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  • 1
    Online Resource
    Online Resource
    Berlin, Heidelberg :Springer Berlin / Heidelberg,
    Keywords: Electronic books.
    Type of Medium: Online Resource
    Pages: 1 online resource (338 pages)
    Edition: 1st ed.
    ISBN: 9783642868207
    Series Statement: Springer Study Edition Series
    Language: English
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  • 2
    Keywords: Natural disasters. ; Electronic books.
    Type of Medium: Online Resource
    Pages: 1 online resource (341 pages)
    Edition: 1st ed.
    ISBN: 9781461571018
    Series Statement: Springer Study Edition Series
    Language: English
    Note: Intro -- 978-1-4615-7101-8_BookFrontmatter_OnlinePDF -- 978-1-4615-7101-8_1_OnlinePDF -- 978-1-4615-7101-8_2_OnlinePDF -- 978-1-4615-7101-8_3_OnlinePDF -- 978-1-4615-7101-8_4_OnlinePDF -- 978-1-4615-7101-8_5_OnlinePDF -- 978-1-4615-7101-8_6_OnlinePDF -- 978-1-4615-7101-8_7_OnlinePDF -- 978-1-4615-7101-8_8_OnlinePDF -- 978-1-4615-7101-8_BookBackmatter_OnlinePDF.
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  • 3
    Publication Date: 2015-02-24
    Description: The spatio-temporal pattern of peak Holocene warmth (Holocene thermal maximum, HTM) is traced over 140 sites across the Western Hemisphere of the Arctic (0–180°W; north of ∼60°N). Paleoclimate inferences based on a wide variety of proxy indicators provide clear evidence for warmer-than-present conditions at 120 of these sites. At the 16 terrestrial sites where quantitative estimates have been obtained, local HTM temperatures (primarily summer estimates) were on average 1.6±0.8°C higher than present (approximate average of the 20th century), but the warming was time-transgressive across the western Arctic. As the precession-driven summer insolation anomaly peaked 12–10 ka (thousands of calendar years ago), warming was concentrated in northwest North America, while cool conditions lingered in the northeast. Alaska and northwest Canada experienced the HTM between ca 11 and 9 ka, about 4000 yr prior to the HTM in northeast Canada. The delayed warming in Quebec and Labrador was linked to the residual Laurentide Ice Sheet, which chilled the region through its impact on surface energy balance and ocean circulation. The lingering ice also attests to the inherent asymmetry of atmospheric and oceanic circulation that predisposes the region to glaciation and modulates the pattern of climatic change. The spatial asymmetry of warming during the HTM resembles the pattern of warming observed in the Arctic over the last several decades. Although the two warmings are described at different temporal scales, and the HTM was additionally affected by the residual Laurentide ice, the similarities suggest there might be a preferred mode of variability in the atmospheric circulation that generates a recurrent pattern of warming under positive radiative forcing. Unlike the HTM, however, future warming will not be counterbalanced by the cooling effect of a residual North American ice sheet.
    Type: Article , PeerReviewed
    Format: text
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  • 4
    Publication Date: 2016-09-16
    Description: As the planet cooled from peak warmth in the early Cenozoic, extensive Northern Hemisphere ice sheets developed by 2.6 Ma ago, leading to changes in the circulation of both the atmosphere and oceans. From not, vert, similar2.6 to not, vert, similar1.0 Ma ago, ice sheets came and went about every 41 ka, in pace with cycles in the tilt of Earth’s axis, but for the past 700 ka, glacial cycles have been longer, lasting not, vert, similar100 ka, separated by brief, warm interglaciations, when sea level and ice volumes were close to present. The cause of the shift from 41 ka to 100 ka glacial cycles is still debated. During the penultimate interglaciation, not, vert, similar130 to not, vert, similar120 ka ago, solar energy in summer in the Arctic was greater than at any time subsequently. As a consequence, Arctic summers were not, vert, similar5 °C warmer than at present, and almost all glaciers melted completely except for the Greenland Ice Sheet, and even it was reduced in size substantially from its present extent. With the loss of land ice, sea level was about 5 m higher than present, with the extra melt coming from both Greenland and Antarctica as well as small glaciers. The Last Glacial Maximum (LGM) peaked not, vert, similar21 ka ago, when mean annual temperatures over parts of the Arctic were as much as 20 °C lower than at present. Ice recession was well underway 16 ka ago, and most of the Northern Hemisphere ice sheets had melted by 6 ka ago. Solar energy reached a summer maximum (9% higher than at present) not, vert, similar11 ka ago and has been decreasing since then, primarily in response to the precession of the equinoxes. The extra energy elevated early Holocene summer temperatures throughout the Arctic 1–3 °C above 20th century averages, enough to completely melt many small glaciers throughout the Arctic, although the Greenland Ice Sheet was only slightly smaller than at present. Early Holocene summer sea ice limits were substantially smaller than their 20th century average, and the flow of Atlantic water into the Arctic Ocean was substantially greater. As summer solar energy decreased in the second half of the Holocene, glaciers re-established or advanced, sea ice expanded, and the flow of warm Atlantic water into the Arctic Ocean diminished. Late Holocene cooling reached its nadir during the Little Ice Age (about 1250–1850 AD), when sun-blocking volcanic eruptions and perhaps other causes added to the orbital cooling, allowing most Arctic glaciers to reach their maximum Holocene extent. During the warming of the past century, glaciers have receded throughout the Arctic, terrestrial ecosystems have advanced northward, and perennial Arctic Ocean sea ice has diminished. Here we review the proxies that allow reconstruction of Quaternary climates and the feedbacks that amplify climate change across the Arctic. We provide an overview of the evolution of climate from the hot-house of the early Cenozoic through its transition to the ice-house of the Quaternary, with special emphasis on the anomalous warmth of the middle Pliocene, early Quaternary warm times, the Mid Pleistocene transition, warm interglaciations of marine isotope stages 11, 5e, and 1, the stage 3 interstadial, and the peak cold of the last glacial maximum.
