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  • 1
    Electronic Resource
    Electronic Resource
    The biology of the P-glycoproteins (1995)
    Springer
    The journal of membrane biology 143 (1995), S. 89-102 
    Details
    ISSN: 1432-1424
    Keywords: Drug resistance ; ATPases ; Chemotherapy ; Cancer ; Membrane Transport ; Xenobiotics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Conclusions The initial discovery of p-glycoprotein in the plasma membrane of MDR cancer cell lines was followed quickly by the cloning of its gene. Sequence analysis of cloned cDNAs revealed that p-glycoprotein was a member of the ABC family of membrane transporters. Subsequent biochemical characterization demonstrated the binding of chemotherapeutic drugs and ATP to p-glycoprotein. P-glycoprotein-mediated drag transport and drug-stimulated ATPase activity were documented in plasma membrane vesicles and in proteoliposomes containing the partially purified protein. P-glycoprotein was shown to be phosphorylated and the effect of this modification on the protein's biological function was explored. P-glycoproteins were found in many normal tissues and their overexpression was documented in numerous cancers. An important role for p-glycoprotein in intrinsic and acquired drug resistance in clinical oncology was established. Despite all that has been learned about p-glycoprotein over the last few years, additional studies will be necessary to address the many questions that have been left unanswered. Determination of p-glycoprotein structure and membrane topology should help elucidate the nature of chemotherapeutic drug binding sites and the mechanism whereby drug movement is coupled to ATP hydrolysis. Complete purification and functional reconstitution of p-glycoprotein into defined lipid vesicles will permit further characterization of drug transport and ATPase activity and give us the means by which p-glycoprotein's apparent dual function as a transporter and a channel can be clarified. Structural and functional studies on p-glycoprotein will also provide information needed to develop specified inhibitors that can be used clinically to overcome MDR in cancer patients. Further study of the mechanisms whereby p-glycoprotein expression is induced and regulated during malignant transformation is indicated. The development of biliary phospholipid deficiency in mdr2 knockout mice and xenobiotic hypersensitivity in mdr3 knockout mice have given us the first clues into the normal physiologic roles for the p-glycoproteins. The search for endogenous substrates for the p-glycoproteins will continue to be an area of active investigation. Continued investigation of p-glycoprotein's functions should result in better understanding of an important class of prokaryotic and eukaryotic membrane transporters. The potential of exploiting the knowledge garnered from these studies in the treatment of neoplastic, parasitic and inherited and acquired liver disease may be greater than we can now imagine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00234655
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Tunable diode laser measurements of peroxynitric acid absorption coefficients near 12.5 .mu.m (1988)
    s.l. : American Chemical Society
    The @journal of physical chemistry 〈Washington, DC〉 92 (1988), S. 4667-4669 
    Details
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/j100327a022
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  • 3
    Electronic Resource
    Electronic Resource
    Laser optogalvanic effect in a pure iodine discharge (1981)
    s.l. : American Chemical Society
    The @journal of physical chemistry 〈Washington, DC〉 85 (1981), S. 1105-1107 
    Details
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/j150609a008
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  • 4
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    Chemical depletion of Arctic ozone in winter 1999/2000 (2002)
    In:  EPIC3Journal of Geophysical ResearchD20), 107, 8276 p.
    Details
    Publication Date: 2019-07-16
    Description: Large losses of Arctic ozone occur during winters with cold, stable stratospheric circulations that result in the extensive occurrence of polar stratospheric clouds (PSCs). Reactions on the surface of PSCs lead to elevated abundances of chlorine monoxide (ClO) that, in the presence of sunlight, destroys ozone. Here we show that PSCs were more widespread during the 1999/2000 Arctic winter than for any other winter in the past two decades. We have used three fundamentally different approaches to derive the degree of chemical ozone loss from ozone sonde, balloon, aircraft and satelite instruments. We show that the ozone losses derived from these different instruments and approaches agree very well, resulting in a high level of confidence in the results. Chemical processes led to a 70% reduction of ozone for a ~1 km thick region of the lower stratosphere, the largest degree of local loss ever reported for the Arctic. The chemical loss of ozone in the total column amounted to about 100 DU by the end of the winter. This total column loss was balanced by transport, resulting in relatively constant total ozone between early January and late March, which is in contrast to the climatological increase of the total ozone column during this period, that is observed during most years.
