Identification of a novel protein kinase mediating Akt survival signaling to the ATM protein

We identified a novel human AMP-activated protein kinase (AMPK) family member, designated ARK5, encoding 661 amino acids with an estimated molecular mass of 74 kDa. The putative amino acid sequence reveals 47, 45.8, 42.4, and 55% homology to AMPK-alpha1, AMPK-alpha2, MELK and SNARE respectively, suggesting that it is a new member of the AMPK family. It has a putative Akt phosphorylation motif at amino acids 595600, and Ser(600) was found to be phosphorylated by active Akt resulting in the activation of kinase activity toward the SAMS peptide, a consensus AMPK substrate. During nutrient starvation, ARK5 supported the survival of cells in an Akt-dependent manner. In addition, we also demonstrated that ARK5, when activated by Akt, phosphorylated the ATM protein that is mutated in the human genetic disorder ataxia-telangiectasia and also induced the phosphorylation of p53. On the basis of our current findings, we propose that a novel AMPK family member, ARK5, is the tumor cell survival factor activated by Akt and acts as an ATM kinase under the conditions of nutrient starvation.

Expression of ephs and ephrins in developing mouse inner ear

Levels of expression of mRNAs encoding the different Ephs and ephrins were measured by semi-quantitative reverse-transcription polymerase chain reaction in developing mouse whole inner ears, and in dissected fractions of the neonatal mouse inner ear. Nineteen of the 24 known Ephs and ephrins were surveyed. The results showed that between embryonic age (E) 11.5 days and E12.5, levels increased 10-300 times per unit of tissue. In neonatal mice, the fraction containing combined organ of Corti and spiral ganglion showed relatively strong expression of EphA4, EphB3, ephrin-A3, ephrin-B2 and ephrin-B3. In the lateral wall, EphA4, ephrin-A3 and ephrin-B2 were strongly expressed, while ephrin-A3 was particularly strongly expressed in utricular and saccular sensory epithelia. The results suggest that the Ephs and ephrins are likely to play a part in the differentiation of the structures of the inner ear, and show which Ephs and ephrins are most likely to play important roles in the different structures. (C) 2003 Elsevier Science B.V. All rights reserved.

Biaxial failure model for fiber reinforced concrete

Steel fiber reinforced concrete (SFRC) is widely applied in the construction industry. Numerical elastoplastic analysis of the macroscopic behavior is complex. This typically involves a piecewise linear failure curve including corner singularities. This paper presents a single smooth biaxial failure curve for SFRC based on a semianalytical approximation. Convexity of the proposed model is guaranteed so that numerical problems are avoided. The model has sufficient flexibility to closely match experimental results. The failure curve is also suitable for modeling plain concrete under biaxial loading. Since this model is capable of simulating the failure states in all stress regimes with a single envelope, the elastoplastic formulation is very concise and simple. The finite element implementation is developed to demonstrate the conciseness and the effectiveness of the model. The computed results display good agreement with published experimental data.

GAIP participates in budding of membrane carriers at the trans-Golgi network

Galpha interacting protein (GAIP) is a regulator of G protein signaling protein that associates dynamically with vesicles and has been implicated in membrane trafficking, although its specific role is not yet known. Using an in vitro budding assay, we show that GAIP is recruited to a specific population of trans-Golgi network-derived vesicles and that these are distinct from coatomer or clathrin-coated vesicles. A truncation mutant (NT-GAIP) encoding only the N-terminal half of GAIP is recruited to trans -Golgi network membranes during the formation of vesicle carriers. Overexpression of NT-GAIP induces the formation of long, coated tubules, which are stabilized by microtubules. Results from the budding assay and from imaging in live cells show that these tubules remain attached to the Golgi stack rather than being released as carrier vesicles. NT-GAIP expression blocks membrane budding and results in the accumulation of tubular carrier intermediates. NT-GAIP-decorated tubules are competent to load vesicular stomatitis virus protein G-green fluorescent protein as post-Golgi, exocytic cargo and in cells expressing NT-GAIP there is reduced surface delivery of vesicular stomatitis virus protein G-green fluorescent protein. We conclude that GAIP functions as an essential part of the membrane budding machinery for a subset of post-Golgi exocytic carriers derived from the trans-Golgi network.

