998 resultados para 1995_01230707 TM-43 4302003


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handschriftl.: Panzer No. 223; Bibliogr. Nachweis: Allg.Portr.Kat. Nr. 23706f.

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Trägerband: Inc. qu. 1272; Vorbesitzer: Dominikanerkloster Frankfurt am Main

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Vorbesitzer: Johann Hartmann Beyer

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Vorbesitzer: Abraham Merzbacher;

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Trägerband: Inc. qu. 719 und ein weiterer Band; Vorbesitzer: Karmeliterkloster Frankfurt am Main

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"Einführung in die Philosophie", Vorlesung, Wintersemester 1956/57, 1 Heft mit eigenhändigen Notizen, 16 Blatt, davon 4 leer, mit 1 zusätzlichem Blatt; "Geschichte des Materialismus (ausgewählte Kapitel)" (GS 13, S. 397-451), Vorlesung, Sommersemester 1957, 1. Max Horkheimer, eigene Notizen, 1 Heft ohne Einband, 16 Blatt und 3 zusätzliche Blätter, 2. Hilmar Tillack: Ausgearbeitete Nachschrift der Vorlesung Max Horkheimers, Typoskript, 46 Blatt; "Society and Value", Vorlesung Chicago 1957, Heft 1: eigene Notizen, 60 Blatt, davon 13 leer, und zusätzliche 6 Blätter; Heft 2: eigene Notizen, 45 Blatt, davon 30 leer, und zusätzlich 8 Blatt; darin auch enthält: Begriff der Seele seit Leibniz", Vorlesung, Sommersemester 1958;

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The epidermal growth factor receptor (EGFR) and its ligands are overexpressed in many human tumors, including bladder and pancreas, correlating with a more aggressive tumor phenotype and poor patient prognosis. We initiated the present study to characterize the heterogeneity of gefitinib responsiveness in a panel of human bladder and pancreatic cancer cell lines in order to identify the biological characteristics of EGFR-dependent proliferation that could be used to prospectively identify drug-sensitive tumors. A second objective was to elucidate how to best exploit these results by utilizing gefitinib in combination therapy. To these ends, we examined the effects of the EGFR antagonist gefitinib on proliferation and apoptosis in a panel of 18 human bladder cancer cell lines and 9 human pancreatic cancer cell lines. Our data confirmed the existence of marked heterogeneity in Iressa responsiveness with less than half of the cell lines displaying significant growth inhibition by clinically relevant concentrations of the drug. Gefitinib responsiveness was found to be p27 kip1 dependent as DNA synthesis was restored following exposure to p27siRNA. Unfortunately, Iressa responsiveness was not closely linked to surface EGFR or TGF-α expression in the bladder cancer cells, however, cellular TGF-α expression correlated directly with Iressa sensitivity in the pancreatic cancer cell lines. These findings provide the potential for prospectively identifying patients with drug-sensitive tumors. ^ Further studies aimed at exploiting gefitinib-mediated cell cycle effects led us to investigate if gefitinib-mediated TRAIL sensitization correlated with increased p27kip1 accumulation. We observed that increased TRAIL sensitivity following gefitinib exposure was not dependent on p27 kip1 expression. Additional studies initiated to examine the role(s) of Akt and Erk signaling demonstrated that exposure to PI3K or MEK inhibitors significantly enhanced TRAIL-induced apoptosis at concentrations that block target phosphorylation. Furthermore, combinations of TRAIL and the PI3K or MEK inhibitors increased procaspase-8 processing above levels observed with TRAIL alone, indicating that the effects were exerted at the level of caspase-8 activation, considered the earliest step in the TRAIL pathway. ^

