Proxy voting in the joint stock company and the limited liability company

Die Ausübung des Stimmrechts durch einen Stellvertreter stellt eine Möglichkeit für einen Aktionär oder einen Gesellschafter dar, sein Stimmrecht auch dann auszuüben, wenn er nicht persönlich an der Haupt- bzw. Gesellschafterversammlung teilnehmen kann. Dieser Sachver-halt ist seit Jahren Gegenstand von Gesetzesänderungen gewesen. In der vorliegenden Arbeit werden insbesondere die aktienrechtlichen Änderungen durch das ARUG auf die Stimm-rechtsvertretung auf ihre Rechtmäßigkeit und Zweckmäßigkeit hin untersucht. Die Arbeit hinterfragt darüber hinaus die Rolle des von der Gesellschaft benannten Stimmrechtsvertreters sowohl in dogmatischer als auch in rechtspolitischer Hinsicht. Neben der freiwilligen Stimmrechtsvertretung werden auch Zulässigkeit und Ausgestaltung des Vertretungszwangs untersucht. Schwerpunkt ist hierbei der im GmbH-Recht mögliche gesellschaftsvertragliche Vertretungszwang durch eine Vertreterklausel. Hierbei werden die Rechtsbeziehungen der von der Vertreterklausel betroffenen Gesellschafter sowie die Überle-gung, wie ein Gesellschafter sich dem Vertretungszwang wieder entziehen kann, untersucht.In case a shareholder is not able to attend the general meeting of shareholders, he can exercise his voting right by proxy. The available dissertation particularly discusses the amendments by the lawmakers with the ARUG, which changed the form of exercising the voting right by proxy. Especially, the proxy voter according to § 134 III 5 AktG is analysed from the dogmatic point of view as well as from a legal policy view. In addition to the voluntarily exercise of voting right, the mandatory representation in general meetings is crucial for shareholders. The author emphasises a constellation, in which the ar-ticles of association oblige a group of shareholders to exercise their voting rights by proxy. The relations between the obliged shareholders and the possibility of termination are analysed

Heat transfer in corrugated passages

Imperial Users onl

Kulturwissenschaftliche Xenologie

Die kulturwissenschaftliche Xenologie liefert das Handwerkszeug, die Begriffe und Methoden, mit denen man einen bestimmten, zentralen Aspekt aus einem Text herausfiltern und einordnen kann: Fremdheit. Fremdheit ist in allen Texten zu finden, in denen eine Begegnung zwischen zwei oder mehr Individuen oder Gruppen thematisiert wird. Da es sich bei einer Fremdheitserfahrung um einen auffallenden Bruch mit dem Gewohnten, ein ‚Ereignis‘, handelt, ist sie als Themenkomplex weitläufig in Texten der unterschiedlichsten Epochen anzutreffen (vgl. Walberg 2014: 88). Deshalb, und weil Fremdheit als anthropologische Konstante gelten darf, bedarf es mit der kulturwissenschaftlichen Xenologie eines Zugriffs- und Analyseapparates. Doch sind überhaupt die gegebenen Methoden ausreichend, um die Komplexität und Vielseitigkeit des Konzepts ‚Fremdheit‘ und die Dimensionen von Fremdheitserfahrungen zu erfassen

A scalable human iPSC-based neuromuscular disease model on suspended biobased elastomer nanofiber scaffolds

Many devastating neuromuscular diseases currently lack effective treatments. This is in part due to a lack of drug discovery platforms capable of assessing complex human neuromuscular disease phenotypes in a scalable manner. A major obstacle has been generating scaffolds to stabilise mature contractile myofibers in a multi-well assay format amenable to high content image analysis (HCI). This study describes the development of a scalable human iPSC-neuromuscular disease model, whereby suspended elastomer nanofibers support long-term stability, alignment, maturation, and repeated contractions of iPSC-myofibers, innervated by iPSC-motor neurons in 96-well assay plates. In this platform, optogenetic stimulation of the motor neurons elicits robust myofiber-contractions, providing a functional readout of neuromuscular transmission. Additionally, HCI provides rapid and automated quantification of axonal outgrowth, myofiber morphology, and neuromuscular synapse number and morphology. By incorporating amyotrophic lateral sclerosis (ALS)-related TDP-43G298S mutant motor neurons and CRISPR-corrected controls, key neuromuscular disease phenotypes are recapitulated, including weaker myofiber contractions, reduced axonal outgrowth, and reduced number of neuromuscular synapses. Treatment with a candidate ALS drug, the receptor-interacting protein kinase-1 (RIPK1)-inhibitor necrostatin-1, rescues these phenotypes in a dose-dependent manner, highlighting the potential of this platform to screen novel treatments for neuromuscular diseases

A scalable human iPSC-based neuromuscular disease model on suspended biobased elastomer nanofiber scaffolds

Many devastating neuromuscular diseases currently lack effective treatments. This is in part due to a lack of drug discovery platforms capable of assessing complex human neuromuscular disease phenotypes in a scalable manner. A major obstacle has been generating scaffolds to stabilise mature contractile myofibers in a multi-well assay format amenable to high content image (HCI) analysis. This study describes the development of a scalable human induced pluripotent stem cell (iPSC)-neuromuscular disease model, whereby suspended elastomer nanofibers support long-term stability, alignment, maturation, and repeated contractions of iPSC-myofibers, innervated by iPSC-motor neurons in 96-well assay plates. In this platform, optogenetic stimulation of the motor neurons elicits robust myofiber-contractions, providing a functional readout of neuromuscular transmission. Additionally, HCI analysis provides rapid and automated quantification of axonal outgrowth, myofiber morphology, and neuromuscular synapse number and morphology. By incorporating amyotrophic lateral sclerosis (ALS)-related TDP-43G298S mutant motor neurons and CRISPR-corrected controls, key neuromuscular disease phenotypes are recapitulated, including weaker myofiber contractions, reduced axonal outgrowth, and reduced number of neuromuscular synapses. Treatment with a candidate ALS drug, the receptor-interacting protein kinase-1 (RIPK1)-inhibitor necrostatin-1, rescues these phenotypes in a dose-dependent manner, highlighting the potential of this platform to screen novel treatments for neuromuscular diseases.</p

3D Compartmentalised Human Pluripotent Stem Cell-derived Neuromuscular Co-cultures.

