01

    Full Text Available A universal deterministic inhibitor Petri net with 14 places, 29 transitions and 138 arcs was constructed via simulation of Neary and Woods' weakly universal Turing machine with 2 states and 4 symbols; the total time complexity is exponential in the running time of their weak machine. To simulate the blank words of the weakly universal Turing machine, a couple of dedicated transitions insert their codes when reaching edges of the working zone. To complete a chain of a given Petri net encoding to be executed by the universal Petri net, a translation of a bi-tag system into a Turing machine was constructed. The constructed Petri net is universal in the standard sense; a weaker form of universality for Petri nets was not introduced in this work.

  13. DNA methylation in plants.

    Science.gov (United States)

    Vanyushin, B F

    2006-01-01

    DNA in plants is highly methylated, containing 5-methylcytosine (m5C) and N6-methyladenine (m6A); m5C is located mainly in symmetrical CG and CNG sequences but it may occur also in other non-symmetrical contexts. m6A but not m5C was found in plant mitochondrial DNA. DNA methylation in plants is species-, tissue-, organelle- and age-specific. It is controlled by phytohormones and changes on seed germination, flowering and under the influence of various pathogens (viral, bacterial, fungal). DNA methylation controls plant growth and development, with particular involvement in regulation of gene expression and DNA replication. DNA replication is accompanied by the appearance of under-methylated, newly formed DNA strands including Okazaki fragments; asymmetry of strand DNA methylation disappears until the end of the cell cycle. A model for regulation of DNA replication by methylation is suggested. Cytosine DNA methylation in plants is more rich and diverse compared with animals. It is carried out by the families of specific enzymes that belong to at least three classes of DNA methyltransferases. Open reading frames (ORF) for adenine DNA methyltransferases are found in plant and animal genomes, and a first eukaryotic (plant) adenine DNA methyltransferase (wadmtase) is described; the enzyme seems to be involved in regulation of the mitochondria replication. Like in animals, DNA methylation in plants is closely associated with histone modifications and it affects binding of specific proteins to DNA and formation of respective transcription complexes in chromatin. The same gene (DRM2) in Arabidopsis thaliana is methylated both at cytosine and adenine residues; thus, at least two different, and probably interdependent, systems of DNA modification are present in plants. Plants seem to have a restriction-modification (R-M) system. RNA-directed DNA methylation has been observed in plants; it involves de novo methylation of almost all cytosine residues in a region of si

  14. Dietary and lifestyle factors of DNA methylation.

    Science.gov (United States)

    Lim, Unhee; Song, Min-Ae

    2012-01-01

    Lifestyle factors, such as diet, smoking, physical activity, and body weight management, are known to constitute the majority of cancer causes. Epigenetics has been widely proposed as a main mechanism that mediates the reversible effects of dietary and lifestyle factors on carcinogenesis. This chapter reviews human studies on potential dietary and lifestyle determinants of DNA methylation. Apart from a few prospective investigations and interventions of limited size and duration, evidence mostly comes from cross-sectional observational studies and supports some associations. Studies to date suggest that certain dietary components may alter genomic and gene-specific DNA methylation levels in systemic and target tissues, affecting genomic stability and transcription of tumor suppressors and oncogenes. Most data and supportive evidence exist for folate, a key nutritional factor in one-carbon metabolism that supplies the methyl units for DNA methylation. Other candidate bioactive food components include alcohol and other key nutritional factors of one-carbon metabolism, polyphenols and flavonoids in green tea, phytoestrogen, and lycopene. Some data also support a link of DNA methylation with physical activity and energy balance. Effects of dietary and lifestyle exposures on DNA methylation may be additionally modified by common genetic variants, environmental carcinogens, and infectious agents, an aspect that remains largely unexplored. In addition, growing literature supports that the environmental conditions during critical developmental stages may influence later risk of metabolic disorders in part through persistent programming of DNA methylation. Further research of these modifiable determinants of DNA methylation will improve our understanding of cancer etiology and may present certain DNA methylation markers as attractive surrogate endpoints for prevention research. Considering the plasticity of epigenetic marks and correlated nature of lifestyle factors, more

  15. Recovery of methane from anaerobic process effluent using poly-di-methyl-siloxane membrane contactors.

    Science.gov (United States)

    Cookney, J; Cartmell, E; Jefferson, B; McAdam, E J

    2012-01-01

    This paper demonstrates the potential for recovering dissolved methane from low temperature anaerobic processes treating domestic wastewater. In the absence of methane recovery, ca. 45% of the produced methane is released as a fugitive emission which results in a net carbon footprint of -0.47 kg CO(2e) m(-3). A poly-di-methyl-siloxane (PDMS) membrane contactor was applied to support sweep gas desorption of dissolved methane using nitrogen. The dense membrane structure controlled gaseous mass transfer thus recovery was maximised at low liquid velocities. At the lowest liquid velocity, V(L), of 0.0025 m s(-1), 72% of the dissolved methane was recovered. A vacuum was also trialled as an alternative to sweep-gas operation. At vacuum pressures below 30 mbar, reasonable methane recovery was observed at an intermediate V(L) of 0.0056 m s(-1). Results from this study demonstrate that dissolved methane recovery could increase net electrical production from low temperature anaerobic processes by ca. +0.043 kWh(e) m(-3) and reduce the net carbon footprint to +0.01 kg CO(2e) m(-3). However, further experimental work to optimise the gas-side hydrodynamics is required as well as validation of the long-term impacts of biofouling on process performance.

  16. High-level Petri Nets

    DEFF Research Database (Denmark)

    High-level Petri nets are now widely used in both theoretical analysis and practical modelling of concurrent systems. The main reason for the success of this class of net models is that they make it possible to obtain much more succinct and manageable descriptions than can be obtained by means...... of low-level Petri nets - while, on the other hand, they still offer a wide range of analysis methods and tools. The step from low-level nets to high-level nets can be compared to the step from assembly languages to modern programming languages with an elaborated type concept. In low-level nets...... there is only one kind of token and this means that the state of a place is described by an integer (and in many cases even by a boolean). In high-level nets each token can carry a complex information/data - which, e.g., may describe the entire state of a process or a data base. Today most practical...

  17. Dynamics and design of space nets for orbital capture

    CERN Document Server

    Yang, Leping; Zhen, Ming; Liu, Haitao

    2017-01-01

    This book covers the topics of theoretical principles, dynamics model and algorithm, mission analysis, system design and experimental studies of space nets system, aiming to provide an initial framework in this field and serve as a ready reference for those interested. Space nets system represents a forefront field in future development of aerospace technologies. However, it involves new challenges and problems such as nonlinear and distorted nets structure, complex rigid flexible coupling dynamics, orbital transfer of space flexible composite and dynamics control. Currently, no comprehensive books on space nets dynamics and design are available, so potential readers can get to know the working mechanism, dynamics elements, and mission design of the space nets system from a Chinese perspective.

  18. Conformal Nets II: Conformal Blocks

    Science.gov (United States)

    Bartels, Arthur; Douglas, Christopher L.; Henriques, André

    2017-08-01

    Conformal nets provide a mathematical formalism for conformal field theory. Associated to a conformal net with finite index, we give a construction of the `bundle of conformal blocks', a representation of the mapping class groupoid of closed topological surfaces into the category of finite-dimensional projective Hilbert spaces. We also construct infinite-dimensional spaces of conformal blocks for topological surfaces with smooth boundary. We prove that the conformal blocks satisfy a factorization formula for gluing surfaces along circles, and an analogous formula for gluing surfaces along intervals. We use this interval factorization property to give a new proof of the modularity of the category of representations of a conformal net.

  19. Neuroprotective potential of quercetin in combination with piperine against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity

    Directory of Open Access Journals (Sweden)

    Shamsher Singh

    2017-01-01

    Full Text Available 1-Methy-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP is a neurotoxin that selectively damages dopaminergic neurons in the substantia nigra pars compacta and induces Parkinson's like symptoms in rodents. Quercetin (QC is a natural polyphenolic bioflavonoid with potent antioxidant and anti-inflammatory properties but lacks of clinical attraction due to low oral bioavailability. Piperine is a well established bioavailability enhancer used pre-clinically to improve the bioavailability of antioxidants (e.g., Quercetin. Therefore, the present study was designed to evaluate the neuroprotective potential of QC together with piperine against MPTP-induced neurotoxicity in rats. MPTP (100 μg/μL/rat, bilaterally was injected intranigrally on days 1, 4 and 7 using a digital stereotaxic apparatus. QC (25 and 50 mg/kg, intragastrically and QC (25 mg/kg, intragastrically in combination with piperine (2.5 mg/kg, intragastrically were administered daily for 14 days starting from day 8 after the 3rd injection of MPTP. On day 22, animals were sacrificed and the striatum was isolated for oxidative stress parameter (thiobarbituric acid reactive substances, nitrite and glutathione, neuroinflammatory cytokine (interleukin-1β, interleukin-6, and tumor necrosis factor-α and neurotransmitter (dopamine, norepinephrine, serotonin, gamma-aminobutyric acid, glutamate, 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindoleacetic acid evaluations. Bilateral infusion of MPTP into substantia nigra pars compacta led to significant motor deficits as evidenced by impairments in locomotor activity and rotarod performance in open field test and grip strength and narrow beam walk performance. Both QC (25 and 50 mg/kg and QC (25 mg/kg in combination with piperine (2.5 mg/kg, in particular the combination therapy, significantly improved MPTP-induced behavioral abnormalities in rats, reversed the abnormal alterations of neurotransmitters in the striatum, and alleviated

  20. Neuroprotective potential of Quercetin in combination with piperine against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity.

    Science.gov (United States)

    Singh, Shamsher; Jamwal, Sumit; Kumar, Puneet

    2017-07-01

    1-Methy-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that selectively damages dopaminergic neurons in the substantia nigra pars compacta and induces Parkinson's like symptoms in rodents. Quercetin (QC) is a natural polyphenolic bioflavonoid with potent antioxidant and anti-inflammatory properties but lacks of clinical attraction due to low oral bioavailability. Piperine is a well established bioavailability enhancer used pre-clinically to improve the bioavailability of antioxidants (e.g., Quercetin). Therefore, the present study was designed to evaluate the neuroprotective potential of QC together with piperine against MPTP-induced neurotoxicity in rats. MPTP (100 μg/μL/rat, bilaterally) was injected intranigrally on days 1, 4 and 7 using a digital stereotaxic apparatus. QC (25 and 50 mg/kg, intragastrically) and QC (25 mg/kg, intragastrically) in combination with piperine (2.5 mg/kg, intragastrically) were administered daily for 14 days starting from day 8 after the 3(rd) injection of MPTP. On day 22, animals were sacrificed and the striatum was isolated for oxidative stress parameter (thiobarbituric acid reactive substances, nitrite and glutathione), neuroinflammatory cytokine (interleukin-1β, interleukin-6, and tumor necrosis factor-α) and neurotransmitter (dopamine, norepinephrine, serotonin, gamma-aminobutyric acid, glutamate, 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindoleacetic acid) evaluations. Bilateral infusion of MPTP into substantia nigra pars compacta led to significant motor deficits as evidenced by impairments in locomotor activity and rotarod performance in open field test and grip strength and narrow beam walk performance. Both QC (25 and 50 mg/kg) and QC (25 mg/kg) in combination with piperine (2.5 mg/kg), in particular the combination therapy, significantly improved MPTP-induced behavioral abnormalities in rats, reversed the abnormal alterations of neurotransmitters in the striatum, and alleviated

  1. Petri Net Tool Overview 1986

    DEFF Research Database (Denmark)

    Jensen, Kurt; Feldbrugge, Frits

    1987-01-01

    This paper provides an overview of the characteristics of all currently available net based tools. It is a compilation of information provided by tool authors or contact persons. A concise one page overview is provided as well....

  2. Understanding Net Zero Energy Buildings

    DEFF Research Database (Denmark)

    Salom, Jaume; Widén, Joakim; Candanedo, José

    2011-01-01

    Although several alternative definitions exist, a Net-Zero Energy Building (Net ZEB) can be succinctly described as a grid-connected building that generates as much energy as it uses over a year. The “net-zero” balance is attained by applying energy conservation and efficiency measures...... and by incorporating renewable energy systems. While based on annual balances, a complete description of a Net ZEB requires examining the system at smaller time-scales. This assessment should address: (a) the relationship between power generation and building loads and (b) the resulting interaction with the power grid....... This paper presents and categorizes quantitative indicators suitable to describe both aspects of the building’s performance. These indicators, named LMGI - Load Matching and Grid Interaction indicators, are easily quantifiable and could complement the output variables of existing building simulation tools...

  3. PolicyNet Publication System

    Data.gov (United States)

    Social Security Administration — The PolicyNet Publication System project will merge the Oracle-based Policy Repository (POMS) and the SQL-Server CAMP system (MSOM) into a new system with an Oracle...

  4. KM3NeT

    CERN Multimedia

    KM3NeT is a large scale next-generation neutrino telescope located in the deep waters of the Mediterranean Sea, optimized for the discovery of galactic neutrino sources emitting in the TeV energy region.

  5. Net Neutrality: Background and Issues

    National Research Council Canada - National Science Library

    Gilroy, Angele A

    2006-01-01

    .... The move to place restrictions on the owners of the networks that compose and provide access to the Internet, to ensure equal access and nondiscriminatory treatment, is referred to as "net neutrality...

  6. Petri Nets in Cryptographic Protocols

    DEFF Research Database (Denmark)

    Crazzolara, Federico; Winskel, Glynn

    2001-01-01

    A process language for security protocols is presented together with a semantics in terms of sets of events. The denotation of process is a set of events, and as each event specifies a set of pre and postconditions, this denotation can be viewed as a Petri net. By means of an example we illustrate...... how the Petri-net semantics can be used to prove security properties....

  7. The Economics of Net Neutrality

    OpenAIRE

    Hahn, Robert W.; Wallsten, Scott

    2006-01-01

    This essay examines the economics of "net neutrality" and broadband Internet access. We argue that mandating net neutrality would be likely to reduce economic welfare. Instead, the government should focus on creating competition in the broadband market by liberalizing more spectrum and reducing entry barriers created by certain local regulations. In cases where a broadband provider can exercise market power the government should use its antitrust enforcement authority to police anticompetitiv...

  8. Spectroscopic (FT-IR, FT-Raman, UV, 1H and 13C NMR) profiling and computational studies on methyl 5-methoxy-1H-indole-2-carboxylate: A potential precursor to biologically active molecules

    Science.gov (United States)

    Almutairi, Maha S.; Xavier, S.; Sathish, M.; Ghabbour, Hazem A.; Sebastian, S.; Periandy, S.; Al-Wabli, Reem I.; Attia, Mohamed I.

    2017-04-01

    Methyl 5-methoxy-1H-indole-2-carboxylate (MMIC) was prepared via esterification of commercially available 5-methoxyindole-2-carboxylic acid. The title molecule MMIC was characterised using FT-IR and FT-Raman in the ranges of 4000-500 and 4000-50 cm-1, respectively. The fundamental modes of the vibrations were assigned and the UV-visible spectrum of the MMIC molecule was recorded in the range of 200-400 nm to explore its electronic nature. The HOMO-LUMO energy distribution was calculated and the bonding and anti-bonding structures of the title molecule were studied and analysed using the natural bond orbital (NBO) approach. The reactivity of the MMIC molecule was also investigated and both the positive and negative centres of the molecule were identified using chemical descriptors and molecular electrostatic potential (MEP) analysis. The chemical shifts of the 1H and 13C NMR spectra were noted and the magnetic field environment of the MMIC molecule are discussed. The non-linear optical (NLO) properties of the title molecule were studied based on its calculated values of polarisability and hyperpolarisability. All computations were obtained by DFT methods using the 6-311++G (d,p) basis set.

  9. Methylation of DNA in cancer.

    Science.gov (United States)

    Watanabe, Yoshihisa; Maekawa, Masato

    2010-01-01

    Epigenetic mechanisms are essential for normal development and maintenance of tissue-specific gene expression patterns in mammals. Disruption of epigenetic processes can lead to altered gene function and malignant cellular transformation. Global changes in the epigenetic landscape are a hallmark of cancer. Methylation of cytosine bases in DNA provides a layer of epigenetic control in many eukaryotes that has important implications for normal biology and disease. DNA methylation is a crucial epigenetic modification of the genome that is involved in regulating many cellular processes. These include embryonic development, transcription, chromatin structure, X-chromosome inactivation, genomic imprinting, and chromosome stability. Consistent with these important roles, a growing number of human diseases including cancer have been found to be associated with aberrant DNA methylation. Recent advancements in the rapidly evolving field of cancer epigenetics have described extensive reprogramming of every component of the epigenetic machinery in cancer, such as DNA demethylation. Hypomethylation of the genome largely affects the intergenic and intronic regions of the DNA, particularly repeat sequences and transposable elements, and it is believed to result in chromosomal instability and increased mutation events. Therefore, we propose that R/G-chromosome band boundaries, which correspond with the early/late-switch regions of replication timing and a transition in relative GC content, correspond to "unstable" genomic regions in which concentrated occurrences of repetitive sequences and transposable elements including LINE and Alu elements are hypomethylated during tumorigenesis. In this review, we discuss the current understanding of alterations in DNA methylation composing the epigenetic landscape that occurs in cancer compared with normal cells, the roles of these changes in cancer initiation and progression, and the potential use of this knowledge in designing more

  10. Genome-wide methylation profiling identifies novel methylated genes in neuroblastoma tumors.

    Science.gov (United States)

    Olsson, Maja; Beck, Stephan; Kogner, Per; Martinsson, Tommy; Carén, Helena

    2016-01-01

    Neuroblastoma is a very heterogeneous tumor of childhood. The clinical spectra range from very aggressive metastatic disease to spontaneous regression, even without therapy. Aberrant DNA methylation pattern is a common feature of most cancers. For neuroblastoma, it has been demonstrated both for single genes as well as genome-wide, where a so-called methylator phenotype has been described. Here, we present a study using Illumina 450K methylation arrays on 60 neuroblastoma tumors. We show that aggressive tumors, characterized by International Neuroblastoma Risk Group (INRG) as stage M, are hypermethylated compared to low-grade tumors. On the contrary, INRG stage L tumors display more non-CpG methylation. The genes with the highest number of hypermethylated CpG sites in INRG M tumors are TERT, PCDHGA4, DLX5, and DLX6-AS1. Gene ontology analysis showed a representation of neuronal tumor relevant gene functions among the differentially methylated genes. For validation, we used a set of independent tumors previously analyzed with the Illumina 27K methylation arrays, which confirmed the differentially methylated sites. Top candidate genes with aberrant methylation were analyzed for altered gene expression through the R2 platform ( http://r2.amc.nl), and for correlations between methylation and gene expression in a public dataset. Altered expression in nonsurvivors was found for the genes B3GALT4 and KIAA1949, CLIC5, DLX6-AS, TERT, and PIRT, and strongest correlations were found for TRIM36, KIAA0513, and PIRT. Our data indicate that methylation profiling can be used for patient stratification and informs on epigenetically deregulated genes with the potential of increasing our knowledge about the underlying mechanisms of tumor development.

  11. Inheritance and Variation of Genomic DNA Methylation in Diploid and Triploid Pacific Oyster (Crassostrea gigas).

    Science.gov (United States)

    Jiang, Qun; Li, Qi; Yu, Hong; Kong, Lingfeng

    2016-02-01

    DNA methylation is an important epigenetic mechanism that could be responsive to environmental changes indicating a potential role in natural selection and adaption. In order to evaluate an evolutionary role of DNA methylation, it is essential to first gain a better insight into inheritability. To address this question, this study investigated DNA methylation variation from parents to offspring in the Pacific oyster Crassostrea gigas using fluorescent-labeled methylation-sensitive amplified polymorphism (F-MSAP) analysis. Most of parental methylated loci were stably transmitted to offspring segregating following Medelian expectation. However, methylated loci deviated more often than non-methylated loci and offspring showed a few de novo methylated loci indicating DNA methylation changes from parents to offspring. Interestingly, some male-specific methylated loci were found in this study which might help to explore sex determination in oyster. Despite environmental stimuli, genomic stresses such as polyploidization also can induce methylation changes. This study also compared global DNA methylation level and individual methylated loci between diploid and triploid oysters. Results showed no difference in global methylation state but a few ploidy-specific loci were detected. DNA methylation variation during polyploidization was less than autonomous methylation variation from parents to offspring.

  12. Prognostic DNA Methylation Markers for Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Siri H. Strand

    2014-09-01

    Full Text Available Prostate cancer (PC is the most commonly diagnosed neoplasm and the third most common cause of cancer-related death amongst men in the Western world. PC is a clinically highly heterogeneous disease, and distinction between aggressive and indolent disease is a major challenge for the management of PC. Currently, no biomarkers or prognostic tools are able to accurately predict tumor progression at the time of diagnosis. Thus, improved biomarkers for PC prognosis are urgently needed. This review focuses on the prognostic potential of DNA methylation biomarkers for PC. Epigenetic changes are hallmarks of PC and associated with malignant initiation as well as tumor progression. Moreover, DNA methylation is the most frequently studied epigenetic alteration in PC, and the prognostic potential of DNA methylation markers for PC has been demonstrated in multiple studies. The most promising methylation marker candidates identified so far include PITX2, C1orf114 (CCDC181 and the GABRE~miR-452~miR-224 locus, in addition to the three-gene signature AOX1/C1orf114/HAPLN3. Several other biomarker candidates have also been investigated, but with less stringent clinical validation and/or conflicting evidence regarding their possible prognostic value available at this time. Here, we review the current evidence for the prognostic potential of DNA methylation markers in PC.

  13. Qualifications of Petri nets for modeling of logistical systems

    Directory of Open Access Journals (Sweden)

    Petr Jedlička

    2006-01-01

    Full Text Available Simulation and optimization is one of the most popular approaches to improve the use of simulation models as a tool to obtain the best system configuration. Petri nets have proved to be useful for examining the performance of different system configurations and/or alternative operating procedures for various systems. Based on their precise semantics and easy-to-understand graphical representation, Petri nets are appropriate to model logistic systems together with their quantitative and qualitative properties. In this paper, potential benefits of usage of object-oriented Petri nets for optimization of logistical systems are discussed.

  14. DNA Methylation Biomarkers: Cancer and Beyond

    Science.gov (United States)

    Mikeska, Thomas; Craig, Jeffrey M.

    2014-01-01

    Biomarkers are naturally-occurring characteristics by which a particular pathological process or disease can be identified or monitored. They can reflect past environmental exposures, predict disease onset or course, or determine a patient’s response to therapy. Epigenetic changes are such characteristics, with most epigenetic biomarkers discovered to date based on the epigenetic mark of DNA methylation. Many tissue types are suitable for the discovery of DNA methylation biomarkers including cell-based samples such as blood and tumor material and cell-free DNA samples such as plasma. DNA methylation biomarkers with diagnostic, prognostic and predictive power are already in clinical trials or in a clinical setting for cancer. Outside cancer, strong evidence that complex disease originates in early life is opening up exciting new avenues for the detection of DNA methylation biomarkers for adverse early life environment and for estimation of future disease risk. However, there are a number of limitations to overcome before such biomarkers reach the clinic. Nevertheless, DNA methylation biomarkers have great potential to contribute to personalized medicine throughout life. We review the current state of play for DNA methylation biomarkers, discuss the barriers that must be crossed on the way to implementation in a clinical setting, and predict their future use for human disease. PMID:25229548

  15. DNA Methylation Biomarkers: Cancer and Beyond

    Directory of Open Access Journals (Sweden)

    Thomas Mikeska

    2014-09-01

    Full Text Available Biomarkers are naturally-occurring characteristics by which a particular pathological process or disease can be identified or monitored. They can reflect past environmental exposures, predict disease onset or course, or determine a patient’s response to therapy. Epigenetic changes are such characteristics, with most epigenetic biomarkers discovered to date based on the epigenetic mark of DNA methylation. Many tissue types are suitable for the discovery of DNA methylation biomarkers including cell-based samples such as blood and tumor material and cell-free DNA samples such as plasma. DNA methylation biomarkers with diagnostic, prognostic and predictive power are already in clinical trials or in a clinical setting for cancer. Outside cancer, strong evidence that complex disease originates in early life is opening up exciting new avenues for the detection of DNA methylation biomarkers for adverse early life environment and for estimation of future disease risk. However, there are a number of limitations to overcome before such biomarkers reach the clinic. Nevertheless, DNA methylation biomarkers have great potential to contribute to personalized medicine throughout life. We review the current state of play for DNA methylation biomarkers, discuss the barriers that must be crossed on the way to implementation in a clinical setting, and predict their future use for human disease.

  16. "It is about how the net looks": a qualitative study of perceptions and practices related to mosquito net care and repair in two districts in eastern Uganda.

    Science.gov (United States)

    Scandurra, Leah; Acosta, Angela; Koenker, Hannah; Kibuuka, Daniel Musoke; Harvey, Steven

    2014-12-17

    Prolonging net durability has important implications for reducing both malaria transmission and the frequency of net replacement. Protective behaviour, such as net care and repair, offers promise for improving net integrity and durability. Given the potential cost-savings and public health benefit associated with extending the useful life of long-lasting insecticidal nets (LLINs), prevention and mitigation of damage will become ever more critical to ensuring adequate net coverage at the population level. A qualitative assessment was conducted in two districts in central eastern Uganda in September 2013. Data on household net care and repair behaviour, attitudes and practices were collected from 30 respondents through in-depth interviews (IDIs), observations, photos, and video to gather an in-depth understanding of these behaviours. Net damage was common and the most cited causes were children and rodents. Responses revealed strong social norms about net cleanliness and aesthetics, and strong expectations that others should care for and repair their own nets. Respondents were receptive and able to repair nets, though longer-term repair methods, such as sewing and patching, were not as commonly reported or observed. Self-reported behaviour was not always consistent with observed or demonstrated behaviour, revealing potential misconceptions and the need for clear and consistent net care and repair messaging. Respondents considered both aesthetics and malaria protection important when deciding whether, when, and how to care for and repair nets. BCC should continue to emphasize the importance of maintaining net integrity for malaria prevention purposes as well as for maintaining aesthetic appeal. Additional research is needed, particularly surrounding washing, drying, daily storage routines, and gender roles in care and repair, in order to understand the complexity of these behaviours, and refine existing or develop new behaviour change communication (BCC) messages for

  17. 26 CFR 1.904(f)-3 - Allocation of net operating losses and net capital losses.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 9 2010-04-01 2010-04-01 false Allocation of net operating losses and net....904(f)-3 Allocation of net operating losses and net capital losses. For rules relating to the allocation of net operating losses and net capital losses, see § 1.904(g)-3T. ...

  18. 29 CFR 4204.13 - Net income and net tangible assets tests.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Net income and net tangible assets tests. 4204.13 Section....13 Net income and net tangible assets tests. (a) General. The criteria under this section are that either— (1) Net income test. The purchaser's average net income after taxes for its three most recent...

  19. Lanthanide complexes containing 5-methyl-1,2,4-triazolo[1,5-a] pyrimidin-7(4H)-one and their therapeutic potential to fight leishmaniasis and Chagas disease.

    Science.gov (United States)

    Caballero, Ana B; Rodríguez-Diéguez, Antonio; Salas, Juan M; Sánchez-Moreno, Manuel; Marín, Clotilde; Ramírez-Macías, Inmaculada; Santamaría-Díaz, Noelia; Gutiérrez-Sánchez, Ramón

    2014-09-01

    In the last years, numerous and significant advances in lanthanide coordination chemistry have been achieved. The unique chemical nature of these metal ions which is conferred by their f-electrons has led to a wide range of coordination compounds with interesting structural, physical and also biological properties. Consequently, lanthanide complexes have found applications mainly in catalysis, gas adsorption, photochemistry and as diagnostic tools. However, research on their therapeutic potential and the understanding of their mechanism of action is still taking its first steps, and there is a distinct lack of research in the parasitology field. In the present work, we describe the synthesis and physical properties of seven new lanthanide complexes with the anionic form of the bioactive ligand 5-methyl-1,2,4-triazolo[1,5-a]pyrimidin-7(4H)-one (HmtpO), namely [Ln(mtpO)3(H2O)6]·9H2O (Ln=La(III), Nd(III), Eu(III), Gd(III), Tb(III), Dy(III) and Er(III)). In addition, results on the in vitro antiproliferative activity against Leishmania spp. and Trypanosoma cruzi are described. The high activity of the new compounds against parasite proliferation and their low cytotoxicity against reference host cell lines show a great potential of this type of compounds to become a new generation of highly effective and non-toxic antiparasitic agents to fight the so considered neglected diseases leishmaniasis and Chagas disease. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Energy Dependence of Moments of Net-Proton, Net-Kaon, and Net-Charge Multiplicity Distributions at STAR

    CERN Document Server

    ,

    2016-01-01

    One of the main goals of the RHIC Beam Energy Scan (BES) program is to study the QCD phase structure, which includes the search for the QCD critical point, over a wide range of chemical potential. Theoretical calculations predict that fluctuations of conserved quantities, such as baryon number (B), charge (Q), and strangeness (S), are sensitive to the correlation length of the dynamical system. Experimentally, higher moments of multiplicity distributions have been utilized to search for the QCD critical point in heavy-ion collisions. In this paper, we report recent efficiency-corrected cumulants and cumulants ratios of the net- proton, net-kaon, and net-charge multiplicity distributions in Au+Au collisions at 7.7, 11.5, 14.5, 19.6, 27, 39, 62.4, and 200 GeV collected in the years 2010, 2011, and 2014 with STAR at RHIC. The centrality and energy dependence of the cumulants up to the fourth order, as well as their ratios, are presented. Furthermore, the comparisons with baseline calculations (Poisson) and non-c...

  1. EnviroNET: Space environment for Strategic Defense Initiative experiments

    Science.gov (United States)

    Lauriente, Michael

    1989-01-01

    EnviroNET is an operational system available to the Strategic Defense Initiative (SDI) experimenters who have access to a terminal or dial-up port. It is a tail node on Space Physics Analysis Network (SPAN) accessible directly or through the national networks via NPSS. Some of the benefits to using EnviroNET include: validated NASA environmental information and interactive space models; facilitating the payload integration process; easy access to expert assistance; and potential for time and cost savings.

  2. DNA methylation in states of cell physiology and pathology.

    Directory of Open Access Journals (Sweden)

    Lech Chyczewski

    2007-10-01

    Full Text Available DNA methylation is one of epigenetic mechanisms regulating gene expression. The methylation pattern is determined during embryogenesis and passed over to differentiating cells and tissues. In a normal cell, a significant degree of methylation is characteristic for extragenic DNA (cytosine within the CG dinucleotide while CpG islands located in gene promoters are unmethylated, except for inactive genes of the X chromosome and the genes subjected to genomic imprinting. The changes in the methylation pattern, which may appear as the organism age and in early stages of cancerogenesis, may lead to the silencing of over ninety endogenic genes. It has been found, that these disorders consist not only of the methylation of CpG islands, which are normally unmethylated, but also of the methylation of other dinucleotides, e.g. CpA. Such methylation has been observed in non-small cell lung cancer, in three regions of the exon 5 of the p53 gene (so-called "non-CpG" methylation. The knowledge of a normal methylation process and its aberrations appeared to be useful while searching for new markers enabling an early detection of cancer. With the application of the Real-Time PCR technique (using primers for methylated and unmethylated sequences five new genes which are potential biomarkers of lung cancer have been presented.

  3. Readmissions at a public safety net hospital.

    Directory of Open Access Journals (Sweden)

    Eri Shimizu

    Full Text Available OBJECTIVE: We aimed to determine factors related to avoidability of 30-day readmissions at our public, safety net hospital in the United States (US. METHODS: We prospectively reviewed medical records of adult internal medicine patients with scheduled and unscheduled 30-day readmissions. We also interviewed patients if they were available. An independent panel used pre-specified, objective criteria to adjudicate potential avoidability. RESULTS: Of 153 readmissions evaluated, 68% were unscheduled. Among these, 67% were unavoidable, primarily due to disease progression and development of new diagnoses. Scheduled readmissions accounted for 32% of readmissions and most (69% were clinically appropriate and unavoidable. The scheduled but avoidable readmissions (31% were attributed largely to limited resources in our healthcare system. CONCLUSIONS: Most readmissions at our public, safety net hospital were unavoidable, even among our unscheduled readmissions. Surprisingly, one-third of our overall readmissions were scheduled, the majority reflecting appropriate management strategies designed to reduce unnecessary hospital days. The scheduled but avoidable readmissions were due to constrained access to non-emergent, expensive procedures that are typically not reimbursed given our system's payor mix, a problem which likely plague other safety net systems. These findings suggest that readmissions do not necessarily reflect inadequate medical care, may reflect resource constraints that are unlikely to be addressable in systems caring for a large burden of uninsured patients, and merit individualized review.

