Nomination--National Transportation Safety Board : hearing before the Committee on Commerce, Science, and Transportation, United States Senate, Ninety-seventh Congress, second session, on nomination of Adm. Donald D. Engen, to be a member, National Transportation Safety Board, June 9, 1982

"Serial no. 97-117."

Aspectos jurídicos del contrato de franquicia en Colombia

El proyecto de tesis de grado titulado Aspectos Jurídicos del Contrato de Franquicia en Colombia aborda el tema de las franquicias desde una doble perspectiva: La económica y la jurídica.

(Supplement 3) Radar sounding observations including bedrock and surface elevation and ice thickness in the ASB region, Antarctica

The first Cenozoic ice sheets initiated in Antarctica from the Gamburtsev Subglacial Mountains and other highlands as a result of rapid global cooling ~34 million years ago. In the subsequent 20 million years, at a time of declining atmospheric carbon dioxide concentrations and an evolving Antarctic circumpolar current, sedimentary sequence interpretation and numerical modelling suggest that cyclical periods of ice-sheet expansion to the continental margin, followed by retreat to the subglacial highlands, occurred up to thirty times. These fluctuations were paced by orbital changes and were a major influence on global sea levels. Ice-sheet models show that the nature of such oscillations is critically dependent on the pattern and extent of Antarctic topographic lowlands. Here we show that the basal topography of the Aurora Subglacial Basin of East Antarctica, at present overlain by 2-4.5 km of ice, is characterized by a series of well-defined topographic channels within a mountain block landscape. The identification of this fjord landscape, based on new data from ice-penetrating radar, provides an improved under¬standing of the topography of the Aurora Subglacial Basin and its surroundings, and reveals a complex surface sculpted by a succession of ice-sheet configurations substantially different from today's. At different stages during its fluctuations, the edge of the East Antarctic Ice Sheet lay pinned along the margins of the Aurora Subglacial Basin, the upland boundaries of which are currently above sea level and the deepest parts of which are more than 1 km below sea level. Although the timing of the channel incision remains uncertain, our results suggest that the fjord landscape was carved by at least two ice- flow regimes of different scales and directions, each of which would have over-deepened existing topographic depressions, reversing valley floor slopes.

(Table 1) Ice thickness of new subglacial lakes identified in the ICECAP RES data and of previously known subglacial lakes

Subglacial hydrology in East Antarctica is poorly understood, yet may be critical to the manner in which ice flows. Data from a new regional airborne geophysical survey (ICECAP) have transformed our understanding of the topography and glaciology associated with the 287,000 km**2 Aurora Subglacial Basin in East Antarctica. Using these data, in conjunction with numerical ice sheet modeling, we present a suite of analyses that demonstrate the potential of the 1000 km-long basin as a route for subglacial water drainage from the ice sheet interior to the ice sheet margin. We present results from our analysis of basal topography, bed roughness and radar power reflectance and from our modeling of ice sheet flow and basal ice temperatures. Although no clear-cut subglacial lakes are found within the Aurora Basin itself, dozens of lake-like reflectors are observed that, in conjunction with other results reported here, support the hypothesis that the basin acts as a pathway allowing discharge from subglacial lakes near the Dome C ice divide to reach the coast via the Totten Glacier.

