89,390 research outputs found
Creative process and personal symbols a performance: facts and fantasies of the life of Judy Lehner an exhibit: recent works
No full textFor this Project, I chose two elements: a performance andan exhibit. The performance, 'Facts and Fantasies of the Life of Judy Lehner, "took place at Cat's Paw Palace of Performing Arts Theatre in Berkeley on the evening of October 29, 1976 in front of an audience of invited friends and artists. The exhibit took place at the Fiberworks Gallery December 8-22, 1976 and included some of the pieces from the performance, as well as four other pieces.
Within the following pages, I will elaborate on my motivation in choosing a performance and its significance for me and others. The work of my exhibit is personal in nature and much of what motivated my performance also applies to my exhibited work. However, I give some explanation of these specific works
Targeted delivery of advanced functionality by nanomaterials : focus on nucleic acids delivery by novel block copolymers
No full textAbstract: Smart drug delivery systems are versatile examples of successful nanomedicine with
potential in diagnostics and medical therapy. The thesis presents selected
approaches in current drug delivery systems in the (pre-)clinical trials, and deals with
potential side effects, including complement activation and hypersensitivity reactions
as well as the design requirements of the delivery systems. Furthermore, it presents
approaches of cationic block copolymers, which are capable to condense negatively
charged nucleic acid molecules such as plasmid deoxyribonucleic acid (pDNA) and
small interfering ribonucleic acid (siRNA) with the aim of efficient cell gene delivery
and specific gene suppression, respectively.
The first part addresses the transfection efficiency of circular versus linearized
plasmid DNA using a green fluorescent protein expressing vector with Lipofectamine
2000 and linear 25 kDA polyethylenimine (PEI). These results show a considerably
improved transfection efficiency with the circular compared to the linearized DNA for
the two transfection reagents. The electron microscopy images with Lipofectamine or
PEI demonstrate that the circular DNA gives rise to random coil appearance of
compact, spherical shape, while linearized DNA appear as worm-like strands.
Particle size and shape are important in the cell biology of endocytosis and
phagocytosis. The findings indicate that the shape of the transfection particle is vital
for successful gene transfer.
To develop a delivery system for gene therapy, two cationic diblock copolymers
consisting of primary and tertiary amines were synthesized and analyzed with
respect to DNA condensation properties, morphology of the condensed plasmid DNA
and transfection efficiency using two cell lines. This study revealed proof-of-concept
showing an order of magnitude lower transfection efficiency of primary amine diblock
copolymers compared to PEI after 48 h with increasing plasmid DNA concentration.
Furthermore, primary amines compared to tertiary ones show much stronger binding
to DNA and improved transfection efficiency. Transmission electron and atomic force
microscopy data revealed morphologies of primary and tertiary amines regarding the
condensation of the plasmid DNA, in agreement with the transfection efficiency.
In a second part the design and characterization of pentablock-based polyplexes
based on the combination of cationic pentablock copolymers with folic acid
functionalized copolymers for targeted specific siRNA delivery is described. The
achieved 31 % knockdown efficiency shows its potential regarding cancer gene
therapy. The pentablock architecture allows the formation of highly stable
micelleplexes of (21 ± 3) nm in 10 mM PBS buffer solution with a neutral surface
charge, excellent siRNA condensation properties, outstanding colloidal stability in
10 % serum over 24 h and biocompatibility deduced from the absence of
considerable cytotoxicity even after 48 h incubation. Furthermore, selective delivery
of the siRNA could be proven by the introduction of a ligand-linked block copolymer,
resulting in 31 % compared to 8 % gene suppression for targeted a non-targeted
micelleplexes. This pentablock-based delivery system might yield impact to future
delivery systems as well as being a potential platform to be applied in vivo for cancer
gene therapy. ---------- Zusammenfassung
Innerhalb des Bereichs der Nanomedizin weisen intelligente Wirkstoffabgabesysteme
ein großes Potenzial auf, sowohl hinsichtlich der Diagnostik wie auch der
medizinischen Therapie. Die vorliegende Arbeit stellt im Rahmen einer
Literaturrecherche ausgewählte Wirkstoffabgabesysteme vor, welche sich in (vor-)
klinischen Studien befinden, den Nebenwirkungen welche durch diese entstehen
können, im speziellen der Komplementaktivierung und Überempfindlichkeitsreaktionen,
sowie deren Konstruktionsanforderungen. Des weiteren werden in einem
experimentellen Teil kationische Block-Kopolymere präsentiert, welche in der Lage
sind, negativ geladene Nukleinsäuremoleküle zu binden - wie etwa Plasmid
Desoxyribonukleinsäure (pDNA) und kleine interferierende Ribonukleinsäuren
(siRNA) - mit dem Ziel der Transfektion von fremder DNA in die Wirtszellen und
damit der spezifischen Unterdrückung der Genexpression.