  4. A family tree of methyl oleate-based compounds

    Science.gov (United States)

    A family of compounds starting with potentially bio-based methyl oleate have been synthesized through a variety of chemical methods. Grandpa EMO (Epoxidized Methyl Oleate) is the most well represented in terms of ancestors, but other catalytic cousins are also presented. Featured material on aunt Et...

  5. Coulomb explosion of methyl iodide clusters using giga watt laser ...

    Indian Academy of Sciences (India)

    Administrator

    (9⋅54 eV). This higher ionization potential of water decreases the multiphoton ionization probability of the water molecules/clusters as compared to that of methyl iodide molecules/clusters under identical laser excitation conditions. Further, the water has much lower vapour pressure as compared to that of methyl iodide.

  6. Methyl vinyl glycolate as a diverse platform molecule

    DEFF Research Database (Denmark)

    Sølvhøj, Amanda Birgitte; Taarning, Esben; Madsen, Robert

    2016-01-01

    Methyl vinyl glycolate (methyl 2-hydroxybut-3-enoate, MVG) is available by zeolite catalyzed degradation of mono- and disaccharides and has the potential to become a renewable platform molecule for commercially relevant catalytic transformations. This is further illustrated here by the development...

  7. Histone Lysine Methylation in Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Guang-dong Sun

    2014-01-01

    Full Text Available Diabetic nephropathy (DN belongs to debilitating microvascular complications of diabetes and is the leading cause of end-stage renal diseases worldwide. Furthermore, outcomes from the DCCT/EDIC study showed that DN often persists and progresses despite intensive glucose control in many diabetes patients, possibly as a result of prior episode of hyperglycemia, which is called “metabolic memory.” The underlying mechanisms responsible for the development and progression of DN remain poorly understood. Activation of multiple signaling pathways and key transcription factors can lead to aberrant expression of DN-related pathologic genes in target renal cells. Increasing evidence suggests that epigenetic mechanisms in chromatin such as DNA methylation, histone acetylation, and methylation can influence the pathophysiology of DN and metabolic memory. Exciting researches from cell culture and experimental animals have shown that key histone methylation patterns and the related histone methyltransferases and histone demethylases can play important roles in the regulation of inflammatory and profibrotic genes in renal cells under diabetic conditions. Because histone methylation is dynamic and potentially reversible, it can provide a window of opportunity for the development of much-needed novel therapeutic potential for DN in the future. In this minireview, we discuss recent advances in the field of histone methylation and its roles in the pathogenesis and progression of DN.

  8. DNA methylation in an engineered heart tissue model of cardiac hypertrophy: common signatures and effects of DNA methylation inhibitors.

    Science.gov (United States)

    Stenzig, Justus; Hirt, Marc N; Löser, Alexandra; Bartholdt, Lena M; Hensel, Jan-Tobias; Werner, Tessa R; Riemenschneider, Mona; Indenbirken, Daniela; Guenther, Thomas; Müller, Christian; Hübner, Norbert; Stoll, Monika; Eschenhagen, Thomas

    2016-01-01

    DNA methylation affects transcriptional regulation and constitutes a drug target in cancer biology. In cardiac hypertrophy, DNA methylation may control the fetal gene program. We therefore investigated DNA methylation signatures and their dynamics in an in vitro model of cardiac hypertrophy based on engineered heart tissue (EHT). We exposed EHTs from neonatal rat cardiomyocytes to a 12-fold increased afterload (AE) or to phenylephrine (PE 20 µM) and compared DNA methylation signatures to control EHT by pull-down assay and DNA methylation microarray. A 7-day intervention sufficed to induce contractile dysfunction and significantly decrease promoter methylation of hypertrophy-associated upregulated genes such as Nppa (encoding ANP) and Acta1 (α-skeletal actin) in both intervention groups. To evaluate whether pathological consequences of AE are affected by inhibiting de novo DNA methylation we applied AE in the absence and presence of DNA methyltransferase (DNMT) inhibitors: 5-aza-2'-deoxycytidine (aza, 100 µM, nucleosidic inhibitor), RG108 (60 µM, non-nucleosidic) or methylene disalicylic acid (MDSA, 25 µM, non-nucleosidic). Aza had no effect on EHT function, but RG108 and MDSA partially prevented the detrimental consequences of AE on force, contraction and relaxation velocity. RG108 reduced AE-induced Atp2a2 (SERCA2a) promoter methylation. The results provide evidence for dynamic DNA methylation in cardiac hypertrophy and warrant further investigation of the potential of DNA methylation in the treatment of cardiac hypertrophy.

  9. TimeNET Optimization Environment

    Directory of Open Access Journals (Sweden)

    Christoph Bodenstein

    2015-12-01

    Full Text Available In this paper a novel tool for simulation-based optimization and design-space exploration of Stochastic Colored Petri nets (SCPN is introduced. The working title of this tool is TimeNET Optimization Environment (TOE. Targeted users of this tool are people modeling complex systems with SCPNs in TimeNET who want to find parameter sets that are optimal for a certain performance measure (fitness function. It allows users to create and simulate sets of SCPNs and to run different optimization algorithms based on parameter variation. The development of this tool was motivated by the need to automate and speed up tests of heuristic optimization algorithms to be applied for SCPN optimization. A result caching mechanism is used to avoid recalculations.

  10. Implementing NetScaler VPX

    CERN Document Server

    Sandbu, Marius

    2014-01-01

    An easy-to-follow guide with detailed step-by step-instructions on how to implement the different key components in NetScaler, with real-world examples and sample scenarios.If you are a Citrix or network administrator who needs to implement NetScaler in your virtual environment to gain an insight on its functionality, this book is ideal for you. A basic understanding of networking and familiarity with some of the different Citrix products such as XenApp or XenDesktop is a prerequisite.

  11. Net4Care PHMR Library

    DEFF Research Database (Denmark)

    2014-01-01

    The Net4Care PHMR library contains a) A GreenCDA approach for constructing a data object representing a PHMR document: SimpleClinicalDocument, and b) A Builder which can produce a XML document representing a valid Danish PHMR (following the MedCom profile) document from the SimpleClinicalDocument......The Net4Care PHMR library contains a) A GreenCDA approach for constructing a data object representing a PHMR document: SimpleClinicalDocument, and b) A Builder which can produce a XML document representing a valid Danish PHMR (following the MedCom profile) document from the Simple...

  12. Pro DLR in NET 4

    CERN Document Server

    Wu, Chaur

    2011-01-01

    Microsoft's Dynamic Language Runtime (DLR) is a platform for running dynamic languages such as Ruby and Python on an equal footing with compiled languages such as C#. Furthermore, the runtime is the foundation for many useful software design and architecture techniques you can apply as you develop your .NET applications. Pro DLR in .NET 4 introduces you to the DLR, showing how you can use it to write software that combines dynamic and static languages, letting you choose the right tool for the job. You will learn the core DLR components such as LINQ expressions, call sites, binders, and dynami

  13. Hierarchies in Coloured Petri Nets

    DEFF Research Database (Denmark)

    Huber, Peter; Jensen, Kurt; Shapiro, Robert M.

    1991-01-01

    The paper shows how to extend Coloured Petri Nets with a hierarchy concept. The paper proposes five different hierarchy constructs, which allow the analyst to structure large CP-nets as a set of interrelated subnets (called pages). The paper discusses the properties of the proposed hierarchy...... constructs, and it illustrates them by means of two examples. The hierarchy constructs can be used for theoretical considerations, but their main use is to describe and analyse large real-world systems. All of the hierarchy constructs are supported by the editing and analysis facilities in the CPN Palette...

  14. Physicochemical, pharmacokinetic, efficacy and toxicity profiling of a potential nitrofuranyl methyl piperazine derivative IIIM-MCD-211 for oral tuberculosis therapy via in-silico-in-vitro-in-vivo approach.

    Science.gov (United States)

    Magotra, Asmita; Sharma, Anjna; Singh, Samsher; Ojha, Probir Kumar; Kumar, Sunil; Bokolia, Naveen; Wazir, Priya; Sharma, Shweta; Khan, Inshad Ali; Singh, Parvinder Pal; Vishwakarma, Ram A; Singh, Gurdarshan; Nandi, Utpal

    2017-11-21

    Recent tuberculosis (TB) drug discovery programme involve continuous pursuit for new chemical entity (NCE) which can be not only effective against both susceptible and resistant strains of Mycobacterium tuberculosis (Mtb) but also safe and faster acting with the target, thereby shortening the prolonged TB treatments. We have identified a potential nitrofuranyl methyl piperazine derivative, IIIM-MCD-211 as new antitubercular agent with minimum inhibitory concentration (MIC) value of 0.0072 μM against H37Rv strain. Objective of the present study is to investigate physicochemical, pharmacokinetic, efficacy and toxicity profile using in-silico, in-vitro and in-vivo model in comprehensive manner to assess the likelihood of developing IIIM-MCD-211 as a clinical candidate. Results of computational prediction reveal that compound does not violate Lipinski's, Veber's and Jorgensen's rule linked with drug like properties and oral bioavailability. Experimentally, IIIM-MCD-211 exhibits excellent lipophilicity that is optimal for oral administration. IIIM-MCD-211 displays evidence of P-glycoprotein (P-gp) induction but no inhibition ability in rhodamine cell exclusion assay. IIIM-MCD-211 shows high permeability and plasma protein binding based on parallel artificial membrane permeability assay (PAMPA) and rapid equilibrium dialysis (RED) model, respectively. IIIM-MCD-211 has adequate metabolic stability in rat liver microsomes (RLM) and favourable pharmacokinetics with admirable correlation during dose escalation study in Swiss mice. IIIM-MCD-211 has capability to appear into highly perfusable tissues. IIIM-MCD-211 is able to actively prevent progression of TB infection in chronic infection mice model. IIIM-MCD-211 shows no substantial cytotoxicity in HepG2 cell line. In acute toxicity study, significant increase of total white blood cell (WBC) count in treatment group as compared to control group is observed. Overall, amenable preclinical data make IIIM-MCD-211 ideal

  15. Insulin-Like Growth Factor I Produces an Antidepressant-Like Effect and Elicits N-Methyl-D-Aspartate Receptor Independent Long-Term Potentiation of Synaptic Transmission in Medial Prefrontal Cortex and Hippocampus.

    Science.gov (United States)

    Burgdorf, Jeffrey; Zhang, Xiao-lei; Colechio, Elizabeth M; Ghoreishi-Haack, Nayereh; Gross, Amanda; Kroes, Roger A; Stanton, Patric K; Moskal, Joseph R

    2015-09-15

    Growth factors play an important role in regulating neurogenesis and synapse formation and may be involved in regulating the antidepressant response to conventional antidepressants. To date, Insulin-like growth factor I (IGFI) is the only growth factor that has shown antidepressant properties in human clinical trials. However, its mechanism of action remains unclear. The antidepressant-like effect of a single IV dose of IGFI was determined using a chronic unpredictable stress paradigm in the rat Porsolt, sucrose preference, novelty-induced hypophagia, and ultrasonic vocalization models. The dependence of the medial prefrontal cortex for these effects was determined by direct medial prefrontal cortex injection followed by Porsolt testing as well as IGFI receptor activation in the medial prefrontal cortex following an optimal IV antidepressant-like dose of IGFI. The effect of IGFI on synaptic transmission and long-term potentiation (LTP) of synaptic strength was assessed in the hippocampus and medial prefrontal cortex. The dependence of these effects on IGFI and AMPA receptor activation and protein synthesis were also determined. IGFI produced a rapid-acting and long-lasting antidepressant-like effect in each of the depression models. These effects were blocked by IGFI and AMPA receptor antagonists, and medial prefrontal cortex was localized. IGFI robustly increased synaptic strength in the hippocampus and medial prefrontal cortex and these effects were IGFI receptor and protein synthesis-dependent but N-methyl-d-aspartate receptor independent. IGFI also robustly facilitated hippocampal metaplasticity 24 hours postdosing. These data support the conclusion that the antidepressant-like effects of IGFI are mediated by a persistent, LTP-like enhancement of synaptic strength requiring both IGFIR activation and ongoing protein synthesis. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  16. Theoretical analysis (NBO, NPA, Mulliken Population Method) and molecular orbital studies (hardness, chemical potential, electrophilicity and Fukui function analysis) of (E)-2-((4-hydroxy-2-methylphenylimino)methyl)-3-methoxyphenol

    Science.gov (United States)

    Demircioğlu, Zeynep; Kaştaş, Çiğdem Albayrak; Büyükgüngör, Orhan

    2015-07-01

    The molecular structure and spectroscopic properties of (E)-2-((4-hydroxy-2-methylphenylimino)methyl)-3-methoxyphenol, were characterized by X-ray diffraction, FT-IR and UV-Vis spectroscopy. All of theoretical calculations and optimized geometric parameters have been calculated by using density functional theory (DFT) with hybrid method B3LYP by 6-31G(d,p) basis set. The title compound of C15H15N1O3 have been analyzed according to electronic and energetics behaviors for enol-imine and keto-amine tautomers. Both these tautomers engender six-membered ring due to intramolecular hydrogen bonded interactions. Two types of intramolecular hydrogen bonds (a) strong O-H⋯N interactions in enol-imine form and (b) N-H⋯O interactions in keto-amine form are compared particularly. The theoretical vibrational frequencies have been found in good agreement with the corresponding experimental data. A study on the electronic and optical properties, absorption wavelengths, excitation energy, dipole moment, molecular electrostatic potential (MEP) and frontier molecular orbital energies are performed using DFT method. Additionally, geometry optimizations in solvent media were performed with the same level of theory by the polarizable continuum model (PCM). The effect of solvents on the tautomeric stability has been investigated. Mulliken Population Method and natural population analysis (NPA) have been studied. NBO analysis is carried out to picture the charge transfer between the localized bonds and lone pairs. The local reactivity of the molecule has been studied using the Fukui function. NLO properties related to polarizability and hyperpolarizability are also discussed.

  17. Evaluation of the teratogenic potential of N-[N-[3-(3-hydroxy-4-methoxyphenyl) propyl]-α-aspartyl]-L-phenylalanine 1-methyl ester, monohydrate (advantame) in the rat and rabbit.

    Science.gov (United States)

    Otabe, A; Fujieda, T; Masuyama, T

    2011-11-01

    To assess its teratogenic potential, advantame (N-[N-[3-(3-hydroxy-4-methoxyphenyl) propyl]-α-aspartyl]-L-phenylalanine 1-methyl ester, monohydrate) was administered to mated rats (22/group) in the diet at 0, 5000, 15,000, and 50,000 ppm (providing approximately 465, 1418, and 4828 mg/kg body weight/day), and to mated rabbits (24/group) via oral gavage at 0, 500, 1000, and 2000 mg/kg body weight/day throughout gestation. Shortly before delivery (rats: day 20; rabbits: day 29), animals were killed and subjected to a detailed necropsy. Fetuses were examined for external, visceral, and skeletal alterations. Atypical coloration of the feces and cage liners seen with test diets in both rats and rabbits was attributed to excretion of test material/metabolites in the feces and urine. Advantame had no adverse effect on rat offspring survival or development. The no-observed-adverse-effect level (NOAEL) for both maternal and developmental toxicity in rats was 50,000 ppm, the highest dietary concentration tested. Due to adverse effects associated with reduced food intake and fecal output, approximately 20% of mated rabbits receiving 200 0mg/kg body weight/day and 1 animal at 1000 mg/kg body weight/day had to be terminated before scheduled necropsy. A NOAEL of 500 mg/kg body weight/day was established for maternal toxicity in rabbits. No teratogenic effects were observed in any animals, and based on a slightly increased incidence of fetal deaths at 2000 mg/kg body weight/day, a finding that was considered to be indirectly related to advantame treatment, 1000 mg/kg body weight/day was considered the NOAEL for developmental toxicity. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. DNA methylation in obesity

    Directory of Open Access Journals (Sweden)

    Małgorzata Pokrywka

    2014-11-01

    Full Text Available The number of overweight and obese people is increasing at an alarming rate, especially in the developed and developing countries. Obesity is a major risk factor for diabetes, cardiovascular disease, and cancer, and in consequence for premature death. The development of obesity results from the interplay of both genetic and environmental factors, which include sedentary life style and abnormal eating habits. In the past few years a number of events accompanying obesity, affecting expression of genes which are not directly connected with the DNA base sequence (e.g. epigenetic changes, have been described. Epigenetic processes include DNA methylation, histone modifications such as acetylation, methylation, phosphorylation, ubiquitination, and sumoylation, as well as non-coding micro-RNA (miRNA synthesis. In this review, the known changes in the profile of DNA methylation as a factor affecting obesity and its complications are described.

  19. Relationship between methylation status of vitamin D-related genes, vitamin D levels, and methyl-donor biochemistry

    Directory of Open Access Journals (Sweden)

    Emma Louise Beckett

    2016-12-01

    Full Text Available Vitamin D is known for its role in the regulation of gene expression via the vitamin D receptor, a nuclear transcription factor. More recently, a role for vitamin D in regulating DNA methylation has been identified as an additional mechanism of modulation of gene expression. How methylation status influences vitamin D metabolism and response pathways is not yet clear. Therefore, we aimed to assess the relationship between plasma 25-hydroxycholecalciferol (25(OHD and the methylation status of vitamin D metabolism enzyme genes (CYP2R1, CYP27B1 and CYP24A1 and the vitamin D receptor gene (VDR. This analysis was conducted in the context of dietary vitamin D, and background methyl donor related biochemistry, with adjustment for several dietary and lifestyle variables. Percentage methylation at CpG sites was assessed in peripheral blood cells using methylation sensitive and dependent enzymes and qPCR. Standard analytical techniques were used to determine plasma 25(OHD and homocysteine, and serum folate and B12, with the relationship to methylation status assessed using multi-variable regression analysis. CYP2R1 and VDR methylation were found to be independent predictors of plasma 25(OHD, when adjusted for vitamin D intake and other lifestyle variables. CYP24A1 was related to plasma 25(OHD directly, but not in the context of vitamin D intake. Methyl-group donor biochemistry was associated with the methylation status of some genes, but did not alter the relationship between methylation and plasma 25(OHD. Modulation of methylation status of CYP2R1, CYP24A1 and VDR in response to plasma 25(OHD may be part of feedback loops involved in maintaining vitamin D homeostasis, and may explain a portion of the variance in plasma 25(OHD levels in response to intake and sun exposure. Methyl-group donor biochemistry, while a potential independent modulator, did not alter this effect.

  20. Experimental hut evaluation of bednets treated with an organophosphate (chlorpyrifos-methyl or a pyrethroid (lambdacyhalothrin alone and in combination against insecticide-resistant Anopheles gambiae and Culex quinquefasciatus mosquitoes

    Directory of Open Access Journals (Sweden)

    Corbel Vincent

    2005-05-01

    Full Text Available Abstract Background Pyrethroid resistant mosquitoes are becoming increasingly common in parts of Africa. It is important to identify alternative insecticides which, if necessary, could be used to replace or supplement the pyrethroids for use on treated nets. Certain compounds of an earlier generation of insecticides, the organophosphates may have potential as net treatments. Methods Comparative studies of chlorpyrifos-methyl (CM, an organophosphate with low mammalian toxicity, and lambdacyhalothrin (L, a pyrethroid, were conducted in experimental huts in Côte d'Ivoire, West Africa. Anopheles gambiae and Culex quinquefasciatus mosquitoes from the area are resistant to pyrethroids and organophosphates (kdr and insensitive acetylcholinesterase Ace.1R. Several treatments and application rates on intact or holed nets were evaluated, including single treatments, mixtures, and differential wall/ceiling treatments. Results and Conclusion All of the treatments were effective in reducing blood feeding from sleepers under the nets and in killing both species of mosquito, despite the presence of the kdr and Ace.1R genes at high frequency. In most cases, the effects of the various treatments did not differ significantly. Five washes of the nets in soap solution did not reduce the impact of the insecticides on A. gambiae mortality, but did lead to an increase in blood feeding. The three combinations performed no differently from the single insecticide treatments, but the low dose mixture performed encouragingly well indicating that such combinations might be used for controlling insecticide resistant mosquitoes. Mortality of mosquitoes that carried both Ace.1R and Ace.1S genes did not differ significantly from mosquitoes that carried only Ace.1S genes on any of the treated nets, indicating that the Ace.1R allele does not confer effective resistance to chlorpyrifos-methyl under the realistic conditions of an experimental hut.

  1. Methanol levels in methylated spirit drinking alcoholics.

    Science.gov (United States)

    Caldwell, K

    1986-10-08

    On three different occasions, blood samples sent to this laboratory from the accident and emergency department were found to contain potentially toxic amounts of methanol (30, 34 and 41 mmol/l) during analysis for ethanol by a gas chromatographic method. It is suggested that the simultaneous determination of both alcohols may be clinically important in methylated spirit drinking alcoholics.

  2. Apoptosis and DNA Methylation

    Directory of Open Access Journals (Sweden)

    Richard R. Meehan

    2011-04-01

    Full Text Available Epigenetic mechanisms assist in maintaining gene expression patterns and cellular properties in developing and adult tissues. The molecular pathology of disease states frequently includes perturbation of DNA and histone methylation patterns, which can activate apoptotic pathways associated with maintenance of genome integrity. This perspective focuses on the pathways linking DNA methyltransferases and methyl-CpG binding proteins to apoptosis, and includes new bioinformatic analyses to characterize the evolutionary origin of two G/T mismatch-specific thymine DNA glycosylases, MBD4 and TDG.

  3. Implications of DNA Methylation in Parkinson’s Disease

    Science.gov (United States)

    Miranda-Morales, Ernesto; Meier, Karin; Sandoval-Carrillo, Ada; Salas-Pacheco, José; Vázquez-Cárdenas, Paola; Arias-Carrión, Oscar

    2017-01-01

    It has been 200 years since Parkinson’s disease (PD) was first described, yet many aspects of its etiopathogenesis remain unclear. PD is a progressive and complex neurodegenerative disorder caused by genetic and environmental factors including aging, nutrition, pesticides and exposure to heavy metals. DNA methylation may be altered in response to some of these factors; therefore, it is proposed that epigenetic mechanisms, particularly DNA methylation, can have a fundamental role in gene–environment interactions that are related with PD. Epigenetic changes in PD-associated genes are now widely studied in different populations, to discover the mechanisms that contribute to disease development and identify novel biomarkers for early diagnosis and future pharmacological treatment. While initial studies sought to find associations between promoter DNA methylation and the regulation of associated genes in PD brain tissue, more recent studies have described concordant DNA methylation patterns between blood and brain tissue DNA. These data justify the use of peripheral blood samples instead of brain tissue for epigenetic studies. Here, we summarize the current data about DNA methylation changes in PD and discuss the potential of DNA methylation as a potential biomarker for PD. Additionally, we discuss environmental and nutritional factors that have been implicated in DNA methylation. Although the search for significant DNA methylation changes and gene expression analyses of PD-associated genes have yielded inconsistent and contradictory results, epigenetic modifications remain under investigation for their potential to reveal the link between environmental risk factors and the development of PD. PMID:28769760

  4. Implications of DNA Methylation in Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Ernesto Miranda-Morales

    2017-07-01

    Full Text Available It has been 200 years since Parkinson’s disease (PD was first described, yet many aspects of its etiopathogenesis remain unclear. PD is a progressive and complex neurodegenerative disorder caused by genetic and environmental factors including aging, nutrition, pesticides and exposure to heavy metals. DNA methylation may be altered in response to some of these factors; therefore, it is proposed that epigenetic mechanisms, particularly DNA methylation, can have a fundamental role in gene–environment interactions that are related with PD. Epigenetic changes in PD-associated genes are now widely studied in different populations, to discover the mechanisms that contribute to disease development and identify novel biomarkers for early diagnosis and future pharmacological treatment. While initial studies sought to find associations between promoter DNA methylation and the regulation of associated genes in PD brain tissue, more recent studies have described concordant DNA methylation patterns between blood and brain tissue DNA. These data justify the use of peripheral blood samples instead of brain tissue for epigenetic studies. Here, we summarize the current data about DNA methylation changes in PD and discuss the potential of DNA methylation as a potential biomarker for PD. Additionally, we discuss environmental and nutritional factors that have been implicated in DNA methylation. Although the search for significant DNA methylation changes and gene expression analyses of PD-associated genes have yielded inconsistent and contradictory results, epigenetic modifications remain under investigation for their potential to reveal the link between environmental risk factors and the development of PD.

  5. D.NET case study

    International Development Research Centre (IDRC) Digital Library (Canada)

    lremy

    developing products, marketing tools and building capacity of the grass root telecentre workers. D.Net recognized that it had several ideas worth developing into small interventions that would make big differences, but resource constraints were a barrier for scaling-up these initiatives. More demands, limited resources.

  6. Surgery for GEP-NETs

    DEFF Research Database (Denmark)

    Knigge, Ulrich; Hansen, Carsten Palnæs

    2012-01-01

    Surgery is the only treatment that may cure the patient with gastroentero-pancreatic (GEP) neuroendocrine tumours (NET) and neuroendocrine carcinomas (NEC) and should always be considered as first line treatment if R0/R1 resection can be achieved. The surgical and interventional procedures for GEP...

  7. Net Neutrality in the Netherlands

    NARCIS (Netherlands)

    van Eijk, N.

    2014-01-01

    The Netherlands is among the first countries that have put specific net neutrality standards in place. The decision to implement specific regulation was influenced by at least three factors. The first was the prevailing social and academic debate, partly due to developments in the United States. The

  8. Complexity Metrics for Workflow Nets

    DEFF Research Database (Denmark)

    Lassen, Kristian Bisgaard; van der Aalst, Wil M.P.

    2009-01-01

    Process modeling languages such as EPCs, BPMN, flow charts, UML activity diagrams, Petri nets, etc.\\ are used to model business processes and to configure process-aware information systems. It is known that users have problems understanding these diagrams. In fact, even process engineers and system...

  9. Synthesis of new oxadiazole, pyrazole and pyrazolin-5-one bearing 2-((4-methyl-2-oxo-2H-chromen-7-yl)oxy)acetohydrazide analogs as potential antibacterial and antifungal agents.

    Science.gov (United States)

    Mahesh, M; Bheemaraju, G; Manjunath, G; Venkata Ramana, P

    2016-01-01

    Two series of diversely substituted phenyldiazenyl(2-(4-methyl-2-oxo-2H-chromen-7-yloxy)acetyl)3,5-dimethyl-1H-pyrazole 11a-g and phenyldiazenyl-1-(2-(4-methyl-2-oxo-4-chromen-7-yloxy)acetyl)-3-methyl-1H-pyrazol-5(4)H-one 12a-j were synthesized. All these compounds were characterized by IR, NMR, mass spectra and elemental analyses. The compounds were evaluated for their in vitro antibacterial activity against some Gram-positive bacteria, Staphylococcus aureus, Bacillus subtilis, Gram-negative bacteria, Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi and screened for antifungal activity against A. niger, U. maydis. The compounds showed moderate to very good antibacterial activities. Copyright © 2015 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.

  10. Rapid analysis of heterogeneously methylated DNA using digital methylation-sensitive high resolution melting: application to the CDKN2B (p15) gene

    DEFF Research Database (Denmark)

    Candiloro, Ida Lm; Mikeska, Thomas; Hokland, Peter

    2008-01-01

    MS-HRM) that involves the amplification of single templates after limiting dilution to quantify and to determine the degree of methylation. We used this approach to study methylation of the CDKN2B (p15) cell cycle progression inhibitor gene which is inactivated by DNA methylation in haematological malignancies...... and other heterogeneously methylated genes. It eliminates both PCR and cloning bias towards either methylated or unmethylated DNA. Potentially complex information is simplified into a digital output, allowing counting of methylated and unmethylated alleles and providing an overall picture of methylation...... at the given locus. Downstream sequencing is minimised as dMS-HRM acts as a screen to select only methylated clones for further analysis....

  11. Forensic DNA methylation profiling from evidence material for investigative leads

    Science.gov (United States)

    Lee, Hwan Young; Lee, Soong Deok; Shin, Kyoung-Jin

    2016-01-01

    DNA methylation is emerging as an attractive marker providing investigative leads to solve crimes in forensic genetics. The identification of body fluids that utilizes tissue-specific DNA methylation can contribute to solving crimes by predicting activity related to the evidence material. The age estimation based on DNA methylation is expected to reduce the number of potential suspects, when the DNA profile from the evidence does not match with any known person, including those stored in the forensic database. Moreover, the variation in DNA implicates environmental exposure, such as cigarette smoking and alcohol consumption, thereby suggesting the possibility to be used as a marker for predicting the lifestyle of potential suspect. In this review, we describe recent advances in our understanding of DNA methylation variations and the utility of DNA methylation as a forensic marker for advanced investigative leads from evidence materials. [BMB Reports 2016; 49(7): 359-369] PMID:27099236

  12. Forensic DNA methylation profiling from evidence material for investigative leads.

    Science.gov (United States)

    Lee, Hwan Young; Lee, Soong Deok; Shin, Kyoung-Jin

    2016-07-01

    DNA methylation is emerging as an attractive marker providing investigative leads to solve crimes in forensic genetics. The identification of body fluids that utilizes tissue-specific DNA methylation can contribute to solving crimes by predicting activity related to the evidence material. The age estimation based on DNA methylation is expected to reduce the number of potential suspects, when the DNA profile from the evidence does not match with any known person, including those stored in the forensic database. Moreover, the variation in DNA implicates environmental exposure, such as cigarette smoking and alcohol consumption, thereby suggesting the possibility to be used as a marker for predicting the lifestyle of potential suspect. In this review, we describe recent advances in our understanding of DNA methylation variations and the utility of DNA methylation as a forensic marker for advanced investigative leads from evidence materials. [BMB Reports 2016; 49(7): 359-369].

  13. Whole-genome methylation caller designed for methyl-DNA ...

    African Journals Online (AJOL)

    DNA methylation is an indispensable epigenetic modification required for regulating the expression of mammalian genomes. Continued efforts have been made to unravel the methylation states genome-wide, featuring the methyl-DNA immunoprecipitation (MeDIP) coupled with next-generation sequencing. Our method ...

  14. Syntrophs dominate sequences associated with the mercury methylation-related gene hgcA in the water conservation areas of the Florida Everglades.

    Science.gov (United States)

    Bae, Hee-Sung; Dierberg, Forrest E; Ogram, Andrew

    2014-10-01

    The mechanisms and rates of mercury methylation in the Florida Everglades are of great concern because of potential adverse impacts on human and wildlife health through mercury accumulation in aquatic food webs. We developed a new PCR primer set targeting hgcA, a gene encoding a corrinoid protein essential for Hg methylation across broad phylogenetic boundaries, and used this primer set to study the distribution of hgcA sequences in soils collected from three sites along a gradient in sulfate and nutrient concentrations in the northern Everglades. The sequences obtained were distributed in diverse phyla, including Proteobacteria, Chloroflexi, Firmicutes, and Methanomicrobia; however, hgcA clone libraries from all sites were dominated by sequences clustering within the order Syntrophobacterales of the Deltaproteobacteria (49 to 65% of total sequences). dsrB mRNA sequences, representing active sulfate-reducing prokaryotes at the time of sampling, obtained from these sites were also dominated by Syntrophobacterales (75 to 89%). Laboratory incubations with soils taken from the site low in sulfate concentrations also suggested that Hg methylation activities were primarily mediated by members of the order Syntrophobacterales, with some contribution by methanogens, Chloroflexi, iron-reducing Geobacter, and non-sulfate-reducing Firmicutes inhabiting the sites. This suggests that prokaryotes distributed within clades defined by syntrophs are the predominant group controlling methylation of Hg in low-sulfate areas of the Everglades. Any strategy for managing mercury methylation in the Everglades should consider that net mercury methylation is not limited to the action of sulfate reduction. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  15. Methylated β-Cyclodextrins

    DEFF Research Database (Denmark)

    Schönbeck, Jens Christian Sidney; Westh, Peter; Madsen, Jens Christian

    2011-01-01

    groups at O2 promote complexation by extending the hydrophobic cavity. Like in the case of 2-hydroxypropylated cyclodextrins, the methyl substituents cause an increased release of ordered water from the hydration shell of the bile salts, resulting in a strong increase in both the enthalpy and the entropy...

  16. Methyl Esters for Tumor Drug Delivery

    Directory of Open Access Journals (Sweden)

    José Portilla-Arias

    2010-01-01

    Full Text Available New copolyesters derived from poly(β,L-malic acid have been designed to serve as nanoconjugate platforms in drug delivery. 25% and 50% methylated derivatives (coPMLA-Me25H75 and coPMLA-Me50H50 with absolute molecular weights of 32 600 Da and 33 100 Da, hydrodynamic diameters of 3.0 nm and 5.2 nm and zeta potential of −15 mV and −8.25 mV, respectively, were found to destabilize membranes of liposomes at pH 5.0 and pH 7.5 at concentrations above 0.05 mg/mL. The copolymers were soluble in PBS (half life of 40 hours and in human plasma (half life of 15 hours but they showed tendency to aggregate at high levels of methylation. Fluorescence-labeled copolymers were internalized into MDA-MB-231 breast cancer cells with increased efficiency for the higher methylated copolymer. Viability of cultured brain and breast cancer cell lines indicated moderate toxicity that increased with methylation. The conclusion of the present work is that partially methylated poly(β,L-malic acid copolyesters are suitable as nanoconjugate platforms for drug delivery.

