Exposure to aristolochic acid (AA) causes aristolochic acid nephropathy (AAN) and Balkan endemic nephropathy (BEN). Conflicting results have been found for the role of human sulfotransferase 1A1 (SULT1A1) contributing to the metabolic activation of aristolochic acid I (AAI) in vitro. We evaluated the role of human SULT1A1 in AA bioactivation in vivo after treatment of transgenic mice carrying a functional human SULT1A1-SULT1A2 gene cluster (i.e. hSULT1A1/2 mice) and Sult1a1(−/−) mice with AAI and aristolochic acid II (AAII). Both compounds formed characteristic DNA adducts in the intact mouse and in cytosolic incubations in vitro. However, we did not find differences in AAI-/AAII-DNA adduct levels between hSULT1A1/2 and wild-type (WT) mice in all tissues analysed including kidney and liver despite strong enhancement of sulfotransferase activity in both kidney and liver of hSULT1A1/2 mice relative to WT, kidney and liver being major organs involved in AA metabolism. In contrast, DNA adduct formation was strongly increased in hSULT1A1/2 mice compared to WT after treatment with 3-nitrobenzanthrone (3-NBA), another carcinogenic aromatic nitro compound where human SULT1A1/2 is known to contribute to genotoxicity. We found no differences in AAI-/AAII-DNA adduct formation in Sult1a1(−/−) and WT mice in vivo. Using renal and hepatic cytosolic fractions of hSULT1A1/2, Sult1a1(−/−) and WT mice, we investigated AAI-DNA adduct formation in vitro but failed to find a contribution of human SULT1A1/2 or murine Sult1a1 to AAI bioactivation. Our results indicate that sulfo-conjugation catalysed by human SULT1A1 does not play a role in the activation pathways of AAI and AAII in vivo, but is important in 3-NBA bioactivation.
Exposure to aristolochic acid (AA) causes aristolochic acid nephropathy (AAN) and Balkan endemic nephropathy (BEN). Conflicting results have been found for the role of human sulfotransferase 1A1 (SULT1A1) contributing to the metabolic activation of aristolochic acid I (AAI) in vitro. We evaluated the role of human SULT1A1 in AA bioactivation in vivo after treatment of transgenic mice carrying a functional human SULT1A1-SULT1A2 gene cluster (i.e. hSULT1A1/2 mice) and Sult1a1(−/−) mice with AAI and aristolochic acid II (AAII). Both compounds formed characteristic DNA adducts in the intact mouse and in cytosolic incubations in vitro. However, we did not find differences in AAI-/AAII-DNA adduct levels between hSULT1A1/2 and wild-type (WT) mice in all tissues analysed including kidney and liver despite strong enhancement of sulfotransferase activity in both kidney and liver of hSULT1A1/2 mice relative to WT, kidney and liver being major organs involved in AA metabolism. In contrast, DNA adduct formation was strongly increased in hSULT1A1/2 mice compared to WT after treatment with 3-nitrobenzanthrone (3-NBA), another carcinogenic aromatic nitro compound where human SULT1A1/2 is known to contribute to genotoxicity. We found no differences in AAI-/AAII-DNA adduct formation in Sult1a1(−/−) and WT mice in vivo. Using renal and hepatic cytosolic fractions of hSULT1A1/2, Sult1a1(−/−) and WT mice, we investigated AAI-DNA adduct formation in vitro but failed to find a contribution of human SULT1A1/2 or murine Sult1a1 to AAI bioactivation. Our results indicate that sulfo-conjugation catalysed by human SULT1A1 does not play a role in the activation pathways of AAI and AAII in vivo, but is important in 3-NBA bioactivation.
Resumo A educacao profissional e tecnologica constitui-se em um elemento importante no âmbito do desenvolvimento socioeconomico e produtivo-tecnologico regional a demandar politicas publicas para a educacao basica e de correlatas politicas de fomento a ciencia e tecnologia, devidamente, balizadas por efetivo planejamento participativo e de analise diagnostica da realidade local/nacional. Destaca-se a relevância do processo legislativo na elaboracao/regulamentacao de politicas publicas a requerer o reexame da legislacao federal de ensino. No Brasil, a reforma da legislacao da educacao profissional e tecnologica desenvolveu-se sob a egide da Lei de Diretrizes e Bases da Educacao Nacional no 9.394/96, e posterior legislacao complementar: Decreto Federal 2.208/97, Resolucao do Conselho Nacional de Educacao/Câmara de Educacao Basica (CNE/CEB) no 04/99, e Parecer CNE/CEB no 16/99. A reforma foi marcadamente caracterizada pelo Decreto Federal no 2.208/97 que determinou a dissociacao entre ensino tecnico e medio, de forma a reavivar a historica dicotomia entre: formacao geral/propedeutica e formacao/qualificacao profissional. Tal Decreto foi objetivo de severas criticas, especialmente, pelas ingerencias e distorcoes acarretadas ao principio de integracao/articulacao entre ensino medio e ensino tecnico. Nao obstante, o Decreto Federal no 2.208/97 foi revogado mediante a publicacao do atual Decreto Federal no 5.154/04. Ja em 16 de julho de 2008, ocorre a publicacao da Lei no 11.741 que altera redacao de artigos do capitulo da Educacao Profissional e Tecnologica da LDB no 9394/96. Outrossim, contempla-se a retomada do principio de articulacao/integracao entre ensino medio e ensino tecnico (na modalidade educacao profissional tecnica de nivel medio). Hoje, vivenciamos ‘a reforma da reforma’, e continuamos em busca da construcao de um corpo legislativo solido, coerente e capaz de contemplar a especificidade e, concomitantemente, a demanda pela diversidade de politicas/e organizacoes curriculares correlatas aos diferentes itinerarios formativos a considerar a necessidade de formacao/qualificacao profissional dos sujeitos sociais (jovens e cidadaos trabalhadores) em diferentes faixas etarias na perspectiva da cidadania ativa e de constantes mudancas economicas. Palavras-Chave: politicas publicas, educacao profissional, reforma da legislacao federal de ensino Historical and regulatory policy course path of vocational education technical middle level: the 1996 to 2008 Abstract The vocational and technological education constitutes an important element in the socio-economic and regional productive and technological development to demand public policies for basic education and promotion policies related to science and technology, properly, buoyed by effective participatory planning and diagnostic analysis of local / national reality. The relevance of the legislative process in the development / regulatory policies to apply for a