    Type: Article , PeerReviewed
    Format: text
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  • 5
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    U.S. Geological Survey
    In:  In: Past Climate Variability and Change in the Arctic and at High Latitudes. , ed. by US Climate Change Program and Subcommittee on Global Change Rese, U.S. Geological Survey, Reston, VA, pp. 77-246.
    Publication Date: 2012-02-23
    Type: Book chapter , PeerReviewed
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  • 6
    Publication Date: 2016-09-16
    Description: The warmest millennia of at least the past 250,000 years occurred during the Last Interglaciation, when global ice volumes were similar to or smaller than today and systematic variations in Earth's orbital parameters aligned to produce a strong positive summer insolation anomaly throughout the Northern Hemisphere. The average insolation during the key summer months (M, J, J) was ca 11% above present across the Northern Hemisphere between 130,000 and 127,000 years ago, with a slightly greater anomaly, 13%, over the Arctic. Greater summer insolation, early penultimate deglaciation, and intensification of the North Atlantic Drift, combined to reduce Arctic Ocean sea ice, allow expansion of boreal forest to the Arctic Ocean shore across vast regions, reduce permafrost, and melt almost all glaciers in the Northern Hemisphere. Insolation, amplified by key boundary condition feedbacks, collectively produced Last Interglacial summer temperature anomalies 4–5 °C above present over most Arctic lands, significantly above the average Northern Hemisphere anomaly. The Last Interglaciation demonstrates the strength of positive feedbacks on Arctic warming and provides a potentially conservative analogue for anticipated future greenhouse warming.
    Type: Article , PeerReviewed
    Format: text
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  • 7
    Publication Date: 2015-10-01
    Description: A statistical analysis of the largest weather-driven hazards in the UK contradicts the typical view that each predominates in distinct events that do not interact with those of other hazard types (i.e., are ‘primary’); this potentially has implications for any multi-hazard environments globally where some types of severe event are still thought to occur independently. By a first co-investigation of long (1884–2008) meteorological time-series and nationwide insurance losses for UK domestic houses (averaging £1.1 billion/yr), new systematic interactions within a 1 year timeframe are identified between temporally-distinct floods, winter wind storms, and shrink–swell subsidence events ( P 
    Print ISSN: 1748-9318
    Electronic ISSN: 1748-9326
    Topics: Biology , Energy, Environment Protection, Nuclear Power Engineering
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  • 8
    Publication Date: 2017-06-02
    Description: In this study, we have synthesized and evaluated 18 F-JNJ64349311, a tracer with high affinity for aggregated tau (inhibition constant value, 8 nM) and high (≥500 x ) in vitro selectivity for tau over β-amyloid, in comparison with the benchmark compound 18 F-AV1451 ( 18 F-T807) in mice, rats, and a rhesus monkey. Methods: In vitro binding characteristics were determined for Alzheimer's disease, progressive supranuclear palsy, and corticobasal degeneration patient brain tissue slices using autoradiography studies. Ex vivo biodistribution studies were performed in mice. Radiometabolites were quantified in the brain and plasma of mice and in the plasma of a rhesus monkey using high-performance liquid chromatography. Dynamic small-animal PET studies were performed in rats and a rhesus monkey to evaluate tracer pharmacokinetics in the brain. Results: Mouse biodistribution studies showed moderate initial brain uptake and rapid brain washout. Radiometabolite analyses after injection of 18 F-JNJ64349311 in mice showed the presence of a polar radiometabolite in plasma, but not in the brain. Semiquantitative autoradiography studies on postmortem tissue sections of human Alzheimer's disease brains showed highly displaceable binding to tau-rich regions. No specific binding was, however, found on human progressive supranuclear palsy and corticobasal degeneration brain slices. Small-animal PET scans of Wistar rats revealed moderate initial brain uptake (SUV, ~1.5 at 1 min after injection) and rapid brain washout. Gradual bone uptake was, however, also observed. Blocking and displacement did not affect brain time–activity curves, suggesting no off-target specific binding of the tracer in the healthy rat brain. A small-animal PET scan of a rhesus monkey revealed moderate initial brain uptake (SUV, 1.9 at 1 min after injection) with a rapid washout. In the monkey, no bone uptake was detected during the 120-min scan. Conclusion: This biologic evaluation suggests that 18 F-JNJ64349311 is a promising tau PET tracer candidate, with a favorable pharmacokinetic profile, as compared with 18 F-AV1451.