  17. DNA Methylation and Cancer Diagnosis

    Science.gov (United States)

    Delpu, Yannick; Cordelier, Pierre; Cho, William C.; Torrisani, Jérôme

    2013-01-01

    DNA methylation is a major epigenetic modification that is strongly involved in the physiological control of genome expression. DNA methylation patterns are largely modified in cancer cells and can therefore be used to distinguish cancer cells from normal tissues. This review describes the main technologies available for the detection and the discovery of aberrantly methylated DNA patterns. It also presents the different sources of biological samples suitable for DNA methylation studies. We discuss the interest and perspectives on the use of DNA methylation measurements for cancer diagnosis through examples of methylated genes commonly documented in the literature. The discussion leads to our consideration for why DNA methylation is not commonly used in clinical practice through an examination of the main requirements that constitute a reliable biomarker. Finally, we describe the main DNA methylation inhibitors currently used in clinical trials and those that exhibit promising results. PMID:23873296

  18. DNA methylation-based variation between human populations.

    Science.gov (United States)

    Kader, Farzeen; Ghai, Meenu

    2017-02-01

    Several studies have proved that DNA methylation affects regulation of gene expression and development. Epigenome-wide studies have reported variation in methylation patterns between populations, including Caucasians, non-Caucasians (Blacks), Hispanics, Arabs, and numerous populations of the African continent. Not only has DNA methylation differences shown to impact externally visible characteristics, but is also a potential biomarker for underlying racial health disparities between human populations. Ethnicity-related methylation differences set their mark during early embryonic development. Genetic variations, such as single-nucleotide polymorphisms and environmental factors, such as age, dietary folate, socioeconomic status, and smoking, impacts DNA methylation levels, which reciprocally impacts expression of phenotypes. Studies show that it is necessary to address these external influences when attempting to differentiate between populations since the relative impacts of these factors on the human methylome remain uncertain. The present review summarises several reported attempts to establish the contribution of differential DNA methylation to natural human variation, and shows that DNA methylation could represent new opportunities for risk stratification and prevention of several diseases amongst populations world-wide. Variation of methylation patterns between human populations is an exciting prospect which inspires further valuable research to apply the concept in routine medical and forensic casework. However, trans-generational inheritance needs to be quantified to decipher the proportion of variation contributed by DNA methylation. The future holds thorough evaluation of the epigenome to understand quantification, heritability, and the effect of DNA methylation on phenotypes. In addition, methylation profiling of the same ethnic groups across geographical locations will shed light on conserved methylation differences in populations.

  19. Caught in the Net: Perineuronal Nets and Addiction

    Directory of Open Access Journals (Sweden)

    Megan Slaker

    2016-01-01

    Full Text Available Exposure to drugs of abuse induces plasticity in the brain and creates persistent drug-related memories. These changes in plasticity and persistent drug memories are believed to produce aberrant motivation and reinforcement contributing to addiction. Most studies have explored the effect drugs of abuse have on pre- and postsynaptic cells and astrocytes; however, more recently, attention has shifted to explore the effect these drugs have on the extracellular matrix (ECM. Within the ECM are unique structures arranged in a net-like manner, surrounding a subset of neurons called perineuronal nets (PNNs. This review focuses on drug-induced changes in PNNs, the molecules that regulate PNNs, and the expression of PNNs within brain circuitry mediating motivation, reward, and reinforcement as it pertains to addiction.

  20. Army Net Zero Prove Out. Army Net Zero Training Report

    Science.gov (United States)

    2014-11-20

    sensors were strategically placed throughout the installation by magnetically attaching them to water main valve stems. The sensors check sound...Recycle Wrap  Substitutes for Packaging Materials  Re-Use of Textiles and Linens  Setting Printers to Double-Sided Printing Net Zero Waste...can effectively achieve source reduction. Clean and Re-Use Shop Rags - Shop rags represent a large textile waste stream at many installations. As a

  1. Army Net Zero Prove Out. Net Zero Waste Best Practices

    Science.gov (United States)

    2014-11-20

    Anaerobic Digesters – Although anaerobic digestion is not a new technology and has been used on a large-scale basis in wastewater treatment , the...technology and has been used on a large-scale basis in wastewater treatment , the use of the technology should be demonstrated with other...approaches can be used for cardboard and cellulose -based packaging materials. This approach is in line with the Net Zero Waste hierarchy in terms of

  2. Involvement of PTEN promoter methylation in cerebral cavernous malformations.

    Science.gov (United States)

    Zhu, Yuan; Wloch, Andreas; Wu, Qun; Peters, Christian; Pagenstecher, Axel; Bertalanffy, Helmut; Sure, Ulrich

    2009-03-01

    Cerebral cavernous malformations (CCMs) are prevalent cerebral vascular lesions involving aberrant angiogenesis. However, the underlying mechanism is poorly understood. Phosphatase and tension homolog deleted on chromosome 10 (PTEN), a tumor suppressor, is frequently deficient in various pathologies due to mutation or epigenetic alterations. PTEN promoter hypermethylation is a major epigenetic silencing mechanism leading to activation of angiogenesis in tumors. The present study aimed to investigate whether PTEN promoter methylation was involved in CCMs. PTEN promoter methylation was detected in surgical specimens of CCMs (n=69) by methylation-specific polymerase chain reaction. The methylation status was correlated to the clinical manifestations and to PTEN expression, which was analyzed by both Western blot and immunohistochemistry. To investigate the endothelial proliferation and the potential signaling pathways affected by PTEN methylation, proliferating cell nuclear antigen as well as phosphor-Akt and phosphor-Erk1,2 were detected by immunofluorescence and Western blot, respectively, in CCM specimens. Methylation-specific polymerase chain reaction revealed PTEN promoter methylation in 15.9% CCMs. Strikingly, 5 of 6 familial CCMs showed PTEN promoter methylation (83.3%), which was significantly higher than in sporadic cases (9.4%; P<0.001). In addition, PTEN promoter methylation appeared more frequently in multiple CCMs, including familial cases (46.7%), than that in single-lesioned CCMs (11.8%; P<0.05). Immunostaining and Western blot revealed a more significant PTEN downregulation in PTEN-methylated CCMs in comparison to PTEN-unmethylated CCMs. Reduced PTEN expression was inversely correlated to the expression of proliferating cell nuclear antigen and to the activation of Erk1,2, but not of Akt. We reported here for the first time the involvement of PTEN promoter methylation in CCMs, particularly in familial CCMs, suggesting this epigenetic alteration as a

  3. A new norepinephrine transporter imaging agent for cardiac sympathetic nervous function imaging: radioiodinated (R)-N-methyl-3-(2-iodophenoxy)-3-phenylpropanamine

    Energy Technology Data Exchange (ETDEWEB)

    Kiyono, Yasushi E-mail: hsaji@pharm.kyoto-u.ac.jp; Kanegawa, Naoki; Kawashima, Hidekazu; Fujiwara, Hiromi; Iida, Yasuhiko; Nishimura, Hiroshi; Saji, Hideo

    2003-10-01

    Changes of the cardiac norepinephrine transporter (NET) have been reported in several cardiac failures. (R)-N-methyl-3-(2-iodophenoxy)-3-phenylpropanamine (MIPP), the 3-phenoxy-3-phenylpropylamine analogue iodinated at the 2-position of the phenoxy ring, was synthesized and evaluated as a potential radiopharmaceutical for investigating the cardiac norepinephrine transporter by single photon emission computed tomography (SPECT). (R)-[{sup 125}I]MIPP was synthesized via a halogen exchange reaction under no-carrier-added conditions and purified by high-performance liquid chromatography (HPLC) with high radiochemical yield (60%) and high radiochemical purity (> 98%). The binding affinity of (R)-MIPP for cardiac NET was measured in terms of the displacement of [{sup 3}H]desipramine and (R)-[{sup 125}I]MIPP from binding sites in rat heart membranes. The binding data revealed that the affinity of (R)-MIPP was 5 times that of nisoxetine which is a selective NET inhibitor. In biodistribution studies, (R)-[{sup 125}I]MIPP showed a high uptake followed by rapid clearance in the heart. (R)-[{sup 125}I]MIPP binding sites were saturable and the administration of nisoxetine and desipramine, selective NET inhibitors, decreased the cardiac accumulation of (R)-[{sup 125}I]MIPP. These results suggested that (R)-[{sup 123}I]MIPP may be an useful radiopharmaceutical for imaging cardiac sympathetic nervous functions.

  4. Electrophysiological study, biodistribution in mice, and preliminary PET evaluation in a rhesus monkey of 1-amino-3-[F-18]fluoromethyl-5-methyl-adamantane (F-18-MEM) : A potential radioligand for mapping the NMDA-receptor complex

    NARCIS (Netherlands)

    Samnick, S; Ametamey, S; Leenders, KL; Vontobel, P; Quack, G; Parsons, CG; Neu, H; Schubiger, PA

    The effect of the fluorinated memantine derivative and NMDA receptor antagonist, 1-amino-3-fluoromethyl-5-methyl-adamantane (F-19-MEM), at the NMDA receptor ion channel was studied by patch clamp recording. The results showed that F-19-MEM is a moderate NMDA receptor channel blocker. A procedure for

  5. Integrative analyses of gene expression and DNA methylation profiles in breast cancer cell line models of tamoxifen-resistance indicate a potential role of cells with stem-like properties

    DEFF Research Database (Denmark)

    Lin, Xue; Li, Jian; Yin, Guangliang

    2013-01-01

    Development of resistance to tamoxifen is an important clinical issue in the treatment of breast cancer. Tamoxifen resistance may be the result of acquisition of epigenetic regulation within breast cancer cells, such as DNA methylation, resulting in changed mRNA expression of genes pivotal...

  6. HANPP Collection: Human Appropriation of Net Primary Productivity as a Percentage of Net Primary Productivity

    Data.gov (United States)

    National Aeronautics and Space Administration — The Human Appropriation of Net Primary Productivity (HANPP) as a Percentage of Net Primary Productivity (NPP) portion of the Human Appropriation of Net Primary...

  7. Hydrodynamic characteristics of plane netting used for aquaculture net cages in uniform current

    National Research Council Canada - National Science Library

    DONG, SHUCHUANG; HU, FUXIANG; KUMAZAWA, TAISEI; SIODE, DAISUKE; TOKAI, TADASHI

    2016-01-01

      The hydrodynamic characteristics of polyethylene (PE) netting and chain link wire netting with different types of twine diameter and mesh size for aquaculture net cages were examined by experiments in a flume tank...

  8. Implications of bio-efficacy and persistence of insecticides when indoor residual spraying and long-lasting insecticide nets are combined for malaria prevention

    Directory of Open Access Journals (Sweden)

    Okumu Fredros O

    2012-11-01

    Full Text Available Abstract Background Bio-efficacy and residual activity of insecticides used for indoor residual spraying (IRS and long-lasting insecticide nets (LLINs were assessed against laboratory-reared and wild populations of the malaria vector, Anopheles arabiensis in south eastern Tanzania. Implications of the findings are examined in the context of potential synergies and redundancies where IRS and LLINs are combined. Methods Bioassays were conducted monthly for six months on three LLIN types (Olyset® PermaNet 2.0®,and Icon Life® and three IRS treatments (2 g/m2 pirimiphos-methyl, 2 g/m2 DDT and 0.03 g/m2 lambda-cyhalothrin, sprayed on mud walls and palm ceilings of experimental huts. Tests used susceptible laboratory-reared An. arabiensis exposed in cones (nets and IRS or wire balls (nets only. Susceptibility of wild populations was assessed using WHO diagnostic concentrations and PCR for knock-down resistance (kdr genes. Results IRS treatments killed ≥ 85% of mosquitoes exposed on palm ceilings and ≥ 90% of those exposed on mud walls, but up to 50% of this toxicity decayed within 1–3 months, except for DDT. By 6th month, only 7.5%, 42.5% and 30.0% of mosquitoes died when exposed to ceilings sprayed with pirimiphos-methyl, DDT or lambda-cyhalothrin respectively, while 12.5%, 36.0% and 27.5% died after exposure to mud walls sprayed with the same insecticides. In wire-ball assays, mortality decreased from 98.1% in 1st month to 92.6% in 6th month in tests on PermaNet 2.0®, from 100% to 61.1% on Icon Life® and from 93.2% to 33.3% on Olyset® nets. In cone bioassays, mortality reduced from 92.8% in 1st month to 83.3% in 6th month on PermaNet 2.0®, from 96.9% to 43.80% on Icon Life® and from 85.6% to 14.6% on Olyset®. Wild An. arabiensis were 100% susceptible to DDT, 95.8% to deltamethrin, 90.2% to lambda cyhalothrin and 95.2% susceptible to permethrin. No kdr gene mutations were detected. Conclusions In bioassays where sufficient contact with

  9. Nanomicellar formulation of coenzyme Q10 (Ubisol-Q10) effectively blocks ongoing neurodegeneration in the mouse 1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine model: potential use as an adjuvant treatment in Parkinson’s disease

    Science.gov (United States)

    Sikorska, Marianna; Lanthier, Patricia; Miller, Harvey; Beyers, Melissa; Sodja, Caroline; Zurakowski, Bogdan; Gangaraju, Sandhya; Pandey, Siyaram; Sandhu, Jagdeep K.

    2016-01-01

    Although the support for the use of antioxidants, such as coenzyme Q10 (CoQ10), to treat Parkinson’s disease (PD) comes from the extensive scientific evidence, the results of conducted thus far clinical trials are inconclusive. It is assumed that the efficacy of CoQ10 is hindered by insolubility, poor bioavailability, and lack of brain penetration. We have developed a nanomicellar formulation of CoQ10 (Ubisol-Q10) with improved properties, including the brain penetration, and tested its effectiveness in mouse MPTP (1-methyl-4-phenyl- 1, 2, 3, 6-tetrahydropyridine) model with the objectives to assess its potential use as an adjuvant therapy for PD. We used a subchronic MPTP model (5-daily MPTP injections), characterized by 50% loss of dopamine neurons over a period of 28 days. Ubisol-Q10 was delivered in drinking water. Prophylactic application of Ubisol-Q10, started 2 weeks before the MPTP exposure, significantly offset the neurotoxicity (approximately 50% neurons died in MPTP group vs. 17% in MPTP+ Ubisol-Q10 group by day 28). Therapeutic application of Ubisol-Q10, given after the last MPTP injection, was equally effective. At the time of intervention on day 5 nearly 25% of dopamine neurons were already lost, but the treatment saved the remaining 25% of cells, which otherwise would have died by day 28. This was confirmed by cell counts, analyses of striatal dopamine levels, and improved animals’ motor skill on a beam walk test. Similar levels of neuroprotection were obtained with 3 different Ubisol-Q10 concentrations tested, that is, 30 mg, 6 mg, or 3 mg CoQ10/kg body weight/day, showing clearly that high doses of CoQ10 were not required to deliver these effects. Furthermore, the Ubisol-Q10 treatments brought about a robust astrocytic activation in the brain parenchyma, indicating that astroglia played an active role in this neuroprotection. Thus, we have shown for the first time that Ubisol-Q10 was capable of halting the neurodegeneration already in progress

  10. Expression of an antisense Datura stramonium S-adenosylmethionine decarboxylase cDNA in tobacco: changes in enzyme activity, putrescine-spermidine ratio, rhizogenic potential, and response to methyl jasmonate.

    Science.gov (United States)

    Torrigiani, Patrizia; Scaramagli, Sonia; Ziosi, Vanina; Mayer, Melinda; Biondi, Stefania

    2005-05-01

    S-adenosylmethionine decarboxylase activity (SAMDC; EC 4.1.1.21) leads to spermidine and spermine synthesis through specific synthases which use putrescine, spermidine and decarboxylated S-adenosylmethionine as substrates. In order to better understand the regulation of polyamine (PA), namely spermidine and spermine, biosynthesis, a SAMDC cDNA of Datura stramonium was introduced in tobacco (Nicotiana tabacum L. cv. Xanthi) in antisense orientation under the CaMV 35S promoter, by means of Agrobacterium tumefaciens and leaf disc transformation. The effect of the genetic manipulation on PA metabolism, ethylene production and plant morphology was analysed in primary transformants (R0), and in the transgenic progeny (second generation, R1) of self-fertilised primary transformants, relative to empty vector-transformed (pBin19) and wild-type (WT) controls. All were maintained in vitro by micropropagation. Primary transformants, which were confirmed by Southern and northern analyses, efficiently transcribed the antisense SAMDC gene, but SAMDC activity and PA titres did not change. By contrast, in most transgenic R1 shoots, SAMDC activity was remarkably lower than in controls, and the putrescine-to-spermidine ratio was altered, mainly due to increased putrescine, even though putrescine oxidising activity (diamine oxidase, EC 1.4.3.6) did not change relative to controls. Despite the reduction in SAMDC activity, the production of ethylene, which shares with PAs the common precursor SAM, was not influenced by the foreign gene. Some plants were transferred to pots and acclimatised in a growth chamber. In these in vivo-grown second generation transgenic plants, at the vegetative stage, SAMDC activity was scarcely reduced, and PA titres did not change. Finally, the rhizogenic potential of in vitro-cultured leaf explants excised from antisense plants was significantly diminished as compared with WT ones, and the response to methyl jasmonate, a stress-mimicking compound, in terms

  11. Isolated unit tests in .Net

    OpenAIRE

    Haukilehto, Tero

    2013-01-01

    In this thesis isolation in unit testing is studied to get a precise picture of the isolation frameworks available for .Net environment. At the beginning testing is discussed in theory with the benefits and the problems it may have been linked with. The theory includes software development in general in connection with testing. Theory of isolation is also described before the actual isolation frameworks are represented. Common frameworks are described in more detail and comparable informa...

  12. DNA methylation dynamics in neurogenesis

    Science.gov (United States)

    Wang, Zhiqin; Tang, Beisha; He, Yuquan; Jin, Peng

    2016-01-01

    Neurogenesis is not limited to the embryonic stage, but continually proceeds in the adult brain throughout life. Epigenetic mechanisms, including DNA methylation, histone modification and noncoding RNA, play important roles in neurogenesis. For decades, DNA methylation was thought to be a stable modification, except for demethylation in the early embryo. In recent years, DNA methylation has proved to be dynamic during development. In this review, we summarize the latest understanding about DNA methylation dynamics in neurogenesis, including the roles of different methylation forms (5-methylcytosine, 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine), as well as their ‘writers’, ‘readers’ and interactions with histone modifications. PMID:26950681

  13. Demand and willingness-to-pay for bed nets in Tanzania: results from a choice experiment.

    Science.gov (United States)

    Gingrich, Chris D; Ricotta, Emily; Kahwa, Amos; Kahabuka, Catherine; Koenker, Hannah

    2017-07-14

    Universal coverage campaigns for long-lasting insecticide-treated nets do not always reach the goal of one net for every two household members, and even when ownership of at least one net per household is high, many households may not own enough nets. The retail market provides these households options for replacing or increasing the number of nets they own with products that best fit their needs since a variety of net shapes, sizes, and colours are available. Hence, it is important to understand the factors affecting private net demand. This study explores private demand for nets in Tanzania using a discrete choice experiment. The experiment provides participants the option to buy nets with their own money, and thus should prove more accurate than a hypothetical survey of net preferences. Nearly 800 participants sampled in two regions showed an overall strong demand for nets, with 40% choosing to buy a net across all seven combinations of net prices and characteristics such as size, shape, and insecticide treatment. Only 8% of all participants chose not to buy a single net. A key factor influencing demand was whether a participant's household currently owned sufficient nets for all members, with rural participants showing lower net coverage and greater demand than urban participants. Both poor and less poor households showed strong evidence of making purchase decisions based on more than price alone. Mean willingness-to-pay values for a net started at US$1.10 and grew by US$0.50-1.40 for various attributes such as rectangular shape, large size, and insecticide treatment. The impact of price on demand was negative but small, with elasticity values between -0.25 and -0.45. The results suggest that private demand for nets in Tanzania could potentially supplement future coverage campaigns. Net manufacturers and retailers should advertise and promote consumers' preferred net attributes to improve sales and further expand net access and coverage. To overcome household

  14. Characterization of methyl bromide and methyl chloride fluxes at temperate freshwater wetlands

    Science.gov (United States)

    Hardacre, Catherine J.; Heal, Mathew R.

    2013-01-01

    Methyl bromide (CH3Br) and methyl chloride (CH3Cl) are important natural sources of halogens to the atmosphere. A total of 568 CH3Br and 418 CH3Cl net flux measurements were made for up to 2 years at the same locations within four different wetlands in Scotland. Mean (± 1 standard deviation (SD)) CH3Br and CH3Cl net fluxes across all measurements at each wetland were: Auchencorth Moss, 8 (± 7) and 3560 (± 1260) ng m-2 h-1; Old Castle Farm, 420 (± 70) and 500 (± 260) ng m-2 h-1; Red Moss of Balerno, 500 (± 90) and 140,000 (± 36,000) ng m-2 h-1; and St Margaret's Marsh, 3600 (± 600) and -270 (± 450) ng m-2 h-1. None of the wetlands was a large net sink. Where substantial emissions were observed, these followed seasonal trends, increasing early in the growing season and declining in early autumn. Some diurnal cycles were observed, with emissions greatest during the day, although lower emissions were present at night. None of the measured environmental parameters was a strong "universal" driver for fluxes, which were heterogeneous within and between the wetlands, and larger on average than reported to date; plant species appeared to be the dominant factor, the latter confirmed by vegetation removal experiments. Calluna vulgaris and Phragmites australis emitted particularly large amounts of CH3Br, the former also emitting substantial CH3Cl. While acknowledging the substantial uncertainties in extrapolating globally, observations from this work suggest that wetlands contribute more CH3Br and CH3Cl to the atmosphere than current World Meteorological Organization estimates.

  15. Information Thermodynamics of Cytosine DNA Methylation.

    Science.gov (United States)

    Sanchez, Robersy; Mackenzie, Sally A

    2016-01-01

    Cytosine DNA methylation (CDM) is a stable epigenetic modification to the genome and a widespread regulatory process in living organisms that involves multicomponent molecular machines. Genome-wide cytosine methylation patterning participates in the epigenetic reprogramming of a cell, suggesting that the biological information contained within methylation positions may be amenable to decoding. Adaptation to a new cellular or organismal environment also implies the potential for genome-wide redistribution of CDM changes that will ensure the stability of DNA molecules. This raises the question of whether or not we would be able to sort out the regulatory methylation signals from the CDM background ("noise") induced by thermal fluctuations. Here, we propose a novel statistical and information thermodynamic description of the CDM changes to address the last question. The physical basis of our statistical mechanical model was evaluated in two respects: 1) the adherence to Landauer's principle, according to which molecular machines must dissipate a minimum energy ε = kBT ln2 at each logic operation, where kB is the Boltzmann constant, and T is the absolute temperature and 2) whether or not the binary stretch of methylation marks on the DNA molecule comprise a language of sorts, properly constrained by thermodynamic principles. The study was performed for genome-wide methylation data from 152 ecotypes and 40 trans-generational variations of Arabidopsis thaliana and 93 human tissues. The DNA persistence length, a basic mechanical property altered by CDM, was estimated with values from 39 to 66.9 nm. Classical methylome analysis can be retrieved by applying information thermodynamic modelling, which is able to discriminate signal from noise. Our finding suggests that the CDM signal comprises a language scheme properly constrained by molecular thermodynamic principles, which is part of an epigenomic communication system that obeys the same thermodynamic rules as do current

  16. Event hierarchies in DanNet

    DEFF Research Database (Denmark)

    Pedersen, Bolette Sandford; Nimb, Sanni

    2008-01-01

    Artiklen omhandler udarbejdelsen af et verbumshierarki i det leksikalsk-semantiske ordnet, DanNet.......Artiklen omhandler udarbejdelsen af et verbumshierarki i det leksikalsk-semantiske ordnet, DanNet....

  17. The Uniframe .Net Web Service Discovery Service

    National Research Council Canada - National Science Library

    Berbeco, Robert W

    2003-01-01

    Microsoft .NET allows the creation of distributed systems in a seamless manner Within NET small, discrete applications, referred to as Web services, are utilized to connect to each other or larger applications...

  18. Long Term RadNet Quality Data

    Data.gov (United States)

    U.S. Environmental Protection Agency — This RadNet Quality Data Asset includes all data since initiation and when ERAMS was expanded to become RadNet, name changed to reflect new mission. This includes...

  19. Methyl 2-(5-methyl-3-methyl-sulfinyl-1-benzofuran-2-yl)acetate.

    Science.gov (United States)

    Choi, Hong Dae; Seo, Pil Ja; Son, Byeng Wha; Lee, Uk

    2008-08-06

    The title compound, C(13)H(14)O(4)S, was prepared by oxidation of methyl 2-(5-methyl-3-methyl-sulfanyl-1-benzofuran-2-yl)acetate with 3-chloro-peroxy-benzoic acid. The O atom and methyl group of the methyl-sulfinyl substituent lie on opposite sides of the plane of the benzofuran system. The crystal structure is stabilized by inter-molecular aromatic π-π inter-actions between the benzene rings of neighbouring mol-ecules, with a centroid-centroid separation of 3.841 (3) Å.

  20. PsychoNet: a psycholinguistc commonsense ontology

    OpenAIRE

    Mohtasseb, Haytham; Ahmed, Amr

    2010-01-01

    Ontologies have been widely accepted as the most advanced knowledge representation model. This paper introduces PsychoNet, a new knowledgebase that forms the link between psycholinguistic taxonomy, existing in LIWC, and its semantic textual representation in the form of commonsense semantic ontology, represented by ConceptNet. The integration of LIWC and ConceptNet and the added functionalities facilitate employing ConceptNet in psycholinguistic studies. Furthermore, it simplifies utilization...

  1. Towards new information resources for public health--from WordNet to MedicalWordNet.

    Science.gov (United States)

    Fellbaum, Christiane; Hahn, Udo; Smith, Barry

    2006-06-01

    In the last two decades, WordNet has evolved as the most comprehensive computational lexicon of general English. In this article, we discuss its potential for supporting the creation of an entirely new kind of information resource for public health, viz. MedicalWordNet. This resource is not to be conceived merely as a lexical extension of the original WordNet to medical terminology; indeed, there is already a considerable degree of overlap between WordNet and the vocabulary of medicine. Instead, we propose a new type of repository, consisting of three large collections of (1) medically relevant word forms, structured along the lines of the existing Princeton WordNet; (2) medically validated propositions, referred to here as medical facts, which will constitute what we shall call MedicalFactNet; and (3) propositions reflecting laypersons' medical beliefs, which will constitute what we shall call the MedicalBeliefNet. We introduce a methodology for setting up the MedicalWordNet. We then turn to the discussion of research challenges that have to be met to build this new type of information resource. We build a database of sentences relevant to the medical domain. The sentences are generated from WordNet via its relations as well as from medical statements broken down into elementary propositions. Two subcorpora of sentences are distinguished, MedicalBeliefNet and MedicalFactNet. The former is rated for assent by laypersons; the latter for correctness by medical experts. The sentence corpora will be valuable for a variety of applications in information retrieval as well as in research in linguistics and psychology with respect to the study of expert and non-expert beliefs and their linguistic expressions. Our work has to meet several considerable challenges. These include accounting for the distinction between medical experts and laypersons, the social issues of expert-layperson communication in different media, the linguistic aspects of encoding medical knowledge, and

  2. Mass Spectrometry Based Ultrasensitive DNA Methylation Profiling Using Target Fragmentation Assay.

    Science.gov (United States)

    Lin, Xiang-Cheng; Zhang, Ting; Liu, Lan; Tang, Hao; Yu, Ru-Qin; Jiang, Jian-Hui

    2016-01-19

    Efficient tools for profiling DNA methylation in specific genes are essential for epigenetics and clinical diagnostics. Current DNA methylation profiling techniques have been limited by inconvenient implementation, requirements of specific reagents, and inferior accuracy in quantifying methylation degree. We develop a novel mass spectrometry method, target fragmentation assay (TFA), which enable to profile methylation in specific sequences. This method combines selective capture of DNA target from restricted cleavage of genomic DNA using magnetic separation with MS detection of the nonenzymatic hydrolysates of target DNA. This method is shown to be highly sensitive with a detection limit as low as 0.056 amol, allowing direct profiling of methylation using genome DNA without preamplification. Moreover, this method offers a unique advantage in accurately determining DNA methylation level. The clinical applicability was demonstrated by DNA methylation analysis using prostate tissue samples, implying the potential of this method as a useful tool for DNA methylation profiling in early detection of related diseases.

  3. 78 FR 72451 - Net Investment Income Tax

    Science.gov (United States)

    2013-12-02

    ... Revenue Service 26 CFR Part 1 RIN 1545-BL74 Net Investment Income Tax AGENCY: Internal Revenue Service...). These regulations provide guidance on the computation of net investment income. The regulations affect... lesser of: (A) The individual's net investment income for such taxable year, or (B) the excess (if any...

  4. 47 CFR 69.302 - Net investment.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Net investment. 69.302 Section 69.302... Apportionment of Net Investment § 69.302 Net investment. (a) Investment in Accounts 2001, 1220 and Class B Rural...) Investment in Accounts 2002, 2003 and to the extent such inclusions are allowed by this Commission, Account...

  5. 47 CFR 65.450 - Net income.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Net income. 65.450 Section 65.450... OF RETURN PRESCRIPTION PROCEDURES AND METHODOLOGIES Exchange Carriers § 65.450 Net income. (a) Net income shall consist of all revenues derived from the provision of interstate telecommunications services...

  6. 47 CFR 65.500 - Net income.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Net income. 65.500 Section 65.500... OF RETURN PRESCRIPTION PROCEDURES AND METHODOLOGIES Interexchange Carriers § 65.500 Net income. The net income methodology specified in § 65.450 shall be utilized by all interexchange carriers that are...

  7. NetBeans IDE 8 cookbook

    CERN Document Server

    Salter, David

    2014-01-01

    If you're a Java developer of any level using NetBeans and want to learn how to get the most out of NetBeans, then this book is for you. Learning how to utilize NetBeans will provide a firm foundation for your Java application development.

  8. Characterizing behavioural congruences for Petri nets

    DEFF Research Database (Denmark)

    Nielsen, Mogens; Priese, Lutz; Sassone, Vladimiro

    1995-01-01

    We exploit a notion of interface for Petri nets in order to design a set of net combinators. For such a calculus of nets, we focus on the behavioural congruences arising from four simple notions of behaviour, viz., traces, maximal traces, step, and maximal step traces, and from the corresponding...

  9. 27 CFR 4.37 - Net contents.

    Science.gov (United States)

    2010-04-01

    ... the volume of wine within the container, except that the following tolerances shall be allowed: (1... THE TREASURY LIQUORS LABELING AND ADVERTISING OF WINE Labeling Requirements for Wine § 4.37 Net contents. (a) Statement of net contents. The net contents of wine for which a standard of fill is...

  10. Synthesis and in vitro evaluation of N-alkyl-3-hydroxy-3-(2-imino-3-methyl-5-oxoimidazolidin-4-yl)indolin-2-one analogs as potential anticancer agents

    Science.gov (United States)

    Penthala, Narsimha Reddy; Yerramreddy, Thirupathi Reddy; Madadi, Nikhil Reddy; Crooks, Peter A.

    2013-01-01

    A series of novel 3-hydroxy-3-(2-imino-3-methyl-5-oxoimidazolidin-4-yl)indolin-2-one analogs (3) have been synthesized under microwave irradiation and conventional heating methods. These analogs were evaluated for in vitro cytotoxicity against a panel of 57 human tumor cell lines. Compound 3o had GI50 values of 190 nM and 750 nM against A549/ATTC non-small cell lung cancer and LOX IMVI melanoma cell lines, respectively, and both 3n and 3o exhibited GI50 values ranging from 2–5 μM against CCRF-CEM, HL-60(TB), K-562, MOLT-4, and RPMI-8226 leukemia cell lines. These results indicate that N-4-methoxybenzyl-3-hydroxy-(2-imino-3-methyl-5-oxo-4-yl)indolin-2-one analogs may be useful leads for anticancer drug development. PMID:20598531

  11. Methylation in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Regina M. Santella

    2007-02-01

    Full Text Available

    The development of HCC is a complex, multistep, multistage process. The molecular pathogenesis of HCC appears to involve multiple genetic aberrations in the molecular control of hepatocyte proliferation, differentiation and death and the maintenance of genomic integrity. This process is influenced by the cumulative activation and inactivation of oncogenes, tumor suppressor genes and other genes. p53, a tumor suppressor gene, is the most frequently mutated gene in human cancers. There is also a striking sequence specific binding and induction of mutations by AFB1 at codon 249 of p53 in HCC.