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The relative effects of paleoceanographic and paleogeographic variations, sediment lithology, and diagenetic processes on the final preserved chemistry of Japan Sea sediments are evaluated by investigating the rare earth element (REE), major element, and trace element concentrations in 59 squeeze-cake whole-round and 27 physical-property sample residues from Sites 794, 795, and 797, cored during ODP Leg 127. The most important variation in sedimentary chemical composition is the increase in SiO2 concentration through the Pliocene diatomaceous sequences, which dilutes most other major and trace element components by various degrees. This biogenic input is largest at Site 794 (Yamato Basin), moderately developed at Site 797 (Yamato Basin), and of only minor importance at Site 795 (Japan Basin), potentially reflecting basinal contrasts in productivity with the Yamato Basin recording greater biogenic input than the Japan Basin and with the easternmost sequence of Site 794 lying beneath the most productive waters. There are few systematic changes in solid-phase chemistry resulting from the opal-A/opal-CT or opal-CT/quartz silica phase transformations. Most major and trace element concentrations are controlled by the aluminosilicate fraction of the sediment, although the effects of diagenetic silica phases and manganese carbonates are of localized importance. REE total abundances (Sum REE) in the Japan Sea are strongly dependent upon the paleoceanographic position of a given site with respect to terrigenous and biogenic sources. REE concentrations at Site 794 overall correspond well to aluminosilicate chemical indices and are strongly diluted by SiO2 within the upper Miocene-Pliocene diatomaceous sequence. Eu/Eu* values at Site 794 reach a maximum through the diatomaceous interval as well, most likely suggesting an association of Eu/Eu* with the siliceous component, or reflecting slight incorporation of a detrital feldspar phase. SumREE at Site 795 also is affiliated strongly with aluminosilicate phases and yet is diluted only slightly by siliceous input. At Site 797, SumREE is not as clearly associated with the aluminosilicate fraction, is correlated moderately to siliceous input, and may be sporadically influenced by detrital heavy minerals originating from the nearby rifted continental fragment composing the Yamato Rise. Ce/Ce* profiles at all three sites increase essentially monotonically with depth and record progressive diagenetic LREE fractionation. The observed Ce/Ce* increases are not responding to changes in the paleoceanographic oxygenation state of the overlying water, as there is no independent evidence to suggest the proper oceanographic conditions. Ce/Ce* correlates slightly better with depth than with age at the two Yamato Basin sites. The downhole increase in Ce/Ce* at Sites 794 and 797 is a passive response to the diagenetic transfer of LREE (except Ce) from sediment to interstitial water. At Site 795, the overall lack of correlation between Ce/Ce* and Lan/Ybn suggests that other processes mask the diagenetic behavior of all LREEs. First-order calculations of the Ce budget in Japan Sea waters and sediment indicate that ~20% of the excess Ce adsorbed by settling particles is recycled within the water column and that an additional ~38% is recycled at or near the seafloor. Thus, because the remaining excess Ce is only ~10% of the total Ce, there is not a large source of Ce to the deeply buried sediment, further suggesting that the downhole increase in Ce/Ce* is a passive response to diagenetic behavior of the other LREEs. The REE chemistry of Japan Sea sediment therefore predicts successive downhole addition of LREEs to deeply buried interstitial waters.

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Modern thermohaline circulation plays a role in latitudinal heat transport and in deep-ocean ventilation, yet ocean circulation may have functioned differently during past periods of extreme warmth, such as the Cretaceous. The Late Cretaceous (100-65 Ma) was an important period in the evolution of the North Atlantic Ocean, characterized by opening ocean gateways, long-term climatic cooling and the cessation of intermittent periods of anoxia (oceanic anoxic events, OAEs). However, how these phenomena relate to deep-water circulation is unclear. We use a proxy for deep-water mass composition (neodymium isotopes; e-Nd) to show that, at North Atlantic ODP Site 1276, deep waters shifted in the early Campanian (~78-83 Ma) from e-Nd values of ~-7 to values of ~-9, consistent with a change in the style of deep-ocean circulation but >10 Myr after a change in bottom water oxygenation conditions. A similar, but more poorly dated, trend exists in e-Nd data from DSDP Site 386. The Campanian e-Nd transition observed in the North Atlantic records is also seen in the South Atlantic and proto-Indian Ocean, implying a widespread and synchronous change in deep-ocean circulation. Although a unique explanation does not exist for the change at present, we favor an interpretation that invokes Late Cretaceous climatic cooling as a driver for the formation of Southern Component Water, which flowed northward from the Southern Ocean and into the North Atlantic and proto-Indian Oceans.

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Controversy has surrounded the issue of whether mantle plume activity was responsible for Pangaean continental rifting and massive flood volcanism (resulting in the Central Atlantic Magmatic Province or CAMP, emplaced around 200 Ma) preceding the opening of the central Atlantic Ocean in the Early Mesozoic. Our new Sr-Nd-Pb isotopic and trace element data for the oldest basalts sampled from central Atlantic oceanic crust by deep-sea drilling show that oceanic crust generated from about 160 to 120 Ma displays clear isotopic and chemical signals of plume contamination (e.g., 87Sr/86Sr(i) = 0.7032-0.7036, epsilonNd(t) =+6.2 to +8.2, incompatible element patterns with positive Nb anomalies), but these signals are muted or absent in crust generated between 120 and 80 Ma, which resembles young Atlantic normal mid-ocean ridge basalt. The plume-affected pre-120 Ma Atlantic crustal basalts are isotopically similar to lavas from the Ontong Java Plateau, and may represent one isotopic end-member for CAMP basalts. The strongest plume signature is displayed near the center of CAMP magmatism but the hotspots presently located nearest this location in the mantle reference frame do not appear to be older than latest Cretaceous and are isotopically distinct from the oldest Atlantic crust. The evidence for widespread plume contamination of the nascent Atlantic upper mantle, combined with a lack of evidence for a long-lived volcanic chain associated with this plume, leads us to propose that the enriched signature of early Atlantic crust and possibly the eruption of the CAMP were caused by a relatively short-lived, but large volume plume feature that was not rooted at a mantle boundary layer. Such a phenomenon has been predicted by recent numerical models of mantle circulation.