Der erste Teil der experimentellen Arbeit untersucht die Transfektionseffizienz von
zirkulärer gegenüber linearisierter Plasmid-DNA mittels eines Vektors, welcher ein
grün fluoreszierendes Protein exprimiert. Transfiziert wurde einerseits mit
Lipofectamine 2000 und andererseits mit linearem 25 kDa Polyethylenimin (PEI),
zwei etablierten Transfektionsreagenzien. Die Ergebnisse zeigen eine wesentlich
verbesserte Transfektionseffizienz der zirkulären, verglichen mit der linearisierten
DNA für beide Transfektionsreagenzien. Die elektronenmikroskopischen Bilder von
Lipofectamine sowie PEI komplexiert mit DNA zeigen, dass die zirkuläre DNA
zufällige, kompakte Kugelformen bildet, während die linearisierte DNA wurmartige
Stränge aufweist. Partikelgröße und -form spielen in der Zellbiologie eine wichtige
Rolle bei der Endozytose und Phagozytose. Die Ergebnisse legen die Vermutung
nahe dass die Form der zu transfizierenden DNA-Transfektions-Komplexen eine
wichtige Rolle einnimmt für einen erfolgreichen Gentransfer.
Für die Entwicklung eines intelligenten Wirkstoffabgabe-Systems für die Gentherapie
wurden zwei kationische Diblock-Kopolymere, die aus primären und tertiären Aminen
bestehen synthetisiert und im Hinblick auf deren DNA-Kondensationseigenschaften,
Morphologie der kondensierten Plasmid-DNA sowie Transfektionseffizienz unter
Verwendung von zwei Zelllinien analysiert. Die Studie bestätigt trotz einer um den
Faktor 10 schwächeren Transfektionseffizienz der primären Amin-DiblockKopolymeren
im Vergleich zu PEI nach 48 h mit zunehmender pDNA Konzentration
eine Bestätigung des Konzepts. Außerdem weisen die primären Amin-Block-
Kopolymere im Vergleich zu den tertiären eine viel stärkere Komplexbildung der DNA
auf - wie transmissions-elektronen- und rasterkraft-mikroskopische Daten ergaben -
als auch eine verbesserte Transfektionseffizienz. Diese physikalischmorphologischem
Erkenntnisse über die Kondensation der primären und tertiären
Amine mit Plasmid-DNA konnten mittels der biologischen Transfektionseffizienzdaten
validiert werden.
Der zweite Teil der experimentellen Arbeit befasst sich mit dem Design sowie der
Charakterisierung von pentablock-basierten Polyplexen für einen gezielten siRNA
Transport. Diese Polyplexe beruhen auf einer Kombination von kationischen
Pentablock-Kopolymeren mit folsäure-funktionalisierten Kopolymeren. Die erreichten
31% Gen-Suppression in einem Krebszellkulturmodell, zeigen das Potenzial des
Wirkstoffabgabesystems in Bezug auf eine Krebstherapie auf. Die Architektur
ermöglicht die Bildung von sehr stabilen Mizellen mit einer Grösse von (21 ± 3) nm in
10 mM PBS Pufferlösung, eine neutrale Oberflächenladung, ausgezeichneten siRNAKondensationseigenschaften,
hervorragender kolloidaler Stabilität in
Zellkulturmedium supplementiert mit 10 % Serum über 24 h, sowie guter
Biokompatibilität aufgrund fehlender erheblicher Zytotoxizität auch nach 48 h
Inkubation in einem Zellkulturmodell. Ferner konnte durch die Einführung eines
liganden-gebundenen Block-Kopolymers der selektive Transport der siRNA
nachgewiesen werden, was zu einer Gen Suppression von 31% gegenüber 8% nicht
funktionalisierter Polyplexen führte. Das in dieser Arbeit eingeführte und
charakterisierte pentablock-basierte Wirkstoffabgabesystem könnte Auswirkungen
auf das Design zukünftiger Wirkstoffabgabesystem haben als auch als eine
potentielle Plattform für in vivo-Krebsgentherapien angewendet werden
Kann man aus der Geschichte des Industriekapitalismus lernen?