    Epigenetic alterations are also involved in cancer development and progression. Methylation of promoter CpG islands is associated with inhibition of transcriptional initiation and permanent silencing of downstream genes.

    It is now known that most important tumor suppressor genes are inactivated, not only by mutations and deletions but also by promoter methylation. Several studies indicated that p16, p15, RASSF1A, MGMT, and GSTP1 promoter hypermethylation are prevalent in HCC. In addition, geographic variation in the methylation status of tumor DNA indicates that environmental factors may influence the frequent and concordant degree of hypermethylation in multiple genes in HCC and that epigeneticenvironmental interactions may be involved in hepatocarcinogenesis. We have found significant relationships between promoter methylation and AFB1-DNA adducts confirming the impact of environmental exposures on gene methylation.

    DNA isolated from serum or plasma of cancer patients frequently contains the same genetic and

  12. DNA methylation variation of human-specific Alu repeats

    Science.gov (United States)

    Bakshi, Arundhati; Herke, Scott W.; Batzer, Mark A.; Kim, Joomyeong

    2016-01-01

    ABSTRACT DNA methylation is the major repression mechanism for human retrotransposons, such as the Alu family. Here, we have determined the methylation levels associated with 5238 loci belonging to 2 Alu subfamilies, AluYa5 and AluYb8, using high-throughput targeted repeat element bisulfite sequencing (HT-TREBS). The results indicate that ∼90% of loci are repressed by high methylation levels. Of the remaining loci, many of the hypomethylated elements are found near gene promoters and show high levels of DNA methylation variation. We have characterized this variation in the context of tumorigenesis and interindividual differences. Comparison of a primary breast tumor and its matched normal tissue revealed early DNA methylation changes in ∼1% of AluYb8 elements in response to tumorigenesis. Simultaneously, AluYa5/Yb8 elements proximal to promoters also showed differences in methylation of up to one order of magnitude, even between normal individuals. Overall, the current study demonstrates that early loss of methylation occurs during tumorigenesis in a subset of young Alu elements, suggesting their potential clinical relevance. However, approaches such as deep-bisulfite-sequencing of individual loci using HT-TREBS are required to distinguish clinically relevant loci from the background observed for AluYa5/Yb8 elements in general with regard to high levels of interindividual variation in DNA methylation. PMID:26890526

  13. Effect of varicocelectomy on sperm functional characteristics and DNA methylation.

    Science.gov (United States)

    Tavalaee, M; Bahreinian, M; Barekat, F; Abbasi, H; Nasr-Esfahani, M H

    2015-10-01

    In individuals with varicocele, DNA is damaged due to high level of oxidative stress, and varicocelectomy can overcome this effect. Damaged DNA is less liable to DNA methylation, and antioxidant therapy appears to have the potential to reduce sperm oxidative stress and DNA damage and thereby maintain DNA methylation, while effect of varicocelectomy on DNA methylation patterns has remained unclear. In the light of these considerations, we aimed to examine the effect of varicocelectomy on sperm DNA methylation and functional characteristics. Fifty-two men with left-sided varicocele (grade II &III) were included. Sperm parameters, DNA fragmentation, protamine deficiency, oxidative stress and global DNA methylation were evaluated before and 3 months after surgery. Our data show that sperm concentration, percentages of spermatozoon with abnormal morphology, DNA fragmentation, protamine deficiency and oxidative stress significantly improved after surgery. Percentage of sperm motility, global DNA methylation and intensity of DNA methylation also improved after surgery, although the differences were not significant when compared with before surgery. Categorisation of individuals to subgroups revealed that improvement of DNA methylation appears to take place in oligozoospermic individuals, which are more severely affected by state of varicocele. However, this is a preliminary study, and further studies are required to solidify this conclusion. © 2014 Blackwell Verlag GmbH.

  14. Grey Communities : A Scientometric Approach to Grey Literature, In and Outside of GreyNet

    OpenAIRE

    Prost, Hélène; Schöpfel, Joachim

    2014-01-01

    International audience; The paper explores grey communities outside the Grey Literature Network Service (GreyNet) and identifies potential members for GreyNet. GreyNet can be compared to a Learned Society or a special interest group specialised in grey literature as a particular field of library and information sciences (LIS). Its relevance is related to its capacity to enforce the terminology and definition of grey literature in LIS research and publications, and its impact and outreach can ...

  15. NET 40 Generics Beginner's Guide

    CERN Document Server

    Mukherjee, Sudipta

    2012-01-01

    This is a concise, practical guide that will help you learn Generics in .NET, with lots of real world and fun-to-build examples and clear explanations. It is packed with screenshots to aid your understanding of the process. This book is aimed at beginners in Generics. It assumes some working knowledge of C# , but it isn't mandatory. The following would get the most use out of the book: Newbie C# developers struggling with Generics. Experienced C++ and Java Programmers who are migrating to C# and looking for an alternative to other generic frameworks like STL and JCF would find this book handy.

  16. The Net Reclassification Index (NRI)

    DEFF Research Database (Denmark)

    Pepe, Margaret S.; Fan, Jing; Feng, Ziding

    2015-01-01

    The Net Reclassification Index (NRI) is a very popular measure for evaluating the improvement in prediction performance gained by adding a marker to a set of baseline predictors. However, the statistical properties of this novel measure have not been explored in depth. We demonstrate the alarming...... marker is proven to erroneously yield a positive NRI. Some insight into this phenomenon is provided. Since large values for the NRI statistic may simply be due to use of poorly fitting risk models, we suggest caution in using the NRI as the basis for marker evaluation. Other measures of prediction...

  17. DNA methylation as a biomarker for preeclampsia.

    Science.gov (United States)

    Anderson, Cindy M; Ralph, Jody L; Wright, Michelle L; Linggi, Bryan; Ohm, Joyce E

    2014-10-01

    Preeclampsia contributes significantly to pregnancy-associated morbidity and mortality as well as future risk of cardiovascular disease in mother and offspring, and preeclampsia in offspring. The lack of reliable methods for early detection limits the opportunities for prevention, diagnosis, and timely treatment. The purpose of this study was to explore distinct DNA methylation patterns associated with preeclampsia in both maternal cells and fetal-derived tissue that represent potential biomarkers to predict future preeclampsia and inheritance in children. A convenience sample of nulliparous women (N = 55) in the first trimester of pregnancy was recruited for this prospective study. Genome-wide DNA methylation was quantified in first-trimester maternal peripheral white blood cells and placental chorionic tissue from normotensive women and those with preeclampsia (n = 6/group). Late-onset preeclampsia developed in 12.7% of women. Significant differences in DNA methylation were identified in 207 individual linked cytosine and guanine (CpG) sites in maternal white blood cells collected in the first trimester (132 sites with gain and 75 sites with loss of methylation), which were common to approximately 75% of the differentially methylated CpG sites identified in chorionic tissue of fetal origin. This study is the first to identify maternal epigenetic targets and common targets in fetal-derived tissue that represent putative biomarkers for early detection and heritable risk of preeclampsia. Findings may pave the way for diagnosis of preeclampsia prior to its clinical presentation and acute damaging effects, and the potential for prevention of the detrimental long-term sequelae. © The Author(s) 2013.

  18. DNA Methylation as a Biomarker for Preeclampsia

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Cindy M.; Ralph, Jody L.; Wright, Michelle L.; Linggi, Bryan E.; Ohm, Joyce E.

    2014-10-01

    Background: Preeclampsia contributes significantly to pregnancy-associated morbidity and mortality as well as future risk of cardiovascular disease in mother and offspring, and preeclampsia in offspring. The lack of reliable methods for early detection limits the opportunities for prevention, diagnosis, and timely treatment. Purpose: The purpose of this study was to explore distinct DNA methylation patterns associated with preeclampsia in both maternal cells and fetal-derived tissue that represent potential biomarkers to predict future preeclampsia and inheritance in children. Method: A convenience sample of nulliparous women (N = 55) in the first trimester of pregnancy was recruited for this prospective study. Genome-wide DNA methylation was quantified in first-trimester maternal peripheral white blood cells and placental chorionic tissue from normotensive women and those with preeclampsia (n = 6/group). Results: Late-onset preeclampsia developed in 12.7% of women. Significant differences in DNA methylation were identified in 207 individual linked cytosine and guanine (CpG) sites in maternal white blood cells collected in the first trimester (132 sites with gain and 75 sites with loss of methylation), which were common to approximately 75% of the differentially methylated CpG sites identified in chorionic tissue of fetal origin. Conclusion: This study is the first to identify maternal epigenetic targets and common targets in fetal-derived tissue that represent putative biomarkers for early detection and heritable risk of preeclampsia. Findings may pave the way for diagnosis of preeclampsia prior to its clinical presentation and acute damaging effects, and the potential for prevention of the detrimental long-term sequelae.

  19. Near Net Manufacturing Using Thin Gage Friction Stir Welding

    Science.gov (United States)

    Takeshita, Jennifer; Potter, David; Holquin, Michael

    2006-01-01

    Friction Stir Welding (FSW) and near net spin forming of FSW aluminumn blanks were investigated for large-scale pressure vessel applications. With a specific focus on very thin gage 2xxx and 7xxx aluminum alloys, the program concentrated on the following: the criteria used for material selection, a potential manufacturing flow, and the effectiveness and associated risks of near net spin forming. Discussion will include the mechanical properties of the friction stir welds and the parent material from before and after the spin forming process. This effort was performed under a NASA Space Exploration initiative focused on increasing the affordability, reliability and performance of pressure vessels larger than 10 ft. diameter.

  20. Squaroglitter: A 3,4-Connected Carbon Net

    KAUST Repository

    Prasad, Dasari L. V. K.

    2013-08-13

    Theoretical calculations are presented on a new hypothetical 3,4-connected carbon net (called squaroglitter) incorporating 1,4 cyclohexadiene units. The structure has tetragonal space group P4/mmm (No. 123) symmetry. The optimized geometry shows normal distances, except for some elongated bonds in the cyclobutane ring substructures in the network. Squaroglitter has an indirect bandgap of about 1.0 eV. The hypothetical lattice, whose density is close to graphite, is more stable than other 3,4-connected carbon nets. A relationship to a (4,4)nanotube is explored, as is a potential threading of the lattice with metal needles. © 2013 American Chemical Society.

  1. DNA methylation program during development.

    Science.gov (United States)

    Zhou, Feng C

    2012-12-01

    DNA methylation is a key epigenetic mark when occurring in the promoter and enhancer regions regulates the accessibility of the binding protein and gene transcription. DNA methylation is inheritable and can be de novo-synthesized, erased and reinstated, making it arguably one of the most dynamic upstream regulators for gene expression and the most influential pacer for development. Recent progress has demonstrated that two forms of cytosine methylation and two pathways for demethylation constitute ample complexity for an instructional program for orchestrated gene expression and development. The forum of the current discussion and review are whether there is such a program, if so what the DNA methylation program entails, and what environment can change the DNA methylation program. The translational implication of the DNA methylation program is also proposed.

  2. Biodiversity offsets and the challenge of achieving no net loss.

    Science.gov (United States)

    Gardner, Toby A; VON Hase, Amrei; Brownlie, Susie; Ekstrom, Jonathan M M; Pilgrim, John D; Savy, Conrad E; Stephens, R T Theo; Treweek, Jo; Ussher, Graham T; Ward, Gerri; Ten Kate, Kerry

    2013-12-01

    Businesses, governments, and financial institutions are increasingly adopting a policy of no net loss of biodiversity for development activities. The goal of no net loss is intended to help relieve tension between conservation and development by enabling economic gains to be achieved without concomitant biodiversity losses. biodiversity offsets represent a necessary component of a much broader mitigation strategy for achieving no net loss following prior application of avoidance, minimization, and remediation measures. However, doubts have been raised about the appropriate use of biodiversity offsets. We examined what no net loss means as a desirable conservation outcome and reviewed the conditions that determine whether, and under what circumstances, biodiversity offsets can help achieve such a goal. We propose a conceptual framework to substitute the often ad hoc approaches evident in many biodiversity offset initiatives. The relevance of biodiversity offsets to no net loss rests on 2 fundamental premises. First, offsets are rarely adequate for achieving no net loss of biodiversity alone. Second, some development effects may be too difficult or risky, or even impossible, to offset. To help to deliver no net loss through biodiversity offsets, biodiversity gains must be comparable to losses, be in addition to conservation gains that may have occurred in absence of the offset, and be lasting and protected from risk of failure. Adherence to these conditions requires consideration of the wider landscape context of development and offset activities, timing of offset delivery, measurement of biodiversity, accounting procedures and rule sets used to calculate biodiversity losses and gains and guide offset design, and approaches to managing risk. Adoption of this framework will strengthen the potential for offsets to provide an ecologically defensible mechanism that can help reconcile conservation and development. Balances de Biodiversidad y el Reto de No Obtener P

  3. Mercury methylation and bacterial activity associated to tropical phytoplankton

    Energy Technology Data Exchange (ETDEWEB)

    Coelho-Souza, Sergio A. [Laboratorio de Tracadores Wolfgang Pfeiffer, SL 62, Instituto de Biofisica Carlos Chagas Filho, Bloco G, Ilha do Fundao, Universidade Federal do Rio de Janeiro (IBCCF/UFRJ), RJ, CEP 21949-900 (Brazil); Guimaraes, Jean R.D. [Laboratorio de Tracadores Wolfgang Pfeiffer, SL 62, Instituto de Biofisica Carlos Chagas Filho, Bloco G, Ilha do Fundao, Universidade Federal do Rio de Janeiro (IBCCF/UFRJ), RJ, CEP 21949-900 (Brazil)]. E-mail: jeanrdg@biof.ufrj.br; Mauro, Jane B.N. [Laboratorio de Tracadores Wolfgang Pfeiffer, SL 62, Instituto de Biofisica Carlos Chagas Filho, Bloco G, Ilha do Fundao, Universidade Federal do Rio de Janeiro (IBCCF/UFRJ), RJ, CEP 21949-900 (Brazil); Miranda, Marcio R. [Laboratorio de Tracadores Wolfgang Pfeiffer, SL 62, Instituto de Biofisica Carlos Chagas Filho, Bloco G, Ilha do Fundao, Universidade Federal do Rio de Janeiro (IBCCF/UFRJ), RJ, CEP 21949-900 (Brazil); Azevedo, Sandra M.F.O. [Laboratorio de Ecofisiologia e Toxicologia de Cianobacterias, IBCCF/UFRJ, RJ (Brazil)

    2006-07-01

    The methylated form of mercury (Hg), methylmercury (MeHg), is one of the most toxic pollutants. Biotic and/or abiotic methylation, often associated to sulfate-reducing bacteria metabolism, occurs in aquatic environments and in many tropical areas, mostly in the periphyton associated to floating macrophyte roots. Data about mercury methylation by phytoplankton are scarce and the aim of this study was to verify the biotic influence in the methylation process in Microcystis aeruginosa and Sineccocystis sp. laboratory strains and in natural populations of phytoplankton from two different aquatic systems, the mesotrophic Ribeirao das Lajes reservoir and hypereutrophic oligohaline Jacarepagua lagoon, Rio de Janeiro state, Brazil. Adapted radiochemical techniques were used to measure sulfate-reduction, mercury methylation and bacterial activity in phytoplankton samples. Methyl-{sup 203}Hg formation from added inorganic {sup 203}Hg and {sup 3}H-Leucine uptake were measured by liquid scintillation as well as sulfate-reduction, estimated as H{sub 2} {sup 35}S produced from added Na{sub 2} {sup 35}SO{sub 4}. There was no significant difference in low methylation potentials (0.37%) among the two cyanobacterium species studied in laboratory conditions. At Ribeirao das Lajes reservoir, there was no significant difference in methylation, bacterial activity and sulfate-reduction of surface sediment between the sampling points. Methylation in sediments (3-4%) was higher than in phytoplankton (1.5%), the opposite being true for bacterial activity (sediment mean 6.6 against 150.3 nmol gdw{sup -1} h{sup -1} for phytoplankton samples). At Jacarepagua lagoon, an expressive bacterial activity (477.1 x 10{sup 3} nmol gdw{sup -1} h{sup -1} at a concentration of 1000 nM leucine) and sulfate-reduction ({approx}21% H{sub 2} {sup 35}S trapped) associated to phytoplankton (mostly cyanobacteria M. aeruginosa) was observed, but mercury methylation was not detected.

  4. Mass distribution of free insecticide-treated nets do not interfere with continuous net distribution in Tanzania.

    Science.gov (United States)

    Eze, Ikenna C; Kramer, Karen; Msengwa, Amina; Mandike, Renata; Lengeler, Christian

    2014-05-27

    To protect the most vulnerable groups from malaria (pregnant women and infants) the Tanzanian Government introduced a subsidy (voucher) scheme in 2004, on the basis of a public-private partnership. These vouchers are provided to pregnant women at their first antenatal care visit and mothers of infants at first vaccination. The vouchers are redeemed at registered retailers for a long-lasting insecticidal net against the payment of a modest top-up price. The present work analysed a large body of data from the Tanzanian National Voucher Scheme, focusing on interactions with concurrent mass distribution campaigns of free nets. In an ecologic study involving all regions of Tanzania, voucher redemption data for the period 2007-2011, as well as data on potential determinants of voucher redemption were analysed. The four outcome variables were: pregnant woman and infant voucher redemption rates, use of treated bed nets by all household members and by under- five children. Each of the outcomes was regressed with selected determinants, using a generalized estimating equation model and accounting for regional data clustering. There was a consistent improvement in voucher redemption rates over the selected time period, with rates >80% in 2011. The major determinants of redemption rates were the top-up price paid by the voucher beneficiary, the retailer- clinic ratio, and socio-economic status. Improved redemption rates after 2009 were most likely due to reduced top-up prices (following a change in policy). Redemption rates were not affected by two major free net distribution campaigns. During this period, there was a consistent improvement in net use across all the regions, with rates of up to 75% in 2011. The key components of the National Treated Nets Programme (NATNETS) seem to work harmoniously, leading to a high level of net use in the entire population. This calls for the continuation of this effort in Tanzania and for emulation by other countries with endemic malaria.

  5. Comparative analysis of rubber seed methyl ester with other methyl ...

    African Journals Online (AJOL)

    The important properties of biodiesel such as specific gravity, flash point, cloud point and pour point were determined and compared with that of diesel. Other properties such as kinematic viscosity sulphur content, Aniline point and Acid value of rubber seed methyl ester were deduced and compared with other methyl esters.

  6. Reuse of polyethylene fibres from discarded fishing nets as reinforcement in gypsym-based materials

    DEFF Research Database (Denmark)

    Bertelsen, Ida Maria Gieysztor; Ottosen, Lisbeth M.

    In this study, the potential of reusing plastic fibres from discarded waste fishing nets of polyethylene (PE) as fibre reinforcement in gypsum-based building materials is investigated. The fishing nets were not reprocessed, but simply washed and cut to monofilament fibres by an industrial operation...

  7. Effects of climate change and shifts in forest composition on forest net primary production

    Science.gov (United States)

    Jyh-Min Chiang; Louts [Louis] R. Iverson; Anantha Prasad; Kim J. Brown

    2008-01-01

    Forests are dynamic in both structure and species composition, and these dynamics are strongly influenced by climate. However, the net effects of future tree species composition on net primary production (NPP) are not well understood. The objective of this work was to model the potential range shifts of tree species (DISTRIB Model) and predict their impacts on NPP (...

  8. Penggunaan Biosorben Biji Pepaya Sebagai Penjerap Zat Warna Methyl Orange, Methyl Violet dan Methyl Red

    OpenAIRE

    Ranita, Lara Indra

    2017-01-01

    120405009 Biosorben adalah bahan yang memiliki banyak pori dimana proses adsorpsi berlangsung pada dinding pori atau terjadi pada daerah tertentu di dalam partikel tersebut. Biosorben dari biji pepaya digunakan untuk menyerap zat warna tekstil, yaitu methyl orange, methyl violet dan methyl red. Tujuan dari penelitian ini adalah mempelajari pengaruh waktu adsorpsi dan massa biosorben terhadap kemampuan daya serap zat warna. Penelitian ini menggunakan biji pepaya sebagai ba...

  9. -Net Approach to Sensor -Coverage

    Directory of Open Access Journals (Sweden)

    Fusco Giordano

    2010-01-01

    Full Text Available Wireless sensors rely on battery power, and in many applications it is difficult or prohibitive to replace them. Hence, in order to prolongate the system's lifetime, some sensors can be kept inactive while others perform all the tasks. In this paper, we study the -coverage problem of activating the minimum number of sensors to ensure that every point in the area is covered by at least sensors. This ensures higher fault tolerance, robustness, and improves many operations, among which position detection and intrusion detection. The -coverage problem is trivially NP-complete, and hence we can only provide approximation algorithms. In this paper, we present an algorithm based on an extension of the classical -net technique. This method gives an -approximation, where is the number of sensors in an optimal solution. We do not make any particular assumption on the shape of the areas covered by each sensor, besides that they must be closed, connected, and without holes.

  10. Targeted deep DNA methylation analysis of circulating cell-free DNA in plasma using massively parallel semiconductor sequencing.

    Science.gov (United States)

    Vaca-Paniagua, Felipe; Oliver, Javier; Nogueira da Costa, Andre; Merle, Philippe; McKay, James; Herceg, Zdenko; Holmila, Reetta

    2015-01-01

    To set up a targeted methylation analysis using semiconductor sequencing and evaluate the potential for studying methylation in circulating cell-free DNA (cfDNA). Methylation of VIM, FBLN1, LTBP2, HINT2, h19 and IGF2 was analyzed in plasma cfDNA and white blood cell DNA obtained from eight hepatocellular carcinoma patients and eight controls using Ion Torrent™ PGM sequencer. h19 and IGF2 showed consistent methylation levels and methylation was detected for VIM and FBLN1, whereas LTBP2 and HINT2 did not show methylation for target regions. VIM gene promoter methylation was higher in HCC cfDNA than in cfDNA of controls or white blood cell DNA. Semiconductor sequencing is a suitable method for analyzing methylation profiles in cfDNA. Furthermore, differences in cfDNA methylation can be detected between controls and hepatocellular carcinoma cases, even though due to the small sample set these results need further validation.

  11. Association of DNA Methylation with Acute Mania and Inflammatory Markers.

    Directory of Open Access Journals (Sweden)

    Sarven Sabunciyan

    Full Text Available In order to determine whether epigenetic changes specific to the manic mood state can be detected in peripheral blood samples we assayed DNA methylation levels genome-wide in serum samples obtained from 20 patients hospitalized for mania and 20 unaffected controls using the Illumina 450K methylation arrays. We identified a methylation locus in the CYP11A1 gene, which is regulated by corticotropin, that is hypo-methylated in individuals hospitalized for mania compared with unaffected controls. DNA methylation levels at this locus appear to be state related as levels in follow-up samples collected from mania patients six months after hospitalization were similar to those observed in controls. In addition, we found that methylation levels at the CYP11A1 locus were significantly correlated with three inflammatory markers in serum in acute mania cases but not in unaffected controls. We conclude that mania is associated with alterations in levels of DNA methylation and inflammatory markers. Since epigenetic markers are potentially malleable, a better understanding of the role of epigenetics may lead to new methods for the prevention and treatment of mood disorders.

  12. Minireview: protein arginine methylation of nonhistone proteins in transcriptional regulation.

    Science.gov (United States)

    Lee, Young-Ho; Stallcup, Michael R

    2009-04-01

    Endocrine regulation frequently culminates in altered transcription of specific genes. The signal transduction pathways, which transmit the endocrine signal from cell surface to the transcription machinery, often involve posttranslational modifications of proteins. Although phosphorylation has been by far the most widely studied protein modification, recent studies have indicated important roles for other types of modification, including protein arginine methylation. Ten different protein arginine methyltransferase (PRMT) family members have been identified in mammalian cells, and numerous substrates are being identified for these PRMTs. Whereas major attention has been focused on the methylation of histones and its role in chromatin remodeling and transcriptional regulation, there are many nonhistone substrates methylated by PRMTs. This review primarily focuses on recent progress on the roles of the nonhistone protein methylation in transcription. Protein methylation of coactivators, transcription factors, and signal transducers, among other proteins, plays important roles in transcriptional regulation. Protein methylation may affect protein-protein interaction, protein-DNA or protein-RNA interaction, protein stability, subcellular localization, or enzymatic activity. Thus, protein arginine methylation is critical for regulation of transcription and potentially for various physiological/pathological processes.

  13. Use of Biomonitoring Data to Evaluate Methyl Eugenol Exposure

    Science.gov (United States)

    Robison, Steven H.; Barr, Dana B.

    2006-01-01

    Methyl eugenol is a naturally occurring material found in a variety of food sources, including spices, oils, and nutritionally important foods such as bananas and oranges. Given its natural occurrence, a broad cross-section of the population is likely exposed. The availability of biomonitoring and toxicology data offers an opportunity to examine how biomonitoring data can be integrated into risk assessment. Methyl eugenol has been used as a biomarker of exposure. An analytical method to detect methyl eugenol in human blood samples is well characterized but not readily available. Human studies indicate that methyl eugenol is short-lived in the body, and despite the high potential for exposure through the diet and environment, human blood levels are relatively low. The toxicology studies in animals demonstrate that relatively high-bolus doses administered orally result in hepatic neoplasms. However, an understanding is lacking regarding how this effect relates to the exposures that result when food containing methyl eugenol is consumed. Overall, the level of methyl eugenol detected in biomonitoring studies indicates that human exposure is several orders of magnitude lower than the lowest dose used in the bioassay. Furthermore, there are no known health effects in humans that result from typical dietary exposure to methyl eugenol. PMID:17107870

  14. High-resolution analysis of cytosine methylation in ancient DNA.

    Directory of Open Access Journals (Sweden)

    Bastien Llamas

    Full Text Available Epigenetic changes to gene expression can result in heritable phenotypic characteristics that are not encoded in the DNA itself, but rather by biochemical modifications to the DNA or associated chromatin proteins. Interposed between genes and environment, these epigenetic modifications can be influenced by environmental factors to affect phenotype for multiple generations. This raises the possibility that epigenetic states provide a substrate for natural selection, with the potential to participate in the rapid adaptation of species to changes in environment. Any direct test of this hypothesis would require the ability to measure epigenetic states over evolutionary timescales. Here we describe the first single-base resolution of cytosine methylation patterns in an ancient mammalian genome, by bisulphite allelic sequencing of loci from late Pleistocene Bison priscus remains. Retrotransposons and the differentially methylated regions of imprinted loci displayed methylation patterns identical to those derived from fresh bovine tissue, indicating that methylation patterns are preserved in the ancient DNA. Our findings establish the biochemical stability of methylated cytosines over extensive time frames, and provide the first direct evidence that cytosine methylation patterns are retained in DNA from ancient specimens. The ability to resolve cytosine methylation in ancient DNA provides a powerful means to study the role of epigenetics in evolution.

  15. Our views of dynamic N6-methyladenosine RNA methylation.

    Science.gov (United States)

    Zhao, Boxuan; Nachtergaele, Sigrid; Roundtree, Ian A; He, Chuan

    2017-12-08

    We thank Darnell et al. in their Divergent Views article for noting our contributions to recent progress in the field of RNA modifications. We agree with many of the viewpoints expressed: that a majority of messenger RNA N6-methyladenosine (m6A) methylation occurs co-transcriptionally, that one of the main functions of m6A methylation on mRNA is to mark sets of transcripts for expedited turnover, and that this methylation may not dramatically affect splicing in HeLa cells. However, although the impact of m6A methylation on splicing appears to be modest in many cell lines, we suggest to be cautious because m6A methylation is enriched in long exons and overrepresented in transcripts with alternative splicing variants. Two recent examples have revealed methylation-dependent changes in splicing: one demonstrated m6A-modulated sex determination in Drosophila melanogaster, and another found enhanced SAM synthetase expression mediated by a specific m6A site installed by METTL16 . The potential effects of RNA methylation on constitutive and alternative splicing in additional physiological contexts need to be further evaluated. Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  16. Methods of DNA methylation detection

    Science.gov (United States)

    Maki, Wusi Chen (Inventor); Filanoski, Brian John (Inventor); Mishra, Nirankar (Inventor); Rastogi, Shiva (Inventor)

    2010-01-01

    The present invention provides for methods of DNA methylation detection. The present invention provides for methods of generating and detecting specific electronic signals that report the methylation status of targeted DNA molecules in biological samples.Two methods are described, direct and indirect detection of methylated DNA molecules in a nano transistor based device. In the direct detection, methylated target DNA molecules are captured on the sensing surface resulting in changes in the electrical properties of a nano transistor. These changes generate detectable electronic signals. In the indirect detection, antibody-DNA conjugates are used to identify methylated DNA molecules. RNA signal molecules are generated through an in vitro transcription process. These RNA molecules are captured on the sensing surface change the electrical properties of nano transistor thereby generating detectable electronic signals.

  17. DNA methylation in metabolic disorders

    DEFF Research Database (Denmark)

    Barres, Romain; Zierath, Juleen R

    2011-01-01

    DNA methylation is a major epigenetic modification that controls gene expression in physiologic and pathologic states. Metabolic diseases such as diabetes and obesity are associated with profound alterations in gene expression that are caused by genetic and environmental factors. Recent reports...... have provided evidence that environmental factors at all ages could modify DNA methylation in somatic tissues, which suggests that DNA methylation is a more dynamic process than previously appreciated. Because of the importance of lifestyle factors in metabolic disorders, DNA methylation provides...... a mechanism by which environmental factors, including diet and exercise, can modify genetic predisposition to disease. This article considers the current evidence that defines a role for DNA methylation in metabolic disorders....

  18. Application and Theory of Petri Nets

    DEFF Research Database (Denmark)

    This volume contains the proceedings of the 13th International Conference onApplication and Theory of Petri Nets, held in Sheffield, England, in June 1992. The aim of the Petri net conferences is to create a forum for discussing progress in the application and theory of Petri nets. Typically....... Balbo and W. Reisig, 18 submitted papers, and seven project papers. The submitted papers and project presentations were selectedby the programme committee and a panel of referees from a large number of submissions....

  19. Are You Neutral About Net Neutrality

    Science.gov (United States)

    2007-06-20

    Information Resources Management College National Defense University Are You Neutral About Net Neutrality ? A presentation for Systems & Software...author uses Verizon FiOS for phone, TV, and internet service 3 Agenda Net Neutrality —Through 2 Lenses Who Are the Players & What Are They Saying...Medical Treatment Mini-Case Studies Updates Closing Thoughts 4 Working Definitions of Net Neutrality "Network Neutrality" is the concept that

  20. Texture Based Image Analysis With Neural Nets

    Science.gov (United States)

    Ilovici, Irina S.; Ong, Hoo-Tee; Ostrander, Kim E.

    1990-03-01

    In this paper, we combine direct image statistics and spatial frequency domain techniques with a neural net model to analyze texture based images. The resultant optimal texture features obtained from the direct and transformed image form the exemplar pattern of the neural net. The proposed approach introduces an automated texture analysis applied to metallography for determining the cooling rate and mechanical working of the materials. The results suggest that the proposed method enhances the practical applications of neural nets and texture extraction features.

  1. Factors associated with mosquito net use by individuals in households owning nets in Ethiopia

    Directory of Open Access Journals (Sweden)

    Graves Patricia M

    2011-12-01

    Full Text Available Abstract Background Ownership of insecticidal mosquito nets has dramatically increased in Ethiopia since 2006, but the proportion of persons with access to such nets who use them has declined. It is important to understand individual level net use factors in the context of the home to modify programmes so as to maximize net use. Methods Generalized linear latent and mixed models (GLLAMM were used to investigate net use using individual level data from people living in net-owning households from two surveys in Ethiopia: baseline 2006 included 12,678 individuals from 2,468 households and a sub-sample of the Malaria Indicator Survey (MIS in 2007 included 14,663 individuals from 3,353 households. Individual factors (age, sex, pregnancy; net factors (condition, age, net density; household factors (number of rooms [2006] or sleeping spaces [2007], IRS, women's knowledge and school attendance [2007 only], wealth, altitude; and cluster level factors (rural or urban were investigated in univariate and multi-variable models for each survey. Results In 2006, increased net use was associated with: age 25-49 years (adjusted (a OR = 1.4, 95% confidence interval (CI 1.2-1.7 compared to children U5; female gender (aOR = 1.4; 95% CI 1.2-1.5; fewer nets with holes (Ptrend = 0.002; and increasing net density (Ptrend [all nets in HH good] = 1.6; 95% CI 1.2-2.1; increasing net density (Ptrend [per additional space] = 0.6, 95% CI 0.5-0.7; more old nets (aOR [all nets in HH older than 12 months] = 0.5; 95% CI 0.3-0.7; and increasing household altitude (Ptrend Conclusion In both surveys, net use was more likely by women, if nets had fewer holes and were at higher net per person density within households. School-age children and young adults were much less likely to use a net. Increasing availability of nets within households (i.e. increasing net density, and improving net condition while focusing on education and promotion of net use, especially in school-age children

  2. DNA Methylation in Schizophrenia.

    Science.gov (United States)

    Pries, Lotta-Katrin; Gülöksüz, Sinan; Kenis, Gunter

    2017-01-01

    Schizophrenia is a highly heritable psychiatric condition that displays a complex phenotype. A multitude of genetic susceptibility loci have now been identified, but these fail to explain the high heritability estimates of schizophrenia. In addition, epidemiologically relevant environmental risk factors for schizophrenia may lead to permanent changes in brain function. In conjunction with genetic liability, these environmental risk factors-likely through epigenetic mechanisms-may give rise to schizophrenia, a clinical syndrome characterized by florid psychotic symptoms and moderate to severe cognitive impairment. These pathophysiological features point to the involvement of epigenetic processes. Recently, a wave of studies examining aberrant DNA modifications in schizophrenia was published. This chapter aims to comprehensively review the current findings, from both candidate gene studies and genome-wide approaches, on DNA methylation changes in schizophrenia.

