Na 50 Nachlass Arthur Schopenhauer - 'Schopenhauer-Archiv', 51 - Kritik in Form einer Predigt

u.a.: Auseinandersetzung mit dem Willen; Bibelzitate; Kampf gegen die Amalakiter; Vergleich Schopenhauer mit Josua;

Ms. lat. qu. 51 - Centiloquium de medicis et infirmis

Vorbesitzer: Jakob Heller; Dominikanerkloster Frankfurt am Main

Inc. hebr. 51 - Talmud Bavli : Masekhet Shabat

Vorbesitzer: Abraham Merzbacher;

Na 1 Nachlass Max Horkheimer, 630 - Typoskripte zur Vorlesung "Praktische Philosophie" und zu zwei Referaten (p. VIII 50a.2-VIII 51)

"Praktische Philosophie" (Zur Genealogie der Moral), Vorlesung Sommersemester 1962, Nachschrift (von Hilmar Tillack?): Nachschrift von 20 Vorlesungen 7.5.- 23.7.62, Durchschläge (unvollständig), Typoskript, 135 Blatt; N.N.: "Probleme der Geschichtsphilosophie bei Kant", Referat, Typoskript, 8 Blatt; N.N.: "Geschichtsphilosophie der Südwestdeutschen Schule", Referat, Typoskript mit handschriftlichen Randbemerkungen von Max Horkheimer, 18 Blatt;

Ms.Ff.F.Stoltze 3. 51 - Brief von Ernst Emmerling an Friedrich Stoltze

Stoltze: Notiz in den "Volksblättern", Stuttgart 1866

Ms. lat. oct. 51 - Responsionale secundum usum ecclesiae S. Bartholomaei Francfordensis

Vorbesitzer: Henricus Schurer; Petrus Schmunck; Johann Jakob Hocheisen

Fragm. lat. I 18 - Micrologus (c. 23, 46 - 49, 51 - 61)

Trägerbände: Ms. Barth. 13; Ms. Barth. 18; Ms. Barth. 29; Ms. Barth. 41; Vorbesitzer: Bartholomaeusstift Frankfurt am Main

Tumor heterogeneity dictates sensitivity to gefitinib (Iressa(TM)/ZD1839) in solid tumor models

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. ^

Geochemistry of the oldest Atlantic oceanic crust

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.