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  • 1
    Publication Date: 2019-07-17
    Repository Name: EPIC Alfred Wegener Institut
    Type: Article , isiRev
    Format: application/pdf
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  • 2
    Publication Date: 2019-07-16
    Repository Name: EPIC Alfred Wegener Institut
    Type: Conference , notRev
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  • 3
    Publication Date: 2021-10-26
    Description: Rapid change in the planetary climate regime at the turn of the XX and XXI centuries has been revealed based on the analysis of the observations' data. With respect to the previous climatic regime, evaporation and a latent heat flux have increased from most of the surface of the World Ocean. Recent climatic regime in the XXI century is characterized by a significant increase in the number of strong cyclones, storms, sum of precipitation in wet areas with maritime climate. The number of hazardous extreme weather events is mostly increased in the ocean – continent marginal zone, including the Far East of Russia. The increase in precipitation in 2004 and extreme precipitation in 2015–2016 within the catchment of Lake Khanka in the South of the Russian Far East led to a catastrophic spill of this lake. During the first 17 years of the XXI century the number of extreme precipitation and floods in the warm season has increased in most of the marginal zones of Eurasia and North America. Winter snowfall is also amplified in the zone of temperate latitudes over many continental regions. The observed increase in precipitation is caused due to growth in both the water vapour content in the atmosphere over the ocean and the meridional transfer of heat and water vapour. Decrease in rainfall occurs in some continental areas, including the catchment area of Lake Baikal and the reservoirs of the Angara cascade of hydropower plants.
    Description: На основе анализа результатов наблюдений выявлено быстрое изменение планетарного климатического режима на рубеже XX–XXI вв. По отношению к предшествующему климатическому режиму увеличились испарение и скрытый поток тепла с большей части поверхности Мирового океана. Современный климатический режим в XXI в. характеризуется значительным увеличением количества сильных циклонов, штормов, сумм осадков в районах с морским влажным климатом. Число опасных экстремальных явлений погоды значительно возрастает в пограничной зоне океан – континент, в том числе на Дальнем Востоке России. Увеличение осадков с 2004 г. и экстремальных осадков в 2015–2016 гг. в бассейне водосбора озера Ханка на юге Дальнего Востока привело к катастрофическому разливу этого озера. В течение первых 17 лет XXI в. количество экстремальных осадков и наводнений в теплое время года возросло в большей части окраинной зоны Евразии и Северной Америки. Зимние осадки в виде снега также усиливаются в зоне умеренных широт над многими континентальными районами. Отмеченный рост осадков обусловлен увеличением как содержания водяного пара в атмосфере над океаном, так и меридионального переноса тепла и водяного пара. Уменьшение количества осадков происходит в некоторых континентальных районах, в том числе в бассейнах водосбора озера Байкал и водохранилищ Ангарского каскада гидроэлектростанций.
    Description: Published
    Description: Refereed
    Keywords: Осадки ; Климатические изменения ; Водяной пар ; Water vapour ; ASFA_2015::C::Climatic changes ; ASFA_2015::O::Oceanology ; ASFA_2015::P::Precipitation (atmospheric)
    Repository Name: AquaDocs
    Type: Journal Contribution
    Format: pp.160-169
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  • 4
    Publication Date: 2018-01-03
    Description: Vol. 215, No. 1, January 2018. https://doi.org/10.1084/jem.20171052 JEM regrets that in the original version of this paper, the labels appeared incorrectly in Fig. 7 A and Fig. S5 G as the result of a production error. All...