BALAÃO – O QUE OUVE AS PALAVRAS DE EL, TEM O CONHECIMENTO DE ELYON E VÊ A VISÃO DE SHADDAI: UM ESTUDO DE NÚMEROS 22-24

A presente pesquisa busca avaliar exegeticamente o texto que se encontra na Bíblia, especificamente no livro de Números capítulos 22-24 que relata sobre um personagem conhecido como Balaão. A pesquisa tem também como objeto o estudo sobre o panteão de divindades relatado no mesmo texto, assim como também o estudo dos textos descobertos em Deir Alla, na Jord��nia, que apresentam um personagem designado como Balaão, possivelmente o mesmo personagem de Nm 22-24. A motivação que levou ao desenvolvimento dessa pesquisa foi o fato de se ter deparado com os conceitos dos diversos nomes divinos exibidos no texto, além da questão do profetismo fora de Israel, assim como as possibilidades hermenêuticas que se abrem para a leitura desse texto bíblico. O conceito geral sempre foi o de que Israel era a única nação onde existiam “verdadeiros” profetas e uma adoração a um único Deus, o “monoteísmo”. O que despertou interesse foi perceber, especialmente por meio da leitura dos livros bíblicos, que o profetismo não se restringiu somente a Israel. Ele antecede à formação do antigo Israel e já existia no âmbito das terras do antigo Oriente Médio, e que Israel ainda demorou muito tempo para ser monoteísta. Quem é esse Balaão, filho de Beor? Estudaremos sobre sua pessoa e sua missão. Examinaremos os textos de Deir Alla sobre Balaão e sua natureza de personagem mediador entre o divino e o humano. Esse personagem é apresentado como um grande profeta e que era famoso como intérprete de presságios divinos. Analisaremos a importante questão sobre o panteão de deuses que são apresentados na narrativa de Balaão nomeados como: El, Elyon Elohim e Shaddai, além de Yahweh. Entendemos, a princípio, que o texto possui uma conexão com a sociedade na qual foi criado e usando da metodologia exegética, faremos uma análise da narrativa em questão, buscando compreender o sentido do texto, dentro de seu cenário histórico e social. Cenário este, que nos apresentou esse profeta, não israelita, que profere bênçãos dos deuses sobre Israel e que, além disso, pronuncia maldições sobre os inimigos desse mesmo Israel. Percebemos que, parte do texto pesquisado é apresentado sob a ótica de Israel sobre as outras nações. A pesquisa defende, portanto, que o texto de Nm 22-24, além de nos apresentar um profeta fora de Israel igual aos profetas da Bíblia, defende que, o panteão de divindades também era adorado por Israel e que tais nomes são epítetos de uma mesma divindade, no caso YHWH. Defende, também, um delineamento de um projeto de domínio político e militar de Israel sobre as nações circunvizinhas.

Conformational changes couple Na+ and glucose transport

The mechanism by which cotransport proteins couple their substrates across cell membranes is not known. A commonly proposed model is that cotransport results from ligand-induced conformational transitions that change the accessibility of ligand-binding sites from one side of the membrane to the other. To test this model, we have measured the accessibility of covalent probes to a cysteine residue (Q457C) placed in the putative sugar-translocation domain of the Na+/glucose cotransporter (SGLT1). The mutant protein Q457C was able to transport sugar, but transport was abolished after alkylation by methanethiosulfonate reagents. Alkylation blocked sugar translocation but not sugar binding. Accessibility of Q457C to alkylating reagents required external Na+ and was blocked by external sugar and phlorizin. The voltage dependence of accessibility was directly correlated with the presteady–state charge movement of SGLT1. Voltage-jump experiments with rhodamine-6-maleimide-labeled Q457C showed that the time course and level of changes in fluorescence closely followed the presteady–state charge movement. We conclude that conformational changes are responsible for the coupling of Na+ and sugar transport and that Q457 plays a critical role in sugar translocation by SGLT1.

Restoration of β-adrenergic signaling in failing cardiac ventricular myocytes via adenoviral-mediated gene transfer

Cardiovascular gene therapy is a novel approach to the treatment of diseases such as congestive heart failure (CHF). Gene transfer to the heart would allow for the replacement of defective or missing cellular proteins that may improve cardiac performance. Our laboratory has been focusing on the feasibility of restoring β-adrenergic signaling deficiencies that are a characteristic of chronic CHF. We have now studied isolated ventricular myocytes from rabbits that have been chronically paced to produce hemodynamic failure. We document molecular β-adrenergic signaling defects including down-regulation of myocardial β-adrenergic receptors (β-ARs), functional β-AR uncoupling, and an up-regulation of the β-AR kinase (βARK1). Adenoviral-mediated gene transfer of the human β2-AR or an inhibitor of βARK1 to these failing myocytes led to the restoration of β-AR signaling. These results demonstrate that defects present in this critical myocardial signaling pathway can be corrected in vitro using genetic modification and raise the possibility of novel inotropic therapies for CHF including the inhibition of βARK1 activity in the heart.

