Site-directed mutagenesis of the ATM promoter: Consequences for response to proliferation and ionizing radiation

Although ATM, the protein defective in ataxia-telangiectasia (A-T), is activated primarily by radiation, there is also evidence that expression of the protein can be regulated by both radiation and growth factors. Computer analysis of the ATM promoter proximal 700-bp sequence reveals a number of potentially important cis-regulatory sequences. Using nucleotide substitutions to delete putative functional elements in the promoter of ATM, we examined the importance of some of these sites for both the basal and the radiation-induced activity of the promoter. In lymphoblastoid cells, most of the mutations in transcription factor consensus sequences [Sp1(1), Sp1(2), Cre, Ets, Xre, gammaIre(2), a modified AP1 site (Fse), and GCF] reduced basal activity to various extents, whereas others [gammaIre(1), NF1, Myb] left basal activity unaffected. In human skin fibroblasts, results were generally the same, but the basal activity varied up to 8-fold in these and other cell lines. Radiation activated the promoter approximately 2.5-fold in serum-starved lymphoblastoid cells, reaching a maximum by 3 hr, and all mutated elements equally blocked this activation. Reduction in Sp1 and AP1 DNA binding activity by serum starvation was rapidly reversed by exposure of cells to radiation. This reduction was not evident in A-T cells, and the response to radiation was less marked. Data provided for interaction between ATM and Sp1 by protein binding and co-immunoprecipitation could explain the altered regulation of Sp1 in A-T cells. The data described here provide additional evidence that basal and radiation-induced regulation of the ATM promoter is under multifactorial control. (C) 2003 Wiley-Liss, Inc.

Genetic disruption of the growth hormone receptor does not influence motoneuron survival in the developing mouse

In the rodent central nervous system (CNS) during the five days prior to birth, both growth hormone (GH) and its receptor (GHR) undergo transient increases in expression to levels considerably higher than those found postnatally. This increase in expression coincides with the period of neuronal programmed cell death (PCD) in the developing CNS. To evaluate the involvement of growth hormone in the process of PCD, we have quantified the number of motoneurons in the spinal cord and brain stem of wild type and littermate GHR-deficient mice at the beginning and end of the neuronal PCD period. We found no change in motoneuron survival in either the brachial or lumbar lateral motor columns of the spinal cord or in the trochlear, trigeminal, facial or hypoglossal nuclei in the brain stem. We also found no significant differences in spinal cord volume, muscle fiber diameter, or body weight of GHR-deficient fetal mice when compared to their littermate controls. Therefore, despite considerable in vitro evidence for GH action on neurons and glia, genetic disruption of GHR signalling has no effect on prenatal motoneuron number in the mouse, under normal physiological conditions. This may be a result of compensation by the signalling of other neurotrophic cytokines.

Discovering the Law Again: John Grisham, Ed Stevens and the Postmaterial Lawyer

This paper uses three films adapted from the novels of John Grisham, The Firm, The Rainmaker and A Time To Kill, as well as associated television series like Ed to map a vernacular theory of what I have termed the 'postmaterial' lawyer. Grisham's work has been the focus of much critique by legal scholars who suggests he hates lawyers, is critical of the concept of law, and provides 'outlandishly' happy endings. I will challenge these critiques and, in tracing the history of legal thrillers and trial movies, suggest that Grisham and the related texts' explorations of how a just practitioner can operate in an unjust system constitute a powerful interrogation of what law can be.

Radical formation on gamma-radiolysis of poly [(methacrylic acid)-co-acrylonitri

The radicals formed on gamma-radiolysis of a series of copolymers of methacrylic acid and acrylonitrile have been investigated by ESR spectroscopy. This series of copolymers spanned the full composition range and the study was carried out at 77 K and ambient temperature. The radicals formed in the copolymers at 77 and 303 K were found to be similar to those found in the two homopolymers, but in the intermediate composition range the presence of acrylonitrile propagation radicals was also detected. These radicals were not observed to be formed in significant quantities on the radiolysis of polyacrylonitrile. They are believed to result from a scission of the main chain at methacrylic acid/acrylonitrile diad sequences following loss of the methacrylic acid carboxyl group. At 77 K, the copolymers with high methacrylic acid contents were found to be more sensitive to radical formation than the methacrylic acid homopolymer, but this enhanced sensitivity was not evident at ambient temperature, where the G-values for radical formation for the copolymers were slightly less than the values for the homopolymers. (C) 2003 Society of Chemical Industry.

