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Cathepsin D (CatD) is a lysosomal aspartic proteinase and plays an important role in the degradation of proteins and in apoptotic processes induced by oxidative stress, cytokines, and aging. All of these stimuli are potent inducers of endothelial cell apoptosis. Therefore, we investigated the role of CatD in endothelial cell apoptosis and determined the underlying mechanisms. Incubation with 100-500 microm H2O2 for 12 h induced apoptosis in endothelial cells. To determine a role for CatD, we co-incubated endothelial cells with the CatD inhibitor pepstatin A. Pepstatin A as well as genetic knock down of CatD abolished H2O2-induced apoptosis. In contrast, overexpression of CatD wild type but not a catalytically inactive mutant of CatD (CatDD295N) induced apoptosis under basal conditions. To gain insights into the underlying mechanisms, we investigated the effect of CatD on reactive oxygen species (ROS) formation. Indeed, knocking down CatD expression reduced H2O2-induced ROS formation and apoptosis. The major redox regulator in endothelial cells is thioredoxin-1 (Trx), which plays a crucial role in apoptosis inhibition. Thus, we hypothesized that CatD may alter Trx protein levels and thereby promote formation of ROS and apoptosis. Incubation with 100 microm H2O2 for 6 h decreased Trx protein levels, whereas Trx mRNA was not altered. H2O2-induced Trx degradation was inhibited by pepstatin A and genetic knock down of CatD but not by other protease inhibitors. Incubation of unstimulated cell lysates with recombinant CatD significantly reduced Trx protein levels in vitro, which was completely blocked by pepstatin A pre-incubation. Overexpression of CatD reduced Trx protein in cells. Moreover, H2O2 incubation led to a translocation of Trx to the lysosomes prior to the induction of apoptosis. Taken together, CatD induces apoptosis via degradation of Trx protein, which is an essential anti-apoptotic and reactive oxygen species scavenging protein in endothelial cells.
Human endothelial circulating progenitor cells (CPCs) can differentiate to cardiomyogenic cells during co-culture with neonatal rat cardiomyocytes. Wnt proteins induce myogenic specification and cardiac myogenesis. Here, we elucidated the effect of Wnts on differentiation of CPCs to cardiomyogenic cells. CPCs from peripheral blood mononuclear cells were isolated from healthy volunteers and co-cultured with neonatal rat cardiomyocytes. 6–10 days after co-culture, cardiac differentiation was determined by α-sarcomeric actinin staining of human lymphocyte antigen-positive cells (fluorescence-activated cell-sorting analysis) and mRNA expression of human myosin heavy chain and atrial natriuretic peptide. Supplementation of co-cultures with Wnt11-conditioned medium significantly enhanced the differentiation of CPCs to cardiomyocytes (1.7 ± 0.3-fold), whereas Wnt3A-conditioned medium showed no effect. Cell fusion was not affected by Wnt11-conditioned medium. Because Wnts inhibit glycogen synthase kinase-3β, we further determined whether the glycogen synthase kinase-3β inhibitor LiCl also enhanced cardiac differentiation of CPCs. However, LiCl (10 mm) did not affect CPC differentiation. In contrast, Wnt11-conditioned medium time-dependently activated protein kinase C (PKC). Moreover, the PKC inhibitors bisindolylmaleimide I and III significantly blocked differentiation of CPCs to cardiomyocytes. PKC activation by phorbol 12-myristate 13-acetate significantly increased CPC differentiation to a similar extent as compared with Wnt11-conditioned medium. Our data demonstrate that Wnt11, but not Wnt3A, augments cardiomyogenic differentiation of human CPCs. Wnt11 promotes cardiac differentiation via the non-canonical PKC-dependent signaling pathway.
Within the ADD-model, we elaborate an idea by Vacavant and Hinchliffe [J. Phys. G 27 (2001) 1839] and show quantitatively how to determine the fundamental scale of TeV-gravity and the number of compactified extra dimensions from data at LHC. We demonstrate that the ADD-model leads to strong correlations between the missing ET in gravitons at different center of mass energies. This correlation puts strong constraints on this model for extra dimensions, if probed at s=5.5 TeV and s=14 TeV at LHC.
