5,674 research outputs found
Cultural Factors in Complex Decision Making
No full textComplex decision-making is conceptualised as the process of problem solving in meaningful and important, but complex, dynamic and partially opaque situations. This process is open to a number of cultural influences, among them educational practices, environmental predictability, and power distance. Two empirical studies that explore into the cultural relativity of this type of decision making use interactive computer simulations of complex problems as research instruments. There are a number of behavioural differences between participants from India and Germany which can be explained within a culture-theoretical framework and give reason for the plea to include cultural factors in theories on human decision making
Agrin promotes acetylcholine receptor clustering at the mammalian neuro-muscular junction by PI3K/GSK3ß²-mediated regulation of +TIPs and microtubule capture
No full textNeurotransmission an der neuromuskulären Endplatte von Säugetieren
erfolgt durch Ausschüttung von Acetylcholin (ACh) aus motorischen Nerven
in den synaptischen Spalt und verursacht letztendlich Muskelkontraktion im
angesteuerten Muskel. Der Signalstoff Agrin, welcher ebenfalls vom
Motornerv sekretiert wird, ist hauptverantwortlich für die postsynaptische
Differenzierung der Muskelfasern und bewirkt die räumliche Konzentration
der Rezeptoren für den Neurotransmitter Acetylcholin (AChR) in einem
kleinen - meist zentralen - Areal der Faser unterhalb des Ansatzpunkt der
Motornervendigung. Nach intensiver Beforschung sind die Endeffekte von
Agrin auf Muskelfasern gut dokumentiert und viele involvierte Moleküle
bekannt. Trotzdem ist die Rolle des subsynaptischen Mikrotubuli-Zytoskeletts
beim Transport, bei der Membraninsertion und bei der Konzentrierung von
AChR-Molekülen wenig erforscht und die zugrundeliegenden molekularen
Mechanismen, welche ein Mikrotubuli-Netzwerk unterhalb der Synapse
etablieren, sind grossteils unbekannt. Im Zuge meiner Doktorarbeit
untersuchte ich daher neue Aspekte der agrin-induzierten biochemischen
Signalübertragung im Muskel und deren zellbiologischen Konsequenzen auf
das Mikrotubuli-Zytoskelett.
Gerichteter intrazellulärer Vesikel-Transport erfolgt generell entlang von
polaren Cytoskelettstrukturen, ein grosser Teil davon entlang von Mikrotubuli
- kurzlebige Cytoskelettfilamente, deren dynamischeres „Plus-Ende“
beständig zwischen Wachsen und Schrumpfen wechselt. Bestimmte Stimuli
jedoch können über Signaltransduktions-kaskaden dazu führen, dass die
schnell wachsenden Plus-Enden der Mikrotubuli mithilfe assoziierter Proteine
(+TIP-Proteine) längerfristig an die Innenseite der Zellmembran oder an das
Actinzytoskelett binden und dort verankert werden („Microtubule Capture“).
Dieser Vorgang stabilisiert die betreffenden Mikrotubuli und verlängert ihre
Halbwertszeit – die stabilisierten Microtubuli dienen der Zelle in weiterer
Folge als gerichtete Transportrouten.
In meiner Doktorarbeit konnte ich zeigen, dass die Acetylcholinrezeptorreiche
postsynaptische Zentralregion der Muskelfasern von einem dichten
Netzwerk von Microtubuli umgeben ist, einige dieser Microtubuli sind zudem
durch post-translationale Modifikationen weiter stabilisiert. Weiters konnte
ich demonstrieren, dass der Botenstoff Agrin im Muskel eine biochemische
Signaltransduktions-kaskade auslöst, welche die PI3-Kinase aktiviert und an
deren Ende GSK3β durch Phosphorylierung lokal inaktiviert wird.
Da viele der zuvor erwähnten +TIP-Proteine, zum Beispiel CLASP2, durch
GSK3β negativ reguliert sind, ist eine lokalisierte Inaktivierung von GSK3β
zentrale Voraussetzung dafür, dass +TIP-Proteine an Mikrotubuli Plus-Enden
binden können und somit zur Etablierung von stabilen Mikrotubuli-Filamenten
beitragen. Nach agrin-induzierter Inaktivierung von GSK3β bindet CLASP2 an
Mikrotubuli Plus-Enden und befestigt diese am Zellkortex in der AChR-reichen
Region von Myotuben in Wechselwirkung mit LL5β - welches von PI3K zur
synaptischen Membran rekrutiert wird. Die betreffenden Mikrotubuli werden
dadurch stabilisiert und können der Zelle als intrazelluläre Transportrouten
für postsynaptisches Material wie etwa AChRs und Strukturproteine dienen.
