187 research outputs found
Delta-type senior civil service for the 21st century
No full textO artigo estuda um aspecto da reforma do Estado que, segundo o autor, tem sido
sistematicamente negligenciado pelas atuais propostas que focalizam o modelo da administração
gerencial. Trata-se das funções vitais do governo de tomar decisões críticas e
adotar políticas diante das mudanças provocadas pela revolução global. Segundo Dror, as
tarefas de alto comando (high-order tasks) de definir trajetórias e as novas formas de
governança exigem um ajuste significativo do governo central. Este ajuste refere-se, principalmente,
à concepção e ao desenvolvimento de um novo padrão de funcionários do
primeiro escalão público, o qual contribuiria com conhecimento e perspectivas para
enfrentar as tarefas de alto comando.
O autor estabelece uma tipologia para caraterizar a evolução do perfil do serviço
público, marcando suas fases históricas: a) tipo alpha (status atribuído, fusão de papéis
políticos e administrativos); b) tipo beta (compra de cargos governamentais) e c) tipo
gamma (quase profissionalismo). O novo funcionário sênior, do tipo delta, se concentraria
nas questões de ordem estratégica, deixando as funções gerenciais para servidores do
tipo gamma e para os serviços técnicos.
Após uma breve análise, Dror conclui que o funcionalismo público de primeiro
escalão, na maioria dos países (com exceção de alguns países do Sudeste Asiático),
encontra-se obsoleto, com base profissional inadequada e capacidade insuficiente para
lidar com escolhas críticas.El artículo estudia un aspecto de la reforma del Estado que, según el autor, ha sido
sistematicamente negligenciado por las actuales propuestas que enfocan el modelo de la
administración gerencial. Se trata de las funciones vitales del gobierno de tomar decisiones
críticas y adoptar políticas delante de los cambios provocados por la revolución global.
Según Dror, las tareas de alto comando (high-order tasks) de definir trayectorias y las
nuevas formas de governanza exigen un ajuste significativo del gobierno central. Este
ajuste se refiere, principalmente, a la concepción y al desarollo de un nuevo padrón de
funcionarios de primera jerarquía, lo que contribuiria con conocimiento y perspectivas
para afrontar las tareas de alto comando.
El autor establece una tipologia para caracterizar la evolución del perfil del servicio
público, marcando sus fases historicas: a) tipo alpha: (status atribuido, fusión de papeles
políticos y administrativos); b) tipo beta: (compra de cargos gubernamentales) y c) tipo
gamma: (casi profesionalismo). El nuevo funcionario senior, del tipo delta, se concentraria
en las cuestiones de orden estratégica, quedándose las funciones gerenciales para los
servidores del tipo gamma y para los servicios técnicos.
Tras un breve análisis, Dror concluye que el funcionarismo público de primera jerarquía,
en la mayoria de los países (excepto algunos países del Sudeste Asiático), se encuentra
obsoleto, con bases professionales inadecuadas y capacidad insuficiente para lidar con
opciones críticas.The article alludes to one aspect of the State reform that, according to the author, has
been systematically neglected by present proposals focused on the management
administration model. Government’s vital functions are to make critical decisions and to
adopt policies when facing changes brought about by the global revolution. According to
Dror, the high-order tasks of defining trajectories and new forms of governance demand
a significant adjustment of central governments. This adjustment refers mainly to the
creation and development of a new profile of senior civil servants, who would present
their contribution to high-order tasks with more knowledge and perspective.
The author establishes a categorization to illustrate the evolution of the civil servant
profile, highlighting its historical phases: a) alpha type (attributed status, fusion of
political and administrative roles); b) beta type (purchase of governmental positions);
and c) gamma type (quasi-professionalism). The new delta-type senior civil servant
should concentrate on strategical issues, leaving managerial functions to gamma-type
civil servants and to technical services.
After a brief analysis, Dror declares that the senior civil service in most countries
(exceptions to be made to some East-Asian countries) is obsolete, lacking adequate
professional basis and capacity to deal with critical decisions.Número padronizado: v. 48, n. 2 (1997)
Revista do Serviço Público - RSP, ano 48, n. 2, p. 5-26Administração PúblicaISSN impresso: 0034-9240ISSN eletrônico: 2357-801
Abstract 1369: A novel anti-angiogenic vector with vascular disrupting activity as a promising treatment for metastatic cancer
No full textAbstract
A novel anti-angiogenic vector with vascular disrupting activity as a promising treatment for metastatic cancer
Breitbart E1, Greenberger S2, Varda-Bloom N2, Bangio L1, Harats D1
1VBL Therapeutics, Or Yehuda, Israel, 2Sheba Medical Center, Ramat Gan, Israel
Background: A major drawback of current approaches to cancer therapy is the lack of tissue-specific targeting. We have developed both tissue and condition-specific expression vascular targeting system (VTS) platform directed to areas in which angiogenesis is taking place, without perpetually harming the body's healthy tissues, to destroy these newly formed blood vessels of solid tumors. We have constructed VB-111 as a vascular disruptive (VDA) and anti-angiogenic agent.
Results: In vitro, VB-111 induced a dose dependent apoptotic death in HUVEC but not in non endothelial cells confirming its specificity. In a comprehensive set of in vivo studies employing the Lewis Lung metastasis mouse model, VB111 was safe and specific with activity only in the metastatic lesion themselves. VB-111 induced a dose dependent reduction of 90% in tumor burden of lung metastases with one injection and similar efficacy in other tumor models. Evaluation of the activity of Sutent in Lewis lung metastasis model showed better efficacy of VB-111 as compared to Sutent 40 or 80 mg/kg. Additive effect was reached when mice were treated with VB-111 and Doxorubicin 2.5mg/kg.