Human neuromuscular diseases represent a diverse group of disorders with unmet clinical need, ranging from muscular dystrophies, such as Duchenne muscular dystrophy (DMD), to neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS). In many of these conditions, axonal and neuromuscular synapse dysfunction have been implicated as crucial pathological events, highlighting the need for in vitro disease models that accurately recapitulate these aspects of human neuromuscular physiology. The protocol reported here describes the co-culture of neural spheroids composed of human pluripotent stem cell (PSC)-derived motor neurons and astrocytes, and human PSC-derived myofibers in 3D compartmentalised microdevices to generate functional human neuromuscular circuits in vitro. In this microphysiological model, motor axons project from a central nervous system (CNS)-like compartment along microchannels to innervate skeletal myofibers plated in a separate muscle compartment. This mimics the spatial organization of neuromuscular circuits in vivo. Optogenetics, particle image velocimetry (PIV) analysis, and immunocytochemistry are used to control, record, and quantify functional neuromuscular transmission, axonal outgrowth, and neuromuscular synapse number and morphology. This approach has been applied to study disease-specific phenotypes for DMD and ALS by incorporating patient-derived and CRISPR-corrected human PSC-derived motor neurons and skeletal myogenic progenitors into the model, as well as testing candidate drugs for rescuing pathological phenotypes. The main advantages of this approach are: i) its simple design; ii) the in vivo-like anatomical separation between CNS and peripheral muscle; and iii) the amenability of the approach to high power imaging. This opens up the possibility for carrying out live axonal transport and synaptic imaging assays in future studies, in addition to the applications reported in this study. Graphical abstract Graphical abstract abbreviations: Channelrhodopsin-2 (CHR2+), pluripotent stem cell (PSC), motor neurons (MNs), myofibers (MFs), neuromuscular junction (NMJ)

Restoring motor function using optogenetics and neural engraftment

Controlling muscle function is essential for human behaviour and survival, thus, impairment of motor function and muscle paralysis can severely impact quality of life and may be immediately life-threatening, as occurs in many cases of traumatic spinal cord injury (SCI) and in patients with amyotrophic lateral sclerosis (ALS). Repairing damaged spinal motor circuits, in either SCI or ALS, currently remains an elusive goal. Therefore alternative strategies are needed to artificially control muscle function and thereby enable essential motor tasks. This review focuses on recent advances towards restoring motor function, with a particular focus on stem cell-derived neuronal engraftment strategies, optogenetic control of motor function and the potential future translational application of these approaches

Aberrant axon initial segment plasticity and intrinsic excitability of ALS hiPSC motor neurons

Dysregulated neuronal excitability is a hallmark of amyotrophic lateral sclerosis (ALS). We sought to investigate how functional changes to the axon initial segment (AIS), the site of action potential generation, could impact neuronal excitability in ALS human induced pluripotent stem cell (hiPSC) motor neurons. We find that early TDP-43 and C9orf72 hiPSC motor neurons show an increase in the length of the AIS and impaired activity-dependent AIS plasticity that is linked to abnormal homeostatic regulation of neuronal activity and intrinsic hyperexcitability. In turn, these hyperactive neurons drive increased spontaneous myofiber contractions of in vitro hiPSC motor units. In contrast, late hiPSC and postmortem ALS motor neurons show AIS shortening, and hiPSC motor neurons progress to hypoexcitability. At a molecular level, aberrant expression of the AIS master scaffolding protein ankyrin-G and AIS-specific voltage-gated sodium channels mirror these dynamic changes in AIS function and excitability. Our results point toward the AIS as an important site of dysfunction in ALS motor neurons

Reconstruction of phrenic neuron identity in embryonic stem cell-derived motor neurons

Air breathing is an essential motor function for vertebrates living on land. The rhythm that drives breathing is generated within the central nervous system and relayed via specialised subsets of spinal motor neurons to muscles that regulate lung volume. In mammals, a key respiratory muscle is the diaphragm, which is innervated by motor neurons in the phrenic nucleus. Remarkably, relatively little is known about how this crucial subtype of motor neuron is generated during embryogenesis. Here, we used direct differentiation of motor neurons from mouse embryonic stem cells as a tool to identify genes that direct phrenic neuron identity. We find that three determinants, Pou3f1, Hoxa5 and Notch, act in combination to promote a phrenic neuron molecular identity. We show that Notch signalling induces Pou3f1 in developing motor neurons in vitro and in vivo. This suggests that the phrenic neuron lineage is established through a local source of Notch ligand at mid-cervical levels. Furthermore, we find that the cadherins Pcdh10, which is regulated by Pou3f1 and Hoxa5, and Cdh10, which is controlled by Pou3f1, are both mediators of like-like clustering of motor neuron cell bodies. This specific Pcdh10/Cdh10 activity might provide the means by which phrenic neurons are assembled into a distinct nucleus. Our study provides a framework for understanding how phrenic neuron identity is conferred and will help to generate this rare and inaccessible yet vital neuronal subtype directly from pluripotent stem cells, thus facilitating subsequent functional investigations