The kaon nuclear optical potential is studied including the effect of the Θ+ pentaquark. The one-nucleon contribution is obtained using an extension of the Jülich meson-exchange potential as bare kaon–nucleon interaction. Significant differences between a fully self-consistent calculation and the usually employed low-density Tρ approach are observed. The influence of the one-nucleon absorption process, KN→Θ+, on the kaon optical potential is negligible due to the small width of the pentaquark. In contrast, the two-nucleon mechanism, KNN→Θ+N, estimated from the coupling of the pentaquark to a two-meson cloud, provides the required amount of additional kaon absorption to reconcile with data the systematically low K+-nucleus reaction cross sections found by the theoretical models.
We solve the coupled Wong Yang–Mills equations for both U(1) and SU(2) gauge groups and anisotropic particle momentum distributions numerically on a lattice. For weak fields with initial energy density much smaller than that of the particles we confirm the existence of plasma instabilities and of exponential growth of the fields which has been discussed previously. Also, the SU(2) case is qualitatively similar to U(1), and we do find significant “abelianization” of the non-Abelian fields during the period of exponential growth. However, the effect nearly disappears when the fields are strong. This is because of the very rapid isotropization of the particle momenta by deflection in a strong field on time scales comparable to that for the development of Yang–Mills instabilities. This mechanism for isotropization may lead to smaller entropy increase than collisions and multiplication of hard gluons, which is interesting for the phenomenology of high-energy heavy-ion collisions.
Large extra dimensions could lower the Planck scale to experimentally accessible values. Not only is the Planck scale the energy scale at which effects of modified gravity become important. The Planck length also acts as a minimal length in nature, providing a natural ultraviolet cutoff and a limit to the possible resolution of spacetime.
In this Letter we examine the influence of the minimal length on the Casimir energy between two plates.
Alternative NADH dehydrogenases (NADH:ubiquinone oxidoreductases) are single subunit respiratory chain enzymes found in plant and fungal mitochondria and in many bacteria. It is unclear how these peripheral membrane proteins interact with their hydrophobic substrate ubiquinone. Known inhibitors of alternative NADH dehydrogenases bind with rather low affinities. We have identified 1-hydroxy-2-dodecyl-4(1H)quinolone as a high affinity inhibitor of alternative NADH dehydrogenase from Yarrowia lipolytica. Using this compound, we have analyzed the bisubstrate and inhibition kinetics for NADH and decylubiquinone. We found that the kinetics of alternative NADH dehydrogenase follow a ping-pong mechanism. This suggests that NADH and the ubiquinone headgroup interact with the same binding pocket in an alternating fashion.
Generation of reactive oxygen species (ROS) is increasingly recognized as an important cellular process involved in numerous physiological and pathophysiological processes. Complex I (NADH:ubiquinone oxidoreductase) is considered as one of the major sources of ROS within mitochondria. Yet, the exact site and mechanism of superoxide production by this large membrane-bound multiprotein complex has remained controversial. Here we show that isolated complex I from Yarrowia lipolytica forms superoxide at a rate of 0.15% of the rate measured for catalytic turnover. Superoxide production is not inhibited by ubiquinone analogous inhibitors. Because mutant complex I lacking a detectable iron-sulfur cluster N2 exhibited the same rate of ROS production, this terminal redox center could be excluded as a source of electrons. From the effect of different ubiquinone derivatives and pH on this side reaction of complex I we concluded that oxygen accepts electrons from FMNH or FMN semiquinone either directly or via more hydrophilic ubiquinone derivatives.