Funktionsverändernde Mutationen beteiligter Moleküle sowie
pharmakologische Eingriffe in den PI3K/GSK3β-Signalweg zeigten allesamt
Effekte auf die lokale Konzentrierung von AChRs, die mit oben angeführter
Kausalkette konsistent sind: Die Depolymerisierung von Microtubuli, die
Hemmung der PI3-Kinase, der Verlust des Clasp2-Gens, die shRNAvermittelte
Unterdrückung der LL5β-Expression sowie die Hyperaktivierung
von GSK3β führten jeweils zu reduzierter Grösse der AChR-Ansammlungen,
während die Hemmung von GSK3β die Grösse der AChR-Ansammlungen
erhöhte. Zusammengefasst trägt agrin-induzierte und +TIP-vermittelte
Befestigung von Mikrotubuli an der subsynaptischen Membran zur fokalen
Insertion und zum lokalen Konzentration von AChRs bei.
Abstract
Neurotransmission at the neuromuscular synapse of mammals occurs after
secretion of acetylcholine (ACh) from the motor nerve into the synaptic cleft
and ultimately results in contraction of the target muscle. The signaling
molecule agrin, which is also secreted by the motoneuron, is the main
organizer of postsynaptic differentiation and induces the clustering of
receptors for the neurotransmitter acetylcholine (AChR) in a small – mostly
central – area of the myofiber directly underneath the motoneuron terminal
bouton. After intense research, the end results of agrin-induced
differentiation are well documented and many involved molecules are known.
Nevertheless, the role of the subsynaptic microtubule (MT) cytoskeleton in
the process of AChR transport, insertion and clustering and the molecular
mechanisms of the establishment of such a microtubule network are poorly
defined. During my thesis, I analyzed new aspects of agrin-induced
biochemical signaling and the cell biological consequences for the
microtubule cytoskeleton.
Targeted intracellular transport of vesicles generally occurs along polar
cytoskeletal structures, a major part along microtubules – cytoskeletal
filaments that are normally short-lived with a highly dynamic “plus-end”,
which alternates between periods of growing and shrinking. However, certain
stimuli induce signal transduction cascades which result in the “capture” of
microtubule plus-ends at the cell cortex by interaction of plus-end binding
proteins (+TIPS) with factors that localize to the cortex or the actin
cytoskeleton. This event stabilizes microtubules and can drastically increase
their lifetime – affected microtubule then serve the cell as stable, directional
transport tracks.
During my thesis, I could show that the AChR-rich postsynaptic membrane
encompasses a dense subsynaptic MT network, with some MTs further
stabilized by post-translational modifications. In addition, I could
demonstrate that agrin induces PI3 kinase signaling in muscle, which
ultimately inactivates GSK3β by phosphorylation.
Since many of the former mentioned +TIP proteins are negatively regulated
by GSK3β, localized inactivation of GSK3β is crucial to enable +TIP-mediated
microtubule capture and establishment of stable transport tracks at sites with
elevated protein requirements such as the postsynaptic membrane. +TIP
proteins, in particular Clasp2, then capture MTs at the cell cortex within
AChR-rich sites by interacting with the membrane PIP3-sensor LL5β and thus
establish intracellular transport routes for focal transport of postsynaptic
material like AChRs and structural proteins towards the synapse.
