Null mutation of endothelin receptor type B gene in spotting lethal rats causes aganglionic megacolon and white coat color.

Mutations in the gene encoding the endothelin receptor type B (EDNRB) produce congenital aganglionic megacolon and pigment abnormalities in mice and humans. Here we report a naturally occurring null mutation of the EDNRB gene in spotting lethal (sl) rats, which exhibit aganglionic megacolon associated with white coat color. We found a 301-bp deletion spanning the exon 1-intron 1 junction of the EDNRB gene in sl rats. A restriction fragment length polymorphism caused by this deletion perfectly cosegregates with the sl phenotype. The deletion leads to production of an aberrantly spliced EDNRB mRNA that lacks the coding sequence for the first and second putative transmembrane domains of the G-protein-coupled receptor. Radioligand binding assays revealed undetectable levels of functional EDNRB in tissues from homozygous sl/sl rats. We conclude that EDNRB plays an essential role in the normal development of two neural crest-derived cell lineages, epidermal melanocytes and enteric neurons, in three mammalian species--humans, mice, and rats. The EDNRB-deficient rat may also prove valuable in defining the postnatal physiologic role of this receptor.

Membrane-associated CD19-LYN complex is an endogenous p53-independent and Bc1-2-independent regulator of apoptosis in human B-lineage lymphoma cells.

CD19 receptor is expressed at high levels on human B-lineage lymphoid cells and is physically associated with the Src protooncogene family protein-tyrosine kinase Lyn. Recent studies indicate that the membrane-associated CD19-Lyn receptor-enzyme complex plays a pivotal role for survival and clonogenicity of immature B-cell precursors from acute lymphoblastic leukemia patients, but its significance for mature B-lineage lymphoid cells (e.g., B-lineage lymphoma cells) is unknown. CD19-associated Lyn kinase can be selectively targeted and inhibited with B43-Gen, a CD19 receptor-specific immunoconjugate containing the naturally occurring protein-tyrosine kinase inhibitor genistein (Gen). We now present experimental evidence that targeting the membrane-associated CD19-Lyn complex in vitro with B43-Gen triggers rapid apoptotic cell death in highly radiation-resistant p53-Bax- Ramos-BT B-lineage lymphoma cells expressing high levels of Bcl-2 protein without affecting the Bcl-2 expression level. The therapeutic potential of this membrane-directed apoptosis induction strategy was examined in a scid mouse xenograft model of radiation-resistant high-grade human B-lineage lymphoma. Remarkably, in vivo treatment of scid mice challenged with an invariably fatal number of Ramos-BT cells with B43-Gen at a dose level < 1/10 the maximum tolerated dose resulted in 70% long-term event-free survival. Taken together, these results provide unprecedented evidence that the membrane-associated anti-apoptotic CD19-Lyn complex may be at least as important as Bcl-2/Bax ratio for survival of lymphoma cells.

On the nature of the galactic early-B hypergiants

Aims. Despite their importance to a number of astrophysical fields, the lifecycles of very massive stars are still poorly defined. In order to address this shortcoming, we present a detailed quantitative study of the physical properties of four early-B hypergiants (BHGs) of spectral type B1-4 Ia+; Cyg OB2 #12, ζ1 Sco, HD 190603 and BP Cru. These are combined with an analysis of their long-term spectroscopic and photometric behaviour in order to determine their evolutionary status. Methods. Quantitative analysis of UV–radio photometric and spectroscopic datasets was undertaken with a non-LTE model atmosphere code in order to derive physical parameters for comparison with apparently closely related objects, such as B supergiants (BSGs) and luminous blue variables (LBVs), and theoretical evolutionary predictions. Results. The long-term photospheric and spectroscopic datasets compiled for the early-B HGs revealed that they are remarkably stable over long periods ( ≥ 40 yrs), with the possible exception of ζ1 Sco prior to the 20th century; in contrast to the typical excursions that characterise LBVs. Quantitative analysis of ζ1 Sco, HD 190603 and BP Cru yielded physical properties intermediate between BSGs and LBVs; we therefore suggest that BHGs are the immediate descendants and progenitors (respectively) of such stars, for initial masses in the range ~30−60 M⊙. Comparison of the properties of ζ1 Sco with the stellar population of its host cluster/association NGC 6231/Sco OB1 provides further support for such an evolutionary scenario. In contrast, while the wind properties of Cyg OB2 #12 are consistent with this hypothesis, the combination of extreme luminosity and spectroscopic mass (~110 M⊙) and comparatively low temperature means it cannot be accommodated in such a scheme. Likewise, despite its co-location with several LBVs above the Humphreys-Davidson (HD) limit, the lack of long term variability and its unevolved chemistry apparently excludes such an identification. Since such massive stars are not expected to evolve to such cool temperatures, instead traversing an O4-6Ia → O4-6Ia+ → WN7-9ha pathway, the properties of Cyg OB2 #12 are therefore difficult to understand under current evolutionary paradigms. Finally, we note that as with AG Car in its cool phase, despite exceeding the HD limit, the properties of Cyg OB2 #12 imply that it lies below the Eddington limit – thus we conclude that the HD limit does not define a region of the HR diagram inherently inimical to the presence of massive stars.