    Print ISSN: 0022-1007
    Electronic ISSN: 1540-9538
    Topics: Medicine
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  • 5
    Publication Date: 2018-01-03
    Description: Prostate-specific membrane antigen (PSMA) or folate hydrolase 1 (FOLH1) is highly expressed on prostate cancer. Its expression correlates inversely with survival and increases with tumor grade. However, the biological role of PSMA has not been explored, and its role in prostate cancer remained elusive. Filling this gap, we demonstrate that in prostate cancer, PSMA initiates signaling upstream of PI3K through G protein–coupled receptors, specifically via the metabotropic glutamate receptor (mGluR). PSMA’s carboxypeptidase activity releases glutamate from vitamin B9 and other glutamated substrates, which activate mGluR I. Activated mGluR I subsequently induces activation of phosphoinositide 3-kinase (PI3K) through phosphorylation of p110β independent of PTEN loss. The p110β isoform of PI3K plays a particularly important role in the pathogenesis of prostate cancer, but the origin of its activation was so far unknown. PSMA expression correlated with PI3K–Akt signaling in cells, animal models, and patients. We interrogated the activity of the PSMA–PI3K axis through positron emission tomography and magnetic resonance imaging. Inhibition of PSMA in preclinical models inhibited PI3K signaling and promoted tumor regression. Our data present a novel oncogenic signaling role of PSMA that can be exploited for therapy and interrogated with imaging.
    Keywords: Solid Tumors
    Print ISSN: 0022-1007
    Electronic ISSN: 1540-9538
    Topics: Medicine
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  • 6
    Publication Date: 2018-12-04
    Description: There remains an urgent need for the noninvasive tracking of transfused chimeric antigen receptor (CAR) T cells to determine their biodistribution, viability, expansion, and antitumor functionality. DOTA antibody reporter 1 (DAbR1) comprises a single-chain fragment of the antilanthanoid-DOTA antibody 2D12.5/G54C fused to the human CD4-transmembrane domain and binds irreversibly to lanthanoid ( S )-2-(4-acrylamidobenzyl)-DOTA (AABD). The aim of this study was to investigate whether DAbR1 can be expressed on lymphocytes and used as a reporter gene as well as a suicide gene for therapy of immune-related adverse effects. Methods: DAbR1 was subcloned together with green fluorescent protein into an SFG-retroviral vector and used to transduce CD3/CD28-activated primary human T cells and second-generation 1928z (CAR) T cells. Cell surface expression of DAbR1 was confirmed by cell uptake studies with radiolabeled AABD. In addition, the feasibility of imaging of DAbR1-positive T cells in vivo after intravenous injection of 86 Y/ 177 Lu-AABD was studied and radiation doses determined. Results: A panel of DAbR1-expressing T cells and CAR T cells exhibited greater than 8-fold increased uptake of 86 Y-AABD in vitro when compared with nontransduced cells. Imaging studies showed 86 Y-AABD was retained by DAbR1-positive T cells while it continuously cleared from normal tissues, allowing for in vivo tracking of intravenously administered CAR T cells. Normal-organ dose estimates were favorable for repeated PET/CT studies. Selective T cell ablation in vivo with 177 Lu-AABD seems feasible for clustered T-cell populations. Conclusion: We have demonstrated for the first time that T cells can be modified with DAbR1, enabling their in vivo tracking via PET and SPECT. The favorable biodistribution and high image contrast observed warrant further studies of this new reporter gene.
    Print ISSN: 0022-3123
    Topics: Medicine
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  • 7
    Publication Date: 2015-07-02
    Description: Monitoring genetically altered T cells is an important component of adoptive T cell therapy in patients, and the ability to visualize their trafficking/targeting, proliferation/expansion, and retention/death using highly sensitive reporter systems that do not induce an immunologic response would provide useful information. Therefore, we focused on human reporter gene systems that have the potential for translation to clinical studies. The objective of the in vivo imaging studies was to determine the minimum number of T cells that could be visualized with the different nuclear reporter systems. We determined the imaging sensitivity (lower limit of T cell detection) of each reporter using appropriate radiolabeled probes for PET or SPECT imaging. Methods: Human T cells were transduced with retroviral vectors encoding for the human norepinephrine transporter (hNET), human sodium-iodide symporter (hNIS), a human deoxycytidine kinase double mutant (hdCKDM), and herpes simplex virus type 1 thymidine kinase (hsvTK) reporter genes. After viability and growth were assessed, 10 5 to 3 x 10 6 reporter T cells were injected subcutaneously on the shoulder area. The corresponding radiolabeled probe was injected intravenously 30 min later, followed by sequential PET or SPECT imaging. Radioactivity at the T cell injection sites and in the thigh (background) was measured. Results: The viability and growth of experimental cells were unaffected by transduction. The hNET/ meta- 18 F-fluorobenzylguanidine ( 18 F-MFBG) reporter system could detect less than 1 x 10 5 T cells because of its high uptake in the transduced T cells and low background activity. The hNIS/ 124 I-iodide reporter system could detect approximately 1 x 10 6 T cells; 124 I-iodide uptake at the T cell injection site was time-dependent and associated with high background. The hdCKDM/ 2'- 18 F-fluoro-5-ethyl-1-β- d -arabinofuranosyluracil ( 18 F-FEAU) and hsvTK/ 18 F-FEAU reporter systems detected approximately 3 x 10 5 T cells, respectively. 18 F-FEAU was a more efficient probe (higher uptake, lower background) than 124 I-1-(2-deoxy-2-fluoro-1- d -arabinofuranosyl)-5-iodouracil for both hdCKDM and hsvTK. Conclusion: A comparison of different reporter gene–reporter probe systems for imaging of T cell number was performed, and the hNET/ 18 F-MFBG PET reporter system was found to be the most sensitive and capable of detecting approximately 35–40 x 10 3 T cells at the site of T cell injection in the animal model.