review of federal education legislation Stands out. In Brazil, the reform of vocational education legislation and technology developed under the auspices of the Law of Directives and Bases of National Education No. 9.394 / 96, and further additional legislation: Federal Decree 2.208 / 97, the National Council of Education / Chamber of Basic Education (CNE / CEB) No 04/99, and CNE / CEB No. 16/99. The reform was markedly characterized by Federal Decree No. 2,208 / 97 which determined the dissociation between technical and high school in order to revive the historical dichotomy: general training / exams and training / professional qualification. This decree was goal of severe criticism, especially by interference and distortions brought about the principle of integration / articulation between high school and technical education. Nevertheless, the Federal Decree No. 2,208 / 97 was repealed by publishing the current Federal Decree No. 5,154 / 04. As early as July 16, 2008, is the publication of Law No. 11,741 amending writing articles of chapter of Vocational and Technological Education of LDB No 9394/96. Furthermore, it is contemplated the resumption of the principle of articulation / integration between high school and technical education (vocational education secondary technical mode). Today, we experience 'reform of the reform', and still in search of building a solid legislative body, coherent and able to contemplate the specificity and, concomitantly, the demand for diversity policies / curriculum and related organizations to different training routes to consider the need for training / professional qualification of social subjects (young and citizens workers) in different age groups from the perspective of active citizenship and constant socio-ecnonomicas changes. Keywords: public policy, professional education, reform of federal education legislation
BackgroundThe Comprehensive Headache-related Quality of life Questionnaire (CHQQ), is a recently developed and validated instrument, intended for measuring quality of life of patients with all headache types. Currently no validated headache-specific quality of life questionnaires are available in Serbian. The aim of this study was to translate the CHQQ from Hungarian to Serbian, to make necessary cultural adaptations and to test its psychometric properties in a sample of outpatients with headache.MethodsThe CHQQ was translated and adapted according to internationally accepted guidelines, and then tested on a sample of 216 Serbian headache patients (171 females and 45 males, mean age 42.3 years/SD 13.35; range 18–75). The majority of patients suffered from episodic tension-type headache (TTH); 27 (12.5 %) had episodic migraine. We calculated the internal consistency (Cronbach’s alpha), criterion validity (correlations of individual items, dimensions and whole questionnaire with the clinical characteristics of headache), convergent validity (correlations of the abovementioned scores with results of other instruments measuring headache severity and impact), and discriminative validity (comparison of the scores in the two diagnostic groups) of the CHQQ. We used factor analysis to explore the underlying construct.ResultsThe Serbian translation of CHQQ showed excellent internal consistency, both for the whole instrument (Cronbach’s alpha 0.937) and its dimensions. The validity of the instrument in all aspects (criterion, convergent and discriminative validity) was also excellent when the whole sample and the subgroup of patients with TTH were analyzed, while the results for patients with migraine were less favorable. Factor analysis suggested the existence of a single dimension in this sample.ConclusionsThe Serbian translation of CHQQ is as reliable and valid specific instrument for measuring headache-related quality of life in patients with TTH and probably in patients with migraine.
All resonances, from hydrogen nuclei excited by the high-energy gamma rays in deep space to newly discovered particles produced in Large Hadron Collider, should be described by the same fundamental physical quantities. However, two distinct sets of properties are used to describe resonances: the pole parameters (complex pole position and residue) and the Breit-Wigner parameters (mass, width, and branching fractions). There is an ongoing decades-old debate on which one of them should be abandoned. In this study of nucleon resonances appearing in the elastic pion-nucleon scattering we discover an intricate interplay of the parameters from both sets, and realize that neither set is completely independent or fundamental on its own.
This paper describes the spatial three-dof 3-SUR 1-RU spherical Parallel Platform Robot. This type of robot has been previously proposed by other authors, but the present design, platform-mounted actuators, and application are unique. Further, the inverse kinematics problem is solved analytically. This robot is under development at Ohio University to serve as the active orienting device for aerodynamic testing of unmanned aerial vehicles (UAV) with up to 3 m wingspan. The UAV will be tested on a Windmobile which is a ground vehicle that is driven with the test article on an instrumented truss extended in the front in an undisturbed flow field. This system is an inexpensive substitute for a large-scale wind tunnel for measuring aerodynamic parameters of the UAV. The three-degrees-of-freedom (dof) of the platform robot are actively controlled by three servomotors (R joints) mounted to the underside of the moving platform and there is a passive fourth middle leg with passive R-U joints for support. The inverse orientation kinematics (IOK) problem is formulated and solved analytically in this paper. Given the three desired Euler Angles, the three required actuator angles are found. Geometrically this analytical solution is equivalent to finding the intersection point of two circles on different planes, independently for each of the three platform robot legs. The analytical solution requires finding the roots of a quartic polynomial. There are at most two real solutions (elbow-up and elbow-down) which means that there are always at least two imaginary solutions to the IOK problem, which are discarded. Examples are presented to demonstrate the platform robot IOK solution algorithm for use in practical platform robot control.
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