    Repository Name: EPIC Alfred Wegener Institut
    Type: Article , isiRev
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  • 5
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    Modeling the effect of denitrification on Arctic ozone depletion during winter 1999/2000 (2002)
    In:  EPIC3Journal of Geophysical Research, 108(D5), 8322, 65, pp. 1 - 15
    Details
    Publication Date: 2019-07-17
    Description: We have used the SLIMCAT three-dimensional chemical transport model together with observations from the Stratospheric Aerosol and Gas Experiment (SAGE III) Ozone Loss and Validation Experiment (SOLVE) and the Third European Stratospheric Experiment on Ozone (THESEO 2000) to quantify the effect of denitrification on Arctic ozone loss. We have used two different denitrification schemes in the model: one based on the sedimentation of ice particles containing cocondensed nitric acid trihydrate (NAT) and the other based on large NAT particles. The model was forced using both UK Meteorological Office (UKMO) and European Centre for Medium-Range Weather Forecasts (ECMWF) analyses. In the Arctic lower stratosphere the UKMO analyzed temperatures are similar to the ECMWF, except at temperatures near the ice point where the UKMO analyses are colder by over 2 K. Consequently, the UKMO analyses predicted large regions of ice clouds, in contrast to the ECMWF. The denitrification scheme based on large NAT particles gives the best agreement with ER-2 NOy observations for both sets of meteorological analyses. Although the ice scheme and UKMO analyses also produce denitrification, the vertical extent of denitrification and renitrification does not agree as well with the observed NOy. Uncertainties in the budget of ClOy observations from the ER-2 prevent an indirect validation of the best model denitrification scheme based on these data. The denitrified model runs give the best agreement with the observed HCl and ClONO2 reservoirs in mid March. However, UKMO-forced runs generally overestimate the observed ClOx during the same period. The denitrified model runs indicate that by late March 56-74% O3 loss had occurred at 460 K and that denitrification contributed 21-30% of this loss. The model runs showing the largest O3 depletion (forced by UKMO analyses) agree well with ER-2 and ozone sonde data, although these runs overestimated ClOx.
    Repository Name: EPIC Alfred Wegener Institut
    Type: Article , isiRev
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  • 6
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    Subsidence, mixing and denitrification of Arctic polar vortex air measured during POLARIS (1999)
    In:  EPIC3Journal of Geophysical Research, 104, pp. 26611-26623
    Details
    Publication Date: 2019-07-16
    Description: We determine the degree of denitrification that occurred during the 1996-1997 Arctic winter using a technique that is based on balloon and aircraft borne measurements of NOy, N2O, and CH4. The NOy/N2O relation can undergo significant change due to isentropic mixing of subsided vortex air masses with extravortex air due to the high nonlinearity of the relation. These transport related reductions in NOy can be difficult to distinguish from the effects of denitrification caused by sedimentation of condensed HNO3. In this study, high-altitude balloon measurements are used to define the properties of air masses that later descend in the polar vortex to altitudes sampled by the ER-2 aircraft (i.e., ~20 km) and mix isentropically with extravortex air. Observed correlations of CH4 and N2O are used to quantify the degree of subsidence and mixing for individual air masses. On the basis of these results the expected mixing ratio of NOy resulting from subsidence and mixing, defined here as NOy**, is calculated and compared with the measured mixing ratio of NOy. Values of NOy and NOy** agree well during most parts of the flights. A slight deficit of NOy versus NOy** is found only for a limited region during the ER-2 flight on April 26, 1997. This deficit is interpreted as indication for weak denitrification (~2-3 ppbv) in that air mass. The small degree of denitrification is consistent with the general synoptic-scale temperature history of the sampled air masses, which did not encounter temperatures below the frostpoint and had relatively brief encounters with temperatures below the nitric acid trihydrate equilibrium temperature. Much larger degrees of denitrification would have been inferred if mixing effects had been ignored, which is the traditional approach to diagnose denitrification. Our analysis emphasizes the importance of using other correlations of conserved species to be able to accurately interpret changes in the NOy/N2O relation with respect to denitrification.
