On the long time behaviour of single stochastic Hodgkin-Huxley neurons with constant signal, and a construction of circuits of interacting neurons showing self-organized rhythmic oscillations

The stochastic Hodgkin-Huxley neurons considered in this paper replace time-constant deterministic input $a dt$ of the classical deterministic model by increments $\vartheta dt + dX_t$ of a stochastic process: $X$ is Ornstein-Uhlenbeck with volatility $\sigma>0$ and backdriving force $\tau>0$, and we call $\vartheta>0$ the signal. We have ergodicity and strong laws of large numbers for various functionals of the process, and characterize 'quiet behaviour' and 'regular spiking' as events whose probability depends on the parameters $(\tau,\sigma)$ and on the signal $\vartheta$. The notions of quiet behaviour and regular spiking allow for a construction of circuits of interacting stochastic Hodgkin-Huxley neurons, combining excitation with inhibition according to a bloc structure along the circuit, on which self-organized rhythmic oscillations can be observed.Comment: 53 pages, 8 figure

Modulation of Cargo Transport and Sorting through Endosome Motility and Positioning

Utilizing various systems such as cell-based assays but also multicellular organisms such as Drosophila melanogaster and C.elegans, for example, the endocytic system has been shown to consist of a network of biochemically and morphologically distinct organelles that carry out specialized tasks in the uptake, recycling and catabolism of growth factors and nutrients, serving a plethora of key biological functions (Mellman, 1996). Different classes of endosomes were found to exhibit a characteristic intracellular steady state distribution. This distribution pattern observed at steady state results from a dynamic interaction of endosomes with the actin and the microtubule cytoskeleton. It remains unclear, however, which microtubule-based motors besides Dynein control the intracellular distribution and motility of early endosomes and how their function is integrated with the sorting and transport of cargo. The first part of this thesis research outlines the search for such motor. I describe the identification of KIF16B which functions as a novel endocytic motor protein. This molecular motor, a kinesin-3, transports early endosomes to the plus end of microtubules, in a process regulated by the small GTPase Rab5 and its effector, the phosphatidylinositol-3-OH kinase hVPS34. In vivo, KIF16B overexpression relocated early endosomes to the cell periphery and inhibited transport to the degradative pathway. Conversely, expression of dominant-negative mutants or ablation of KIF16B by RNAi caused the clustering of early endosomes to the peri-nuclear region, delayed receptor recycling to the plasma membrane and accelerated degradation. These results suggest that KIF16B, by regulating the plus end motility of early endosomes, modulates the intracellular localization of early endosomes and the balance between receptor recycling and degradation. In displaying Rab5 and PI(3)P-containing cargo selectivity, a remarkable property of KIF16B is that it is subjected to the same regulatory principles governing the membrane tethering and fusion machinery (Zerial and McBride, 2001). Since KIF16B can modulate growth factor degradation, we propose that this motor could have also important implications for signaling. Importantly, KIF16B has provided novel insight into how intracellular localization of endosomes governs the transport activity of these organelles. The second part of this thesis describes the proof-of-principle of a genome-wide screening strategy aimed at gaining insights into the next level of understanding: How the spatial distribution of organelles is linked to their function in an experimental system which features cellular polarity, for example, a tissue or organ. The suitability of C. elegans as a model organism to identify genes functioning in endocytosis has been demonstrated by previous genetic screens (Grant and Hirsh 1999; Fares and Greenwald, 2001). Offering excellent morphological resolution and polarization, the nematode intestine represents a good system to study the apical sorting of a transmembrane marker. The steady state localization of such a marker is likely the result of a dynamic process that depends on biosynthetic trafficking to the apical surface, apical endocytosis and recycling occurring through apical recycling endosomes. Therefore, mis-sorting of this marker upon RNA-mediated interference will be indicative of a failure in one of the aforementioned processes. Furthermore, since it is still largely unclear why apical endosomes maintain their polarized localization, this screen will also monitor the morphology of this endocytic compartment using a second marker. Following image acquisition based on an automated confocal microscope, data can be analyzed using custom-built software allowing objective phenotypic analysis. The successful establishment of the proof-of-principle marks the current state-of-the-art of this large-scale screening project

A new method of seawater desalination via acrylic acid based hydrogels: Synthesis, characterisation, and experimental realisation

The scarcity of potable water is a great challenge. It may be resolved by the desalination of seawater. In this work, the possibilities of a new desalination technique using polymeric hydrogels as a separation medium for water and salt is explored. The bound charges in such a polymeric network prevent salt from entering it - under pressure the desalinated water is released from the gel. It is demonstrated that the method is viable and the influence of various process parameters investigated