Conclusions: Collectively, our studies demonstrate that VB-111 is safe and specific. VB111 shows a dual action of anti-angiogenic and vascular disruptive agent. VB-111 has the potential to be utilized as a relatively broad-spectrum anticancer agent efficacious in different types of solid tumors. These findings have prompted us to proceed to clinical trials that are reported elsewhere.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1369.</jats:p
Maternal dietary ALA prevents atherogenic lipid disarray in the offspring via fetal gene programming
No full text
Open Access to Research: Changing Researcher Behavior Through University and Funder Mandates
No full textThe primary target of the worldwide Open Access initiative is the 2.5 million articles published every year in the planet's 25,000 peer-reviewed research journals across all scholarly and scientific fields. Without exception, every one of these articles is an author give-away, written, not for royalty income, but solely to be used, applied and built upon by other researchers. The optimal and inevitable solution for this give-away research is that it should be made freely accessible to all its would-be users online and not only to those whose institutions can afford subscription access to the journal in which it happens to be published. Yet this optimal and inevitable solution, already fully within the reach of the global research community for at least two decades now, has been taking a remarkably long time to be grasped. The problem is not particularly an instance of "eDemocracy" one way or the other; it is an instance of inaction because of widespread misconceptions (reminiscent of Zeno's Paradox). The solution is for the world's research institutions and funders to (1) extend their existing "publish or perish" mandates so as to (2) require their employees and fundees to maximize the usage and impact of the research they are employed and funded to conduct and publish by (3) depositing their final drafts in their Open Access (OA) Institutional Repositories immediately upon acceptance for publication in order to (4) make their findings freely accessible to all their potential users webwide. OA metrics can then be used to measure and reward research progress and impact; and multiple layers of links, tags, commentary and discussion can be built upon and integrated with the primary research
Cellular and humoral immune responses to heat shock protein 65 are both involved in promoting fatty-streak formation in LDL-receptor deficient mice
No full textAbstractOBJECTIVESThis study was designed to determine the role of cellular and humoral immune responses to heat shock protein 65 (HSP65) in murine atherosclerosis.BACKGROUNDInflammatory processes appear to influence the progression of atherosclerosis. Immunization with HSP65 was previously shown to induce arteriosclerosis in rabbits and to enhance fatty-streak formation in mice. However, it has not been demonstrated directly whether HSP65-reactive antibodies and lymphocytes are separately capable of influencing lesion formation.METHODSLow density lipoprotein-receptor deficient (LDL-RD) mice were immunized with HSP65 or control bovine serum albumin (BSA). Lymph-node cells, splenocytes and immunoglobulin G (IgG) were obtained from the immunized mice and transferred separately to six groups of syngenic LDL-RD mice.RESULTSAdoptive transfer of HSP65-reactive lymph node cells increased fatty-streak formation in comparison with mice treated with BSA-primed cells. Similarly, transfer of splenocytes reactive with HSP65 led to enhanced fatty-streak generation compared with mice injected with BSA-sensitized splenocytes. Repeated intraperitoneal administration of IgG from serum of HSP65-immunized mice (every 10 days) enhanced fatty-streak formation in mice in comparison with their anti-BSA-IgG injected littermates.CONCLUSIONSAntibodies and lymphocytes reactive to HSP65 promote fatty-streak formation in mice, providing direct evidence for the proatherogenic properties of cellular and humoral immunity to HSP65
Oral tolerance with heat shock protein 65 attenuates mycobacterium tuberculosis-inducedand high-fat-diet-driven atherosclerotic lesions
No full textAbstractObjectivesThe goal of this study was to explore the efficacy of oral tolerance with heat shock protein (HSP) 65 in two apparently non-overlapping models of murine atherosclerosis.BackgroundAtherosclerosis is considered to be a chronic inflammatory process. Autoimmune mechanisms have been shown to influence atherogenesis in experimental animal models. Heat shock protein 65 is a candidate antigen thought to drive a proatherogenic immune-mediated response. Mucosal tolerance is a therapeutic means of accomplishing immune unresponsiveness toward a given antigen by feeding it before active induction of the disorder.MethodsLow-density lipoprotein receptor deficient mice were fed with different doses of HSP65 every other day for 10 days. Feeding with either bovine serum albumin (BSA) or phosphate buffered saline (PBS) served as control. One day after the last feeding, mice were challenged either by immunization with heat killed Mycobacterium tuberculosis or by a high fat diet.ResultsLymphocyte reactivity from mice fed with HSP65 and immunized either against HSP65 or M. tuberculosis was significantly reduced in comparison with BSA-fed mice. Moreover, co-incubation of splenocytes—from mice with tolerance induced with HSP65 but not BSA—with HSP65-reactive lymphocytes resulted in the suppression of HSP65 reactivity by the latter cells. Interleukin-4 production by HSP65-fed and immunized mice was increased upon priming with respective protein. Early atherosclerosis was attenuated in HSP65-fed mice, compared with either BSA- or PBS-fed mice, regardless of the method employed to induce fatty streaks (M. tuberculosis immunization or high-fat diet).ConclusionsOral tolerance induced with HSP65 could prove to be a novel means of suppressing atherogenesis
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