Document retrieval for e-mail search and discovery using Formal Concept Analysis

This paper discusses a document discovery tool based on Conceptual Clustering by Formal Concept Analysis. The program allows users to navigate e-mail using a visual lattice metaphor rather than a tree. It implements a virtual. le structure over e-mail where files and entire directories can appear in multiple positions. The content and shape of the lattice formed by the conceptual ontology can assist in e-mail discovery. The system described provides more flexibility in retrieving stored e-mails than what is normally available in e-mail clients. The paper discusses how conceptual ontologies can leverage traditional document retrieval systems and aid knowledge discovery in document collections.

Role of HuR in skeletal myogenesis through coordinate regulation of muscle differentiation genes

In this report, we investigate the role of the RNA-binding protein HuR during skeletal myogenesis. At the onset of myogenesis in differentiating C2C12 myocytes and in vivo in regenerating mouse muscle, HuR cytoplasmic abundance increased dramatically, returning to a predominantly nuclear presence upon completion of myogenesis. mRNAs encoding key regulators of myogenesis-specific transcription (myogenin and MyoD) and cell cycle withdrawal (p21), bearing AU-rich regions, were found to be targets of HuR in a differentiation-dependent manner. Accordingly, mRNA half-lives were highest during differentiation, declining when differentiation was completed. Importantly, HuR-overexpressing C2C12 cells displayed increased target mRNA expression and half-life and underwent precocious differentiation. Our findings underscore a critical function for HuR during skeletal myogenesis linked to HuR's coordinate regulation of muscle differentiation genes.

OxyR acts as a repressor of catalase expression in Neisseria gonorrhoeae

It has been reported that Neisseria gonorrhoeae possesses a very high level of catalase activity, but the regulation of catalase expression has not been investigated extensively. In Escherichia coli and Salmonella enterica serovar Typhimurium, it has been demonstrated that OxyR is a positive regulator of hydrogen peroxide-inducible genes, including the gene encoding catalase. The oxyR gene from N. gonorrhoeae was cloned and used to complement an E. coli oxyR mutant, confirming its identity and function. The gene was inactivated by inserting a kanamycin resistance cassette and used to make a knockout allele on the chromosome of N. gonorrhoeae strain 1291. In contrast to E. coli, the N. gonorrhoeae oxyR::kan mutant expressed ninefold-more catalase activity and was more resistant to hydrogen peroxide killing than the wild type. These data are consistent with OxyR in N. gonorrhoeae acting as a repressor of catalase expression.

Digitally-implemented naturally sampled PWM suitable for multilevel converter control

For dynamic closed loop control of a multilevel converter with a low pulse number (ratio of switching frequency to synthesized fundamental), natural sampled pulse-width modulation (PWM) is the best form of modulation. Natural sampling does not introduce distortion or a delayed response to the modulating signal. However previous natural sampled PWM implementations have generally been analog. For a modular multilevel converter, a digital implementation has advantages of accuracy and flexibility. Re-sampled uniform PWM is a novel digital modulation technique which approaches the performance of natural PWM. Both hardware and software implementations for a five level multilevel converter phase are presented, demonstrating the improvement over uniform PWM.

3: Rehabilitation principles for treating chronic musculoskeletal injuries

Evaluation of patients for rehabilitation after musculoskeletal injury involves identifying, grading and assessing the injury and its impact on the patient's normal activities. Management is guided by a multidisciplinary team, comprising the patient, doctor and physical therapist, with other health professionals recruited as required. Parallel interventions involving the various team members are specified in a customised management plan. The key component of the plan is active mobilisation utilising strengthening, flexibility and endurance exercise programs. Passive physical treatments (heat, ice, and manual therapy), as well as drug therapy and psychological interventions, are used as adjunctive therapy. Biomechanical devices or techniques (eg, orthotic devices) may also be helpful. Coexisting conditions such as depression and drug dependence are treated at the same time as the injury. Effective team communication, simulated environmental testing and, for those employed, contact with the employer facilitate a staged return to normal living, sports and occupational activities.