No full textWehler H-U. Kann man aus der Geschichte des Industriekapitalismus lernen? In: Lehner F, ed. WertSchöpfung. Arbeit und Technik, 12. München: Hampp; 1999: 108-116
Nuclear elongation during spermiogenesis depends on physical linkage of nuclear pore complexes to bundled microtubules by Drosophila Mst27D
No full textSpermatozoa in animal species are usually highly elongated cells with a long motile tail attached to a head that contains the haploid genome in a compact and often elongated nucleus. In Drosophila melanogaster, the nucleus is compacted two hundred-fold in volume during spermiogenesis and re-modeled into a needle that is thirty-fold longer than its diameter. Nuclear elongation is preceded by a striking relocalization of nuclear pore complexes (NPCs). While NPCs are initially located throughout the nuclear envelope (NE) around the spherical nucleus of early round spermatids, they are later confined to one hemisphere. In the cytoplasm adjacent to this NPC-containing NE, the so-called dense complex with a strong bundle of microtubules is assembled. While this conspicuous proximity argued for functional significance of NPC-NE and microtubule bundle, experimental confirmation of their contributions to nuclear elongation has not yet been reported. Our functional characterization of the spermatid specific Mst27D protein now resolves this deficit. We demonstrate that Mst27D establishes physical linkage between NPC-NE and dense complex. The C-terminal region of Mst27D binds to the nuclear pore protein Nup358. The N-terminal CH domain of Mst27D, which is similar to that of EB1 family proteins, binds to microtubules. At high expression levels, Mst27D promotes bundling of microtubules in cultured cells. Microscopic analyses indicated co-localization of Mst27D with Nup358 and with the microtubule bundles of the dense complex. Time-lapse imaging revealed that nuclear elongation is accompanied by a progressive bundling of microtubules into a single elongated bundle. In Mst27D null mutants, this bundling process does not occur and nuclear elongation is abnormal. Thus, we propose that Mst27D permits normal nuclear elongation by promoting the attachment of the NPC-NE to the microtubules of the dense complex, as well as the progressive bundling of these microtubules.Author summaryThe sperm is a cell highly specialized for delivery of a haploid set of paternal chromosomes to the oocyte. Typically, it has a moving tail for swimming and a compact often elongated head containing specially packed chromosomes. During spermiogenesis in Drosophila melanogaster flies, for example, the nucleus is re-modeled from sphere into elongated needle with a two hundred-fold smaller volume. Nuclear elongation is preceded by a striking redistribution of nuclear pore complexes (NPCs) in the nuclear envelope (NE). At the start of nuclear elongation, NPCs are confined to a hemisphere of the spherical nucleus, and a strong bundle of microtubules is assembled in the cytoplasmic dense complex adjacent to the NPC-NE. Whether and how microtubule bundle and NPC-NE cooperate to achieve nuclear elongation has remained unresolved. Here, we report a functional characterization of Mst27D. This protein functions as a linker, connecting NPCs with microtubules that are bundled progressively into fewer and eventually into a single large bundle within the dense complex, according to our time-lapse imaging of nuclear elongation. In mutants lacking Mst27D, bundling does not proceed and nuclear elongation is defective. Thus, our findings advance the understanding of nuclear elongation in spermatids to the molecular level
Art.73
No full textLa voce del “Commentario della Costituzione inattuata” dedicata all’art. 73 Cost. analizza l’applicazione che il legislatore e la giurisprudenza - costituzionale, ordinaria e amministrativa – hanno fornito alle previsioni della Carta in tema di promulgazione delle leggi formali ordinarie e di pubblicazione degli atti normativi. Coordinando tali riscontri con le elaborazioni dottrinali e giurisprudenziali sulla ratio dell’articolo in questione, con particolare attenzione allo statuto del potere legislativo e ai cardini dello Stato di diritto, il contributo isola i profili di inattuazione del disposto costituzionale tentando di indicarne cause e