Search for K isomers in 252,254 No and 260 Sg and investigation of their nuclear structure

Study of K isomerism in the transfermium region around the deformed shells at N=152, Z=102, and N=162, Z=108 provides important information on the structure of heavy nuclei. Recent calculations suggest that the K-isomerism can enhance the stability of such nuclei against alpha emission and spontaneous fission. Nuclei showing K isomerism have neutron and proton orbitals with large spin projections on the symmetry axis which is due to multi quasiparticle states with aligned spins K. Quasi-particle states are formed by breaking pairs of nucleons and raising one or two nucleons in orbitals near the Fermi surface above the gap, forming high K (multi)quasi-particle states mainly at low excitation energies. Experimental examples are the recently studied two quasi-particle K isomers in 250,256-Fm, 254-No, and 270-Ds. Nuclei in this region, are produced with cross sections ranging from several nb up to µb, which are high enough for a detailed decay study. In this work, K isomerism in Sg and No isotopes was studied at the velocity filter SHIP of GSI, Darmstadt. The data were obtained by using a new data acquisition system which was developed and installed during this work. 252,254-No and 260-Sg were produced in fusion evaporation reactions of 48-Ca and 54-Cr projectiles with 206,208-Pb targets at beam energies close to the Coulomb barrier. A new K isomer was discovered in 252-No at excitation energy of 1.25 MeV, which decays to the ground state rotational band via gamma emission. It has a half-life of about 100 ms. The population of the isomeric state was about 20% of the ground state population. Detailed investigations were performed on 254-No in which two isomeric states (275 ms and 198 µs) were already discovered by R.-D. Herzberg, but due to the higher number of observed gamma decays more detailed information about the decay path of the isomers was obtained in the present work. In 260-Sg, we observed no statistically significant component with a half life different from that of the ground state. A comparison between experimental results and theoretical calculations of the single particle energies shows a fair agreement. The structure of the here studied nuclei is in particular important as single particle levels are involved which are relevant for the next shell closure expected to form the region of the shell stabilized superheavy elements at proton numbers 114, 120, or 126 and neutron number 184. K isomers, in particular, could be an ideal tool for the synthesis and study of these isotopes due to enhanced spontaneous fission life times which could result in higher alpha to spontaneous fission branching ratios and longer half lifes.

SMO inhibitor specifically targets the Hedgehog Pathway and reverts the drug-resistance of Leukemic Stem Cells

Abnormal Hedgehog signaling is associated with human malignancies. Smo, a key player of that signaling, is the most suitable target to inhibit this pathway. To this aim several molecules, antagonists of Smo, have been synthesized, and some of them have started the phase I in clinical trials. Our hospital participated to one of these studies which investigated the oral administration of a new selective inhibitor of Smo (SMOi). To evaluate ex vivo SMOi efficacy and to identify new potential clinical biomarkers of responsiveness, we separated bone marrow CD34+ cells from 5 acute myeloid leukemia (AML), 1 myelofibrosis (MF), 2 blastic phases chronic myeloid leukemia (CML) patients treated with SMOi by immunomagnetic separation, and we analysed their gene expression profile using Affimetrix HG-U133 Plus 2.0 platform. This analysis, showed differential expression after 28 days start of therapy (p-value ≤ 0.05) of 1,197 genes in CML patients and 589 genes in AML patients. This differential expression is related to Hedgehog pathway with a p-value = 0.003 in CML patients and with a p-value = 0.0002 in AML patients, suggesting that SMOi targets specifically this pathway. Among the genes differentially expressed we observed strong up-regulation of Gas1 and Kif27 genes, which may work as biomarkers of responsiveness of SMOi treatment in CML CD34+ cells whereas Hedgehog target genes (such as Smo, Gli1, Gli2, Gli3), Bcl2 and Abca2 were down-regulated, in both AML and CML CD34+ cells. It has been reported that Bcl-2 expression could be correlated with cancer therapy resistance and that Hedgehog signaling modulate ATP-binding (ABC) cassette transporters, whose expression has been correlated with chemoresistance. Moreover we confirmed that in vitro SMOi treatment targets Hedgehog pathway, down-regulate ABC transporters, Abcg2 and Abcb1 genes, and in combination with tyrosine kinase inhibitors (TKIs) could revert the chemoresistance mechanism in K562 TKIs-resistant cell line.

A SMO inhibitor drug reduces the progenitor cell's maintenance in the Drosophila hematopoietic organ: a novel model to study Chronic Myelogenous Leukemia relapse