Carreiras p??blicas em uma ordem democr??tica: entre os modelos burocr??tico e gerencial

Refletindo sobre modelo de carreira mais adequado para a Administra????o P??blica nesta era de economia globalizada e de maiores exig??ncias de efici??ncia e flexibilidade na gest??o dos aparatos governamentais, questiona-se aqui a id??ia de que o modelo burocr??tico deva ser substitu??do pelo modelo gerencial. Considerando essa id??ia apenas parcialmente verdadeira, nossa argumenta????o vai na seguinte dire????o: como a burocracia ?? a forma espec??fica de organiza????o do aparato administrativo do Estado de Direito, este modelo n??o pode ser rejeitado, sob pena de comprometimento desse Estado. Mas ele precisa ser flexibilizado, superando e reduzindo o formalismo excessivo e a rigidez que sua realiza????o hist??rica possa ter gerado nos diferentes pa??ses. Igualmente, deve ser aperfei??oado em seus mecanismos de controle, at?? como condi????o para sua manuten????o eficaz nos governos democr??ticos contempor??neos.

Gobernaciones y nueva gesti??n p??blica en Venezuela

A fines de los ???80, el Estado venezolano inici?? una descentralizaci??n pol??tico-territorial produciendo cambios en las gobernaciones, instancias receptoras de competencias en este proceso, las cuales realizan reformas a trav??s de la estrategia selectiva, incorporando algunas de la propuestas de la nueva gesti??n p??blica. Este trabajo explora estas reformas. Se observan: diferencias entre los servicios sociales y los relacionados directamente con la econom??a; privatizaci??n de ??stos; traspaso a la sociedad civil de algunos servicios sociales, creaci??n de entes descentralizados; automatizaci??n de procesos; flexibilizaci??n laboral; iniciativas con lento avance en rendici??n de cuentas por resultados y capacitaci??n para una nueva cultura administrativa. En conclusi??n: la tendencia es a la conformaci??n de una gesti??n p??blica eficiente sobre la base de la reducci??n del aparato estatal, de costos sociales, as?? como de costos y conflictos laborales y escasa incorporaci??n de las propuestas de participaci??n que permiten profundizar la democracia y promover el bienestar social.

Gest??o do conhecimento como sistema de gest??o para o setor p??blico

O conhecimento e a gest??o do conhecimento t??m sido focos de uma intensa discuss??o sobre como as organiza????es privadas podem obter vantagens competitivas e atingir elevados patamares de flexibilidade, produtividade e inova????o, sem que, no entanto, esta disciplina seja devidamente debatida e/ou incorporada pelo setor p??blico brasileiro. A partir da perspectiva dos autores de maior prest??gio no assunto, este trabalho apresenta os principais conceitos e aspectos relacionados a este novo paradigma de gest??o organizacional, de modo a identificar quais seriam os principais desafios para a implanta????o de projetos de gest??o do conhecimento no ??mbito da administra????o p??blica. Adicionalmente, este trabalho prop??e a ado????o de um novo modelo de gest??o do conhecimento, mais consistente e adequado ??s organiza????es p??blicas. O modelo de gest??o apresentado prop??e-se a servir como susbs??dio para um debate te??rico e metodol??gico sobre como a gest??o do conhecimento poderia ser incorporada ?? tarefa de buscar melhores n??veis de gest??o para as organiza????es p??blicas brasileiras, de forma a torn??-las mais capacitadas a fazerem frente ??s interfer??ncias que j?? provocaram a fal??ncia das inst??ncias de planejamento e or??amento no setor p??blico, o abandono da padroniza????o e da melhoria dos procedimentos administrativos, a desestrutura????o da fun????o p??blica e das pol??ticas de recursos humanos, a persistente descontinuidade de projetos e de pol??ticas p??blicas, assim como permita resgatar a credibilidade nos mecanismos internos de repress??o e de puni????o ??queles agentes que adotam pr??ticas ou condutas que v??o de encontro aos princ??pios morais e ??s normas jur??dicas estabelecidas.