The transporter associated with antigen processing (TAP)-like (TAPL, ABCB9) belongs to the ATP-binding cassette transporter family, which translocates a vast variety of solutes across membranes. The function of this half-size transporter has not yet been determined. Here, we show that TAPL forms a homodimeric complex, which translocates peptides across the membrane. Peptide transport strictly requires ATP hydrolysis. The transport follows Michaelis-Menten kinetics with low affinity and high capacity. Different nucleotides bind and energize the transport with a slight predilection for purine bases. The peptide specificity is very broad, ranging from 6-mer up to at least 59-mer peptides with a preference for 23-mers. Peptides are recognized via their backbone, including the free N and C termini as well as side chain interactions. Although related to TAP, TAPL is unique as far as its interaction partners, transport properties, and substrate specificities are concerned, thus excluding that TAPL is part of the peptide-loading complex in the classic route of antigen processing via major histocompatibility complex class I molecules.
Benzene solutions of Me3SnCl when exposed to moisture yield the adduct Me3SnCl·Me3SnOH·H2O. This adduct represents an intermediate in Me3SnCl hydrolysis. The structure of Me3SnCl·Me3SnOH·H2O features an array of Me3Sn units connected alternatingly by bridging Cl and OH ligands.
Die "lyrische Operette" 'Semele' erscheint zum ersten Mal in der von Schiller anonym herausgegebenen Lyriksammlung 'Anthologie auf das Jahr 1782'. [...] Im Falle der Ovidschen Vorlage handelt es sich - zumal in der der Zeit um 1780 - um ein brisantes Thema, nämlich um die "Götterwollust" des Menschen. [...] Schiller [...] behält das brisante Problem bei, exponiert und steigert es sogar, um es erst danach im Menschheitlichen aufzuheben.
Im Folgenden möchte ich durch Einordnung von Brentanos "Geschichte vom braven Kasperl und dem schönen Annerl" in eine Geschichte des Wissens (Medizin, Recht, Mythologie) zeigen, dass die Organisation der Erzählung der Dynamik zweier gegenlaufiger Textbewegungen geschuldet ist: erstens dem Ausbruch einer rechtlichen Krise als Folge einer fehlenden (in einem gewissen Sinne unmöglichen) sozialen Integration von Sexualität, Kriminalität und Psychopathologie, zweitens den Versuchen, mit einer neuen Ordnung auf diese Krise zu reagieren. Auf der einen Seite stehen die Verbrechen von Kasperl und Annerl, Selbstmord und Kindsmord, ihre psychische und (außer-)gesellschaftliche Genese sowie ihre Folgen, auf der anderen Seite die narrative Bewältigung der Ereignisse durch den Erzähler und die rechtliche durch den Fürsten.
Expansion in die Natur : zum Verhältnis von "ars" und "natura" bei Paracelsus und im Paracelsismus
(2005)
Wenn Paracelsus Naturwissenschaft oder magica als eine Handlung definiert, die "aus ihr", der Natur, ist, diese aber "mer, dan" ihr selbst "zu zu legen ist", steigert und "bessert", dann geschieht dies auf Basis aristotelischer Argumente, die im 13. Jahrhundert auf neuplatonische Weise so kombiniert werden, daß die aristotelischen Vorgaben mit der Vorstellung einer aktiven sympathetischen Teilhabe des Menschen am Kosmos harmonisieren. Diese Überformung wird in der Frühen Neuzeit noch einmal weiterentwickelt. Es sind die protestantische Mystik mit und gegen Luther und die Auslagerung ihrer häretischen Tendenzen in die Naturwissenschaft, die der Theorie von der Steigerung der Natur aus ihrer Mitte die Bedeutung einer wechselseitigen souverinen Teilhabe verleihen.