  3. Methylation regulates HEY1 expression in glioblastoma.

    Science.gov (United States)

    Tsung, Andrew J; Guda, Maheedhara R; Asuthkar, Swapna; Labak, Collin M; Purvis, Ian J; Lu, Yining; Jain, Neha; Bach, Sarah E; Prasad, Durbaka V R; Velpula, Kiran K

    2017-07-04

    Glioblastoma (GBM) remains one of the most lethal and difficult-to-treat cancers of the central nervous system. The poor prognosis in GBM patients is due in part to its resistance to available treatments, which calls for identifying novel molecular therapeutic targets. In this study, we identified a mediator of Notch signaling, HEY1, whose methylation status contributes to the pathogenesis of GBM. Datamining studies, immunohistochemistry and immunoblot analysis showed that HEY1 is highly expressed in GBM patient specimens. Since methylation status of HEY1 may control its expression, we conducted bisulphite sequencing on patient samples and found that the HEY1 promoter region was hypermethylated in normal brain when compared to GBM specimens. Treatment on 4910 and 5310 xenograft cell lines with sodium butyrate (NaB) significantly decreased HEY1 expression with a concomitant increase in DNMT1 expression, confirming that promoter methylation may regulate HEY1 expression in GBM. NaB treatment also induced apoptosis of GBM cells as measured by flow cytometric analysis. Further, silencing of HEY1 reduced invasion, migration and proliferation in 4910 and 5310 cells. Furthermore, immunoblot and q-PCR analysis showed the existence of a potential positive regulatory loop between HEY1 and p53. Additionally, transcription factor interaction array with HEY1 recombinant protein predicted a correlation with p53 and provided various bonafide targets of HEY1. Collectively, these studies suggest HEY1 may be an important predictive marker for GBM and potential target for future GBM therapy.

  4. DNA Methylation in Thyroid Tumorigenesis

    Energy Technology Data Exchange (ETDEWEB)

    Stephen, Josena K., E-mail: jstephe2@hfhs.org [Department of Otolaryngology/Head and Neck Surgery, Henry Ford Hospital, Detroit, MI 48202 (United States); Chitale, Dhananjay [Department of Pathology, Henry Ford Hospital, Detroit, MI 48202 (United States); Narra, Vinod [Essex Surgical Associates, PC, Beverly, MA 01915 (United States); Chen, Kang Mei; Sawhney, Raja; Worsham, Maria J. [Department of Otolaryngology/Head and Neck Surgery, Henry Ford Hospital, Detroit, MI 48202 (United States)

    2011-03-29

    Thyroid cancer is the most common endocrine cancer with 1,690 deaths each year. There are four main types of which the papillary and follicular types together account for >90% followed by medullary cancers with 3% to 5% and anaplastic carcinomas making up <3%. Epigenetic events of DNA hypermethylation are emerging as promising molecular targets for cancer detection. Our immediate and long term goal is to identify DNA methylation markers for early detection of thyroid cancer. This pilot study comprised of 21 patients to include 11 papillary thyroid cancers (PTC), 2 follicular thyroid cancers (FTC), 5 normal thyroid cases, and 3 hyperthyroid cases. Aberrant promoter methylation was examined in 24 tumor suppressor genes using the methylation specific multiplex ligation-dependent probe amplification (MS-MLPA) assay and in the NIS gene using methylation-specific PCR (MSP). The frequently methylated genes were CASP8 (17/21), RASSF1 (16/21) and NIS (9/21). In the normal samples, CASP8, RASSF1 and NIS were methylated in 5/5, 4/5 and 1/5 respectively. In the hyperthyroid samples, CASP8, RASSF1 and NIS were methylated in 3/3, 2/3 and 1/3 respectively. In the thyroid cancers, CASP8, RASSF1, and NIS were methylated in 9/13, 10/13, and 7/13 respectively. CASP8, RASSF1 and NIS were also methylated in concurrently present normal thyroid tissue in 3/11, 4/11 and 3/11 matched thyroid cancer cases (matched for presence of both normal thyroid tissue and thyroid cancer), respectively. Our data suggests that aberrant methylation of CASP8, RASSF1, and NIS maybe an early change in thyroid tumorigenesis regardless of cell type.

  5. Methyl Halide Production by Fungi

    Science.gov (United States)

    Dailey, G. D.; Varner, R. K.; Blanchard, R. O.; Sive, B. C.; Crill, P. M.

    2005-12-01

    Methyl chloride (CH3Cl), methyl bromide (CH3Br) and methyl iodide (CH3I) are methyl halide gases that contribute significant amounts of halogen radicals to the atmosphere. In an effort to better understand the global budget of methyl halides and their impact on the atmosphere, we need to identify the natural sources in addition to the known anthropogenic sources of these compounds. We are investigating the role of fungi in the production of methyl halides in the soils and wetlands in southern New Hampshire, USA. Previous research has shown that wood decay fungi and ectomycorrhizal fungi, which are within a group of fungi called basidiomycetes, emit methyl halides. In our study, measurements of headspace gas extracted from flasks containing fungi grown in culture demonstrate that a variety of fungi, including basidiomycetes and non-basidiomycetes, emit methyl halides. Our research sites include four ecosystems: an agricultural field, a temperate forest, a fresh water wetland, and coastal salt marshes. We have collected and isolated fungi at each site by culturing tissue samples of fruiting bodies and plant material, by using wood baits, and from the direct culture of soil. We compared the rates of methyl halide emissions from the fungi in the four ecosystems. In addition, we measured emissions from previously assayed fungal isolates after reintroducing them to sterilized soils that were collected from their original environments. Fungal biomass was determined by substrate-induced respiration (SIR). The emission rate by the fungus was determined by a linear regression of the concentration of methyl halide in the sample headspace over time divided by the fungal biomass.

  6. Pro Agile NET Development with Scrum

    CERN Document Server

    Blankenship, Jerrel; Millett, Scott

    2011-01-01

    Pro Agile .NET Development with SCRUM guides you through a real-world ASP.NET project and shows how agile methodology is put into practice. There is plenty of literature on the theory behind agile methodologies, but no book on the market takes the concepts of agile practices and applies these in a practical manner to an end-to-end ASP.NET project, especially the estimating, requirements and management aspects of a project. Pro Agile .NET Development with SCRUM takes you through the initial stages of a project - gathering requirements and setting up an environment - through to the development a

  7. Pro ASP.NET MVC 4

    CERN Document Server

    Freeman, Adam

    2012-01-01

    The ASP.NET MVC 4 Framework is the latest evolution of Microsoft's ASP.NET web platform. It provides a high-productivity programming model that promotes cleaner code architecture, test-driven development, and powerful extensibility, combined with all the benefits of ASP.NET. ASP.NET MVC 4 contains a number of significant advances over previous versions. New mobile and desktop templates (employing adaptive rendering) are included together with support for jQuery Mobile for the first time. New display modes allow your application to select views based on the browser that's making the request whi

  8. Professional Visual Basic 2010 and .NET 4

    CERN Document Server

    Sheldon, Bill; Sharkey, Kent

    2010-01-01

    Intermediate and advanced coverage of Visual Basic 2010 and .NET 4 for professional developers. If you've already covered the basics and want to dive deep into VB and .NET topics that professional programmers use most, this is your book. You'll find a quick review of introductory topics-always helpful-before the author team of experts moves you quickly into such topics as data access with ADO.NET, Language Integrated Query (LINQ), security, ASP.NET web programming with Visual Basic, Windows workflow, threading, and more. You'll explore all the new features of Visual Basic 2010 as well as all t

  9. NASA Net Zero Energy Buildings Roadmap

    Energy Technology Data Exchange (ETDEWEB)

    Pless, S.; Scheib, J.; Torcellini, P.; Hendron, B.; Slovensky, M.

    2014-10-01

    In preparation for the time-phased net zero energy requirement for new federal buildings starting in 2020, set forth in Executive Order 13514, NASA requested that the National Renewable Energy Laboratory (NREL) to develop a roadmap for NASA's compliance. NASA detailed a Statement of Work that requested information on strategic, organizational, and tactical aspects of net zero energy buildings. In response, this document presents a high-level approach to net zero energy planning, design, construction, and operations, based on NREL's first-hand experience procuring net zero energy construction, and based on NREL and other industry research on net zero energy feasibility. The strategic approach to net zero energy starts with an interpretation of the executive order language relating to net zero energy. Specifically, this roadmap defines a net zero energy acquisition process as one that sets an aggressive energy use intensity goal for the building in project planning, meets the reduced demand goal through energy efficiency strategies and technologies, then adds renewable energy in a prioritized manner, using building-associated, emission- free sources first, to offset the annual energy use required at the building; the net zero energy process extends through the life of the building, requiring a balance of energy use and production in each calendar year.

  10. Towards a Standard for Modular Petri Nets

    DEFF Research Database (Denmark)

    Kindler, Ekkart; Petrucci, Laure

    2009-01-01

    When designing complex systems, mechanisms for structuring, composing, and reusing system components are crucial. Today, there are many approaches for equipping Petri nets with such mechanisms. In the context of defining a standard interchange format for Petri nets, modular PNML was defined....... Moreover, we present and discuss some more advanced features of modular Petri nets that could be included in the standard. This way, we provide a formal foundation and a basis for a discussion of features to be included in the upcoming standard of a module concept for Petri nets in general and for high...

  11. Reversal of cocaine-conditioned place preference through methyl supplementation in mice: altering global DNA methylation in the prefrontal cortex.

    Directory of Open Access Journals (Sweden)

    Weiping Tian

    Full Text Available Analysis of global methylation in cells has revealed correlations between overall DNA methylation status and some biological states. Recent studies suggest that epigenetic regulation through DNA methylation could be responsible for neuroadaptations induced by addictive drugs. However, there is no investigation to determine global DNA methylation status following repeated exposure to addictive drugs. Using mice conditioned place preference (CPP procedure, we measured global DNA methylation level in the nucleus accumbens (NAc and the prefrontal cortex (PFC associated with drug rewarding effects. We found that cocaine-, but not morphine- or food-CPP training decreased global DNA methylation in the PFC. Chronic treatment with methionine, a methyl donor, for 25 consecutive days prior to and during CPP training inhibited the establishment of cocaine, but not morphine or food CPP. We also found that both mRNA and protein level of DNMT (DNA methytransferase 3b in the PFC were downregulated following the establishment of cocaine CPP, and the downregulation could be reversed by repeated administration of methionine. Our study indicates a crucial role of global PFC DNA hypomethylation in the rewarding effects of cocaine. Reversal of global DNA hypomethylation could significantly attenuate the rewarding effects induced by cocaine. Our results suggest that methionine may have become a potential therapeutic target to treat cocaine addiction.

  12. Experiments and simulation of a net closing mechanism for tether-net capture of space debris

    Science.gov (United States)

    Sharf, Inna; Thomsen, Benjamin; Botta, Eleonora M.; Misra, Arun K.

    2017-10-01

    This research addresses the design and testing of a debris containment system for use in a tether-net approach to space debris removal. The tether-net active debris removal involves the ejection of a net from a spacecraft by applying impulses to masses on the net, subsequent expansion of the net, the envelopment and capture of the debris target, and the de-orbiting of the debris via a tether to the chaser spacecraft. To ensure a debris removal mission's success, it is important that the debris be successfully captured and then, secured within the net. To this end, we present a concept for a net closing mechanism, which we believe will permit consistently successful debris capture via a simple and unobtrusive design. This net closing system functions by extending the main tether connecting the chaser spacecraft and the net vertex to the perimeter and around the perimeter of the net, allowing the tether to actuate closure of the net in a manner similar to a cinch cord. A particular embodiment of the design in a laboratory test-bed is described: the test-bed itself is comprised of a scaled-down tether-net, a supporting frame and a mock-up debris. Experiments conducted with the facility demonstrate the practicality of the net closing system. A model of the net closure concept has been integrated into the previously developed dynamics simulator of the chaser/tether-net/debris system. Simulations under tether tensioning conditions demonstrate the effectiveness of the closure concept for debris containment, in the gravity-free environment of space, for a realistic debris target. The on-ground experimental test-bed is also used to showcase its utility for validating the dynamics simulation of the net deployment, and a full-scale automated setup would make possible a range of validation studies of other aspects of a tether-net debris capture mission.

  13. Electrophysiological study, biodistribution in mice, and preliminary PET evaluation in a rhesus monkey of 1-amino-3-[18F]fluoromethyl-5-methyl-adamantane (18F-MEM): a potential radioligand for mapping the NMDA-receptor complex.

    Science.gov (United States)

    Samnick, S; Ametamey, S; Leenders, K L; Vontobel, P; Quack, G; Parsons, C G; Neu, H; Schubiger, P A

    1998-05-01

    The effect of the fluorinated memantine derivative and NMDA receptor antagonist, 1-amino-3-fluoromethyl-5-methyl-adamantane (19F-MEM), at the NMDA receptor ion channel was studied by patch clamp recording. The results showed that 19F-MEM is a moderate NMDA receptor channel blocker. A procedure for the routine preparation of the 18F-labelled analog 18F-MEM has been developed using a two-step reaction sequence. This involves the no-carrier-added nucleophilic radiofluorination of 1-[N-(tert-butyloxy)carbamoyl]-3-(toluenesulfonyloxy)methyl- 5-methyl-adamantane and the subsequent cleavage of the BOC-protecting group using aqueous HCI. The 18F-MEM was obtained in 22 +/- 7% radiochemical yield (decay-corrected to EOB) in a total synthesis time including HPLC purification of 90 min. A biodistribution study after i.v. injection of 18F-MEM in mice showed a fast clearance of radioactivity from blood and relatively high initial uptake in the kidney and in the lung, which gradually decreased with time. The brain uptake was high (up to 3.6% ID/g, 60 min postinjection) with increasing brain-blood ratios: 2.40, 5.10, 6.33, and 9.27 at 5, 30, 60, and 120 min, respectively. The regional accumulation of the radioactivity in the mouse brain was consistent with the known distribution of the PCP recognition site. Preliminary PET evaluation of the radiotracer in a rhesus monkey demonstrated good uptake and prolonged retention in the brain, with a plateau from 35 min onwards p.i. in the NMDA receptor-rich regions (frontal cortex, striata, and temporal cortex). Delineation of the hippocampus, a region known to contain a high density of NMDA receptors, was not possible owing to the resolution of the PET tomograph. The regional brain uptake of 18F-MEM was changed by memantine and by a pharmacological dose of (+)-MK-801, indicating competition for the same binding sites. In a preliminary experiment, haloperidol, a dopamine D2 and sigma receptor antagonist, decreased the binding of 18F

  14. DNA methylation pathways and their crosstalk with histone methylation

    Science.gov (United States)

    Du, Jiamu; Johnson, Lianna M.; Jacobsen, Steven E.; Patel, Dinshaw J.

    2015-01-01

    Methylation of DNA and of histone 3 at Lys 9 (H3K9) are highly correlated with gene silencing in eukaryotes from fungi to humans. Both of these epigenetic marks need to be established at specific regions of the genome and then maintained at these sites through cell division. Protein structural domains that specifically recognize methylated DNA and methylated histones are key for targeting enzymes that catalyse these marks to appropriate genome sites. Genetic, genomic, structural and biochemical data reveal connections between these two epigenetic marks, and these domains mediate much of the crosstalk. PMID:26296162

  15. MethylRAD: a simple and scalable method for genome-wide DNA methylation profiling using methylation-dependent restriction enzymes.

    Science.gov (United States)

    Wang, Shi; Lv, Jia; Zhang, Lingling; Dou, Jinzhuang; Sun, Yan; Li, Xue; Fu, Xiaoteng; Dou, Huaiqian; Mao, Junxia; Hu, Xiaoli; Bao, Zhenmin

    2015-11-01

    Characterization of dynamic DNA methylomes in diverse phylogenetic groups has attracted growing interest for a better understanding of the evolution of DNA methylation as well as its function and biological significance in eukaryotes. Sequencing-based methods are promising in fulfilling this task. However, none of the currently available methods offers the 'perfect solution', and they have limitations that prevent their application in the less studied phylogenetic groups. The recently discovered Mrr-like enzymes are appealing for new method development, owing to their ability to collect 32-bp methylated DNA fragments from the whole genome for high-throughput sequencing. Here, we have developed a simple and scalable DNA methylation profiling method (called MethylRAD) using Mrr-like enzymes. MethylRAD allows for de novo (reference-free) methylation analysis, extremely low DNA input (e.g. 1 ng) and adjustment of tag density, all of which are still unattainable for most widely used methylation profiling methods such as RRBS and MeDIP. We performed extensive analyses to validate the power and accuracy of our method in both model (plant Arabidopsis thaliana) and non-model (scallop Patinopecten yessoensis) species. We further demonstrated its great utility in identification of a gene (LPCAT1) that is potentially crucial for carotenoid accumulation in scallop adductor muscle. MethylRAD has several advantages over existing tools and fills a void in the current epigenomic toolkit by providing a universal tool that can be used for diverse research applications, e.g. from model to non-model species, from ordinary to precious samples and from small to large genomes, but at an affordable cost. © 2015 The Authors.

  16. Methylation signature of lymph node metastases in breast cancer patients

    Science.gov (United States)

    2012-01-01

    Background Invasion and metastasis are two important hallmarks of malignant tumors caused by complex genetic and epigenetic alterations. The present study investigated the contribution of aberrant methylation profiles of cancer related genes, APC, BIN1, BMP6, BRCA1, CST6, ESR-b, GSTP1, P14 (ARF), P16 (CDKN2A), P21 (CDKN1A), PTEN, and TIMP3, in the matched axillary lymph node metastasis in comparison to the primary tumor tissue and the adjacent normal tissue from the same breast cancer patients to identify the potential of candidate genes methylation as metastatic markers. Methods The quantitative methylation analysis was performed using the SEQUENOM’s EpiTYPER™ assay which relies on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Results The quantitative DNA methylation analysis of the candidate genes showed higher methylation proportion in the primary tumor tissue than that of the matched normal tissue and the differences were significant for the APC, BIN1, BMP6, BRCA1, CST6, ESR-b, P16, PTEN and TIMP3 promoter regions (P<0.05). Among those candidate methylated genes, APC, BMP6, BRCA1 and P16 displayed higher methylation proportion in the matched lymph node metastasis than that found in the normal tissue (P<0.05). The pathway analysis revealed that BMP6, BRCA1 and P16 have a role in prevention of neoplasm metastasis. Conclusions The results of the present study showed methylation heterogeneity between primary tumors and metastatic lesion. The contribution of aberrant methylation alterations of BMP6, BRCA1 and P16 genes in lymph node metastasis might provide a further clue to establish useful biomarkers for screening metastasis. PMID:22695536

  17. Phase 2 Methyl Iodide Deep-Bed Adsorption Tests

    Energy Technology Data Exchange (ETDEWEB)

    Soelberg, Nick [Idaho National Lab. (INL), Idaho Falls, ID (United States); Watson, Tony [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2014-09-01

    Nuclear fission produces fission products (FPs) and activation products, including iodine-129, which could evolve into used fuel reprocessing facility off-gas systems, and could require off-gas control to limit air emissions to levels within acceptable emission limits. Research, demonstrations, and some reprocessing plant experience have indicated that diatomic iodine can be captured with efficiencies high enough to meet regulatory requirements. Research on the capture of organic iodides has also been performed, but to a lesser extent. Several questions remain open regarding the capture of iodine bound in organic compounds. Deep-bed methyl iodide adsorption testing has progressed according to a multi-laboratory methyl iodide adsorption test plan. This report summarizes the second phase of methyl iodide adsorption work performed according to this test plan using the deep-bed iodine adsorption test system at the Idaho National Laboratory (INL), performed during the second half of Fiscal Year (FY) 2014. Test results continue to show that methyl iodide adsorption using AgZ can achieve total iodine decontamination factors (DFs, ratios of uncontrolled and controlled total iodine levels) above 1,000, until breakthrough occurred. However, mass transfer zone depths are deeper for methyl iodide adsorption compared to diatomic iodine (I2) adsorption. Methyl iodide DFs for the Ag Aerogel test adsorption efficiencies were less than 1,000, and the methyl iodide mass transfer zone depth exceeded 8 inches. Additional deep-bed testing and analyses are recommended to (a) expand the data base for methyl iodide adsorption under various conditions specified in the methyl iodide test plan, and (b) provide more data for evaluating organic iodide reactions and reaction byproducts for different potential adsorption conditions.

  18. Lysine methyltransferase G9a is not required for DNMT3A/3B anchoring to methylated nucleosomes and maintenance of DNA methylation in somatic cells

    Directory of Open Access Journals (Sweden)

    Sharma Shikhar

    2012-01-01

    Full Text Available Abstract Background DNA methylation, histone modifications and nucleosome occupancy act in concert for regulation of gene expression patterns in mammalian cells. Recently, G9a, a H3K9 methyltransferase, has been shown to play a role in establishment of DNA methylation at embryonic gene targets in ES cells through recruitment of de novo DNMT3A/3B enzymes. However, whether G9a plays a similar role in maintenance of DNA methylation in somatic cells is still unclear. Results Here we show that G9a is not essential for maintenance of DNA methylation in somatic cells. Knockdown of G9a has no measurable effect on DNA methylation levels at G9a-target loci. DNMT3A/3B remain stably anchored to nucleosomes containing methylated DNA even in the absence of G9a, ensuring faithful propagation of methylated states in cooperation with DNMT1 through somatic divisions. Moreover, G9a also associates with nucleosomes in a DNMT3A/3B and DNA methylation-independent manner. However, G9a knockdown synergizes with pharmacologic inhibition of DNMTs resulting in increased hypomethylation and inhibition of cell proliferation. Conclusions Taken together, these data suggest that G9a is not involved in maintenance of DNA methylation in somatic cells but might play a role in re-initiation of de novo methylation after treatment with hypomethylating drugs, thus serving as a potential target for combinatorial treatments strategies involving DNMTs inhibitors.

  19. The DNA methylation profile of activated human natural killer cells.

    Science.gov (United States)

    Wiencke, John K; Butler, Rondi; Hsuang, George; Eliot, Melissa; Kim, Stephanie; Sepulveda, Manuel A; Siegel, Derick; Houseman, E Andres; Kelsey, Karl T

    2016-05-03

    Natural killer (NK) cells are now recognized to exhibit characteristics akin to cells of the adaptive immune system. The generation of adaptive memory is linked to epigenetic reprogramming including alterations in DNA methylation. The study herein found reproducible genome wide DNA methylation changes associated with human NK cell activation. Activation led predominately to CpG hypomethylation (81% of significant loci). Bioinformatics analysis confirmed that non-coding and gene-associated differentially methylated sites (DMS) are enriched for immune related functions (i.e., immune cell activation). Known DNA methylation-regulated immune loci were also identified in activated NK cells (e.g., TNFA, LTA, IL13, CSF2). Twenty-one loci were designated high priority and further investigated as potential markers of NK activation. BHLHE40 was identified as a viable candidate for which a droplet digital PCR assay for demethylation was developed. The assay revealed high demethylation in activated NK cells and low demethylation in naïve NK, T- and B-cells. We conclude the NK cell methylome is plastic with potential for remodeling. The differentially methylated region signature of activated NKs revealed similarities with T cell activation, but also provided unique biomarker candidates of NK activation, which could be useful in epigenome-wide association studies to interrogate the role of NK subtypes in global methylation changes associated with exposures and/or disease states.

  20. HANPP Collection: Human Appropriation of Net Primary Productivity as a Percentage of Net Primary Productivity

    Data.gov (United States)

    National Aeronautics and Space Administration — The Human Appropriation of Net Primary Productivity (HANPP) as a Percentage of Net Primary Product (NPP) portion of the HANPP Collection represents a map identifying...

  1. Price smarter on the Net.

    Science.gov (United States)

    Baker, W; Marn, M; Zawada, C

    2001-02-01

    Companies generally have set prices on the Internet in two ways. Many start-ups have offered untenably low prices in a rush to capture first-mover advantage. Many incumbents have simply charged the same prices on-line as they do off-line. Either way, companies are missing a big opportunity. The fundamental value of the Internet lies not in lowering prices or making them consistent but in optimizing them. After all, if it's easy for customers to compare prices on the Internet, it's also easy for companies to track customers' behavior and adjust prices accordingly. The Net lets companies optimize prices in three ways. First, it lets them set and announce prices with greater precision. Different prices can be tested easily, and customers' responses can be collected instantly. Companies can set the most profitable prices, and they can tap into previously hidden customer demand. Second, because it's so easy to change prices on the Internet, companies can adjust prices in response to even small fluctuations in market conditions, customer demand, or competitors' behavior. Third, companies can use the clickstream data and purchase histories that it collects through the Internet to segment customers quickly. Then it can offer segment-specific prices or promotions immediately. By taking full advantage of the unique possibilities afforded by the Internet to set prices with precision, adapt to changing circumstances quickly, and segment customers accurately, companies can get their pricing right. It's one of the ultimate drivers of e-business success.

  2. DNA methylation: hemodialysis versus hemodiafiltration.

    Science.gov (United States)

    Ghigolea, Adrian-Bogdan; Moldovan, Raluca Argentina; Gherman-Caprioara, Mirela

    2015-04-01

    Aberrant DNA methylation is an emerging characteristic of chronic kidney disease including dialysis patients. It appears to be associated to inflammation. We compared the global DNA methylation status in 10 control subjects compared to 80 dialysis patients (N = 40 on-line hemodiafiltration, N = 40 high-flux hemodialysis) in relation to the dialysis technique and inflammation. Whole blood DNA methylation was assessed with a 5-mc DNA enzyme linked immunosorbent assay Kit. Global DNA methylation was higher in hemodialysis (HD) compared to on-line hemodiafiltration (HDF) patients (0.045 vs. 0.039; P patients according to the median value of 5-mC. DNA methylation was highest in inflamed patients on hemodialysis. The dialysis technique was the only independent predictor of global DNA methylation in dialysis patients. On-line HDF could be associated with a favorable DNA methylation profile. © 2014 The Authors. Therapeutic Apheresis and Dialysis © 2014 International Society for Apheresis.

  3. Efficacy of the Olyset Duo net against insecticide-resistant mosquito vectors of malaria.

    Science.gov (United States)

    Ngufor, Corine; N'Guessan, Raphael; Fagbohoun, Josias; Todjinou, Damien; Odjo, Abibath; Malone, David; Ismail, Hanafy; Akogbeto, Martin; Rowland, Mark

    2016-09-14

    Olyset Duo is a new long-lasting insecticidal net treated with permethrin (a pyrethroid) and pyriproxyfen, an insect growth regulator that disrupts the maturation of oocytes in mosquitoes exposed to the net. We tested the Olyset Duo net against pyrethroid-resistant Anopheles gambiae mosquitoes, which transmit malaria parasites, in laboratory bioassays and in a trial in Benin using experimental huts that closely resemble local habitations. Host-seeking mosquitoes that entered to feed were free to contact the occupied nets and were collected the next morning from exit traps. Surviving blood-fed mosquitoes were observed for effects on reproduction. Control nets were treated with pyrethroid only or pyriproxyfen only, and nets were tested unwashed and after 20 standardized washes. The Olyset Duo net showed improved efficacy and wash resistance relative to the pyrethroid-treated net in terms of mosquito mortality and prevention of blood feeding. The production of offspring among surviving blood-fed A. gambiae in the hut trial was reduced by the pyriproxyfen-treated net and the Olyset Duo net both before washing (90 and 71% reduction, respectively) and after washing (38 and 43% reduction, respectively). The degree of reproductive suppression in the hut trial was predicted by laboratory tunnel tests but not by cone bioassays. The overall reduction in reproductive rate of A. gambiae with the Olyset Duo net in the trial was 94% with no washing and 78% after 20 washes. The Olyset Duo net has the potential to provide community control of mosquito populations and reduce malaria transmission in areas of high insecticide resistance. Copyright © 2016, American Association for the Advancement of Science.

  4. CG Methylation Covaries with Differential Gene Expression between Leaf and Floral Bud Tissues of Brachypodium distachyon.

    Directory of Open Access Journals (Sweden)

    Kyria Roessler

    Full Text Available DNA methylation has the potential to influence plant growth and development through its influence on gene expression. To date, however, the evidence from plant systems is mixed as to whether patterns of DNA methylation vary significantly among tissues and, if so, whether these differences affect tissue-specific gene expression. To address these questions, we analyzed both bisulfite sequence (BSseq and transcriptomic sequence data from three biological replicates of two tissues (leaf and floral bud from the model grass species Brachypodium distachyon. Our first goal was to determine whether tissues were more differentiated in DNA methylation than explained by variation among biological replicates. Tissues were more differentiated than biological replicates, but the analysis of replicated data revealed high (>50% false positive rates for the inference of differentially methylated sites (DMSs and differentially methylated regions (DMRs. Comparing methylation to gene expression, we found that differential CG methylation consistently covaried negatively with gene expression, regardless as to whether methylation was within genes, within their promoters or even within their closest transposable element. The relationship between gene expression and either CHG or CHH methylation was less consistent. In total, CG methylation in promoters explained 9% of the variation in tissue-specific expression across genes, suggesting that CG methylation is a minor but appreciable factor in tissue differentiation.

  5. Economic Investigation of Community-Scale Versus Building Scale Net-Zero Energy

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez, Nicholas; Katipamula, Srinivas; Brambley, Michael R.; Reddy, T. A.

    2009-12-31

    The study presented in this report examines issues concerning whether achieving net-zero energy performance at the community scale provides economic and potentially overall efficiency advantages over strategies focused on individual buildings.

  6. 78 FR 72393 - Net Investment Income Tax

    Science.gov (United States)

    2013-12-02

    ... Investment Income Tax; Final and Proposed Rules #0;#0;Federal Register / Vol. 78, No. 231 / Monday, December... Parts 1 and 602 RIN 1545-BK44 Net Investment Income Tax AGENCY: Internal Revenue Service (IRS), Treasury... Investment Income Tax and the computation of Net Investment Income. The regulations affect individuals...

  7. 77 FR 72611 - Net Investment Income Tax

    Science.gov (United States)

    2012-12-05

    ... December 5, 2012 Part V Department of the Treasury Internal Revenue Service 26 CFR Part 1 Net Investment... Investment Income Tax AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice of proposed rulemaking...) the individual's net investment income for such taxable year, or (B) the excess (if any) of (i) the...

  8. Net analyte signal based statistical quality control

    NARCIS (Netherlands)

    Skibsted, E.T.S.; Boelens, H.F.M.; Westerhuis, J.A.; Smilde, A.K.; Broad, N.W.; Rees, D.R.; Witte, D.T.

    2005-01-01

    Net analyte signal statistical quality control (NAS-SQC) is a new methodology to perform multivariate product quality monitoring based on the net analyte signal approach. The main advantage of NAS-SQC is that the systematic variation in the product due to the analyte (or property) of interest is

  9. Asynchronous stream processing with S-Net

    NARCIS (Netherlands)

    Grelck, C.; Scholz, S.-B.; Shafarenko, A.

    2010-01-01

    We present the rationale and design of S-Net, a coordination language for asynchronous stream processing. The language achieves a near-complete separation between the application code, written in any conventional programming language, and the coordination/communication code written in S-Net. Our

  10. Using the MVC architecture on . NET platform

    OpenAIRE

    Ježek, David

    2011-01-01

    This thesis deals with usage of MVC (Model View Controller) technology in web development on ASP.NET platform from Microsoft. Mainly it deals with latest version of framework ASP.NET MVC 3. First part describes MVC architecture and the second describes usage of MVC in certain parts of web application an comparing with PHP.

