88 resultados para Horovitz, MarkusHorovitz, MarkusMarkusHorovitz
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hrsg. vom Vorstande der Israelitischen Gemeinde in Frankfurt am Main
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B. Samuel
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Bernhard Heller
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Gotthold Weil
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Dansylcadaverine, a cationic fluorescent probe binds to bacterial lipopolysaccharide and lipid A, and is displaced competitively by other compounds which possess affinity toward endotoxins. The binding parameters of dansylcadaverine for lipid A were determined by Scatchard analysis to be two apparently equivalent sites with apparent dissociation constants (Kd) ranging between 16 μM to 26 μM, while that obtained for core glycolipid from Salmonella minnesota Re595 yielded a Kd of 22 μM to 28 μM with three binding sites. The Kd of polymyxin B for lipid A was computed from dansylcadaverine displacement by the method of Horovitz and Levitzki (Horovitz, A., and Levitzki, A. (1987) Proc. Natl. Acad. Sci. USA 84, 6654–6658). The applicability of this method for analyzing fluorescence data was validated by comparing the Kds of melittin for lipid A obtained by direct Scatchard analysis, and by the Horovitz-Levitzki method. The displacement of dansylcadaverine from lipid A by polymyxin B was distinctly biphasic with Kds for polymyxin B-lipid A interactions corresponding to 0.4 μM and 1.5 μM, probably resulting as a consequence of lipid A being a mixture of mono- and di-phosphoryl species. This was not observed with core glycolipid, for which the Kd for polymyxin was estimated to range from 1.1 μM to 5.8 μM. The use of dansylcadaverine as a displacement probe offers a novel and convenient method of quantitating the interactions of a wide variety of substances with lipid A.
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The musical period of Neoclassicism began in the 1920's, between the first and second world wars. It was initiated by French composers and eventually spread to other countries. One of the most important themes to emerge from the movement was to escape from the formless, rather emotional music of the Romantic era and instead, emphasize balance, order, objectivity and clarity in musical form. Many popular clarinet repertoires are enjoyed by performers and listeners because the music is enjoyable to play and easy to listen to. In particular, classically influenced clarinet music is quite interesting because it features musical elements from both the past and contemporary musical styles. For instance, some composers have integrated preexisting, more traditional styles of composition with lighter styles of modern culture such as popular music and Jazz. It is difficult to discover purely neoclassical clarinet repertoires even though many composers created their pieces during the neoclassical era. What we most commonly find are both neoclassical and non-neoclassical influences in compositions from that time period. Thus, I aim to trace the influence of neoclassicism in selected clarinet repertoires that exist today. It is my hope that increased awareness and knowledge about accessible clarinet music may encourage the general public to develop a deeper interest in a wider sphere of clarinet music, beyond what is considered popular today. The works performed and discussed in this dissertation are the following: (Recital I) Duo Concertante by Darius Milhaud; Sonata by Leonard Bernstein; Sonata for Two Clarinets by Francis Poulenc; Duos for Flute and Clarinet, Op. 34 by Robert Muczynski; Dance Preludes by Witold Lutoslawski, (Recital II) Sonatine by Arthur Honegger; Time pieces by Robert Muczynski; Suite for Clarinet, Violin and Piano by Darius Milhaud; Sonate for Clarinet, Flute and Piano by Maurice Emmanuel; Tarantelle for Flute, Clarinet and Piano, Op. 6 by Camille Saint-Saëns, (Recital III) Sonatina by Joseph Horovitz; Suite from L'histoire du Soldat for Clarinet, Violin and Piano by Igor Stravinsky; Contrasts for Clarinet, Violin and Piano by Béla Bartók The recitals that took place on December 1, 2012 and on April 25, 2013 were performed in the Ulrich Recital Hall of the Clarice Performing Arts Center in College Park, Maryland. The recital that took place on November 2, 2013 was performed at the Gildenhorn Recital Hall of the same performing arts center.