Multiple Magie : zur Verwandlung psychiatrischen Wissens in
Hofmannsthals "Andreas"-Fragmenten
(2005)
In diesem Aufsatz soll Hugo von Hofmannsthals "Andreas"-Projekt als Überlagerung eines psychiatrischen Diskurses durch einen magischen gelesen werden. Ich verfolge in den Fragmenten die Gedankenfigur der Persönlichkeitsspaltung, wie sie in der französischen und amerikanischen Psychiatrie des ausgehenden 19. und frühen 20. Jahrhunderts erarbeitet wurde, und versuche, deren Überschreibung durch Theoreme aus der natürlichen Magie bzw. deren Reformulierungen durch die Rosenkreuzer-Bewegung des 20. Jahrhunderts zu rekonstruieren. Diese Überlagerung, so meine These, ist als eine starke Aneignung der beiden Wissens-Formationen auf dem Boden der Klassischen Moderne zu verstehen: Beschrieben wird eine Transformation, der sowohl die Position eines eximierten Magiers/Psychotherapeuten wie auch die eines in sich geschlossenen metaphysischen bzw. therapeutischen Systems zum Opfer fallen.
Warten auf die Anthologie
(2005)
[...] "der Artushof" ist eine Passage, die als Verbindung zweier belebter Straßen in einem Hauptgeschäftsgebiet einer Stadt liegt, sie ist nur dem Fußgänger zugänglich und schützt ihn vor Witterungseinflüssen. Auch wenn im Artushof noch keine, die Passage des 19. Jahrhunderts prägende, nach Innen gekehrte Ladenstraße verwirklicht ist, so ist doch seine seit den 80er Jahren des 18. Jahrhunderts nachweisbare Umwidmung vom Festsaal zur Börse ein Zeichen dafür, daß auch schon in der Danziger Passage "die Kunst in den Dienst des Kaufmanns" getreten ist.
Elderly people still play a minor role in research on information needs and usage patterns of Internet users. Online research and advocacy groups look optimistically at the (economic and social) potential of the active and technology–skilled elderly; other approaches dealing with the social appropriation of technology see obstacles and stress the dangers of an increasing digital divide between generations. Our objective is to refer to taken for granted normative assumptions of the digital divide discourse, highlighting different requirements for the appropriation of the Internet. Using the concept of technological generations we look at formal and informal learning of young and elderly people in the German context. We use survey material and field impressions we gained in various technology related studies. The results show that the "two worlds apart" assumption (young vs. elderly people) is too simplistic. Factors like gender, education and socio–economic status still play an important role for acceptance and diffusion of a technology. The diffusion rate among the elderly is increasing, but will continue to lag behind the figures of the young users. Cultural preparations and easy access modes are essential for the elderly, who could make use of latecomer advantages. Informal learning and peer group support will be crucial for the diffusion of the Internet among the elderly. In our conclusions we look at the specific social status of the elderly cohort, which makes a comparison with other social groups very difficult.
IN A CASE STUDY IN THE GERMAN RETAIL BANKING BUSINESS IT IS SHOWN THAT ALIGNMENT BETWEEN IT AND BUSINESS UNIT IS CRUCIAL FOR THE ACTUAL USAGE OF IT SYSTEMS WHICH IN TURN IS A KEY DRIVER FOR BUSINESS PROCESS QUALITY. BANKS SHOULD THEREFORE FOSTER INTERRELATIONSHIPS BETWEEN IT AND BUSINESS AS WELL AS CROSS FUNCTIONAL WORK BIOGRAPHIES OF TEAM LEADERS
INDUSTRIALIZATION TENDENCIES WITHIN THE CREDIT BUSINESS ARE IN PARTS BROADER SOPHISTICATED THAN WITHIN FINANCIAL PROCESSES OF OTHER INDUSTRIES. CREDIT PROCESS MANAGERS OF BANKS ESTIMATE ECONOMIES OF SCALE AND SKILL ACHIEVABLE BY OUTSOURCING TO BE HIGHER THAN CHIEF FINANCIAL OFFICERS OF NON-BANKS DO. FURTHERMORE, ECONOMIES OF SCOPE, WHICH INHIBIT SELECTIVE SOURCING, ARE EVALUATED AS LESS PROBLEMATIC.
O objetivo do texto é fazer uma análise da dimensão crítica do conceito de indústria cultural proposto por Adorno e Horkheimer a partir da noção psicanalítica de narcisismo, tal como Adorno a interpretou. A cultura de massa será vista como propiciando o prazer substancialmente ilusório de satisfazer a ânsia de engrandecimento do ego, no mesmo instante em que mantém o indivíduo atado às tendências inerciais de unificação social.