  11. Analysis of Petri Nets and Transition Systems

    Directory of Open Access Journals (Sweden)

    Eike Best

    2015-08-01

    Full Text Available This paper describes a stand-alone, no-frills tool supporting the analysis of (labelled place/transition Petri nets and the synthesis of labelled transition systems into Petri nets. It is implemented as a collection of independent, dedicated algorithms which have been designed to operate modularly, portably, extensibly, and efficiently.

  12. 27 CFR 7.27 - Net contents.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Net contents. 7.27 Section 7.27 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF... the net contents are displayed by having the same blown, branded, or burned in the container in...

  13. Petri nets and other models of concurrency

    DEFF Research Database (Denmark)

    Nielsen, Mogens; Sassone, Vladimiro

    1998-01-01

    This paper retraces, collects, and summarises contributions of the authors - in collaboration with others - on the theme of Petri nets and their categorical relationships to other models of concurrency.......This paper retraces, collects, and summarises contributions of the authors - in collaboration with others - on the theme of Petri nets and their categorical relationships to other models of concurrency....

  14. Delta Semantics Defined By Petri Nets

    DEFF Research Database (Denmark)

    Jensen, Kurt; Kyng, Morten; Madsen, Ole Lehrmann

    This report is identical to an earlier version of May 1978 except that Chapter 5 has been revised. A new paper: "A Petri Net Definition of a System Description Language", DAIMI, April 1979, 20 pages, extends the Petri net model to include a data state representing the program variables. Delta...

  15. Net neutrality and inflation of traffic

    NARCIS (Netherlands)

    Peitz, M.; Schütt, Florian

    Under strict net neutrality Internet service providers (ISPs) are required to carry data without any differentiation and at no cost to the content provider. We provide a simple framework with a monopoly ISP to evaluate the short-run effects of different net neutrality rules. Content differs in its

  16. Net Neutrality and Inflation of Traffic

    NARCIS (Netherlands)

    Peitz, M.; Schütt, F.

    2015-01-01

    Under strict net neutrality Internet service providers (ISPs) are required to carry data without any differentiation and at no cost to the content provider. We provide a simple framework with a monopoly ISP to evaluate different net neutrality rules. Content differs in its sensitivity to delay.

  17. The Net Neutrality Debate: The Basics

    Science.gov (United States)

    Greenfield, Rich

    2006-01-01

    Rich Greenfield examines the basics of today's net neutrality debate that is likely to be an ongoing issue for society. Greenfield states the problems inherent in the definition of "net neutrality" used by Common Cause: "Network neutrality is the principle that Internet users should be able to access any web content they choose and…

  18. Dynamic response of the thermometric net radiometer

    Science.gov (United States)

    J. D. Wilson; W. J. Massman; G. E. Swaters

    2009-01-01

    We computed the dynamic response of an idealized thermometric net radiometer, when driven by an oscillating net longwave radiation intended roughly to simulate rapid fluctuations of the radiative environment such as might be expected during field use of such devices. The study was motivated by curiosity as to whether non-linearity of the surface boundary conditions...

  19. Teaching and Learning with the Net Generation

    Science.gov (United States)

    Barnes, Kassandra; Marateo, Raymond C.; Ferris, S. Pixy

    2007-01-01

    As the Net Generation places increasingly greater demands on educators, students and teachers must jointly consider innovative ways of teaching and learning. In this, educators are supported by the fact that the Net Generation wants to learn. However, these same educators should not fail to realize that this generation learns differently from…

  20. Verification of Timed-Arc Petri Nets

    DEFF Research Database (Denmark)

    Jacobsen, Lasse; Jacobsen, Morten; Møller, Mikael Harkjær

    2011-01-01

    Timed-Arc Petri Nets (TAPN) are an extension of the classical P/T nets with continuous time. Tokens in TAPN carry an age and arcs between places and transitions are labelled with time intervals restricting the age of tokens available for transition firing. The TAPN model posses a number...

  1. A Brief Introduction to Coloured Petri Nets

    DEFF Research Database (Denmark)

    Jensen, Kurt

    1997-01-01

    Coloured Petri Nets (CP-nets or CPN) is a graphical oriented language for design, specification, simulation and verification of systems. It is in particular well- suited for systems in which communication, synchronisation and resource sharing are important. Typical examples of application areas a...

  2. Methylation-Specific PCR Unraveled

    Directory of Open Access Journals (Sweden)

    Sarah Derks

    2004-01-01

    Full Text Available Methylation‐specific PCR (MSP is a simple, quick and cost‐effective method to analyze the DNA methylation status of virtually any group of CpG sites within a CpG island. The technique comprises two parts: (1 sodium bisulfite conversion of unmethylated cytosine's to uracil under conditions whereby methylated cytosines remains unchanged and (2 detection of the bisulfite induced sequence differences by PCR using specific primer sets for both unmethylated and methylated DNA. This review discusses the critical parameters of MSP and presents an overview of the available MSP variants and the (clinical applications.

  3. Gill net and trammel net selectivity in the northern Aegean Sea, Turkey

    Directory of Open Access Journals (Sweden)

    F. Saadet Karakulak

    2008-09-01

    Full Text Available Fishing trials were carried out with gill nets and trammel nets in the northern Aegean Sea from March 2004 to February 2005. Four different mesh sizes for the gill nets and the inner panel of trammel nets (16, 18, 20 and 22 mm bar length were used. Selectivity parameters for the five most economically important species, bogue (Boops boops, annular sea bream (Diplodus annularis, striped red mullet (Mullus surmuletus, axillary sea bream (Pagellus acarne and blotched picarel (Spicara maena, caught by the two gears were estimated. The SELECT method was used to estimate the selectivity parameters of a variety of models. Catch composition and catch proportion of several species were different in gill and trammel nets. The length frequency distributions of the species caught by the two gears were significantly different. The bi-modal model selectivity curve gave the best fit for gill net and trammel net data, and there was little difference between the modal lengths of these nets. However, a clear difference was found in catching efficiency. The highest catch rates were obtained with the trammel net. Given that many discard species and small fish are caught by gill nets and trammel nets with a mesh size of 16 mm, it is clear that these nets are not appropriate for fisheries. Consequently, the best mesh size for multispecies fisheries is 18 mm. This mesh size will considerably reduce the numbers of small sized individuals and discard species in the catch.

  4. Discrete, continuous, and hybrid petri nets

    CERN Document Server

    David, René

    2004-01-01

    Petri nets do not designate a single modeling formalism. In fact, newcomers to the field confess sometimes to be a little puzzled by the diversity of formalisms that are recognized under this "umbrella". Disregarding some extensions to the theoretical modeling capabilities, and looking at the level of abstraction of the formalisms, Condition/Event, Elementary, Place/Transition, Predicate/Transition, Colored, Object Oriented... net systems are frequently encountered in the literature. On the other side, provided with appropriate interpretative extensions, Controled Net Systems, Marking Diagrams (the Petri net generalization of State Diagrams), or the many-many variants in which time can be explicitly incorporated -Time(d), Deterministic, (Generalized) Stochastic, Fuzzy...- are defined. This represents another way to define practical formalisms that can be obtained by the "cro- product" of the two mentioned dimensions. Thus Petri nets constitute a modeling paradigm, understandable in a broad sense as "the total...

  5. A review of bacterial methyl halide degradation: biochemistry, genetics and molecular ecology

    Science.gov (United States)

    McDonald, I.R.; Warner, K.L.; McAnulla, C.; Woodall, C.A.; Oremland, R.S.; Murrell, J.C.

    2002-01-01

    Methyl halide-degrading bacteria are a diverse group of organisms that are found in both terrestrial and marine environments. They potentially play an important role in mitigating ozone depletion resulting from methyl chloride and methyl bromide emissions. The first step in the pathway(s) of methyl halide degradation involves a methyltransferase and, recently, the presence of this pathway has been studied in a number of bacteria. This paper reviews the biochemistry and genetics of methyl halide utilization in the aerobic bacteria Methylobacterium chloromethanicum CM4T, Hyphomicrobium chloromethanicum CM2T, Aminobacter strain IMB-1 and Aminobacter strain CC495. These bacteria are able to use methyl halides as a sole source of carbon and energy, are all members of the α-Proteobacteria and were isolated from a variety of polluted and pristine terrestrial environments. An understanding of the genetics of these bacteria identified a unique gene (cmuA) involved in the degradation of methyl halides, which codes for a protein (CmuA) with unique methyltransferase and corrinoid functions. This unique functional gene, cmuA, is being used to develop molecular ecology techniques to examine the diversity and distribution of methyl halide-utilizing bacteria in the environment and hopefully to understand their role in methyl halide degradation in different environments. These techniques will also enable the detection of potentially novel methyl halide-degrading bacteria.

  6. Relationship of tobacco smoking and smoking-related DNA methylation with epigenetic age acceleration.

    Science.gov (United States)

    Gao, Xu; Zhang, Yan; Breitling, Lutz Philipp; Brenner, Hermann

    2016-07-26

    Recent studies have identified biomarkers of chronological age based on DNA methylation levels. Since active smoking contributes to a wide spectrum of aging-related diseases in adults, this study intended to examine whether active smoking exposure could accelerate the DNA methylation age in forms of age acceleration (AA, residuals of the DNA methylation age estimate regressed on chronological age). We obtained the DNA methylation profiles in whole blood samples by Illumina Infinium Human Methylation450 Beadchip array in two independent subsamples of the ESTHER study and calculated their DNA methylation ages by two recently proposed algorithms. None of the self-reported smoking indicators (smoking status, cumulative exposure and smoking cessation time) or serum cotinine levels was significantly associated with AA. On the contrary, we successfully confirmed that 66 out of 150 smoking-related CpG sites were associated with AA, even after correction for multiple testing (FDR smoking index (SI) based on these loci and demonstrated a monotonic dose-response relationship of this index with AA. In conclusion, DNA methylation-based biological indicators for current and past smoking exposure, but not self-reported smoking information or serum cotinine levels, were found to be related to DNA methylation defined AA. Further research should address potential mechanisms underlying the observed patterns, such as potential reflections of susceptibility to environmental hazards in both smoking related methylation changes and methylation defined AA.

  7. Pro visual C++/CLI and the net 35 platform

    CERN Document Server

    Fraser, Stephen

    2008-01-01

    Pro Visual C++/CLI and the .NET 3.5 Platform is about writing .NET applications using C++/CLI. While readers are learning the ins and outs of .NET application development, they will also be learning the syntax of C++, both old and new to .NET. Readers will also gain a good understanding of the .NET architecture. This is truly a .NET book applying C++ as its development language not another C++ syntax book that happens to cover .NET.

  8. DNA Methylation in Newborns and Maternal Smoking in Pregnancy : Genome-wide Consortium Meta-analysis

    NARCIS (Netherlands)

    Joubert, Bonnie R.; Felix, Janine F.; Yousefi, Paul; Bakulski, Kelly M.; Just, Allan C.; Breton, Carrie; Reese, Sarah E.; Markunas, Christina A.; Richmond, Rebecca C.; Xu, Chengjian; Kupers, Leanne K.; Oh, Sam S.; Hoyo, Cathrine; Gruzieva, Olena; Soderhal, Cilla; Salas, Lucas A.; Baiz, Nour; Zhang, Hongmei; Lepeule, Johanna; Ruiz, Carlos; Ligthart, Symen; Wang, Tianyuan; Taylor, Jack A.; Duijts, Liesbeth; Sharp, Gemma C.; Jankipersadsing, Soesma A.; Nilsen, Roy M.; Vaez, Ahmad; Fallin, M. Daniele; Hu, Donglei; Litonjua, Augusto A.; Fuemmeler, Bernard F.; Huen, Karen; Kere, Juha; Kull, Inger; Munthe-Kaas, Monica Cheng; Gehring, Ulrike; Bustamante, Mariona; Saurel-Coubizolles, Marie Jose; Quraishi, Bilal M.; Ren, Jie; Tost, Jorg; Gonzalez, Juan R.; Peters, Marjolein J.; Haberg, Siri E.; Xu, Zongli; van Meurs, Joyce B.; Gaunt, Tom R.; Kerkhof, Marjan; Corpeleijn, Eva; Feinberg, Andrew P.; Eng, Celeste; Baccarelli, Andrea A.; Neelon, Sara E. Benjamin; Bradman, Asa; Merid, Simon Kebede; Bergstrom, Anna; Herceg, Zdenko; Hernandez-Vargas, Hector; Brunekreef, Bert; Pinart, Mariona; Heude, Barbara; Ewart, Susan; Yao, Jin; Lemonnier, Nathanael; Franco, Oscar H.; Wu, Michael C.; Hofman, Albert; McArdle, Wendy; Van der Vlies, Pieter; Falahi, Fahimeh; Gillman, Matthew W.; Barcellos, Lisa F.; Kumar, Ashish; Wickman, Magnus; Guerra, Stefano; Charles, Marie-Aline; Holloway, John; Auffray, Charles; Tiemeier, Henning W.; Smith, George Davey; Postma, Dirkje; Hivert, Marie-France; Eskenazi, Brenda; Vrijheid, Martine; Arshad, Hasan; Anto, Josep M.; Dehghan, Abbas; Karmaus, Wilfried; Annesi-Maesano, Isabella; Sunyer, Jordi; Ghantous, Akram; Pershagen, Goran; Hollands, Nina; Murphy, Susan K.; DeMeo, Dawn L.; Burchard, Esteban G.; Ladd-Acosta, Christine; Snieder, Harold; Nystad, Wenche; Koppelman, Gerard H.; Relton, Caroline L.; Jaddoe, Vincent W. V.; Wilcox, Allen; Melen, Erik; London, Stephanie J.

    2016-01-01

    Epigenetic modifications, including DNA methylation, represent a potential mechanism for environmental impacts on human disease. Maternal smoking in pregnancy remains an important public health problem that impacts child health in a myriad of ways and has potential lifelong consequences. The

  9. Managing nematodes without methyl bromide.

    Science.gov (United States)

    Zasada, Inga A; Halbrendt, John M; Kokalis-Burelle, Nancy; LaMondia, James; McKenry, Michael V; Noling, Joe W

    2010-01-01

    Methyl bromide is an effective pre-plant soil fumigant used to control nematodes in many high-input, high-value crops in the United States, including vegetables, nursery plants, ornamentals, tree fruits, strawberries, and grapes. Because methyl bromide has provided a reliable return on investment for nematode control, many of these commodities have standardized their production practices based on the use of this chemical and will be negatively impacted if effective and economical alternatives are not identified. Alternative control measures based on other chemicals, genetic resistance, and cultural practices require a greater knowledge of nematode biology to achieve satisfactory results. Here, we provide an overview of nematode management practices that we believe will be relied upon heavily in U.S. high-value crop production systems in a world without methyl bromide. Included are case studies of U.S. high-value crop production systems to demonstrate how nematode management practices other than methyl bromide may be incorporated.

  10. In vivo evaluation in rats of [{sup 18}F]1-(2-fluoroethyl)-4-[(4-cyanophenoxy)methyl]piperidine as a potential radiotracer for PET assessment of CNS sigma-1 receptors

    Energy Technology Data Exchange (ETDEWEB)

    Waterhouse, Rikki N. [Department of Psychiatry, Columbia University, New York, NY 10032 (United States) and Department of Radiology, Columbia University, New York, NY 10032 (United States) and Neurobiology and Imaging Program, Department of Biological Psychiatry, New York State Psychiatric Institute, New York, NY 10032 (United States)]. E-mail: rnw7@columbia.edu; Chang, Raymond C. [Department of Psychiatry, Columbia University, New York, NY 10032 (United States); Neurobiology and Imaging Program, Department of Biological Psychiatry, New York State Psychiatric Institute, New York, NY 10032 (United States); Zhao, Jun [Department of Psychiatry, Columbia University, New York, NY 10032 (United States); Neurobiology and Imaging Program, Department of Biological Psychiatry, New York State Psychiatric Institute, New York, NY 10032 (United States); Carambot, Patty E. [Department of Psychiatry, Columbia University, New York, NY 10032 (United States); Neurobiology and Imaging Program, Department of Biological Psychiatry, New York State Psychiatric Institute, New York, NY 10032 (United States)

    2006-02-15

    Introduction: Sigma-1 receptors are expressed throughout the mammalian central nervous system (CNS) and are implicated in several psychiatric disorders, including schizophrenia and depression. We have recently evaluated the high-affinity (K {sub D}=0.5{+-}0.2 nM, log P=2.9) sigma-1 receptor radiotracer [{sup 18}F]1-(3-fluoropropyl)-4-(4-cyanophenoxymethyl)piperidine, [{sup 18}F]FPS, in humans. In contrast to appropriate kinetics exhibited in baboon brain, in the human CNS, [{sup 18}F]FPS does not reach pseudoequilibrium by 4 h, supporting the development of a lower-affinity tracer [Waterhouse RN, Nobler MS, Chang RC, Zhou Y, Morales O, Kuwabara H, et al. First evaluation of the sigma-1 receptor radioligand [{sup 18}F]1-3-fluoropropyl-4-((4-cyanophenoxy)-methyl)piperidine ([{sup 18}F]FPS) in healthy humans. Neuroreceptor Mapping 2004, July 15-18th, Vancouver, BC Canada 2004]. We describe herein the in vivo evaluation in rats of [{sup 18}F]1-(2-fluoroethyl)-4-[(4-cyanophenoxy)methyl]piperidine ([{sup 18}F]SFE) (K {sub D}=5 nM, log P=2.4), a structurally similar, lower-affinity sigma-1 receptor radioligand. Methods: [{sup 18}F]SFE was synthesized (n=4) as previously described in good yield (54{+-}6% EOB), high specific activity (2.1{+-}0.6 Ci/{mu}mol EOS) and radiochemical purity (98{+-}1%) and evaluated in awake adult male rats. Results: Similar to [{sup 18}F]FPS, regional brain radioactivity concentrations [percentage of injected dose per gram of tissue (%ID/g), 15 min] for [{sup 18}F]SFE were highest in occipital cortex (1.86{+-}0.06 %ID/g) and frontal cortex (1.76{+-}0.38 %ID/g), and lowest in the hippocampus (1.01{+-}0.02%ID/g). Unlike [{sup 18}F]FPS, [{sup 18}F]SFE cleared from the brain with {approx}40% reduction in peak activity over a 90-min period. Metabolite analysis (1 h) revealed that [{sup 18}F]SFE was largely intact in the brain. Blocking studies showed a large degree (>80%) of saturable binding for [{sup 18}F]SFE in discrete brain regions. Conclusions

  11. Methylated genes as new cancer biomarkers

    DEFF Research Database (Denmark)

    Brunner, Nils; Duffy, M.J; Napieralski, R.

    2009-01-01

    that measurement of the methylation status of the promoter regions of specific genes can aid early detection of cancer, determine prognosis and predict therapy responses. Promising DNA methylation biomarkers include the use of methylated GSTP1 for aiding the early diagnosis of prostate cancer, methylated PITX2...

  12. DNA methylation analysis in human cancer

    OpenAIRE

    O'Sullivan, Eileen; Goggins, Michael

    2013-01-01

    The functional impact of aberrant DNA methylation and the widespread alterations in DNA methylation in cancer development has led to the development of a variety of methods to characterize the DNA methylation patterns. This chapter will critique and describe the major approaches to analyzing DNA methylation.

  13. The honey bee epigenomes: differential methylation of brain DNA in queens and workers.

    Directory of Open Access Journals (Sweden)

    Frank Lyko

    2010-11-01

    Full Text Available In honey bees (Apis mellifera the behaviorally and reproductively distinct queen and worker female castes derive from the same genome as a result of differential intake of royal jelly and are implemented in concert with DNA methylation. To determine if these very different diet-controlled phenotypes correlate with unique brain methylomes, we conducted a study to determine the methyl cytosine (mC distribution in the brains of queens and workers at single-base-pair resolution using shotgun bisulfite sequencing technology. The whole-genome sequencing was validated by deep 454 sequencing of selected amplicons representing eight methylated genes. We found that nearly all mCs are located in CpG dinucleotides in the exons of 5,854 genes showing greater sequence conservation than non-methylated genes. Over 550 genes show significant methylation differences between queens and workers, revealing the intricate dynamics of methylation patterns. The distinctiveness of the differentially methylated genes is underscored by their intermediate CpG densities relative to drastically CpG-depleted methylated genes and to CpG-richer non-methylated genes. We find a strong correlation between methylation patterns and splicing sites including those that have the potential to generate alternative exons. We validate our genome-wide analyses by a detailed examination of two transcript variants encoded by one of the differentially methylated genes. The link between methylation and splicing is further supported by the differential methylation of genes belonging to the histone gene family. We propose that modulation of alternative splicing is one mechanism by which DNA methylation could be linked to gene regulation in the honey bee. Our study describes a level of molecular diversity previously unknown in honey bees that might be important for generating phenotypic flexibility not only during development but also in the adult post-mitotic brain.

  14. Aberrantly methylated genes in human papillary thyroid cancer and their association with BRAF/RAS mutation.

    Directory of Open Access Journals (Sweden)

    Yasuko eKikuchi

    2013-12-01

    Full Text Available Cancer arises through accumulation of epigenetic and genetic alteration. Aberrant promoter methylation is a common epigenetic mechanism of gene silencing in cancer cells. We here performed genome-wide analysis of DNA methylation of promoter regions by Infinium HumanMethylation27 BeadChip, using 14 clinical papillary thyroid cancer samples and 10 normal thyroid samples. Among the 14 papillary cancer cases, 11 showed frequent aberrant methylation, but the other three cases showed no aberrant methylation at all. Distribution of the hypermethylation among cancer samples was non-random, which implied existence of a subset of preferentially methylated papillary thyroid cancer. Among 25 frequently methylated genes, methylation status of six genes (HIST1H3J, POU4F2, SHOX2, PHKG2, TLX3, HOXA7 was validated quantitatively by pyrosequencing. Epigenetic silencing of these genes in methylated papillary thyroid cancer cell lines was confirmed by gene re-expression following treatment with 5-aza-2'-deoxycytidine and trichostatin A, and detected by real-time RT-PCR. Methylation of these six genes was validated by analysis of additional 20 papillary thyroid cancer and 10 normal samples. Among the 34 cancer samples in total, 26 cancer samples with preferential methylation were significantly associated with mutation of BRAF/RAS oncogene (P=0.04, Fisher’s exact test. Thus we identified new genes with frequent epigenetic hypermethylation in papillary thyroid cancer, two subsets of either preferentially methylated or hardly methylated papillary thyroid cancer, with a concomitant occurrence of oncogene mutation and gene methylation. These hypermethylated genes may constitute potential biomarkers for papillary thyroid cancer.

  15. Construction of Differential-Methylation Subtractive Library

    Directory of Open Access Journals (Sweden)

    Wei Hu

    2014-01-01

    Full Text Available Stress-induced ROS changes DNA methylation patterns. A protocol combining methylation-sensitive restriction endonuclease (MS-RE digestion with suppression subtractive hybridization (SSH to construct the differential-methylation subtractive library was developed for finding genes regulated by methylation mechanism under cold stress. The total efficiency of target fragment detection was 74.64%. DNA methylation analysis demonstrated the methylation status of target fragments changed after low temperature or DNA methyltransferase inhibitor treatment. Transcription level analysis indicated that demethylation of DNA promotes gene expression level. The results proved that our protocol was reliable and efficient to obtain gene fragments in differential-methylation status.

  16. KONVERGENSI DALAM PROGRAM NET CITIZEN JOURNALISM

    Directory of Open Access Journals (Sweden)

    Rhafidilla Vebrynda

    2017-06-01

    Full Text Available Di dalam artikel ini, peneliti ingin melihat perkembangan teknologi di Indonesia sebagai sebuah peluang untuk menjalankan sebuah program berita berbasis video kiriman masyarakat. Perkembangan teknologi tersebut adalah teknologi penyiaran, teknologi sosial media dan teknologi dalam proses produksi sebuah video. Di Indonesia, jumlah televisi semakin banyak. Setiap stasiun televisi harus bersaing untuk dapat bertahan hidup. Net TV merupakan sebuah stasiun televisi baru di Indonesia yang harus memiliki berbagai program unggulan baru agar dapat bersaing dengan televisi lainnya yang sudah ada. Net TV menggunakan berbagai platform media untuk menjalankan program Net Citizen Journalism (Net CJ. Penggunaan berbagai platform media dikenal dengan istilah multiplatform dan secara teoritis dikenal dengan istilah konvergensi. Konvergensi yaitu saat meleburnya domain-domain dalam berbagai media komunikasi. Artikel ini menggunakan metode studi kasus untuk melihat bagaimana konvergensi terjadi dalam proses pengelolaan program Net CJ. Teknik pengumpulan data adalah dengan wawancara mendalam, observasi dan studi dokumen. Wawancara mendalam dilakukan dari tiga sudut pandang yaitu dari pengelola program, pengguna/audience dan pengamat media. Penelitian ini menemukan bahwa dengan menggunakan berbagai platform media yang fungsinya berbeda, memiliki satu tujuan yang sama yaitu untuk menjalankan program Net CJ. Adapun berbagai platform dalam proses produksi program yaitu tayangan TV konvensional, streaming TV, website, aplikasi Net CJ, facebook, twitter, instagram dan path. Konvergensi media dijalankan dalam dua proses, yaitu proses produksi dan proses promosi program berita.

  17. DNA methylation levels associated with race and childhood asthma severity.

    Science.gov (United States)

    Chan, Marcia A; Ciaccio, Christina E; Gigliotti, Nicole M; Rezaiekhaligh, Mo; Siedlik, Jacob A; Kennedy, Kevin; Barnes, Charles S

    2017-10-01

    Asthma is a common chronic childhood disease worldwide. Socioeconomic status, genetic predisposition and environmental factors contribute to its incidence and severity. A disproportionate number of children with asthma are economically disadvantaged and live in substandard housing with potential indoor environmental exposures such as cockroaches, dust mites, rodents and molds. These exposures may manifest through epigenetic mechanisms that can lead to changes in relevant gene expression. We examined the association of global DNA methylation levels with socioeconomic status, asthma severity and race/ethnicity. We measured global DNA methylation in peripheral blood of children with asthma enrolled in the Kansas City Safe and Healthy Homes Program. Inclusion criteria included residing in the same home for a minimum of 4 days per week and total family income of less than 80% of the Kansas City median family income. DNA methylation levels were quantified by an immunoassay that assessed the percentage of 5-methylcytosine. Our results indicate that overall, African American children had higher levels of global DNA methylation than children of other races/ethnicities (p = 0.029). This difference was more pronounced when socioeconomic status and asthma severity were coupled with race/ethnicity (p = 0.042) where low-income, African American children with persistent asthma had significantly elevated methylation levels relative to other races/ethnicities in the same context (p = 0.006, Hedges g = 1.14). Our study demonstrates a significant interaction effect among global DNA methylation levels, asthma severity, race/ethnicity, and socioeconomic status.

  18. Synthesis, structure activity relationship, radiolabeling and preclinical evaluation of high affinity ligands for the ion channel of the N-methyl-d-aspartate receptor as potential imaging probes for positron emission tomography.

    Science.gov (United States)

    Klein, Pieter J; Christiaans, Johannes A M; Metaxas, Athanasios; Schuit, Robert C; Lammertsma, Adriaan A; van Berckel, Bart N M; Windhorst, Albert D

    2015-03-01

    The N-methyl-d-aspartate receptor (NMDAr) is involved in many neurological and psychiatric disorders including Alzheimer's disease and schizophrenia. Currently, it is not possible to assess NMDAr availability in vivo. The purpose of this study was to develop a positron emission tomography (PET) ligand for the NMDAr ion channel. A series of di- and tri-N-substituted diarylguanidines was synthesized. In addition, in vitro binding affinity for the NMDAr ion channel in rat forebrain membrane fractions was assessed. Compounds 10, 11 and 32 were radiolabeled with either carbon-11 or fluorine-18. Ligands [(11)C]10 and [(18)F]32 were evaluated ex vivo in B6C3 mice. Biodistribution studies showed higher uptake of [(11)C]10 and [(18)F]32 in forebrain regions compared with cerebellum. In addition, for [(11)C]10 54% and for [(18)F]32 70% of activity in the brain at 60min was due to intact tracer. Pre-treatment with MK-801 (0.6mg·kg(-1), ip) slightly decreased uptake in NMDAr-specific regions for [(18)F]32, but not for [(11)C]10. As such [(18)F]32 has the best characteristics as a PET tracer for the ion channel of the NMDAr. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Investigating the potential impact of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) on gene biomarker expression and global DNA methylation in loggerhead sea turtles (Caretta caretta) from the Adriatic Sea.

    Science.gov (United States)

    Cocci, Paolo; Mosconi, Gilberto; Bracchetti, Luca; Nalocca, John Mark; Frapiccini, Emanuela; Marini, Mauro; Caprioli, Giovanni; Sagratini, Gianni; Palermo, Francesco Alessandro

    2017-11-11

    Polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) are priority contaminants that bioaccumulate through the food webs and affect the biology of a variety of resident and migratory species, including sea turtles. Few studies have evaluated toxicological biomarkers of exposure to PAHs and PCBs in these animals. The present paper reports the results of an initial field study to quantify the association between plasma concentrations of PAHs/PCBs and whole blood cell expression of gene biomarkers in juvenile loggerhead sea turtles (Caretta caretta) rescued along the Italian coasts of the northern and central areas of the Adriatic Sea. While detectable levels of PAHs were found in all plasma samples examined, only three PCB congeners (PCB52, PCB95, and PCB149) were noted, with detection percentages ranging between 48% and 57%. A significant correlation was found between 3 of the 6 gene biomarkers assessed (HSP60, CYP1A and ERα) and plasma levels of some PAH congeners. In contrast, no significant association between PCB burden and gene expression was observed. The global DNA methylation levels were significantly and positively correlated with the concentrations of most of the PAHs and only one of the PCB congeners (PCB52). The relation between PAH concentration and gene expression in whole blood cells suggests that these genes may respond to environmental contaminant exposure and are promising candidates for the development of biomarkers for monitoring sea turtle exposure to persistent organic pollutants (POPs). Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Visual Studio 2010 and NET 4 Six-in-One

    CERN Document Server

    Novak, Istvan; Granicz, Adam

    2010-01-01

    Complete coverage of all key .NET 4 and Visual Studio 2010 languages and technologies. .NET 4 is Microsoft's latest version of their core programming platform, and Visual Studio 2010 is the toolset that helps write .NET 4 applications. This comprehensive resource offers one-stop shopping for all you need to know to get productive with .NET 4. Experienced author and .NET guru Mitchel Sellers reviews all the important new features of .NET 4, including .NET charting and ASP.NET charting, ASP.NET dynamic data and jQuery, and the addition of F# as a supported package language. The expansive coverag

  1. Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation.

    Science.gov (United States)

    Yehuda, Rachel; Daskalakis, Nikolaos P; Bierer, Linda M; Bader, Heather N; Klengel, Torsten; Holsboer, Florian; Binder, Elisabeth B

    2016-09-01

    The involvement of epigenetic mechanisms in intergenerational transmission of stress effects has been demonstrated in animals but not in humans. Cytosine methylation within the gene encoding for FK506 binding protein 5 (FKBP5) was measured in Holocaust survivors (n = 32), their adult offspring (n = 22), and demographically comparable parent (n = 8) and offspring (n = 9) control subjects, respectively. Cytosine-phosphate-guanine sites for analysis were chosen based on their spatial proximity to the intron 7 glucocorticoid response elements. Holocaust exposure had an effect on FKBP5 methylation that was observed in exposed parents as well in their offspring. These effects were observed at bin 3/site 6. Interestingly, in Holocaust survivors, methylation at this site was higher in comparison with control subjects, whereas in Holocaust offspring, methylation was lower. Methylation levels for exposed parents and their offspring were significantly correlated. In contrast to the findings at bin 3/site 6, offspring methylation at bin 2/sites 3 to 5 was associated with childhood physical and sexual abuse in interaction with an FKBP5 risk allele previously associated with vulnerability to psychological consequences of childhood adversity. The findings suggest the possibility of site specificity to environmental influences, as sites in bins 3 and 2 were differentially associated with parental trauma and the offspring's own childhood trauma, respectively. FKBP5 methylation averaged across the three bins examined was associated with wake-up cortisol levels, indicating functional relevance of the methylation measures. This is the first demonstration of an association of preconception parental trauma with epigenetic alterations that is evident in both exposed parent and offspring, providing potential insight into how severe psychophysiological trauma can have intergenerational effects. Published by Elsevier Inc.