    Repository Name: EPIC Alfred Wegener Institut
    Type: Article , isiRev
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  • 7
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    Three-dimensional model study of the Arctic ozone loss in 2002/2003 and comparison with 1999/2000 and 2003/2004 (2005)
    In:  EPIC3Atmospheric chemistry and physics, 5, pp. 139-152
    Details
    Publication Date: 2019-07-17
    Description: We have used the SLIMCAT 3-D off-line chemical transport model (CTM) to quantify the Arctic chemical ozone loss in the year 2002/2003 and compare it with similar calculations for the winters 1999/2000 and 2003/2004. Recent changes to the CTM have improved the model's ability to reproduce polar chemical and dynamical processes. The updated CTM uses σ-θ as a vertical coordinate which allows it to extend down to the surface. The CTM has a detailed stratospheric chemistry scheme and now includes a simple NAT-based denitrification scheme in the stratosphere.In the model runs presented here the model was forced by ECMWF ERA40 and operational analyses. The model used 24 levels extending from the surface to ~55km and a horizontal resolution of either 7.5° x 7.5° or 2.8° x 2.8°. Two different radiation schemes, MIDRAD and the CCM scheme, were used to diagnose the vertical motion in the stratosphere. Based on tracer observations from balloons and aircraft, the more sophisticated CCM scheme gives a better representation of the vertical transport in this model which includes the troposphere. The higher resolution model generally produces larger chemical O3 depletion, which agrees better with observations.The CTM results show that very early chemical ozone loss occurred in December 2002 due to extremely low temperatures and early chlorine activation in the lower stratosphere. Thus, chemical loss in this winter started earlier than in the other two winters studied here. In 2002/2003 the local polar ozone loss in the lower stratosphere was ~40% before the stratospheric final warming. Larger ozone loss occurred in the cold year 1999/2000 which had a persistently cold and stable vortex during most of the winter. For this winter the current model, at a resolution of 2.8° x 2.8°, can reproduce the observed loss of over 70% locally. In the warm and more disturbed winter 2003/2004 the chemical O3 loss was generally much smaller, except above 620K where large losses occurred due to a period of very low minimum temperatures at these altitudes.
    Repository Name: EPIC Alfred Wegener Institut
    Type: Article , isiRev
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  • 8
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    Role of NO y as a diagnostic of small‐scale mixing in a denitrified polar vortex (2002)
    American Geophysical Union
    Details
    Publication Date: 2002-12-27
    Print ISSN: 0148-0227
    Electronic ISSN: 2156-2202
    Topics: Geosciences
    Published by American Geophysical Union
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  • 9
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    Maintaining mid-tolerant tree species with uneven-aged forest management: 9-year results from a novel group-selection experiment (2013)
    Oxford University Press
    In: Forestry
    Details
    Publication Date: 2013-10-12
    Description: In forest ecosystems, disturbance intensity affects the ability of species with varying shade tolerances to successfully recruit into the overstory. Small openings (e.g. single treefall) perpetuate shade-tolerant species while larger openings (e.g. those created under group selection and other higher severity disturbances) enhance the abundance of shade-mid-tolerant and -intolerant species. Forty-nine modified group-selection openings in three size classes established during the winter of 2003/04 and 20 single-tree selection sites were re-evaluated in 2012 in order to determine: (1) how the densities of seedlings and saplings changed over time, (2) whether species composition differed between treatments and (3) whether the group-selection openings enhanced recruitment of underrepresented species, especially the mid-tolerant yellow birch ( Betula alleghaniensis ). Sugar and red maple ( Acer saccharum and Acer rubrum ) regeneration dominated at all sites and occurred in greater densities in the group-selection openings as compared with the single-tree selection sites. While yellow birch densities increased with opening size, survival and growth were likely inhibited by the drought conditions that have occurred since 2004. Ironwood ( Ostrya virginiana) and black cherry ( Prunus serotina ) also benefited from opening creation. Consequently, while openings enhanced the representation of mid-tolerant species, they did not greatly alter the developmental trajectory of this forest type.
    Print ISSN: 0015-752X
    Electronic ISSN: 1464-3626
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Published by Oxford University Press
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  • 10
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    Background levels of methane in Mars atmosphere show strong seasonal variations (2018)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2018-06-08
    Description: Variable levels of methane in the martian atmosphere have eluded explanation partly because the measurements are not repeatable in time or location. We report in situ measurements at Gale crater made over a 5-year period by the Tunable Laser Spectrometer on the Curiosity rover. The background levels of methane have a mean value 0.41 ± 0.16 parts per billion by volume (ppbv) (95% confidence interval) and exhibit a strong, repeatable seasonal variation (0.24 to 0.65 ppbv). This variation is greater than that predicted from either ultraviolet degradation of impact-delivered organics on the surface or from the annual surface pressure cycle. The large seasonal variation in the background and occurrences of higher temporary spikes (~7 ppbv) are consistent with small localized sources of methane released from martian surface or subsurface reservoirs.
    Keywords: Geochemistry, Geophysics, Planetary Science
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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