La navigation des axones sur de longues distances est jalonnée de zones de choix, entraînant des changements de direction pour suivre des trajectoires hautement stéréotypées. Dans ce modèle de guidage séquentiel, chaque étape est vue comme essentielle à la suivante. De façon intrigante, quelques exemples suggèrent que le suivi strict de la trajectoire puisse être dispensable pour que les axones atteignent leur destination finale. Nous nous sommes intéressés à cette capacité trajectoire indépendante des axones à localiser leur cible. Pour ce faire, nous avons utilisé deux populations neuronales de la moelle épinière ayant des cibles diamétralement opposées dans l'organisme : les interneurones dorsaux, qui projettent dans le système nerveux central, et les motoneurones ventraux, qui ciblent les muscles en périphérie. Après avoir été déplacés chirurgicalement dans des embryons de poulet, ces deux populations de neurones envoient des axones vers leurs territoires cibles qu'ils atteignent par des trajectoires inédites. Ces observations suggèrent l'existence d'un système de guidage global délivrant aux axones des informations spatiales à large échelle. Outre les signaux moléculaires de guidage bien connus, les signaux bioélectriques sont également des candidats intéressants pour remplir cette fonction. Des champs électriques (CE) ont été détectés dans les embryons en développement et sont connus pour être des vecteurs d'information spatiale. Nous avons testé sur des neurones en culture si des CE comparables à ceux mesurés pendant le développement embryonnaire pourraient guider l'élongation des axones moteurs et d'interneurones dorsaux de poulet. Nous avons trouvé que les deux types d'axones s'orientent en direction de la cathode (-) dans un CE. Cependant, ils présentent des sensibilités significativement différentes aux CE, qui pourraient contribuer à des choix de trajectoires différents in vivo. Ensuite, nous avons observé un effet inhibiteur de la Concanavaline A (ConA) sur la réponse des axones aux champs, indiquant un rôle des récepteurs membranaires connus pour lier la ConA. Nous avons donc réalisé un screen pharmacologique sur des pompes et des canaux ioniques qui se lient à la ConA, conduisant à l'identification des pompes Na+/K+ ATPases comme des candidats prometteurs. Des expériences préliminaires d'invalidation des sous-unités de ces pompes suggèrent qu'elles contribuent à la réponse aux CE et à la navigation axonale in vitro et in vivo. Finalement, nos résultats apportent une vision nouvelle des mécanismes assurant la fidélité et la résilience du guidage axonal, et révèlent la contribution méconnue des signaux bioélectriques et des pompes Na+/K+ ATPases au développement neuronal / Long distance navigation of axons is marked by choice points, instructing highly stereotyped directional changes of axon trajectories. In this stepwise model, each step is thought to be essential for the next one, but intriguingly, examples suggest that pathway experience can be dispensable for axons to reach their final destination. We investigated pathway-independent ability of axons to locate their target, using two populations of spinal cord neurons having drastically different target location in the organism: the dorsal interneurons, which target the central nervous system and ventral motoneurons, which target muscles. After grafting these neurons at ectopic positions in the chicken embryo, both neuron-types were observed to form axons which, remarkably, oriented towards and reached appropriate targets. This suggests that, in the embryo, an overall guidance information might exist that enables the axons to locate positions over large scales. Beside well-studied chemical cues, bioelectric signals are attractive candidates for this function. Electric Fields (EF) were detected in the embryo and reported to encode spatial information. Thus, using in vitro set-ups, we investigated whether EFs in the range of the ones measured in the embryo could influence the navigation of chick motor and dorsal interneuron axons. We found that both axon subsets orient parallel to EFs. Yet, they significantly exhibited different sensitivities, which could contribute to elicit different trajectory choices in vivo. Next, we found that Concanavalin A (ConA) could block axon response to EF, supporting a role of cell surface receptors known to bind to ConA. Thus, we performed a pharmacological screening on ion channels and pumps that bind ConA and identified Na+/K+ ATPases as promising candidates. Preliminary knock-down experiments targeting Na+/K+ ATPases subunits suggest their contribution to CE response and axon navigation in vitro and in vivo. Collectively, our findings should provide novel insights into the mechanisms ensuring axon guidance fidelity and resilience and reveal unknown contributions of bioelectric signals and Na+/K+ ATPases during neuronal development

We present results on the ionospheric structure around Titan observed during numerous deep (<1000 km) flybys by the Cassini spacecraft. Our results are based on measurements by the radio and plasma wave science instrument, in particular the Langmuir probe. In addition, data from the magnetometer and electron spectrometer have contributed. The ionosphere of Titan is created when the atmosphere of the moon becomes ionised. There are several mechanisms that contribute to this, the most important of which are considered to be photoionisation by EUV from the Sun with associated photoelectron ionisation, and particle impact ionisation by electrons and ions from Saturn’s corotating magnetosphere. We investigate the influence of the solar zenith angle on the electron number density at the ionospheric peak. The results show on average four times more plasma on the dayside compared to the nightside, with typical densities of 2500 – 3500 cm-3 and 400 – 1000 cm-3, respectively. In a complementary study, we make a case study of a nightside flyby and show that the altitude structure of the deep ionosphere is reproducible by a simple electron impact ionisation model. Taken together, this leads to the conclusion that solar photons are the main ionisation source of the dayside ionosphere. However, magnetospheric particle precipitation also contributes and can explain the electron densities seen on the nightside. As Titan does not exhibit any large intrinsic magnetic field, the fact that it is embedded in the magnetosphere of Saturn means that the Kronian field drapes around the moon and gives rise to an induced magnetosphere. We show that there are currents of the order of 10 – 100 nA m-2 flowing in the ionosphere of the moon. Associated with the currents are perpendicular electric fields ranging from 0.5 to 3 µV m-1. Finally, we investigate measurements obtained during T70, the deepest Titan flyby performed to date. We show that there is a substantial amount of negative ions present below an altitude of 900 km. This confirms previous result by the electron spectrometer, showing negative ions at higher altitudes in Titan’s ionosphere.