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Les canaux calciques dépendants du voltage CaV font partie de la famille structurale des canaux ioniques à 6 segments transmembranaires. Tout comme les canaux potassiques Kv, les canaux CaV possèdent une série de résidus chargés dans l’hélice S4 de chaque domaine ou sous-unité qui conférerait à la protéine une sensibilité aux changements de voltage. De plus les hélices S6 tapissent la paroi du pore et forment la porte d’activation de la protéine. Comment le mouvement des hélices S4 se traduit par l’ouverture de la porte d’activation des hélices S6 demeure une question encore non résolue. Suite à la publication de la structure cristalline du canal Kv1.2 en 2005, le groupe de MacKinnon a proposé que le mouvement des hélices S4 est mécaniquement couplé à la porte d’activation S6 à travers le glissement de l’hélice amphiphile S4-S5 selon un mécanisme nommé couplage électromécanique (Long et al. 2005b). Dans le but de déterminer si la région S4-S5 joue un rôle dans l’activation du canal calcique CaV2.3, nous avons étudié, par la méthode d’analyse cyclique de mutations doubles (« Double Mutant Cycle Analysis », (Horovitz 1996)), le couplage entre la boucle S4-S5 et l’hélice S6 du domaine II de ce canal. Les mesures d’énergies d’activation, ΔGact, obtenues en présence des sous-unités auxiliaires CaVα2δ et CaVβ3 ont affiché un couplage significatif pour l’activation entre les paires de résidus V593G/L699G, V593G/A700G, V593G/A702G, S595G/V703G L596G/L699G, L596G/A700G, L596G/I701G, L596G/A702G, L596G/V703G, L596G/D704G, M597G/I701G, et S602G/I701G. Aucune de ces paires de résidus n’a affiché de couplage lors de l’inactivation, suggérant que les effets observés sont spécifiques au mécanisme d’activation. Mis ensemble, ces résultats suggèrent que la boucle IIS4-S5 et l’hélice IIS6 interagissent et jouent un rôle déterminant dans l’activation de CaV2.3.
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En la actualidad, el mundo de los negocios está viviendo una etapa muy importante de su historia en la cual el servicio tiene una connotación cada día más amplia y fundamental. Principalmente, se hace referencia a la calidad
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A proposta do presente trabalho é abordar as principais questões referentes às relações entre o câncer e sua expressão psicológica, através do trabalho realizado durante a fase de tratamento e reabilitação de pacientes do Instituto Nacional de Câncer -R.J. portadores de câncer de laringe, submetidos à laringectomia total. Tal objetivo deve-se a verificação de que diversas publicações específicas apontam para avaliações das relações citadas ou pela vertente da busca de etiologia psicológica do câncer, ou pela tentativa da formulação de métodos para assistência de pacientes terminais e que mesmo com o avanço da medicina, com o aumento do tempo de vida de seus portadores, ainda constata-se a escassez de investigações no campo da psicologia que -incidam sobre as possibilidades de planejamento terapêutico que visem o problema do tratamento e da readaptação dos pacientes às suas novas condições. Cabe, contudo, o esclarecimento de que esta dissertação não pretende atender à formulação de uma nova teoria sobre a assistência psicológica a pacientes com câncer, ou até a laringectomizados, mas tentará propor formulações, que colhidas através da verificação empírica, possam contribuir para a elaboração de novos estudos e pesquisas no interior desta perspectiva.