En el sexagésimo aniversario de la liberación del campo de exterminio de Auschwitz, el tema de la dialéctica de la Ilustración (que se situó en el núcleo del pensamiento crítico de posguerra), sigue siendo una cuestión abierta y candente. ¿Qué proceso de transformación atraviesa la visión del mundo occidental para que los valores de la Ilustración resulten de improviso completamente inoperantes para detener la expansión de la barbarie más antihumana? Este interrogante aún desafía la construcción de una cultura universalista a partir de la tradición de la modernidad, moviéndonos a un replanteamiento crítico de su trayectoria. La lúcida obra de J. Habermas: El discurso filosófico de la modernidad oficia aquí de guía en una singladura por la filosofía del siglo XX centrada en torno a las categorías propias de la Teoría Crítica en su compromiso, aún vigente, por restaurar el sentido liberador de la cultura ilustrada.
A sociedade como um todo vivencia uma crise de ordem ética, mas de uma ética, sobretudo, coletiva. As “pequenas” barbáries instalam-se silenciosamente na sociedade, fomentadas por um sistema econômico que, na sua raiz, é excludente e implacável com aqueles que não se enquadram de alguma forma nele. As pequenas banalizações das injustiças criam elementos que alertam para a possibilidade de que Auschwitz se repita, medo presente e evidenciado por Adorno nas suas obras mais importantes. Os objetivos deste trabalho são responder aos seguintes questionamentos: 1) como traduzir para o dia-a-dia da educação a desconstrução da cultura de violência e preconceito que avança em todo o mundo? 2) Como trabalhar uma pedagogia da imaginação, que seja, antes de mais nada, a condição de imaginar o outro, de imaginar-se no lugar do outro? 3) Quais as bases epistemológicas norteadoras de tal objetivo? Para tanto, verificar-se-á que, por meio da pedagogia do antipreconceito, fundamentada sobretudo no pensamento de Adorno, de Horkheimer e de Marcuse, é possível promover a interdisciplinaridade que aproxime razão de afeto e que denuncie a negação do preconceito, esclarecendo, ainda, que para se fazer uma sociedade mais humanizada torna-se impositivo passar pela desconstrução, pela compreensão e pela reconstrução da educação. Entender e esclarecer como o homem médio viabiliza as posturas excludentes e preconceituosas, impostas tanto pela condição humana quanto pelo capitalismo contemporâneo, no cotidiano da educação constitui uma de suas metas. Enfim, o trabalho propõe-se afirmar a possibilidade de uma ética para a sociedade tecnológica e de semiformação, fundamentada na pedagogia do antipreconceito, cuja finalidade seja a formação de sujeitos conscientes das limitações da ciência e do uso da tecnologia para impedir a barbárie, cuja bandeira seja a do combate à intolerância e às violências e o instrumento principal seja a imaginação.
Trata-se de analisar os usos da racionalidade mimética em Jacques Lacan e Theodor Adorno, isto a fim de mostrar como, nos dois casos, encontramos uma estratégia de reflexão sobre a mimesis que a eleva à condição de elemento fundamental para uma teoria do reconhecimento que não se esgote na temática da intersubjetividade. Neste sentido, este estudo insere-se em uma pesquisa mais ampla a respeito dos modos de aproximação entre psicanálise lacaniana e Escola de Frankfurt no que diz respeito ao problema dos destinos da categoria de sujeito e dos processos de reconhecimento.
A crítica de Adorno a posições idealistas acentua que o sujeito, como portador da vontade livre, é sempre mediado social e historicamente. Segundo Adorno, a vontade é razão, mas não somente razão. Junto com ela deve ser sempre usado um “impulso anterior-ao-sentido-do-eu”. Ao final, será apresentada a crítica de Adorno do ideal social de uma vontade forte.