  2. anNET: a tool for network-embedded thermodynamic analysis of quantitative metabolome data

    Directory of Open Access Journals (Sweden)

    Zamboni Nicola

    2008-04-01

    Full Text Available Abstract Background Compared to other omics techniques, quantitative metabolomics is still at its infancy. Complex sample preparation and analytical procedures render exact quantification extremely difficult. Furthermore, not only the actual measurement but also the subsequent interpretation of quantitative metabolome data to obtain mechanistic insights is still lacking behind the current expectations. Recently, the method of network-embedded thermodynamic (NET analysis was introduced to address some of these open issues. Building upon principles of thermodynamics, this method allows for a quality check of measured metabolite concentrations and enables to spot metabolic reactions where active regulation potentially controls metabolic flux. So far, however, widespread application of NET analysis in metabolomics labs was hindered by the absence of suitable software. Results We have developed in Matlab a generalized software called 'anNET' that affords a user-friendly implementation of the NET analysis algorithm. anNET supports the analysis of any metabolic network for which a stoichiometric model can be compiled. The model size can span from a single reaction to a complete genome-wide network reconstruction including compartments. anNET can (i test quantitative data sets for thermodynamic consistency, (ii predict metabolite concentrations beyond the actually measured data, (iii identify putative sites of active regulation in the metabolic reaction network, and (iv help in localizing errors in data sets that were found to be thermodynamically infeasible. We demonstrate the application of anNET with three published Escherichia coli metabolome data sets. Conclusion Our user-friendly and generalized implementation of the NET analysis method in the software anNET allows users to rapidly integrate quantitative metabolome data obtained from virtually any organism. We envision that use of anNET in labs working on quantitative metabolomics will provide the

  3. Climatic Forecasting of Net Infiltration at Yucca Montain Using Analogue Meteororological Data

    Energy Technology Data Exchange (ETDEWEB)

    B. Faybishenko

    2006-09-11

    At Yucca Mountain, Nevada, future changes in climatic conditions will most likely alter net infiltration, or the drainage below the bottom of the evapotranspiration zone within the soil profile or flow across the interface between soil and the densely welded part of the Tiva Canyon Tuff. The objectives of this paper are to: (a) develop a semi-empirical model and forecast average net infiltration rates, using the limited meteorological data from analogue meteorological stations, for interglacial (present day), and future monsoon, glacial transition, and glacial climates over the Yucca Mountain region, and (b) corroborate the computed net-infiltration rates by comparing them with the empirically and numerically determined groundwater recharge and percolation rates through the unsaturated zone from published data. In this paper, the author presents an approach for calculations of net infiltration, aridity, and precipitation-effectiveness indices, using a modified Budyko's water-balance model, with reference-surface potential evapotranspiration determined from the radiation-based Penman (1948) formula. Results of calculations show that net infiltration rates are expected to generally increase from the present-day climate to monsoon climate, to glacial transition climate, and then to the glacial climate. The forecasting results indicate the overlap between the ranges of net infiltration for different climates. For example, the mean glacial net-infiltration rate corresponds to the upper-bound glacial transition net infiltration, and the lower-bound glacial net infiltration corresponds to the glacial transition mean net infiltration. Forecasting of net infiltration for different climate states is subject to numerous uncertainties-associated with selecting climate analogue sites, using relatively short analogue meteorological records, neglecting the effects of vegetation and surface runoff and runon on a local scale, as well as possible anthropogenic climate changes.

  4. PENGEMBANGAN TARGET NET SEBAGAI ALAT PEMBELAJARAN PUKULAN BULUTANGKIS DI SEKOLAH MENENGAH PERTAMA

    Directory of Open Access Journals (Sweden)

    Afif Khoirul Hidayat

    2015-04-01

    Full Text Available Penelitian ini bertujuan untuk mengembangkan dan menghasilkan alat target net untuk memudahkan peserta didik SMP memelajari dan meningkatkan kemampuan teknik dasar pukulan net, smash, drive, dan short serve. Dalam penelitian pengembangan ini, langkah-langkah yang harus ditempuh meliputi: (1 potensi dan masalah, (2 pengumpulan data, (3 desain produk, (4 validasi desain dan instrument, (5 revisi desain, (6 uji coba produk, (7 revisi, dan (8 produksi/implementasi produk. Uji coba penelitian dilakukan terhadap 168 peserta didik dari SMP se-Kecamatan Piyungan, Bantul, Yogyakarta. Teknik analisis data terdiri dari teknik analisis data deskriptif kuantitatif dan teknik analisis data deskriptif kualitatif. Hasil akhir dari penelitian ini adalah sebuah produk alat pembelajaran target net dan buku manual target net yang memiliki kualitas yang sangat baik. Hal tersebut dibuktikan dengan diperolehnya rerata persentase skor penilaian kualitas produk alat pembelajaran dan buku manual target net sebesar 98,66%.   DEVELOP TARGET NET AS A TOOL FOR SHOT LEARNING IN BADMINTON AT JUNIOR HIGH SCHOOL   Abstract This research aims to produce and develop target net tools in facilitating JHS students to improve the basic techniques of net shots, smashes, drives, dan short serves. This research and development study follows the steps of: (1 the potential and problems identification, (2 data collection, (3 product design, (4 the design and validation of the instrumen, (5 revision of the design, (6 product trials, (7 revision, and (8 production/implementation of the product. The trials were conducted to 168 students from JSH in Piyungan districts, Bantul, Yogyakarta. The technique of data analysis is descriptive quantitative analysis and qualitative descriptive analysis. The result of this research is a learning tool of target net product and manual book of the target product, that have a very good quality.  Which is proved by the average percentage quality assessment

  5. Application and Theory of Petri Nets

    DEFF Research Database (Denmark)

    , the conferences have 150-200 participants, one third of these coming from industry and the rest from universities and research institutions. The 1992 conference was organized by the School of Computing and Management Sciences at Sheffield City Polytechnic, England. The volume contains twoinvited papers, by G......This volume contains the proceedings of the 13th International Conference onApplication and Theory of Petri Nets, held in Sheffield, England, in June 1992. The aim of the Petri net conferences is to create a forum for discussing progress in the application and theory of Petri nets. Typically...

  6. Performance Analysis using Coloured Petri Nets

    DEFF Research Database (Denmark)

    Wells, Lisa Marie

    an explicit separation between modelling the behaviour of a system and monitoring the behaviour of the model. As a result, cleaner and more understandable models can be created. The third paper presents a novel method for adding auxiliary information to coloured Petri net models. Coloured Petri nets models...... in a very limited and predictable manner, and it is easy to enable and disable the auxiliary information. The fourth paper is a case study in which the performance of a web server was analysed using coloured Petri nets. This case study has shown that it is relatively easy to analyse the performance...

  7. The KM3NeT project

    Energy Technology Data Exchange (ETDEWEB)

    Katz, U.F., E-mail: katz@physik.uni-erlangen.d [Erlangen Centre for Astroparticle Physics (ECAP), University of Erlangen-Nuernberg, Erwin-Rommel-Str. 1, 91058 Erlangen (Germany)

    2011-01-21

    The KM3NeT research infrastructure in the deep Mediterranean Sea will host a multi-cubic-kilometre neutrino telescope and provide connectivity for continuous, long-term measurements of earth and sea sciences, such as geology, marine biology and oceanography. The KM3NeT neutrino telescope will complement the IceCube telescope currently being installed at the South Pole in its field of view and surpass its sensitivity by a substantial factor. In this document the major aspects of the KM3NeT technical design are described and the expected physics sensitivity is discussed. Finally, the expected time line towards construction is presented.

  8. The net neutrality debate on Twitter

    Directory of Open Access Journals (Sweden)

    Wolf J. Schünemann

    2015-12-01

    Full Text Available The internet has been seen as a medium that empowers individual political actors in relation to established political elites and media gatekeepers. The present article discusses this “net empowerment hypothesis” and tests it empirically by analysing Twitter communication on the regulation of net neutrality. We extracted 503.839 tweets containing #NetNeutrality posted between January and March 2015 and analysed central developments and the network structure of the debate. The empirical results show that traditional actors from media and politics still maintain a central role.

  9. Spring Hydrology Determines Summer Net Carbon Uptake in Northern Ecosystems

    Science.gov (United States)

    Yi, Yonghong; Kimball, John; Reichle, Rolf H.

    2014-01-01

    Increased photosynthetic activity and enhanced seasonal CO2 exchange of northern ecosystems have been observed from a variety of sources including satellite vegetation indices (such as the Normalized Difference Vegetation Index; NDVI) and atmospheric CO2 measurements. Most of these changes have been attributed to strong warming trends in the northern high latitudes (greater than or equal to 50N). Here we analyze the interannual variation of summer net carbon uptake derived from atmospheric CO2 measurements and satellite NDVI in relation to surface meteorology from regional observational records. We find that increases in spring precipitation and snow pack promote summer net carbon uptake of northern ecosystems independent of air temperature effects. However, satellite NDVI measurements still show an overall benefit of summer photosynthetic activity from regional warming and limited impact of spring precipitation. This discrepancy is attributed to a similar response of photosynthesis and respiration to warming and thus reduced sensitivity of net ecosystem carbon uptake to temperature. Further analysis of boreal tower eddy covariance CO2 flux measurements indicates that summer net carbon uptake is positively correlated with early growing-season surface soil moisture, which is also strongly affected by spring precipitation and snow pack based on analysis of satellite soil moisture retrievals. This is attributed to strong regulation of spring hydrology on soil respiration in relatively wet boreal and arctic ecosystems. These results document the important role of spring hydrology in determining summer net carbon uptake and contrast with prevailing assumptions of dominant cold temperature limitations to high-latitude ecosystems. Our results indicate potentially stronger coupling of boreal/arctic water and carbon cycles with continued regional warming trends.

  10. Theoretical spectroscopic characterization at low temperatures of S-methyl thioformate and O-methyl thioformate

    Energy Technology Data Exchange (ETDEWEB)

    Senent, M. L., E-mail: senent@iem.cfmac.csic.es [Departamento de Química y Física Teóricas, Instituto de Estructura de la Materia, IEM-C.S.I.C., Serrano 121, Madrid 28006 (Spain); Puzzarini, C., E-mail: cristina.puzzarini@unibo.it [Dipartimento di Chimica G. Ciamician, Università di Bologna, Via F. Selmi 2, I-40126 Bologna (Italy); Hochlaf, M., E-mail: hochlaf@univ-mlv.fr [Laboratoire de Modélisation et Simulation Multi Echelle, Université Paris-Est, MSME UMR 8208 CNRS, 5 boulevard Descartes, 77454 Marne-la-Vallée (France); Domínguez-Gómez, R., E-mail: rosa.dominguez@upm.es [Departamento de Ingeniería Civil, Cátedra de Química, E.U.I.T. Obras Públicas, Universidad Politécnica de Madrid, Madrid (Spain); Carvajal, M., E-mail: miguel.carvajal@dfa.uhu.es [Departamento de Física Aplicada, Facultad de Ciencias Experimentales, Unidad Asociada IEM-CSIC-U.Huelva, Universidad de Huelva, 21071 Huelva (Spain)

    2014-09-14

    Highly correlated ab initio methods are employed to determine spectroscopic properties at low temperatures of two S-analogs of methyl formate: S-methyl thioformate CH{sub 3}-S-CHO (MSCHO) and O-methyl thioformate CH{sub 3}-O-CHS (MOCHS). Both species are detectable and they are expected to play an important role in Astrochemistry. Molecular properties are compared with those of the O-analog, methyl formate. Both isomers present two conformers cis and trans. cis-CH{sub 3}-S-CHO represents the most stable structure lying 4372.2 cm{sup −1} below cis-CH{sub 3}-O-CHS. The energy difference between the cis and trans forms is drastically lower for MSCHO (1134 cm{sup −1}) than for MOCHS (1963.6 cm{sup −1}). Harmonic and anharmonic fundamentals and the corresponding intensities, as well as the rotational constants for the ground vibrational and first excited torsional states and the centrifugal distortions constants, are provided. Low torsional energy levels have been obtained by solving variationally a two dimensional Hamiltonian expressed in terms of the two torsional degrees of freedom. The corresponding 2D potential energy surfaces have been computed at the CCSD(T)/aug-cc-pVTZ level of theory. The methyl torsional barriers V{sub 3}(cis) are determined to be 139.7 cm{sup −1} (CH{sub 3}-S-CHO) and 670.4 cm{sup −1} (CH{sub 3}-O-CHS). The A/E splitting of ground torsional state has been estimated to be 0.438 cm{sup −1} for CH{sub 3}-S-CHO and negligible for CH{sub 3}-O-CHS.

  11. A SILAC-based screen for Methyl-CpG binding proteins identifies RBP-J as a DNA methylation and sequence-specific binding protein.

    Directory of Open Access Journals (Sweden)

    Stefanie J J Bartels

    Full Text Available BACKGROUND: DNA methylation is an epigenetic modification that plays a crucial role in a variety of biological processes. Methylated DNA is specifically bound by Methyl-CpG Binding Proteins (MBPs. Three different types of MBPs have been identified so far: the Methyl-CpG Binding Domain (MBD family proteins, three BTB/POZ-Zn-finger proteins, and UHRF1. Most of the known MBPs have been identified via homology with the MBD and Zn-finger domains as present in MeCP2 and Kaiso, respectively. It is conceivable that other proteins are capable of recognizing methylated DNA. METHODOLOGY/PRINCIPAL FINDINGS: For the purpose of identifying novel 'readers' we set up a methyl-CpG pull-down assay combined with stable-isotope labeling by amino acids in cell culture (SILAC. In a methyl-CpG pull-down with U937 nuclear extracts, we recovered several known MBPs and almost all subunits of the MBD2/NuRD complex as methylation specific binders, providing proof-of-principle. Interestingly, RBP-J, the transcription factor downstream of Notch receptors, also bound the DNA in a methylation dependent manner. Follow-up pull-downs and electrophoretic mobility shift assays (EMSAs showed that RBP-J binds methylated DNA in the context of a mutated RBP-J consensus motif. CONCLUSIONS/SIGNIFICANCE: The here described SILAC/methyl-CpG pull-down constitutes a new approach to identify potential novel DNAme readers and will advance unraveling of the complete methyl-DNA interactome.

  12. Genes associated with genotype-specific DNA methylation in squamous cell carcinoma as candidate drug targets

    Science.gov (United States)

    2014-01-01

    Background Aberrant DNA methylation is often associated with cancers. Thus, screening genes with cancer-associated aberrant DNA methylation is a useful method to identify candidate cancer-causing genes. Aberrant DNA methylation is also genotype dependent. Thus, the selection of genes with genotype-specific aberrant DNA methylation in cancers is potentially important for tailor-made medicine. The selected genes are important candidate drug targets. Results The recently proposed principal component analysis based selection of genes with aberrant DNA methylation was applied to genotype and DNA methylation patterns in squamous cell carcinoma measured using single nucleotide polymorphism (SNP) arrays. SNPs that are frequently found in cancers are usually highly methylated, and the genes that were selected using this method were reported previously to be related to cancers. Thus, genes with genotype-specific DNA methylation patterns will be good therapeutic candidates. The tertiary structures of the proteins encoded by the selected genes were successfully inferred using two profile-based protein structure servers, FAMS and Phyre2. Candidate drugs for three of these proteins, tyrosine kinase receptor (ALK), EGLN3 protein, and NUAK family SNF1-like kinase 1 (NUAK1), were identified by ChooseLD. Conclusions We detected genes with genotype-specific DNA methylation in squamous cell carcinoma that are candidate drug targets. Using in silico drug discovery, we successfully identified several candidate drugs for the ALK, EGLN3 and NUAK1 genes that displayed genotype-specific DNA methylation. PMID:24565165

  13. Bisulfite sequencing reveals that Aspergillus flavus holds a hollow in DNA methylation.

    Directory of Open Access Journals (Sweden)

    Si-Yang Liu

    Full Text Available Aspergillus flavus first gained scientific attention for its production of aflatoxin. The underlying regulation of aflatoxin biosynthesis has been serving as a theoretical model for biosynthesis of other microbial secondary metabolites. Nevertheless, for several decades, the DNA methylation status, one of the important epigenomic modifications involved in gene regulation, in A. flavus remains to be controversial. Here, we applied bisulfite sequencing in conjunction with a biological replicate strategy to investigate the DNA methylation profiling of A. flavus genome. Both the bisulfite sequencing data and the methylome comparisons with other fungi confirm that the DNA methylation level of this fungus is negligible. Further investigation into the DNA methyltransferase of Aspergillus uncovers its close relationship with RID-like enzymes as well as its divergence with the methyltransferase of species with validated DNA methylation. The lack of repeat contents of the A. flavus' genome and the high RIP-index of the small amount of remanent repeat potentially support our speculation that DNA methylation may be absent in A. flavus or that it may possess de novo DNA methylation which occurs very transiently during the obscure sexual stage of this fungal species. This work contributes to our understanding on the DNA methylation status of A. flavus, as well as reinforces our views on the DNA methylation in fungal species. In addition, our strategy of applying bisulfite sequencing to DNA methylation detection in species with low DNA methylation may serve as a reference for later scientific investigations in other hypomethylated species.

  14. The relationship of DNA methylation with age, gender and genotype in twins and healthy controls.

    Directory of Open Access Journals (Sweden)

    Marco P Boks

    2009-08-01

    Full Text Available Cytosine-5 methylation within CpG dinucleotides is a potentially important mechanism of epigenetic influence on human traits and disease. In addition to influences of age and gender, genetic control of DNA methylation levels has recently been described. We used whole blood genomic DNA in a twin set (23 MZ twin-pairs and 23 DZ twin-pairs, N = 92 as well as healthy controls (N = 96 to investigate heritability and relationship with age and gender of selected DNA methylation profiles using readily commercially available GoldenGate bead array technology. Despite the inability to detect meaningful methylation differences in the majority of CpG loci due to tissue type and locus selection issues, we found replicable significant associations of DNA methylation with age and gender. We identified associations of genetically heritable single nucleotide polymorphisms with large differences in DNA methylation levels near the polymorphism (cis effects as well as associations with much smaller differences in DNA methylation levels elsewhere in the human genome (trans effects. Our results demonstrate the feasibility of array-based approaches in studies of DNA methylation and highlight the vast differences between individual loci. The identification of CpG loci of which DNA methylation levels are under genetic control or are related to age or gender will facilitate further studies into the role of DNA methylation and disease.

  15. Erasing the methyl mark: histone demethylases at the center of cellular differentiation and disease

    DEFF Research Database (Denmark)

    Cloos, Paul A C; Christensen, Jesper; Agger, Karl

    2008-01-01

    The enzymes catalyzing lysine and arginine methylation of histones are essential for maintaining transcriptional programs and determining cell fate and identity. Until recently, histone methylation was regarded irreversible. However, within the last few years, several families of histone...... demethylases erasing methyl marks associated with gene repression or activation have been identified, underscoring the plasticity and dynamic nature of histone methylation. Recent discoveries have revealed that histone demethylases take part in large multiprotein complexes synergizing with histone deacetylases......, histone methyltransferases, and nuclear receptors to control developmental and transcriptional programs. Here we review the emerging biochemical and biological functions of the histone demethylases and discuss their potential involvement in human diseases, including cancer....

  16. Engineering of an Escherichia coli strain for the production of 3-methyl-1-butanol.

    Science.gov (United States)

    Connor, Michael R; Liao, James C

    2008-09-01

    3-Methyl-1-butanol is a potential fuel additive or substitute. Previously this compound was identified in small quantities in yeast fermentation as one of the fusel alcohols. In this work, we engineered an Escherichia coli strain to produce 3-methyl-1-butanol from glucose via the host's amino acid biosynthetic pathways. Strain improvement with the removal of feedback inhibition and competing pathways increased the selectivity and productivity of 3-methyl-1-butanol. This work demonstrates the feasibility of production of 3-methyl-1-butanol as a biofuel and shows promise in using E. coli as a host for production.

  17. RadNet Air Quality (Deployable) Data

    Data.gov (United States)

    U.S. Environmental Protection Agency — RadNet Deployable Monitoring is designed to collect radiological and meteorological information and data asset needed to establish the impact of radiation levels on...

  18. A Lightweight TwiddleNet Portal

    National Research Council Canada - National Science Library

    Rimikis, Antonios M

    2008-01-01

    TwiddleNet is a distributed architecture of personal servers that harnesses the power of the mobile devices, enabling real time information and file sharing of multiple data types from commercial-off-the-shelf platforms...

  19. Homology Groups of a Pipeline Petri Net

    Directory of Open Access Journals (Sweden)

    A. A. Husainov

    2013-01-01

    Full Text Available Petri net is said to be elementary if every place can contain no more than one token. In this paper, it is studied topological properties of the elementary Petri net for a pipeline consisting of n functional devices. If the work of the functional devices is considered continuous, we can come to some topological space of “intermediate” states. In the paper, it is calculated the homology groups of this topological space. By induction on n, using the Addition Sequence for homology groups of semicubical sets, it is proved that in dimension 0 and 1 the integer homology groups of these nets are equal to the group of integers, and in the remaining dimensions are zero. Directed homology groups are studied. A connection of these groups with deadlocks and newsletters is found. This helps to prove that all directed homology groups of the pipeline elementary Petri nets are zeroth.

  20. Net accumulation of the Greenland ice sheet

    DEFF Research Database (Denmark)

    Kiilsholm, Sissi; Christensen, Jens Hesselbjerg; Dethloff, Klaus

    2003-01-01

    improvement compared to the driving OAGCM. Estimates of the regional net balance are also better represented by the RCM. In the future climate the net balance for the Greenland Ice Sheet is reduced in all the simulation, but discrepancies between the amounts when based on ECHAM4/OPYC3 and HIRHAM are found....... In both scenarios, the estimated melt rates are larger in HIRHAM than in the driving model....

  1. CDMA and TDMA based neural nets.

    Science.gov (United States)

    Herrero, J C

    2001-06-01

    CDMA and TDMA telecommunication techniques were established long time ago, but they have acquired a renewed presence due to the rapidly increasing mobile phones demand. In this paper, we are going to see they are suitable for neural nets, if we leave the concept "connection" between processing units and we adopt the concept "messages" exchanged between them. This may open the door to neural nets with a higher number of processing units and flexible configuration.

  2. Mastering AngularJD for .NET developers

    CERN Document Server

    Majid, Mohammad Wadood

    2015-01-01

    This book is envisioned for traditional developers and programmers who want to develop client-side applications using the AngularJS framework and ASP.NET Web API 2 with Visual Studio. .NET developers who have already built web applications or web services and who have a fundamental knowledge of HTML, JavaScript, and CSS and want to explore single-page applications will also find this guide useful. Basic knowledge of AngularJS would be helpful.

  3. .NET 4.5 parallel extensions

    CERN Document Server

    Freeman, Bryan

    2013-01-01

    This book contains practical recipes on everything you will need to create task-based parallel programs using C#, .NET 4.5, and Visual Studio. The book is packed with illustrated code examples to create scalable programs.This book is intended to help experienced C# developers write applications that leverage the power of modern multicore processors. It provides the necessary knowledge for an experienced C# developer to work with .NET parallelism APIs. Previous experience of writing multithreaded applications is not necessary.

  4. A Lightweight TwiddleNet Portal

    Science.gov (United States)

    2008-03-01

    designed to exploit the multiple networking modalities available in the current generation of smartphones . TwiddleNet enables well-organized and well...of Sonopia and will have a comprehensive review of the service in the coming weeks [12]. Twango, which was acquired by Nokia in July 2007, is an...EXPERIMENTATION As already mentioned the main purpose of this thesis is the development of a TwiddleNet portal running on a smartphone or a PDA, which can allow

  5. CCS - and its relationship to net theory

    DEFF Research Database (Denmark)

    Nielsen, Mogens

    1987-01-01

    In this paper we give a short introduction to Milner's Calculus for Communicating Systems - a paradigm for concurrent computation. We put special emphasis on the basic concepts and tools from the underlying "algebraic approach", and their relationship to the approach to concurrency within net...... theory. Furthermore, we provide an operational version of the language CCS with "true concurrency" in the sense of net theory, and a discussion of the possible use of such a marriage of the two theories of concurrency....

  6. Net carbon flux in organic and conventional olive production systems

    Science.gov (United States)

    Saeid Mohamad, Ramez; Verrastro, Vincenzo; Bitar, Lina Al; Roma, Rocco; Moretti, Michele; Chami, Ziad Al

    2014-05-01

    Agricultural systems are considered as one of the most relevant sources of atmospheric carbon. However, agriculture has the potentiality to mitigate carbon dioxide mainly through soil carbon sequestration. Some agricultural practices, particularly fertilization and soil management, can play a dual role in the agricultural systems regarding the carbon cycle contributing to the emissions and to the sequestration process in the soil. Good soil and input managements affect positively Soil Organic Carbon (SOC) changes and consequently the carbon cycle. The present study aimed at comparing the carbon footprint of organic and conventional olive systems and to link it to the efficiency of both systems on carbon sequestration by calculating the net carbon flux. Data were collected at farm level through a specific and detailed questionnaire based on one hectare as a functional unit and a system boundary limited to olive production. Using LCA databases particularly ecoinvent one, IPCC GWP 100a impact assessment method was used to calculate carbon emissions from agricultural practices of both systems. Soil organic carbon has been measured, at 0-30 cm depth, based on soil analyses done at the IAMB laboratory and based on reference value of SOC, the annual change of SOC has been calculated. Substracting sequestrated carbon in the soil from the emitted on resulted in net carbon flux calculation. Results showed higher environmental impact of the organic system on Global Warming Potential (1.07 t CO2 eq. yr-1) comparing to 0.76 t CO2 eq. yr-1 in the conventional system due to the higher GHG emissions caused by manure fertilizers compared to the use of synthetic foliar fertilizers in the conventional system. However, manure was the main reason behind the higher SOC content and sequestration in the organic system. As a resultant, the organic system showed higher net carbon flux (-1.7 t C ha-1 yr-1 than -0.52 t C ha-1 yr-1 in the conventional system reflecting higher efficiency as a

  7. Destruction of methyl bromide sorbed to activated carbon by thiosulfate and electrolysis

    Science.gov (United States)

    Methyl bromide is widely used as a fumigant for post-harvest and quarantine uses at port facilities due to the low treatment times required, but it is vented to the atmosphere after its use. Due to the potential contributions of methyl bromide to stratospheric ozone depletion, technologies for the c...

  8. Synthetic methyl hexagalacturonate hapten inhibitors of antihomogalacturonan monoclonal antibodies LM7, JIM5 and JIM7

    DEFF Research Database (Denmark)

    Clausen, Mads Hartvig; Willats, William George Tycho; Knox, J. Paul

    2003-01-01

    A range of synthetic methyl hexagalacturonates were used as potential hapten inhibitors in competitive-inhibition enzyme-linked immunosorbent assays (ELISAs) with anti-homogalacturonan monoclonal antibodies LM7, JIM5 and JIM7. The selective inhibition of these antibodies by different haptens...... provides insight into the structures of the partially methyl-esterified pectin epitopes of these widely used monoclonal antibodies....

  9. Evaluation of methylation pattern in promoter region of E-cadherin ...

    African Journals Online (AJOL)

    The data indicate that CDH1 promoter methylation might be a potential mechanism for epigenetic silencing of CDH1 in primary breast cancer suggesting a valuable molecular marker for detection of breast cancer progression. Key words: Breast cancer, E-cadherin, methylation pattern, tumor stage, tumor grade.

  10. Net energy analysis: Powerful tool for selecting electric power options

    Science.gov (United States)

    Baron, S.

    A number of net energy analysis studies have been conducted in recent years for electric power production from coal, oil and uranium fuels; synthetic fuels from coal and oil shale; and heat and electric power from solar energy. This technique is an excellent indicator of investment costs, environmental impact and potential economic competitiveness of alternative electric power systems for energy planners from the Eastern European countries considering future options. Energy conservation is also important to energy planners and the net energy analysis technique is an excellent accounting system on the extent of energy resource conservation. The author proposes to discuss the technique and to present the results of his studies and others in the field. The information supplied to the attendees will serve as a powerful tool to the energy planners considering their electric power options in the future.

  11. Targeting Net Zero Energy at Fort Carson: Assessment and Recommendations

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, K.; Markel, T.; Simpson, M.; Leahey, J.; Rockenbaugh, C.; Lisell, L.; Burman, K.; Singer, M.

    2011-10-01

    The U.S. Army's Fort Carson installation was selected to serve as a prototype for net zero energy assessment and planning. NREL performed the comprehensive assessment to appraise the potential of Fort Carson to achieve net zero energy status through energy efficiency, renewable energy, and electric vehicle integration. This report summarizes the results of the assessment and provides energy recommendations. This study is part of a larger cross-laboratory effort that also includes an assessment of renewable opportunities at seven other DoD Front Range installations, a microgrid design for Fort Carson critical loads and an assessment of regulatory and market-based barriers to a regional secure smart grid.

  12. Net energy analysis - powerful tool for selecting elective power options

    Energy Technology Data Exchange (ETDEWEB)

    Baron, S. [Brookhaven National Laboratory, Upton, NY (United States)

    1995-12-01

    A number of net energy analysis studies have been conducted in recent years for electric power production from coal, oil and uranium fuels; synthetic fuels from coal and oil shale; and heat and electric power from solar energy. This technique is an excellent indicator of investment costs, environmental impact and potential economic competitiveness of alternative electric power systems for energy planners from the Eastern European countries considering future options. Energy conservation is also important to energy planners and the net energy analysis technique is an excellent accounting system on the extent of energy resource conservation. The author proposes to discuss the technique and to present the results of his studies and others in the field. The information supplied to the attendees will serve as a powerful tool to the energy planners considering their electric power options in the future.

  13. Visual Studio 2013 and .NET 4.5 expert cookbook

    CERN Document Server

    Sur, Abhishek

    2014-01-01

    If you are a Visual Studio 2013 or .NET developer who would like to sharpen your existing skill set and adapt to new .NET technologies, this is the book for you. A basic understanding of .NET and C# is required.

  14. HANPP Collection: Global Patterns in Net Primary Productivity (NPP)

    Data.gov (United States)

    National Aeronautics and Space Administration — The Global Patterns in Net Primary Productivity (NPP) portion of the Human Appropriation of Net Primary Productivity (HANPP) Collection maps the net amount of solar...

  15. Folate and DNA Methylation: A Review of Molecular Mechanisms and the Evidence for Folate’s Role12

    Science.gov (United States)

    Crider, Krista S.; Yang, Thomas P.; Berry, Robert J; Bailey, Lynn B.

    2012-01-01

    DNA methylation is an epigenetic modification critical to normal genome regulation and development. The vitamin folate is a key source of the one carbon group used to methylate DNA. Because normal mammalian development is dependent on DNA methylation, there is enormous interest in assessing the potential for changes in folate intake to modulate DNA methylation both as a biomarker for folate status and as a mechanistic link to developmental disorders and chronic diseases including cancer. This review highlights the role of DNA methylation in normal genome function, how it can be altered, and the evidence of the role of folate/folic acid in these processes. PMID:22332098

  16. Migration and risk: net migration in marginal ecosystems and hazardous areas

    Science.gov (United States)

    de Sherbinin, Alex; Levy, Marc; Adamo, Susana; MacManus, Kytt; Yetman, Greg; Mara, Valentina; Razafindrazay, Liana; Goodrich, Benjamin; Srebotnjak, Tanja; Aichele, Cody; Pistolesi, Linda

    2012-12-01

    The potential for altered ecosystems and extreme weather events in the context of climate change has raised questions concerning the role that migration plays in either increasing or reducing risks to society. Using modeled data on net migration over three decades from 1970 to 2000, we identify sensitive ecosystems and regions at high risk of climate hazards that have seen high levels of net in-migration and out-migration over the time period. This paper provides a literature review on migration related to ecosystems, briefly describes the methodology used to develop the estimates of net migration, then uses those data to describe the patterns of net migration for various ecosystems and high risk regions. The study finds that negative net migration generally occurs over large areas, reflecting its largely rural character, whereas areas of positive net migration are typically smaller, reflecting its largely urban character. The countries with largest population such as China and India tend to drive global results for all the ecosystems found in those countries. Results suggest that from 1970 to 2000, migrants in developing countries have tended to move out of marginal dryland and mountain ecosystems and out of drought-prone areas, and have moved towards coastal ecosystems and areas that are prone to floods and cyclones. For North America results are reversed for dryland and mountain ecosystems, which saw large net influxes of population in the period of record. Uncertainties and potential sources of error in these estimates are addressed.