Cotransport of water by the Na+/glucose cotransporter

Water is transported across epithelial membranes in the absence of any hydrostatic or osmotic gradients. A prime example is the small intestine, where 10 liters of water are absorbed each day. Although water absorption is secondary to active solute transport, the coupling mechanism between solute and water flow is not understood. We have tested the hypothesis that water transport is directly linked to solute transport by cotransport proteins such as the brush border Na+/glucose cotransporter. The Na+/glucose cotransporter was expressed in Xenopus oocytes, and the changes in cell volume were measured under sugar-transporting and nontransporting conditions. We demonstrate that 260 water molecules are directly coupled to each sugar molecule transported and estimate that in the human intestine this accounts for 5 liters of water absorption per day. Other animal and plant cotransporters such as the Na+/Cl−/γ-aminobutyric acid, Na+/iodide and H+/amino acid transporters are also able to transport water and this suggests that cotransporters play an important role in water homeostasis.

The role of thyroid hormone in zebrafish and axolotl development

Exogenous thyroid hormone (TH) induces premature differentiation of the zebrafish pectoral fins, which are analogous to the forelimbs of tetrapods. It accelerates the growth of the pelvic fins but not precociously. Goitrogens, which are chemical inhibitors of TH synthesis by the thyroid gland, inhibit the transition from larva to juvenile fish including the formation of scales, and pigment pattern; they stunt the growth of both pectoral and pelvic paired fins. Inhibition by goitrogens is rescued by the simultaneous addition of thyroxine. The effect of adding TH to the rearing water of the postembryonic Mexican axolotl was reinvestigated under conditions that permit continued growth and development. In addition to morphological changes that have been described, TH greatly stimulates axolotl limb growth causing the resulting larva to be proportioned as an adult in about two months. This study extends the known evolutionary relatedness of tetrapod limbs and fish fins to include the TH stimulation of salamander limb and zebrafish fin growth, and suggests that TH is required to complete the life cycle of a typical bony fish and a salamander at the same developmental stage that it controls anuran and flounder metamorphosis.

Germ-line transmission of transgenes in Xenopus laevis

Adult Xenopus laevis frogs made transgenic by restriction enzyme-mediated integration were bred to test the feasibility of establishing lines of frogs that express transgenes. All of the 19 animals raised to sexual maturity generated progeny that expressed the transgene(s). The patterns and levels of expression of green fluorescent protein transgenes driven by a viral promoter, rat promoter, and four X. laevis promoters were all unaffected by passage through the germ line. These results demonstrate the ease of establishing transgenic lines in X. laevis.

Preservation of myocardial β-adrenergic receptor signaling delays the development of heart failure after myocardial infarction

When the heart fails, there is often a constellation of biochemical alterations of the β-adrenergic receptor (βAR) signaling system, leading to the loss of cardiac inotropic reserve. βAR down-regulation and functional uncoupling are mediated through enhanced activity of the βAR kinase (βARK1), the expression of which is increased in ischemic and failing myocardium. These changes are widely viewed as representing an adaptive mechanism, which protects the heart against chronic activation. In this study, we demonstrate, using in vivo intracoronary adenoviral-mediated gene delivery of a peptide inhibitor of βARK1 (βARKct), that the desensitization and down-regulation of βARs seen in the failing heart may actually be maladaptive. In a rabbit model of heart failure induced by myocardial infarction, which recapitulates the biochemical βAR abnormalities seen in human heart failure, delivery of the βARKct transgene at the time of myocardial infarction prevents the rise in βARK1 activity and expression and thereby maintains βAR density and signaling at normal levels. Rather than leading to deleterious effects, cardiac function is improved, and the development of heart failure is delayed. These results appear to challenge the notion that dampening of βAR signaling in the failing heart is protective, and they may lead to novel therapeutic strategies to treat heart disease via inhibition of βARK1 and preservation of myocardial βAR function.

Overexpression of Xenopus laevis growth hormone stimulates growth of tadpoles and frogs

The role of growth hormone (GH) in amphibian metamorphosis is ambiguous based on experiments in which mammalian GH was administered to tadpoles and frogs. We have reexamined the effects of GH by producing transgenic Xenopus laevis that overexpress the cDNA encoding X. laevis GH. These transgenic tadpoles take the same length of time to reach metamorphosis as control tadpoles, but the transgenic tadpoles are twice as large. After metamorphosis, the transgenic frogs grow at a greatly accelerated rate and develop skeletal abnormalities reminiscent of acromegaly. The transgenic frogs are larger than mature frogs in a few months and die in about 1 year. At as early as 10 months of age, the males have mature sperm. We conclude that the growth-promoting effects of GH in this amphibian closely resemble those described for mammals. Although excess GH increases the size of the tadpole, it does not alter the developmental programs involved in metamorphosis.