Radio-echo sounding and ice volume estimates of western Nordenskiöld Land glaciers, Svalbard

As part of ongoing work to obtain a reliable estimate of the total ice volume of Svalbard glaciers and their potential contribution to sea-level rise, we present here volume calculations, with detailed error estimates, for ten glaciers on western Nordenskiöld Land, central Spitsbergen, Svalbard. The volume estimates are based upon a dense net of GPR-retrieved ice thickness data collected over several field campaigns spanning the period 1999-2012. On the basis of the pattern of scattering in theradargrams, we also analyse the hydrothermal structure of these glaciers.

Solenes [sic] i grandiosas fiestas, q[ue] la noble i leal ciudad de Valencia a echo por la Beatificacion desu Santo Pastor i Padre D. Tomas de Villanueva...

Sign. : []\p8\s, A-Z-\p8\s, Aa-Nn\p8\s, Oo\p4\s

Jardin engañoso : nueua relacion, y curioso romance, en que se refieren los amores de don Fadrique de Alvara, don Joseph de Alvara, doña Constanza, y doña Theodosia : dase cuenta, como don Fadrique dio muerte a su hermano, y lo echo en un pozo y le entrego el alma al demonio, por gozar de doña Constanza, y como caso con doña Theodosia ... : primera parte

Pie de imp. consta en col

Vista de dos Templos antiguos en la plaza del Eco de Sagunto [Material gráfico] = Vue de deux Temples antiques sur la Place de l'Echo à Sagonte = View of two antique Temples in the square of the Echo at Sagonta

Estampado junto a "Plano de la Plaza del Eco"

Plano de la Plaza del Eco [Material gráfico] = Plan de la Place de l'Echo = Plan of the Square of the Echo

Estampado en la misma hoja con: "Vista de dos Templos antiguos en la plaza del Eco de Sagunto"

DnaA-stimulated transcriptional activation of oriλ: Escherichia coli RNA polymerase β subunit as a transcriptional activator contact site

We present evidence that Escherichia coli RNA polymerase β subunit may be a transcriptional activator contact site. Stimulation of the activity of the pR promoter by DnaA protein is necessary for replication of plasmids derived from bacteriophage λ. We found that DnaA activates the pR promoter in vitro. Particular mutations in the rpoB gene were able to suppress negative effects that certain dnaA mutations had on the replication of λ plasmids; this suppression was allele-specific. When a potential DnaA-binding sequence located several base pairs downstream of the pR promoter was scrambled by in vitro mutagenesis, the pR promoter was no longer activated by DnaA both in vivo and in vitro. Therefore, we conclude that DnaA may contact the β subunit of RNA polymerase during activation of the pR promoter. A new classification of prokaryotic transcriptional activators is proposed.

An antagonistic vascular endothelial growth factor (VEGF) variant inhibits VEGF-stimulated receptor autophosphorylation and proliferation of human endothelial cells

Vascular endothelial growth factor (VEGF) is a potent mitogen with a unique specificity for endothelial cells and a key mediator of aberrant endothelial cell proliferation and vascular permeability in a variety of human pathological situations, such as tumor angiogenesis, diabetic retinopathy, rheumatoid arthritis, or psoriasis. VEGF is a symmetric homodimeric molecule with two receptor binding interfaces lying on each pole of the molecule. Herein we report on the construction and recombinant expression of an asymmetric heterodimeric VEGF variant with an intact receptor binding interface at one pole and a mutant receptor binding interface at the second pole of the dimer. This VEGF variant binds to VEGF receptors but fails to induce receptor activation. In competition experiments, the heterodimeric VEGF variant antagonizes VEGF-stimulated receptor autophosphorylation and proliferation of endothelial cells. A 15-fold excess of the heterodimer was sufficient to inhibit VEGF-stimulated endothelial cell proliferation by 50%, and a 100-fold excess resulted in an almost complete inhibition. By using a rational approach that is based on the structure of VEGF, we have shown the feasibility to construct a VEGF variant that acts as an VEGF antagonist.

Evidence of insulin-stimulated phosphorylation and activation of the mammalian target of rapamycin mediated by a protein kinase B signaling pathway

The effects of insulin on the mammalian target of rapamycin, mTOR, were investigated in 3T3-L1 adipocytes. mTOR protein kinase activity was measured in immune complex assays with recombinant PHAS-I as substrate. Insulin-stimulated kinase activity was clearly observed when immunoprecipitations were conducted with the mTOR antibody, mTAb2. Insulin also increased by severalfold the 32P content of mTOR that was determined after purifying the protein from 32P-labeled adipocytes with rapamycin⋅FKBP12 agarose beads. Insulin affected neither the amount of mTOR immunoprecipitated nor the amount of mTOR detected by immunoblotting with mTAb2. However, the hormone markedly decreased the reactivity of mTOR with mTAb1, an antibody that activates the mTOR protein kinase. The effects of insulin on increasing mTOR protein kinase activity and on decreasing mTAb1 reactivity were abolished by incubating mTOR with protein phosphatase 1. Interestingly, the epitope for mTAb1 is located near the COOH terminus of mTOR in a 20-amino acid region that includes consensus sites for phosphorylation by protein kinase B (PKB). Experiments were performed in MER-Akt cells to investigate the role of PKB in controlling mTOR. These cells express a PKB-mutant estrogen receptor fusion protein that is activated when the cells are exposed to 4-hydroxytamoxifen. Activating PKB with 4-hydroxytamoxifen mimicked insulin by decreasing mTOR reactivity with mTAb1 and by increasing the PHAS-I kinase activity of mTOR. Our findings support the conclusion that insulin activates mTOR by promoting phosphorylation of the protein via a signaling pathway that contains PKB.