    Print ISSN: 0022-3123
    Topics: Medicine
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  • 9
    Publication Date: 2013-08-16
    Description: Modulation of the metabotropic glutamate type 2 (mGlu2) receptor is considered a promising target for the treatment of central nervous system diseases such as schizophrenia. Here, we describe the pharmacological properties of the novel mGlu2 receptor positive allosteric modulator (PAM) 3-cyano-1-cyclopropylmethyl-4-(4-phenyl-piperidin-1-yl)-pyridine-2(1 H )-one (JNJ-40068782) and its radioligand [ 3 H]JNJ-40068782. In guanosine 5'- O -(3-[ 35 S]thio)triphosphate binding, JNJ-40068782 produced a leftward and upward shift in the glutamate concentration-effect curve at human recombinant mGlu2 receptors. The EC 50 of JNJ-40068782 for potentiation of an EC 20 -equivalent concentration of glutamate was 143 nM. Although JNJ-40068782 did not affect binding of the orthosteric antagonist [ 3 H]2 S -2-amino-2-(1 S ,2 S -2-carboxycyclopropyl-1-yl)-3-(xanth-9-yl)propanoic acid (LY-341495), it did potentiate the binding of the agonist [ 3 H](2 S ,2' R ,3' R )-2-(2',3'-dicarboxylcyclopropyl)glycine (DCG-IV), demonstrating that it can allosterically affect binding at the agonist recognition site. The binding of [ 3 H]JNJ-40068782 to human recombinant mGlu2 receptors in Chinese hamster ovary cells and rat brain receptors was saturable with a K D of ~10 nM. In rat brain, the anatomic distribution of [ 3 H]JNJ-40068782 was consistent with mGlu2 expression previously described and was most abundant in cortex and hippocampus. The ability of structurally unrelated PAMs to displace [ 3 H]JNJ-40068782 suggests that PAMs may bind to common determinants within the same site. It is noteworthy that agonists also increased the binding affinity of [ 3 H]JNJ-40068782. JNJ-40068782 influenced rat sleep-wake organization by decreasing rapid eye movement sleep with a lowest active dose of 3 mg/kg PO. In mice, JNJ-40068782 reversed phencyclidine-induced hyperlocomotion with an ED 50 of 5.7 mg/kg s.c. Collectively, the present data demonstrate that JNJ-40068782 has utility in investigating the potential of mGlu2 modulation for the treatment of diseases characterized by disturbed glutamatergic signaling and highlight the value of [ 3 H]JNJ-40068782 in exploring allosteric binding.
    Print ISSN: 0022-3565
    Electronic ISSN: 1521-0103
    Topics: Medicine
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  • 10
    Publication Date: 2012-06-19
    Description: All marketed antipsychotics act by blocking dopamine D 2 receptors. Fast dissociation from D 2 receptors may be one of the elements contributing to the lower incidence of extrapyramidal symptoms (EPS) exhibited by newer antipsychotics. Therefore, we screened for specific D 2 receptor blockers with a fast rate of dissociation. Radioligand binding experiments identified N- [1-(3,4-difluorobenzyl)piperidin-4-yl]-6-(trifluoromethyl)pyridazin-3-amine (JNJ-37822681) as a fast-dissociating D 2 ligand. Its D 2 receptor specificity was high compared with atypical antipsychotics, with little activity at receptors associated with unwanted effects [α 1 , α 2 , H 1 , muscarinic, and 5-hydroxytryptamine (5-HT) type 2C] and for receptors that may interfere with the effects of D 2 antagonism (D 1 , D 3 , and 5-HT 2A ). JNJ-37822681 occupied D 2 receptors in rat brain at relatively low doses (ED 50 0.39 mg/kg) and was effective in animal models of psychosis (e.g., inhibition of apomorphine-induced stereotypy or d -amphetamine/phencyclidine-induced hyperlocomotion). Prolactin levels increased from an ED 50 (0.17 mg/kg, peripheral D 2 receptors) close to the ED 50 required for apomorphine antagonism (0.19 mg/kg, central D 2 receptors), suggesting excellent brain disposition and minimal prolactin release at therapeutic doses. JNJ-37822681 induced catalepsy and inhibited avoidance behavior, but with a specificity margin relative to apomorphine antagonism that was larger than that obtained for haloperidol and similar to that obtained for olanzapine. This larger specificity margin (compared with haloperidol) may reflect lower EPS liability and less behavioral suppression after JNJ-37822681. JNJ-37822681 is a novel, potent, specific, centrally active, fast-dissociating D 2 antagonist with optimal brain disposition, and it is the first compound that allows the evaluation of the potential value of fast D 2 antagonism for the treatment of schizophrenia and bipolar disorder.
    Print ISSN: 0022-3565
    Electronic ISSN: 1521-0103
    Topics: Medicine
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