A study of the radiation degradation of styrene/alkane and α-methylstyrene/alkane copolymers

The effects of copolymer composition and microstructure on the radiation chemistry of styrene/alkane and alpha-methylstyrene/alkane copolymers have been studied. The primary radical species formed on radiolysis of the copolymers at 77 K, and identified by ESR spectroscopy, are the same as those formed during radiolysis of the homopolymers. The yields of radicals for the copolymer are as predicted assuming that the cross-section is proportional to the electron density of each component; however, there is some evidence of radical migration to aromatic groups at 77 K. Changes in molecular structure on irradiation were detected by using C-13 NMR spectroscopy. Evidence of the consumption of terminal double bonds, and chain scission in alpha-methylstyrene/alkane copolymers was found. Measurements of viscosity supported the mechanism of cross-linking predominating in styrene/alkane copolymers, while in alpha-methylstyrene/alkane copolymers chain scission was the major result of irradiation. (C) 2003 Society of Chemical Industry.

Colet??nea planejamento e or??amento governamental: volume 1: pref??cio

Pref??cio da colet??nea, estabelece seu objetivo de fornecer material did??tico focado no desenvolvimento profissional da administra????o p??blica brasileira.

Colet??nea planejamento e or??amento governamental: volume 1: introdu????o

Esta introdu????o, al??m de apresentar e contextualizar cada tem??tica, objetiva ser um texto did??tico b??sico para os cursos da ENAP. Nesse sentido, traz, adicionalmente, uma s??ntese dos temas desenvolvidos nos respectivos textos da colet??nea.

Colet??nea planejamento e or??amento governamental: volume 1: o plano como aposta

O texto sintetiza os principais fundamentos do m??todo PES. Esse m??todo contrap??e-se ao planejamento tradicional e prop??e uma abordagem tecnopol??tica do planejamento.

Colet??nea planejamento e or??amento governamental: volume 1: o quadro l??gico - um m??todo para planejar e gerenciar mudan??as

O texto traz uma s??ntese do Enfoque do Quadro L??gico e constr??i um exemplo da matriz de planejamento do projeto, que ilustra para o leitor a estrutura do QL

Colet??nea planejamento e or??amento governamental: volume 1: a experi??ncia brasileira em planejamento econ??mico - uma s??ntese hist??rica

O texto faz uma s??ntese did??tica dos planos de desenvolvimento e de estabiliza????o econ??mica implementados no Brasil, nas ??ltimas seis d??cadas. O relato abrange desde os primeiros exerc??cios de planejamento, no imediato p??s-Segunda Guerra Mundial, at?? os ??ltimos PPAs e, ainda, faz refer??ncias ??s tentativas de planejamento de longo prazo com o ???Brasil 2020???, no governo Fernando Henrique.

Colet??nea planejamento e or??amento governamental: volume 1: a retomada do planejamento governamental no Brasil e seus desafios

O texto apresenta um cen??rio dos avan??os recentes no planejamento governamental. Em sua primeira parte, procura referenciar o debate atual acerca das possibilidades, das limita????es e dos avan??os introduzidos pelo PPA, especialmente a partir de 2000, com destaque para a integra????o ???plano-or??amento???, por meio de programas formulados com origem em problemas ou demandas da sociedade; um plano e um or??amento orientados para resultado; e o novo sistema de planejamento e or??amento como pe??a fundamental para a implanta????o da gest??o por resultados no Pa??s. A segunda parte do texto refere-se ao modelo de gest??o do plano. S??o apresentados os fundamentos do modelo de sua gest??o e os avan??os propostos para o PPA 2004-2007. Em s??ntese, a gest??o do plano ?? fundamentada no princ??pio da responsabiliza????o e nos processos de monitoramento, avalia????o e retroalimenta????o do ciclo do gasto p??blico

Colet??nea planejamento e or??amento governamental: volume 1: a metodologia de gest??o estrat??gica do NAE

O texto incorpora uma diversidade de ferramentas de planejamento estrat??gico. Sua principal caracter??stica ?? a de ver o planejamento estrat??gico como um processo e n??o apenas como um projeto que se finda com a antevis??o de cen??rios prospectivos e suas poss??veis solu????es estrat??gicas.