conseguenze.The entry in the "Commentary on the unimplemented Constitution" dedicated to Art. 73 of the Constitution analyzes the application that Legislator and Jurisprudence - constitutional, ordinary and administrative - have provided to the Charter’s provisions regarding promulgation of Ordinary Formal Laws and publication of Regulatory Acts. Coordinating these findings with the doctrinal and jurisprudential elaborations on the ratio of this article, with particular attention to the statute of Legislative Power and the cornerstones of the Rule of Law, the contribution isolates the profiles of non-implementation of the constitutional provision by attempting to indicate causes and consequences
Modular symbols over number fields
No full textLet K be a number field, R its ring of integers. For some classes of fields, spaces of cusp forms of weight 2 for GL(2;K) have been computed using methods based on modular symbols. J.E. Cremona [9] began the programme of extending the classical methods over Q to the case of imaginary quadratic fields. This work was continued by some of his Ph.D. students [35, 6, 22], and results have been obtained for some imaginary quadratic fields with small class number. More recently, P. Gunnells and D. Yasaki [18] have developed related algorithms for real quadratic fields.
The aim of this thesis is to contribute to the extension of the modular symbols method, when possible developing algorithms and implementations for effective computations. Some parts of the theory are purely algebraic and can be extended to all number fields. We generalise the theory for cusps and Manin symbols; we also describe a generalisation of Atkin-Lehner involutions and study other normaliser elements. On the other hand, all previous explicit computations for the imaginary quadratic field case were done only for specific fields. In the last part of this thesis we begin work towards a general implementation of the techniques used in this case. In particular, we are able to compute a fundamental domain of the hyperbolic 3-space for any imaginary quadratic field.
Implementations of the algorithms described in this thesis have been written by the author in the open-source mathematics software Sage [31]
Incorporation of Drosophila CID/CENP-A and CENP-C into centromeres during early embryonic anaphase.
No full textThe centromere/kinetochore complex is indispensable for accurate segregation of chromosomes during cell divisions when it serves as the attachment site for spindle microtubules. Centromere identity in metazoans is believed to be governed by epigenetic mechanisms, because the highly repetitive centromeric DNA is neither sufficient nor required for specifying the assembly site of the kinetochore. A candidate for an epigenetic mark is the centromere-specific histone H3 variant CENP-A that replaces H3 in alternating blocks of chromatin exclusively in active centromeres. CENP-A acts as an initiator of kinetochore assembly, but the detailed dynamics of the deposition of metazoan CENP-A and of other constitutive kinetochore components are largely unknown. Here we show by quantitative fluorescence measurements in living early embryos that functional fluorescent fusion proteins of the Drosophila CENP-A and CENP-C homologs are rapidly incorporated into centromeres during anaphase. This incorporation is independent of ongoing DNA synthesis and pulling forces generated by the mitotic spindle, but strictly coupled to mitotic progression. Thus, our findings uncover a strikingly dynamic behavior of centromere components in anaphase
Shimura curve Atkin--Lehner quotients of genus at most two
No full textWe provide a complete enumeration of all quotients of genus and of the Shimura curves over by non-trivial subgroups of Atkin--Lehner involutions. For all genus quotients with squarefree, we determine the isomorphism class of the Jacobian . For non-elliptic genus curves and for curves genus quotients , we provide a defining equation for . A main tool for us is the theory of Čerednik--Drinfeld uniformizations of the curves , which we implement in wider generality than has previously been done in the literature
Variations on the Author
No full text“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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