The chronic myeloid leukemia complexity and the difficulties of disease eradication have recently led to the development of drugs which, together with the inhibitors of TK, could eliminate leukemia stem cells preventing the occurrence of relapses in patients undergoing transplantation. The Hedgehog (Hh) signaling pathway positively regulates the self-renewal and the maintenance of leukemic stem cells and not, and this function is evolutionarily conserved. Using Drosophila as a model, we studied the efficacy of the SMO inhibitor drug that inhibit the human protein Smoothened (SMO). SMO is a crucial component in the signal transduction of Hh and its blockade in mammals leads to a reduction in the disease induction. Here we show that administration of the SMO inhibitor to animals has a specific effect directed against the Drosophila ortholog protein, causing loss of quiescence and hematopoietic precursors mobilization. The SMO inhibitor induces in L3 larvae the appearance of melanotic nodules generated as response by Drosophila immune system to the increase of its hemocytes. The same phenotype is induced even by the dsRNA:SMO specific expression in hematopoietic precursors of the lymph gland. The drug action is also confirmed at cellular level. The study of molecular markers has allowed us to demonstrate that SMO inhibitor leads to a reduction of the quiescent precursors and to an increase of the differentiated cells. Moreover administering the inhibitor to heterozygous for a null allele of Smo, we observe a significant increase in the phenotype penetrance compared to administration to wild type animals. This helps to confirm the specific effect of the drug itself. These data taken together indicate that the study of inhibitors of Smo in Drosophila can represent a useful way to dissect their action mechanism at the molecular-genetic level in order to collect information applicable to the studies of the disease in humans.

Von den heutigen Juden Salonikis : (Fortsetzung von Seite 253/254)

Fränkel

Na 50 Nachlass Arthur Schopenhauer - 'Schopenhauer-Archiv', 254 - Zusendung einer Abschrift des Kammergerichts und Zusicherung der Rechtsvertretung im vorliegenden Gerichtsverfahren

u.a.: Kreditbrief; Georg Carl Friedrich Kunowski; Justizrat Schütz;

Na 1 Nachlass Max Horkheimer, 505 - Korrespondenzen mit Theodor W. Adorno (p. VI 1C, 1 - 254)

Briefwechsel und Beilagen zwischen Max Horkheimer, Theodor W. und Gretel Adorno, 1945; 1 Brief von Gretel Adorno an Frederick Wild, 1945; 1 Brief von Theodor W. Adorno an Leo Löwenthal, 1945; Briefwechsel zwischen Theodor W. Adorno und John Slawson, 1945; 1 Brief von Else Frenkel-Brunswick an Theodor W. Adorno, 1944; 2 Briefe von Gretel Adorno an Margot von Mendelssohn, 1945; Briefwechsel und Beilagen zwischen Max Horkheimer und Theodor W. und Gretel Adorno, 1946 - 1948; 1 Brief von Theodor W. Adorno an Ralph L. Beals, 1948; Briefwechsel zwischen Gretel Adorno und Frederick Wild, 1946 - 1947;

Ms.Ff.F.Stoltze 3. 254 - Brief von Wilhelm Rieger an Friedrich Stoltze

Einladung zum Abendessen

Na 1 Nachlass Max Horkheimer, 552 - Korrespondenzen mit Leo Löwenthal (p. VI 21, 254-497)

143 Briefe zwischen Leo Löwenthal und Max Horkheimer, Mai - Dezember 1947; 6 Briefe zwischen Max Horkheimer und Samuel H. Flowerman; 4 Briefe zwischen Samuel H. Flowerman und Leo Löwenthal; 3 Briefe von Max Horkheimer an Paul Lazarsfeld; 7 Briefe zwischen John Slawson und Max Horkheimer;

Na 1 Nachlass Max Horkheimer, 564 - Korrespondenzen u.a. mit Alice H. Maier und Leo Löwenthal (p. VI 27, 254-402)

Briefwechsel zwischen Max Horkheimer und Alice H. Maier; 5 Briefe an Maurice und Carolyn Tumarkin von Max Horkheimer, 1957/1964; 3 Briefe zwischen Alice H. Maier und H. P. Edelman, 1957/1963; 2 Briefe von Alice H. Maier an Friedrich Pollock, 1960/1966; 2 Briefe von Max Horkheimer an The Diners Club (New York), 1965; 1 Brief an Patricia und Edward R. Wilbur von Alice H. Maier, 17.05.1965; 2 Briefe von Max Horkheimer an Patricia und Edward R. Wilbur, 1964; 2 Briefe zwischen Alice H. Maier und Alfred L. Copley, 1965; 5 Briefe zwischen William C. Kirkwood und Max Horkheimer, 1964; 2 Briefe von Max Horkheimer an Ulla Posnansky, 1964; 1 Brief an Leo Löwenthal von Max Horkheimer, 23.06.1964; 1 Brief von Max Horkheimer an Amerino Lionetti, 03.06.1964; 10 Briefe zwischen Herbert Marcuse und Max Horkheimer, 1935 - 1936; 1 Brief von R. Piper an Herbert Marcuse, 26.03.1936;

Ms. lat. oct. 254 - Schriften zum Regalienstreit. Venezianische Akten.

Die Foliierung geht nur bis Bl. 313; zusätzlich gibt es das Blatt 160a

Oscar Caeiro. Córdoba. Imágenes y visiones literarias. Córdoba, Alción, 2004, 254 p.

Fil: Bujaldón de Esteves, Lila. Universidad Nacional de Cuyo. Facultad de Filosofía y Letras

J. Ebbeler, Disciplining Christians: Correction and Community in Augustine’s Letters, Oxford University Press, New York 2012, 254 pp. ISBN 9780195372564.

Fil: Correa, Soledad. Universidad Nacional de Rosario

El derecho de toda persona al disfrute del más alto nivel posible de salud física y mental. Documento A/66/254. Asamblea General. 2011

El Relator Especial examina los efectos de las restricciones jurídicas penales y de otra índole en el aborto