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As mucopolissacaridoses (MPS) são doenças genéticas raras causadas pela deficiência de enzimas lisossômicas específicas que afetam o catabolismo de glicosaminoglicanos (GAG). O acúmulo de GAG em vários órgãos e tecidos nos pacientes afetados pelas MPS resulta em uma série de sinais e sintomas, integrantes de um quadro clínico multissistêmico que compromete ossos e articulações, vias respiratórias, sistema cardiovascular e muitos outros órgãos e tecidos, incluindo, em alguns casos, as funções cognitivas. Já foram identificados 11 defeitos enzimáticos que causam sete tipos diferentes de MPS. Antes do advento de terapias dirigidas para a restauração da atividade da enzima deficiente, o tratamento das MPS tinha como principal foco a prevenção e o cuidado das complicações, aspecto ainda bastante importante no manejo desses pacientes. Na década de 80 foi proposto o tratamento das MPS com transplante de medula óssea/transplante de células tronco hematopoiéticas (TMO/TCTH) e na década de 90 começou o desenvolvimento da Terapia de Reposição Enzimática (TRE), que se tornou uma realidade aprovada para uso clínico nas MPS I, II e VI na primeira década do século 21. Os autores deste trabalho têm a convicção de que um melhor futuro para os pacientes afetados pelas MPS depende da identificação, compreensão e manejo adequado das manifestações multissistêmicas dessas doenças, incluindo medidas de suporte (que devem fazer parte da assistência multidisciplinar regular destes pacientes) e terapias específicas. Embora a inibição da síntese de GAG e o resgate da atividade enzimática com moléculas pequenas também possam vir a ter um papel no manejo das MPS, o grande avanço disponível no momento é a TRE intravenosa. A TRE permitiu modificar radicalmente o panorama do tratamento das mucopolissacaridoses I, II e VI na última década, sendo que ainda pode estender seus benefícios em breve para a MPS IV A (cuja TRE já está em desenvolvimento clínico), com perspectivas para o tratamento da MPS III A e do déficit cognitivo na MPS II através de administração da enzima diretamente no sistema nervoso central (SNC). Um grande número de centros brasileiros, incluindo serviços de todas as regiões do país, já têm experiência com TRE para MPS I, II e VI. Essa experiência foi adquirida não só com o tratamento de pacientes como também com a participação de alguns grupos em ensaios clínicos envolvendo TRE para essas condições. Somados os três tipos de MPS, mais de 250 pacientes já foram tratados com TRE em nosso país. A experiência dos profissionais brasileiros, somada aos dados disponíveis na literatura internacional, permitiu elaborar este documento, produzido com o objetivo de reunir e harmonizar as informações disponíveis sobre o tratamento destas doenças graves e progressivas, mas que, felizmente, são hoje tratáveis, uma realidade que traz novas perspectivas para os pacientes brasileiros afetados por essas condições.
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Mucopolysaccharidoses (MPS) are rare genetic diseases caused by the deficiency of one of the lysosomal enzymes involved in the glycosaminoglycan (GAG) breakdown pathway. This metabolic block leads to the accumulation of GAG in various organs and tissues of the affected patients, resulting in a multisystemic clinical picture, sometimes including cognitive impairment. Until the beginning of the XXI century, treatment was mainly supportive. Bone marrow transplantation improved the natural course of the disease in some types of MPS, but the morbidity and mortality restricted its use to selected cases. The identification of the genes involved, the new molecular biology tools and the availability of animal models made it possible to develop specific enzyme replacement therapies (ERT) for these diseases. At present, a great number of Brazilian medical centers from all regions of the country have experience with ERT for MPS I, II, and VI, acquired not only through patient treatment but also in clinical trials. Taking the three types of MPS together, over 200 patients have been treated with ERT in our country. This document summarizes the experience of the professionals involved, along with the data available in the international literature, bringing together and harmonizing the information available on the management of these severe and progressive diseases, thus disclosing new prospects for Brazilian patients affected by these conditions.
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Mucopolysaccharidosis type I (MPS I) is a rare lysosomal disorder caused by deficiency of alpha-L-iduronidase. Few clinical trials have assessed the effect of enzyme replacement therapy (ERT) for this condition. We conducted an exploratory, open-label, non-randomized, multicenter cohort study of patients with MPS I. Data were collected from questionnaires completed by attending physicians at the time of diagnosis (T1; n = 34) and at a median time of 2.5 years later (T2; n = 24/34). The 24 patients for whom data were available at T2 were allocated into groups: A, no ERT (9 patients; median age at T1 = 36 months; 6 with severe phenotype); B, on ERT (15 patients; median age at T1 = 33 months; 4 with severe phenotype). For all variables in which there was no between-group difference at baseline, a delta of ≥ ± 20% was considered clinically relevant. The following clinically relevant differences were identified in group B in T2: lower rates of mortality and reported hospitalization for respiratory infection; lower frequency of hepatosplenomegaly; increased reported rates of obstructive sleep apnea syndrome and hearing loss; and stabilization of gibbus deformity. These changes could be due to the effect of ERT or of other therapies which have also been found more frequently in group B. Our findings suggest MPS I patients on ERT also receive a better overall care. ERT may have a positive effect on respiratory morbidity and overall mortality in patients with MPS I. Additional studies focusing on these outcomes and on other therapies should be performed.
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von M. Horovitz