Mutants of involved molecules as well as pharmacologic manipulation of the
PI3K/GSK3β-axis displayed effects on the clustering of AChRs, which are fully
consistent with the aforementioned chain of events: Microtubule
depolymerization, inhibition of PI3K, loss of the clasp2 gene, shRNAmediated
repression of LL5β expression and hyper-activation of GSK3β lead
to reduced AChR clustering, while inhibition of GSK3β elevates AChR
clustering. Taken together, agrin-induced and +TIP-mediated MT capture at
the subsynaptic muscle membrane contributes to focal insertion and
clustering of AChRs at the neuromuscular junction
Stefan Morawski’s Critique of Postmodernism
No full textThe matter under consideration is Stefan Morawski’s criticism of postmodernism. The author presents Morawski’s main arguments against postmodernism and analyzes their accuracy for the Richard Rorty’s and Francois Lyotard’s theories. In addition to this the author considers the impact of the art on the possibility of integration consumer society
Ep. #044 - Stefan Helmreich
No full textThis recording and transcript form part of a collection of podcasts conducted by the Cultures of Energy at Rice University. Cultures of Energy brings writers, artists and scholars together to talk, think and feel their way into the Anthropocene. We cover serious issues like climate change, species extinction and energy transition. But we also try to confront seemingly huge and insurmountable problems with insight, creativity and laughter.On this week’s podcast, Dominic and Cymene continue to process election aftermath and offer thoughts on how to escape the dungeon. Then (14:20) things get wavy when Stefan Helmreich from MIT—author of Alien Ocean (U California Press, 2009) and Sounding the Limits of Life (Princeton U Press, 2016)—joins the conversation and we talk about his recent work on waves and water. We start with the submarine trip that got him interested in the sound of fieldwork underwater and these strange entities known as “waves.” He then introduces us to the world of wave science and explains how it can be viewed as anthropology by other means given its constant attention to social concerns like coastal infrastructure, shipping, recreation, and insurance. Stefan discusses why the problem of the 21st century is the problem of the waterline—rising sea level, changing sea surface, and wavy dynamics that modulate sea level. He also explains that even though current models of wave action are based on northern ocean data, it looks increasingly likely that the future will belong to southern ocean dynamics. We visit the largest tsunami simulation basin in the world, learn what “rogue waves” are, and come to understand how, with the coming of wave energy, waves are being reimagined not as enemies but rather as allies whose labor can be harnessed in the struggle against climate change. Stefan offers some reflections on “blue humanities,” the shipwreckocene and Haraway’s Chthulucene. Finally, we turn toward his current research in the Netherlands with its long and complex relationship to water. And, yes, Cymene asks him about surfing and his answer is the best. Listen on
Macroeconomic imbalances and comparative advantages in the Euro Area
No full textThe emergence of macroeconomic imbalances among EU member states is often seen as a major underlying factor of the recent European debt crisis. In order to identify and tackle these imbalances, the European authorities established, in 2011, a new surveillance tool incorporating rules to prevent future imbalances and labelled the Excessive Imbalance Procedure (EIP).
Stefan Collignon argues that the premises of the Excessive Imbalance Procedure are in fact wrong, and its implementation therefore misguided, in that they take for granted the policy framework of the nation state whereas the Euro Area economy is, in reality, integrated into a single market with a single currency, such that so-called ‘foreign’ debt is, effectively, debt to other residents in the Euro Area.
The author demonstrates, furthermore, that strict adherence to the EIP could, in conjunction with other new economic governance instruments, entail devastating consequences for peripheral countries in the European Union.
Following his observation that current indicators used by the Commission fail to provide a correct or accurate assessment of imbalances in the Euro Area, the author devises a new ‘Competitive Index’, calculated as the difference between actual and equilibrium unit labour costs, which he recommends as an alternative and better indicator in the context of the Alert Mechanism Reports to be issued by the European Commission in the future
Solution of vector Stefan problems with cross-diffusion
No full textA general model for the dissolution of particles in multi-component alloys is proposed and analyzed. The model is based on diffusion equations with cross-terms for the several species, combined with a Stefan condition as the equation of motion of the interface between the particle and diffusant phase. To facilitate the analysis we use a diagonalization argument or Jordan factorization for the diffusion matrix. Self-similar solutions with the Boltzmann transformation are derived to get insight into qualitative behavior of the solution and for comparison with numerical solutions. Several numerical schemes for the solution of the Stefan problem are proposed and compared. It turns out that diagonalization is usefull for numerical purposes too. However, for the case of position dependent diffusion coefficients or a non diagonalizable diffusion matrix, one has to use a different scheme. Here, we analyze stability and workload of several time integrations.Electrical Engineering, Mathematics and Computer Scienc
On Stefan Żółkiewski
No full textThe author writes about Professor Stefan Żółkiewski’s theoretical concepts and three decades of scholarship, beginning with the 1960s and including lectures at the University of Warsaw’s Department of Polish Philology, directing work in the Department of Social Sciences of the Polish Academy of Sciences, initiating interdisciplinary studies of contemporary culture, editing journal ‘Kultura i Społeczeństwo’, and popularizing semiotics. The author writes about Professor Żółkiewski’s connection with the Institute of Literary Research, of which he was the founder and first director, and about the establishment of the Workshop on Research into Literary Culture and the creation of a new discipline—knowledge of literary culture. The author remembers Professor Żółkiewski as her mentor and friend
The labor foundation as a strategy against technological unemployment
No full textAuthor Stefan Paul Miejski, B.A.Abstract in englischer SpracheMasterarbeit Universität Linz 201
The entrepreneurial ecosystem: a case study of the central Upper Austrian area
No full textAuthor Stefan Döberl, BScMasterarbeit Universität Linz 201
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