  17. To What Extent Does DNA Methylation Affect Phenotypic Variation in Cattle?

    Directory of Open Access Journals (Sweden)

    Stephanie McKAY

    2015-07-01

    Full Text Available DNA methylation is an environmentally influenced epigenetic modification that regulates gene transcription and has the potential to influence variation in economically important phenotypes in agricultural species. We have utilized a novel approach to evaluate the relationship between genetic and epigenetic variation and downstream phenotypes. To begin with, we have integrated RNA-Seq and methyl binding domain sequencing (MBD-Seq data in order to determine the extent to which DNA methylation affects phenotypic variation in economically important traits of cattle. MBD-Seq is a technique that involves the sample enrichment of methylated genomic regions followed by their next-generation sequencing. This study utilized Illumina next generation sequencing technology to perform both RNA-Seq and MBD-Seq. NextGENe software (SoftGenetics, State College, PA was employed for quality trimming and aligning the sequence reads to the UMD3.1 bovine reference genome, generating counts of matched reads and methylated peak identification. Subsequently, we identified and quantified genome-wide methylated regions and characterized the extent of differential methylation and differential expression between two groups of animals with extreme phenotypes. The program edgeR from the R software package (version 3.0.1 was employed for identifying differentially methylated regions and regions of differential expression. Finally, Partial Correlation with Information Theory (PCIT was performed to identify transcripts and methylation events that exhibit differential hubbing. A differential hub is defined as a gene network hub that is more highly connected in one treatment group than the other. This analysis produced every possible pair-wise interaction that subsequently enabled us to look at network interactions of how methylation affects expression. (co-expression, co-methylation, methylation x expression. Genomic regions of interest derived from this analysis were then aligned

  18. Micronutrient status and global DNA methylation in school-age children.

    Science.gov (United States)

    Perng, Wei; Rozek, Laura S; Mora-Plazas, Mercedes; Duchin, Ofra; Marin, Constanza; Forero, Yibby; Baylin, Ana; Villamor, Eduardo

    2012-10-01

    Aberrations in global LINE-1 DNA methylation have been related to risk of cancer and cardiovascular disease. Micronutrients including methyl-donors and retinoids are involved in DNA methylation pathways. We investigated associations of micronutrient status and LINE-1 methylation in a cross-sectional study of school-age children from Bogotá, Colombia. Methylation of LINE-1 repetitive elements was quantified in 568 children 5-12 years of age using pyrosequencing technology. We examined the association of LINE-1 methylation with erythrocyte folate, plasma vitamin B12, vitamin A ferritin (an indicator of iron status) and serum zinc concentrations using multivariable linear regression. We also considered associations of LINE-1 methylation with socio-demographic and anthropometric characteristics. Mean (± SD) LINE-1 methylation was 80.25 (± 0.65) percentage of 5-mC (%5-mC). LINE-1 methylation was inversely related to plasma vitamin A. After adjustment for potential confounders, children with retinol levels higher than or equal to 1.05 µmol/L showed 0.19% 5-mC lower LINE-1 methylation than children with retinol levels lower than 0.70 µmol/L. LINE-1 methylation was also inversely associated with C-reactive protein, a marker of chronic inflammation, and female sex. We identified positive associations of maternal body mass index and socioeconomic status with LINE-1 methylation. These associations were not significantly different by sex. Whether modification of these exposures during school-age years leads to changes in global DNA methylation warrants further investigation.

  19. Transmission of epi-alleles with MET1-dependent dense methylation in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Michael Watson

    Full Text Available DNA methylation in plants targets cytosines in three sequence contexts, CG, CHG and CHH (H representing A, C or T. Each of these patterns has traditionally been associated with distinct DNA methylation pathways with CHH methylation being controlled by the RNA dependent DNA methylation (RdDM pathway employing small RNAs as a guide for the de novo DOMAINS REARRANGED METHYLTRANSFERASE (DRM2, and maintenance DNA METHYLTRANSFERASE1 (MET1 being responsible for faithful propagation of CG methylation. Here we report an unusual 'dense methylation' pattern under the control of MET1, with methylation in all three sequence contexts. We identified epi-alleles of dense methylation at a non coding RNA locus (At4g15242 in Arabidopsis ecotypes, with distinct dense methylation and expression characteristics, which are stably maintained and transmitted in genetic crosses and which can be heritably altered by depletion of MET1. This suggests that, in addition to its classical CG maintenance function, at certain loci MET1 plays a role in creating transcriptional diversity based on the generation of independent epi-alleles. Database inspection identified several other loci with MET1-dependent dense methylation patterns. Arabidopsis ecotypes contain distinct epi-alleles of these loci with expression patterns that inversely correlate with methylation density, predominantly within the transcribed region. In Arabidopsis, dense methylation appears to be an exception as it is only found at a small number of loci. Its presence does, however, highlight the potential for MET1 as a contributor to epigenetic diversity, and it will be interesting to investigate the representation of dense methylation in other plant species.

  20. Negative regulation of DNA methylation in plants.

    Science.gov (United States)

    Saze, Hidetoshi; Sasaki, Taku; Kakutani, Tetsuji

    2008-01-01

    Cytosine methylation of repeats and genes is important for coordination of genome stability and proper gene function. In plants, DNA methylation is regulated by DNA methyltransferases, chromatin remodeling factors and RNAi machinery. Ectopic DNA hypermethylation at genes causes transcriptional repression and silencing, and the methylation patterns often become heritable over generations. DNA methylation is antagonized by the DNA demethylation enzymes. Recently, we identified a novel jmjC-domain containing gene IBM1 (increase in bonsai methylation1) that also negatively regulates DNA methylation in Arabidopsis. The ibm1 plants show a variety of developmental phenotypes. IBM1 prevents ectopic accumulation of DNA methylation at the BNS genic region, likely through removal of heterochromatic H3K9 methylation mark. DNA and histone demethylation pathways are important for genome-wide patterning of DNA methylation and for epigenetic regulation of plant development.

  1. Evaluation of [(11)C]methyl-losartan and [(11)C]methyl-EXP3174 for PET imaging of renal AT1receptor in rats.

    Science.gov (United States)

    Ismail, Basma; Hadizad, Tayebeh; Antoun, Rawad; Lortie, Mireille; deKemp, Robert A; Beanlands, Rob S B; DaSilva, Jean N

    2015-11-01

    The angiotensin II type 1 receptor (AT1R) is responsible for the main effects of the renin-angiotensin system (RAS), and its expression pattern is altered in several diseases. The [(11)C]methylated derivatives of the clinically used AT1R blocker (ARB) losartan and its active metabolite EXP3174, that binds with higher affinity to AT1R, were evaluated as potential PET imaging tracers in rat kidneys. [(11)C]Methyl-losartan and [(11)C]methyl-EXP3174 were synthesized by [(11)C]methylation of the tetrazole-protected analogs using [11C]methyl iodide. Tissue uptake and binding selectivity of [(11)C]methyl-losartan were assessed by ex-vivo biodistribution and in-vitro autoradiography. Radiolabeled metabolites in rat plasma and kidneys were analysed by column-switch HPLC. Both tracers were evaluated with small animal PET imaging. Due to better pharmacokinetics, [(11)C]methyl-EXP3174 was further investigated via PET by co-injection with AT1R antagonist candesartan or the AT2R antagonist PD123,319. Binding selectivity to renal AT1 over AT2 and Mas receptors was demonstrated for [(11)C]methyl-losartan. Plasma metabolite analysis at 10 min revealed stability of [(11)C]methyl-losartan and [(11)C]methyl-EXP3174 with the presence of unchanged tracer at 70.8 ± 9.9% and 81.4 ± 6.0%, of total radioactivity, respectively. Contrary to [(11)C]methyl-losartan, co-injection of candesartan with [(11)C]methyl-EXP3174 reduced the proportion of unchanged tracer (but not metabolites), indicating that these metabolites do not bind to AT1R in rat kidneys. MicroPET images for both radiotracers displayed high kidney-to-background contrast. Candesartan significantly reduced [(11)C]methyl-EXP3174 uptake in the kidney, whereas no difference was observed following PD123,319 indicating binding selectivity for AT1R. [(11)C]Methyl-EXP3174 displayed a favorable binding profile compared to [(11)C]methyl-losartan for imaging renal AT1Rs supporting further studies to assess its full potential as a

  2. NetB, a Pore-Forming Toxin from Necrotic Enteritis Strains of Clostridium perfringens

    Directory of Open Access Journals (Sweden)

    Anthony L. Keyburn

    2010-07-01

    Full Text Available The Clostridium perfringens necrotic enteritis B-like toxin (NetB is a recently discovered member of the β-barrel pore-forming toxin family and is produced by a subset of avian C. perfringens type A strains. NetB is cytotoxic for avian cells and is associated with avian necrotic enteritis. This review examines the current state of knowledge of NetB: its role in pathogenesis, its distribution and expression in C. perfringens and its vaccine potential.

  3. Effects of DNA methylation inhibitors and conventional antidepressants on mice behaviour and brain DNA methylation levels.

    Science.gov (United States)

    Sales, Amanda Juliana; Joca, Sâmia Regiane Lourenço

    2016-02-01

    Stress increases DNA methylation and decreases the expression of genes involved in neural plasticity, while treatment with DNA methyltransferase inhibitors (DNMTi) increases gene expression and induces antidepressant-like effects in preclinical models. Therefore, the aim of the present work was to further investigate the potential antidepressant-like effect induced by DNMTi by evaluating the behavioural effects induced by associating DNMTi treatment with conventional antidepressant drugs in mice submitted to the forced swimming test (FST). In addition, brain levels of DNA methylation were also investigated. Mice received systemic injections of 5-aza-2'-deoxycytidine (5-AzaD, 0.1, 0.2 mg/kg), RG108 (0.1, 0.2, 0.4 mg/kg), desipramine (DES, 2.5, 5, 10 mg/kg) or fluoxetine (FLX, 5, 10, 20, 30 mg/kg) and were submitted to the FST or to the open field test (OFT). Additional groups received a combination of subeffective doses of 5-AzaD or RG108 (DNMTi) with subeffective doses of DES or FLX (antidepressants). Subeffective doses of RG108 (0.1 mg/kg) or 5-AzaD (0.1 mg/kg) in association with subeffective doses of DES (2.5 mg/kg) or FLX (10 mg/kg) induced significant antidepressant-like effects. Effective doses of RG108 (0.2 mg/kg), 5-AzaD (0.2 mg/kg), DES (10 mg/kg) and FLX (20 mg/kg) atenuated stress-induced changes in DNA methylation levels in the hippocampus and prefrontal cortex. None of the treatments induced locomotor effects in the OFT. These results suggest that DNMTi potentiate the behavioural effects of antidepressant drugs in the FST and that antidepressants, as well as DNMTi, are able to modulate stress-induced changes in DNA methylation in brain regions closely associated with the neurobiology of depression.

  4. ASP.NET web API build RESTful web applications and services on the .NET framework

    CERN Document Server

    Kanjilal, Joydip

    2013-01-01

    This book is a step-by-step, practical tutorial with a simple approach to help you build RESTful web applications and services on the .NET framework quickly and efficiently.This book is for ASP.NET web developers who want to explore REST-based services with C# 5. This book contains many real-world code examples with explanations whenever necessary. Some experience with C# and ASP.NET 4 is expected.

  5. Freeze-out conditions from net-proton and net-charge fluctuations at RHIC

    Energy Technology Data Exchange (ETDEWEB)

    Alba, Paolo; Alberico, Wanda [Department of Physics, Torino University and INFN, Sezione di Torino, via P. Giuria 1, 10125 Torino (Italy); Bellwied, Rene [Department of Physics, University of Houston, Houston, TX 77204 (United States); Bluhm, Marcus [Department of Physics, Torino University and INFN, Sezione di Torino, via P. Giuria 1, 10125 Torino (Italy); Department of Physics, North Carolina State University, Raleigh, NC 27695 (United States); Mantovani Sarti, Valentina [Department of Physics, Torino University and INFN, Sezione di Torino, via P. Giuria 1, 10125 Torino (Italy); Nahrgang, Marlene [Department of Physics, Duke University, Durham, NC 27708-0305 (United States); Frankfurt Institute for Advanced Studies (FIAS), Ruth-Moufang-Str. 1, 60438 Frankfurt am Main (Germany); Ratti, Claudia [Department of Physics, Torino University and INFN, Sezione di Torino, via P. Giuria 1, 10125 Torino (Italy)

    2014-11-10

    We calculate ratios of higher-order susceptibilities quantifying fluctuations in the number of net-protons and in the net-electric charge using the Hadron Resonance Gas (HRG) model. We take into account the effect of resonance decays, the kinematic acceptance cuts in rapidity, pseudo-rapidity and transverse momentum used in the experimental analysis, as well as a randomization of the isospin of nucleons in the hadronic phase. By comparing these results to the latest experimental data from the STAR Collaboration, we determine the freeze-out conditions from net-electric charge and net-proton distributions and discuss their consistency.

  6. Effects of pirimiphos-methyl (an organophosphate insecticide) on ...

    African Journals Online (AJOL)

    Effects of pirimiphos-methyl (an organophosphate insecticide) on the fertility of adult male rats. ... African Health Sciences ... Background: Organophosphate insecticides represent one of the most widely used classes of pesticides with high potential for human exposure in both rural and residential environments. Objective: In ...

  7. Cdc5 influences phosphorylation of Net1 and disassembly of the RENT complex.

    Science.gov (United States)

    Shou, Wenying; Azzam, Ramzi; Chen, Susan L; Huddleston, Michael J; Baskerville, Christopher; Charbonneau, Harry; Annan, Roland S; Carr, Steve A; Deshaies, Raymond J

    2002-04-17

    In S. cerevisiae, the mitotic exit network (MEN) proteins, including the Polo-like protein kinase Cdc5 and the protein phosphatase Cdc14, are required for exit from mitosis. In pre-anaphase cells, Cdc14 is sequestered to the nucleolus by Net1 as a part of the RENT complex. When cells are primed to exit mitosis, the RENT complex is disassembled and Cdc14 is released from the nucleolus. Here, we show that Cdc5 is necessary to free nucleolar Cdc14 in late mitosis, that elevated Cdc5 activity provokes ectopic release of Cdc14 in pre-anaphase cells, and that the phosphorylation state of Net1 is regulated by Cdc5 during anaphase. Furthermore, recombinant Cdc5 and Xenopus Polo-like kinase can disassemble the RENT complex in vitro by phosphorylating Net1 and thereby reducing its affinity for Cdc14. Surprisingly, although RENT complexes containing Net1 mutants (Net1(7m) and Net1(19m') lacking sites phosphorylated by Cdc5 in vitro are refractory to disassembly by Polo-like kinases in vitro, net1(7m) and net1(19m') cells grow normally and exhibit only minor defects in releasing Cdc14 during anaphase. However, net1(19m') cells exhibit a synergistic growth defect when combined with mutations in CDC5 or DBF2 (another MEN gene). We propose that although Cdc5 potentially disassembles RENT by directly phosphorylating Net1, Cdc5 mediates exit from mitosis primarily by phosphorylating other targets. Our study suggests that Cdc5/Polo is unusually promiscuous and highlights the need to validate Cdc5/Polo in vitro phosphorylation sites by direct in vivo mapping experiments.

  8. Modest net autotrophy in the oligotrophic ocean

    Science.gov (United States)

    Letscher, Robert T.; Moore, J. Keith

    2017-04-01

    The metabolic state of the oligotrophic subtropical ocean has long been debated. Net community production (NCP) represents the balance of autotrophic carbon fixation with heterotrophic respiration. Many in vitro NCP estimates based on oxygen incubation methods and the corresponding scaling relationships used to predict the ecosystem metabolic balance have suggested the ocean gyres to be net heterotrophic; however, all in situ NCP methods find net autotrophy. Reconciling net heterotrophy requires significant allochthonous inputs of organic carbon to the oligotrophic gyres to sustain a preponderance of respiration over in situ production. Here we use the first global ecosystem-ocean circulation model that contains representation of the three allochthonous carbon sources to the open ocean, to show that the five oligotrophic gyres exhibit modest net autotrophy throughout the seasonal cycle. Annually integrated rates of NCP vary in the range 1.5-2.2 mol O2 m-2 yr-1 across the five gyre systems; however, seasonal NCP rates are as low as 1 ± 0.5 mmol O2 m-2 d-1 for the North Atlantic. Volumetric NCP rates are heterotrophic below the 10% light level; however, they become net autotrophic when integrated over the euphotic zone. Observational uncertainties when measuring these modest autotrophic NCP rates as well as the metabolic diversity encountered across space and time complicate the scaling up of in vitro measurements to the ecosystem scale and may partially explain the previous reports of net heterotrophy. The oligotrophic ocean is autotrophic at present; however, it could shift toward seasonal heterotrophy in the future as rising temperatures stimulate respiration.

  9. GPX3 promoter methylation predicts platinum sensitivity in colorectal cancer.

    Science.gov (United States)

    Pelosof, Lorraine; Yerram, Sashidhar; Armstrong, Todd; Chu, Nina; Danilova, Ludmila; Yanagisawa, Breann; Hidalgo, Manuel; Azad, Nilofer; Herman, James G

    2017-07-03

    Epigenetic control of gene expression is a major determinant of tumor phenotype and has been found to influence sensitivity to individual chemotherapeutic agents. Glutathione peroxidase 3 (GPX3, plasma glutathione peroxidase) is a key component of cellular antioxidant regulation and its gene has been reported to be methylated in specific tumor types. GPX3 role in oxidative damage has been associated with sensitivity to platinums in other tumors but its importance in colorectal cancer (CRC) has not been determined. We examined the role of GPX3 methylation in colorectal carcinoma in determining sensitivity to platinum drugs using primary tumor specimens, cell lines, knockdown cell lines, and tumor cell line xenografts. We find GPX3 promoter region methylation in approximately one third of CRC samples and GPX3 methylation leads to reduced GPX3 expression and increased oxaliplatin and cisplatin sensitivity. In contrast, in cell lines with high baseline levels of GPX3 expression or with the ability to increase GPX3 expression, platinum resistance is increased. The cisplatin IC50 in GPX3-methylated cell lines is approximately 6-fold lower than that in GPX3-unmethylated lines. Additionally, knockdown cell lines with essentially no GPX3 expression require N-acetylcysteine to survive in culture underscoring the importance of GPX3 in redox biology. In vivo, GPX3 methylation predicts tumor xenograft sensitivity to platinum with regression of GPX3 knockdown xenografts with platinum treatment but continued growth of GPX3 wild type xenografts in the presence of platinum. These studies demonstrate the importance of GPX3 for CRC cells resistance to platinums and the potential utility of GPX3 methylation status as a predictive biomarker for platinum sensitivity in CRC.

  10. Investigation of correlations between DNA methylation, suicidal behavior and aging.

    Science.gov (United States)

    Jeremian, Richie; Chen, Yi-An; De Luca, Vincenzo; Vincent, John B; Kennedy, James L; Zai, Clement C; Strauss, John

    2017-02-01

    Suicidal behavior (SB) is a major cause of mortality for patients diagnosed with bipolar disorder (BD). In this study, we investigated epigenetic differences in BD participants with and without a history of SB. We used suicidality scores constructed from Schedule for Clinical Assessments in Neuropsychiatry (SCAN) interview questions about suicidal thought and behavior to identify individuals from a BD cohort of n=452; participants with the most extreme high (H-SB, n=18) and most extreme low (L-SB, n=22) scores were used as cases and controls, respectively. Epigenome-wide DNA methylation patterns were compared between the two groups using the Illumina Infinium Human Methylation 450 BeadChip microarray. DNA methylation age was compared to chronological tissue age. We observed highly significant differences in methylation between cases and controls in three genomic regions enriched for epigenetic modifications corresponding to gene regulatory regions. BD participants with a history of SB showed less overall methylation in the 5' untranslated region of Membrane palmitoylated protein 4 (MPP4) (P=7.42×10(-7) ) and in intron 3 of TRE2/BUB2/CDC16 domain family member 16 (TBC1D16) (P=6.47×10(-7) ), while exon 1 of Nucleoporin 133 (NUP133) was less methylated in controls (P=1.17x10(-6) ). Moreover, we observed a greater correlation between DNA methylation age and tissue age in controls (r=.91, Psuicide attempters. Despite the small sample size, our proof-of-concept study highlights the potential for epigenetic factors to be useful in understanding the molecular underpinnings of suicide with the ultimate aim of its prevention. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Abundance of genes involved in mercury methylation in oceanic environments

    Science.gov (United States)

    Palumbo, A. V.; Podar, M.; Gilmour, C. C.; Brandt, C. C.; Brown, S. D.; Crable, B. R.; Weighill, D.; Jacobson, D. A.; Somenahally, A. C.; Elias, D. A.

    2016-02-01

    The distribution and diversity of genes involved in mercury methylation in oceanic environments is of interest in determining the source of mercury in ocean environments and may have predictive value for mercury methylation rates. The highly conserved hgcAB genes involved in mercury methylation provide an avenue for evaluating the genetic potential for mercury methylation. The genes are sporadically present in a few diverse groups of bacteria and Archaea including Deltaproteobacteria, Firmicutes and Archaea and of over 7000 sequenced species they are only present in about 100 genomes. Examination of sequence data from methylators and non-methylators indicates that these genes are associated with other genes involved in metal transformations and transport. We examined hgcAB presence in over 3500 microbial metagenomes (from all environments) and found the hgcAB genes were present in anaerobic oceanic environments but not in aerobic layers of the open ocean. The genes were common in sediments from marine, coastal and estuarine sources as well as polluted environments. The genes were rare, found in 7 of 138 samples, in metagenomes from the pelagic water column including profiles though the oxygen minimum zone. Other oxic and sub-oxic coastal waters also demonstrated a lack of hgcAB genes including the OMZ in the Eastern North Pacific Ocean. There were some unique hgcA like unique sequences found in metagenomes from depth in the Pacific and Southern Atlantic Ocean. Coastal "dead zone" waters may be important sources of MeHg as the hgcAB genes were abundant in the anoxic waters of a stratified fjord. The genes were absent in microbiomes from vertebrates but were in invertebrate microbiomes However, oceanic species were underrepresented in these samples. Climate change could provide an additional flux of MeHg to the oceans as we found the most abundant representation of hgcAB genes in arctic permafrost. Thus warming could increase flux of methyl mercury to arctic waters.

  12. Ancestry dependent DNA methylation and influence of maternal nutrition.

    Directory of Open Access Journals (Sweden)

    Khyobeni Mozhui

    Full Text Available There is extensive variation in DNA methylation between individuals and ethnic groups. These differences arise from a combination of genetic and non-genetic influences and potential modifiers include nutritional cues, early life experience, and social and physical environments. Here we compare genome-wide DNA methylation in neonatal cord blood from African American (AA; N = 112 and European American (EA; N = 91 participants of the CANDLE Study (Conditions Affecting Neurocognitive Development and Learning in Early Childhood. Our goal is to determine if there are replicable ancestry-specific methylation patterns that may implicate risk factors for diseases that have differential prevalence between populations. To identify the most robust ancestry-specific CpG sites, we replicate our results in lymphoblastoid cell lines from Yoruba African and CEPH European panels of HapMap. We also evaluate the influence of maternal nutrition--specifically, plasma levels of vitamin D and folate during pregnancy--on methylation in newborns. We define stable ancestry-dependent methylation of genes that include tumor suppressors and cell cycle regulators (e.g., APC, BRCA1, MCC. Overall, there is lower global methylation in African ancestral groups. Plasma levels of 25-hydroxy vitamin D are also considerably lower among AA mothers and about 60% of AA and 40% of EA mothers have concentrations below 20 ng/ml. Using a weighted correlation analysis, we define a network of CpG sites that is jointly modulated by ancestry and maternal vitamin D. Our results show that differences in DNA methylation patterns are remarkably stable and maternal micronutrients can exert an influence on the child epigenome.

  13. Vibrational normal modes calculation in the crystalline state of methylated monosaccharides: Anomers of the methyl-D-glucopyranoside and methyl-D-xylopyranoside molecules.

    Science.gov (United States)

    Taleb-Mokhtari, Ilham Naoual; Lazreg, Abbassia; Sekkal-Rahal, Majda; Bestaoui, Noreya

    2016-01-15

    A structural investigation of the organic molecules is being carried out using vibrational spectroscopy. In this study, normal co-ordinate calculations of anomers of the methyl-D-glucopyranoside and methyl-β-D-xylopyranoside in the crystalline state have been performed using the modified Urey-Bradley-Shimanouchi force field (mUBSFF) combined with an intermolecular potential energy function. The latter includes Van der Waals interactions, electrostatic terms, and explicit hydrogen bond functions. The vibrational spectra of the compounds recorded in the crystalline state, in the 4000-500 cm(-1) spectral region for the IR spectra, and in the 4000-20 cm(-1) spectral range for the Raman spectra are presented. After their careful examination, several differences in the intensities and frequency shifts have been observed. The theoretical spectra have been obtained after a tedious refinement of the force constants. Thus, on the basis of the obtained potential distribution, each observed band in IR and in Raman has been assigned to a vibrational mode. The obtained results are indeed in agreement with those observed experimentally and thus confirm the previous assignments made for the methyl-α and β-D-glucopyranoside, as well as for the methyl-β-D-xylopyranoside. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Challenges for the application of DNA methylation biomarkers in molecular diagnostic testing for cancer.

    Science.gov (United States)

    Jain, Surbhi; Wojdacz, Tomasz K; Su, Ying-Hsiu

    2013-04-01

    Aberrant DNA methylation is ubiquitous in human cancer and has been shown to occur early during carcinogenesis, thus providing attractive potential biomarkers for the early detection of cancer. The introduction of genome-wide DNA methylation analysis comparing tumor and nonmalignant tissues resulted in the discovery of many regions that undergo aberrant methylation during carcinogenesis. Those regions can potentially be used as biomarkers for cancer detection. However, a biomarker will be useful for screening or early detection of cancer only if it can be detected in a noninvasive or minimally invasive fashion without tissue biopsy. The authors discuss the challenges in translating DNA methylation biomarkers to cancer diagnosis - including obstacles in assay development, tissue-specific methylation load on tumor suppressor genes, detecting markers with sufficient sensitivity and specificity in the periphery, and ways in which these obstacles can be overcome.

  15. SOCIAL NET: A CASE STUDY OF THE UNIVERSITY NET OF POPULAR COOPERATIVES TECHNOLOGICAL INCUBATORS (PCTIS NET FROM THE INTERACTION AMONG THE INCUBATORS

    Directory of Open Access Journals (Sweden)

    Marília Matos Pereira Lopes

    2014-07-01

    Full Text Available The objective of this assignment was to identify if the University Net of Popular Cooperatives Technological Incubators (PCTIs Net is a social net. The research was an exploratory nature study with descriptive character, the technical procedure of the present research was the case study. The questionnaire was applied in 82% of the incubators belonging to the PCTIs Net, and interviews. The information acquired through the questionnaire was gathered and tabulated to compose the characterization of the net incubators and the social analyzer. With the Pajek program was created the social analyzer and the centralizing box. Was performed to compare the results with previous work Rennó et al. (2010 proposed that the same goal using a different approach. Ending the analysis guided by the characteristics of a social net, it was observed that the PCTIs Net is a social net, however it was emphasized that the existing communication is a point where the net needs to be fortified.

  16. Activation of PAD4 in NET formation

    Directory of Open Access Journals (Sweden)

    Amanda eRohrbach

    2012-11-01

    Full Text Available Peptidyl arginine deiminases, or PADs, convert arginine residues to the non-ribosomally encoded amino acid citrulline in a variety of protein substrates. PAD4 is expressed in granulocytes and is essential for the formation of neutrophil extracellular traps (NETs via PAD4-mediated histone citrullination. Citrullination of histones is thought to promote NET formation by inducing chromatin decondensation and facilitating the expulsion of chromosomal DNA that is coated with antimicrobial molecules. Numerous stimuli have been reported to lead to PAD4 activation and NET formation. However, how this signaling process proceeds and how PAD4 becomes activated in cells is largely unknown. Herein, we describe the various stimuli and signaling pathways that have been implicated in PAD4 activation and NET formation, including the role of reactive oxygen species generation. To provide a foundation for the above discussion, we first describe PAD4 structure and function, and how these studies led to the development of PAD-specific inhibitors. A comprehensive survey of the receptors and signaling pathways that regulate PAD4 activation will be important for our understanding of innate immunity, and the identification of signaling intermediates in PAD4 activation may also lead to the generation of pharmaceuticals to target NET-related pathogenesis.

  17. The net charge at interfaces between insulators

    Science.gov (United States)

    Bristowe, N. C.; Littlewood, P. B.; Artacho, Emilio

    2011-03-01

    The issue of the net charge at insulating oxide interfaces is briefly reviewed with the ambition of dispelling myths of such charges being affected by covalency and related charge density effects. For electrostatic analysis purposes, the net charge at such interfaces is defined by the counting of discrete electrons and core ion charges, and by the definition of the reference polarization of the separate, unperturbed bulk materials. The arguments are illustrated for the case of a thin film of LaAlO3 over SrTiO3 in the absence of free carriers, for which the net charge is exactly 0.5e per interface formula unit, if the polarization response in both materials is referred to zero bulk values. Further consequences of the argument are extracted for structural and chemical alterations of such interfaces, in which internal rearrangements are distinguished from extrinsic alterations (changes of stoichiometry, redox processes), only the latter affecting the interfacial net charge. The arguments are reviewed alongside the proposal of Stengel and Vanderbilt (2009 Phys. Rev. B 80 241103) of using formal polarization values instead of net interfacial charges, based on the interface theorem of Vanderbilt and King-Smith (1993 Phys. Rev. B 48 4442-55). Implications for non-centrosymmetric materials are discussed, as well as for interfaces for which the charge mismatch is an integer number of polarization quanta.

  18. Development of net cage acoustic alarm system

    Science.gov (United States)

    Hong, Shih-Wei; Wei, Ruey-Chang

    2004-05-01

    In recent years, the fishery production has been drastically decreased in Taiwan, mainly due to overfishing and coast pollution; therefore, fishermen and corporations are encouraged by government to invest in ocean net cage aquaculture. However, the high-price fishes in the net cage are often coveted, so incidences of fish stealing and net cage breaking were found occasionally, which cause great economical loss. Security guards or a visual monitoring system has limited effect, especially in the night when these intrusions occur. This study is based on acoustic measure to build a net cage alarm system, which includes the sonobuoy and monitor station on land. The sonobuoy is a passive sonar that collects the sounds near the net cage and transmits the suspected signal to the monitor station. The signals are analyzed by the control program on the personal computer in the monitor station, and the alarms at different stages could be activated by the sound levels and durations of the analyzed data. To insure long hours of surveillance, a solar panel is applied to charge the battery, and a photodetector is used to activate the system.

  19. The NeuroDevNet vision.

    Science.gov (United States)

    Goldowitz, Dan; McArthur, Dawn

    2011-03-01

    The NeuroDevNet Network of Centres of Excellence has created the first trans-Canada effort devoted to the study of brain development from basic to clinical to societal perspectives. NeuroDevNet's vision is to accelerate efforts to (i) understand normal brain development; (ii) enhance our ability to make diagnoses of when normal development goes awry; and (iii) develop interventions to improve or prevent neurodevelopmental disorders. An early diagnosis coupled with the right therapies, The NeuroDevNet Network of Centres of Excellence has created the first trans-Canada effort devoted to the study of brain development from basic to clinical to societal perspectives. NeuroDevNet's vision is to accelerate efforts to (i) understand normal brain development; (ii) enhance our ability to make diagnoses of when normal development goes awry; and (iii) develop interventions to improve or prevent neurodevelopmental disorders. An early diagnosis coupled with the right therapies, Demonstration Projects. Funds were also allocated for an Opportunities Initiative. There is a wide of expertise amongst NeuroDevNet members. Researchers are supported by the management centre, three Platforms (Imaging; Genetics/ Epigenetics; Animal Models) and three Cores (Neuroethics; Neuroinformatics; Knowledge Translation). We emphasize multidisciplinary training of young researchers to advance the understanding of brain disorders that affect children. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. The net charge at interfaces between insulators

    Energy Technology Data Exchange (ETDEWEB)

    Bristowe, N C; Littlewood, P B [Theory of Condensed Matter Group, Cavendish Laboratory, University of Cambridge, J J Thomson Avenue, Cambridge CB3 0HE (United Kingdom); Artacho, Emilio, E-mail: ncb30@cam.ac.uk [Department of Earth Sciences, University of Cambridge, Downing Street, Cambridge CB2 3EQ (United Kingdom)

    2011-03-02

    The issue of the net charge at insulating oxide interfaces is briefly reviewed with the ambition of dispelling myths of such charges being affected by covalency and related charge density effects. For electrostatic analysis purposes, the net charge at such interfaces is defined by the counting of discrete electrons and core ion charges, and by the definition of the reference polarization of the separate, unperturbed bulk materials. The arguments are illustrated for the case of a thin film of LaAlO{sub 3} over SrTiO{sub 3} in the absence of free carriers, for which the net charge is exactly 0.5e per interface formula unit, if the polarization response in both materials is referred to zero bulk values. Further consequences of the argument are extracted for structural and chemical alterations of such interfaces, in which internal rearrangements are distinguished from extrinsic alterations (changes of stoichiometry, redox processes), only the latter affecting the interfacial net charge. The arguments are reviewed alongside the proposal of Stengel and Vanderbilt (2009 Phys. Rev. B 80 241103) of using formal polarization values instead of net interfacial charges, based on the interface theorem of Vanderbilt and King-Smith (1993 Phys. Rev. B 48 4442-55). Implications for non-centrosymmetric materials are discussed, as well as for interfaces for which the charge mismatch is an integer number of polarization quanta. (viewpoint)