La costruzione giuridica del modello sociale europeo (con una postilla sul MSE al tempo della crisi globale) [The legal construction of the European social model (with a note on the MSE at the time of the global crisis)]. WP C.S.D.L.E. "Massimo D'Antona" .INT - 88/2011

No abstract.

L’Europa sociale e il diritto: il contributo del metodo comparato [Social Europe and the law: the contribution of the comparative method]. WP C.S.D.L.E. "Massimo D'Antona" .INT - 94/2012

The essay explores the evolution of comparative law and the contribution of its more recent methodological results on the process of European social integration through law. The analysis of the comparative method in general glides on a discipline, such a as labour law, traditionally linked to the "nomos" of the nation state and looks at the process of its own supranationalization through the lens which is the comparative method; a method used mainly by the juridical format (national and supranational courts). The analysis focuses on the fixed term contract and on the vexing question of collective social fundamental rights vis a vis fundamental economic freedoms in the EU where national constitutional traditions and supranational principals risk collision due also to the comparative method.

A B C of gothic architecture /

Includes index.

Sumerian mythology, a study of spiritual and literary achievement in the third millennium, B.C.

Frontispiece accompanied by leaf with descriptive letterpress.

Dedications from the Athenian Akropolis; a catalogue of the inscriptions of the sixth and fifth centuries B. C.

Includes bibliographical references.

The complete confectioner, or, Housekeeper's guide to a simple and speedy method of understanding the whole art of confectionary : the various ways of preserving and candying, dry and liquid, all kinds of fruit, nuts, flowers, herbs, &c. And the method of keeping them fresh and fine all the year round; the different ways of clarifying sugar; with directions for making fruit pastes, bomboons, pastils, compotes, fruit ices, cream ices, marmalades, jellies, jams, cakes, puffs, biscuits, tarts, custards, cheesecakes, sweetmeats, fritters, creams, syllabubs, blanc-mange, flummeries, ornaments for grand entertainments, dragees, syrups of all kinds, nicknacks and trifles for desserts, strong cordials, oils, simple waters, milk punch that will keep 20 years, and all sorts of English wines. Also, the art of making artificial fruit, with the stalks in it, so as to resemble the natural fruit. To which are added, some bills of fare for desserts for private families /

Originally published under title: The compleat confectioner. Cf. Bitting, K.G. Gastronomic bib., p. 190.

Report to the President by the Emergency Board created June 23, 1948 by Executive order 9971 pursuant to Section 10 of the Railway Labor Act : to investigate and report upon a dispute between the Grand Trunk Western Railroad Co., Chesapeake and Ohio Railway Co., Wabash Railroad and the Ann Arbor Railroad Co. and certain of its employees represented by the National Maritime Union of America, N.M.B. cases A-2801, A-2802, A-2803, A-2804, Detroit, Michigan, July 20, 1948.

Signed: Robert G. Simmons, chairman, Thomas F. Gallagher, member, Joseph L. Miller, member.

Records - Columbia Historical Society of Washington, D.C.

Beginning with v. 29/30, issued in 1928, one book often numbered as more than one vol. With v. 42/43, 1940/41 years covered were added to the title. Vol. numbering omitted, 1957/59- , 1944/45 called '50th anniversary volume'; 1948/50 called v. 50 but was the 40th vol. in the series; 1980 called "Fiftieth volume" and is the 50th separately bound book in the series.--Cf. introd. 50th vol., 1980, p. xi.