A moderniza????o do estado e a ger??ncia p??blica

O artigo analisa a problem??tica da moderniza????o do Estado vista como um processo de constitui????o de cidadania e de otimiza????o dos recursos p??blicos. Os autores focalizam, por um lado, o atendimento aos usu??rios, a qualidade dos servi??os e a transpar??ncia. Por outro lado, a incorpora????o de t??cnicas de gest??o avan??adas ?? considerada indispens??vel para o aumento da efic??cia e da efici??ncia no setor p??blico. Os principais problemas discutidos no artigo incluem: racionalidade do setor p??blico racionalidade das empresas privadas; incentivos e motiva????o dos servidores p??blicos; rigidez dos procedimentos administrativos; margem de decis??o dos gestores; sistemas de acesso a informa????o; import??ncia da gest??o de pessoal e da valoriza????o do trabalho no setor p??blico; papel dos gerentes na moderniza????o das institui????es p??blicas; cargos de carreira, cargos de confian??a; mecanismos de recrutamento e reten????o e sistemas de capacita????o dos servidores p??blicos. Os autores concluem que, devido ??s inova????es constantes em mat??ria de ger??ncia p??blica, n??o existe hoje um perfil gerencial definitivo como resposta ??s necessidades do Estado. Pelo contr??rio, o que se observa ?? uma crescente complexidade da gest??o p??blica que continuar?? oscilando entre a pol??tica e a tecnocracia, entre a maior flexibilidade e as exig??ncias de controle, entre a ado????o das t??cnicas de gest??o e a recupera????o da tradi????o administrativa e a cultura da fun????o p??blica.

Reformas pr??-mercado, rigidez constitucional e revis??o judicial: Brasil, Argentina e Uruguai em perspectiva comparada

Este artigo aborda a import??ncia da distribui????o de poderes de agenda e de veto dos cidad??os e dos Poderes Executivo, Legislativo e Judici??rio para viabilizar a implementa????o de reformas pr??-mercado no Brasil, na Argentina e no Uruguai em perspectiva comparada. Nesse sentido, o artigo aborda os temas da flexibilidade constitucional, da din??mica de forma????o das leis e da presen??a ou aus??ncia de revis??o judicial. A hip??tese subjacente a este artigo ?? a de que quanto mais r??gida a Constitui????o ??? vari??vel que envolve o poder de agenda e de veto dos cidad??os, do Executivo, do Legislativo e do Judici??rio ??? mais bem desenhado deve ser o jogo pol??tico para a viabiliza????o de implementa????o das reformas. Para exemplificar este artigo, foram analisadas as reformas previdenci??rias implantadas nos pa??ses em estudo.

Uma breve compara????o entre os mercados de trabalho do setor p??blico e privado

Este artigo apresenta diversas caracter??sticas dos mercados de trabalho do setor p??blico e privado, ressaltando as disparidades entre ambos e, mais especificamente, as distor????es observadas no setor p??blico, a fim de demonstrar o grau de segmenta????o entre ambos. As compara????es se d??o em torno do comportamento do emprego, do perfil dos trabalhadores e da din??mica das remunera????es. A an??lise evidencia que a crise fiscal e a rigidez da legisla????o s??o determinantes fundamentais das caracter??sticas e distor????es (e conseq??entemente da segmenta????o) observadas no setor p??blico e que a flexibiliza????o das regras atuais, assim como as reformas constitucionais em curso, constituem importante condi????o para a aproxima????o entre os dois mercados e a melhoria da gest??o de recursos humanos na administra????o p??blica.