    Print ISSN: 0022-3123
    Topics: Medicine
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  • 8
    Publication Date: 2018-08-03
    Description: The DNA repair enzyme poly(ADP-ribose) polymerase 1 (PARP-1) is overexpressed in glioblastoma, with overall low expression in healthy brain tissue. Paired with the availability of specific small molecule inhibitors, PARP-1 is a near-ideal target to develop novel radiotherapeutics to induce DNA damage and apoptosis in cancer cells, while sparing healthy brain tissue. Methods: We synthesized an 131 I-labeled PARP-1 therapeutic and investigated its pharmacology in vitro and in vivo. A subcutaneous tumor model was used to quantify retention times and therapeutic efficacy. A potential clinical scenario, intratumoral convection-enhanced delivery, was mimicked using an orthotopic glioblastoma model combined with an implanted osmotic pump system to study local administration of 131 I-PARPi (PARPi is PARP inhibitor). Results: 131 I-PARPi is a 1(2H)-phthalazinone, similar in structure to the Food and Drug Administration–approved PARP inhibitor AZD-2281. In vitro studies have shown that 131 I-PARPi and AZD-2281 share similar pharmacologic profiles. 131 I-PARPi delivered 134.1 cGy/MBq intratumoral injected activity. Doses to nontarget tissues, including liver and kidney, were significantly lower. Radiation damage and cell death in treated tumors were shown by p53 activation in U87-MG cells transfected with a p53-bioluminescent reporter. Treated mice showed significantly longer survival than mice receiving vehicle (29 vs. 22 d, P 〈 0.005) in a subcutaneous model. Convection-enhanced delivery demonstrated efficient retention of 131 I-PARPi in orthotopic brain tumors, while quickly clearing from healthy brain tissue. Conclusion: Our results demonstrate 131 I-PARPi’s high potential as a therapeutic and highlight PARP’s relevance as a target for radionuclide therapy. Radiation plays an integral role in brain tumor therapy, and radiolabeled PARP therapeutics could ultimately lead to improvements in the standard of care.
    Print ISSN: 0022-3123
    Topics: Medicine
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  • 9
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Psychophysiology 34 (1997), S. 0 
    ISSN: 1469-8986
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine , Psychology
    Notes: The impulse activity of 183 multiunits was recorded from the premotor cortex, the caudate nucleus, the globus pallidus, and the thalamus in 15 Parkinson's disease patients bearing inert gold electrodes implanted for diagnosis and therapy. The patients performed a task in which stimulus triplets (each consisting of two informational and one trigger stimulus) were presented. The patients initiated or inhibited actions (naming or counting) depending on the particular informational stimuli, thus allowing discrimination between different components of multiunit responses associated with attention and preparatory set and with disengagement from these states. The data indicate the existence of two overlapping circuits: one responsible for preparation for and assessment of the behavioral meaning of the stimulus and the other responsible for preparation for and performance of verbal action.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 0370-2693
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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