Electroporation is the critical step in an electric field mediated drug or gene delivery protocol. Electroporation based protocols have been successfully demonstrated in cancer clinical trials, however, its impact in other applications is still under investigation. A significant roadblock to long term functioning of implantable biosensors in vivo is the tissue reaction in the form of fibrous encapsulation that results in reduced transport to the sensing element of the biosensor. In vivo gene electroporation has a great potential as a means to modify the transport properties of tissues in the proximity of the sensing element of implantable biosensors. This dissertation examines two postulated electroporation based strategies to modify tissue for enhanced performance of an implantable biosensor. In the first, the implantation protocol is modified to accommodate in vivo electroporation. In the second strategy, the the modification is applied post implantation. This post-implantation in vivo electroporation application requires that electric energy be delivered at the site of electroporation close to the biosensor while minimizing effects far from such site. A novel method, focusing electric fields, developed for this purpose is presented. A theoretical framework as well as in vitro and in vivo experiments are provided as the introduction to the method and in support of its potential as the basis of a viable technology.

London or dispersion interactions are weak van der Waals (vdW) interactions. They are important in determining the structure and properties of many chemical and biochemical systems. In this thesis, an optimizer using the nonempirical generalized gradient approximation (GGA) functional PW86+PBE+XDM, to capture van der Waals interactions, is presented. The work in this thesis covers the assessment of a variety of basis sets for their ability to reproduce accurate GGA repulsive and binding energies. Selected basis sets were then used to compute binding energies of 65 vdW complexes at equilibrium. This functional was also tested for binding energies of two sets of vdW complexes at distorted geometries. The last part deals with forces to investigate their accuracy using PW86+PBE+XDM in order to build an optimizer for vdW complexes using a nonempirical DFT method. Eventually, after confirming a high reproducibility of the optimizer on the geometries and binding energies, it was used in two biologically relevant applications. This optimizer is a unique tool to compute deformation energies with a nonempirical DFT method. The second part of this thesis covers a biologically relevant application where a conventional DFT is used. This application is related to the carrier of the genetic codes in living cells, DNA. DNA undergoes harmful mutations under external perturbations such as applied external electric fields. In this study, DNA base pairs were first mimicked by a simpler model, namely, the formic acid dimer. The effect of applied external electric fields on the geometries of the formic acid dimer is studied. The effect of these applied fields on the potential energy surface, the barrier height and the frequency of the double proton transfer in the formic acid dimer are also investigated. The study was then repeated on DNA base pairs to study the effect of an external applied electric field on the tunneling corrected rate constants of the double proton transfer reactions in AT and GC.

No description available.

Thesis (MScEng)--University of Stellenbosch, 2000. / ENGLISH ABSTRACT: An electro-optic sensor system was developed which uses the modulated scatterer technique [1] to measure the fine structure-amplitude and phase-of electric fields with the minimum of perturbation. The theory for the technique is discussed in detail, with the Lorentz Reciprocity theorem as foundation. The system is also treated as a general two port and solved in terms of the impedances present. This comprises self impedances and mutual impedances. The signals scattered by the dipole scatterer are modeled as amplitude modulated signals and a detailed detection scheme is presented. The detection of the signals is done by a digital correlation process. This is quite similar to synchronous detection. A detailed sensitivity analysis is presented that was used to determine the quality of the system. This analysis is backed by a practical sensitivity measurement. A few antennas and scatterers are measured in the X-band using the system, and results are compared with theory. These systems include a pyramidal horn, an E-plane sectoral horn and a simple waveguide. Half plane diffraction by a metal sheet is also presented. The practical implementation of the theory is emphasized. / AFRIKAANSE OPSOMMING: 'n Elektro-optiese meetsisteem is ontwikkel wat die gemoduleerde strooier tegniek [11 gebruik om die fyn struktuur-amplitude en fase-van elektriese velde te meet. Hierdie tegniek versteur die velde minimaal. 'n Volledige ondersoek word gedoen na die teorie van die stelsel. Die basis van die metode Ie in die Lorentz Resiprook teorie. Alhoewcl daar gekonsentreer word op hierdie teorie, is die stelsel ook beskou as 'n tweepoort. Die wedersydse en ei impedansies van die verskillende komponente word gebruik om die velde op te los. Die gestrooide seine, as gevolg van die dipool strooier, word gemodelleer met b hulp van amplitude modulasie. Die deteksie van hierdie seine word deeglik bespreek. In plaas van 'n analoogstelsel, word 'n digitale korrellasie proses gebruik om die velde te meet. Di sensitiwiteit van die stelsel word geanaliseer. Verder word metings met di stelsel gen em om die teoretiese analise te staaf. 'n Paar X-band sisteme word gebruik om metings te neem. Hicrdi metings word ook vergelyk met teor ti se resultate. Stelsels wat gemeet is sluit die volgencle in: 'n piramidale horing antenna, 'n E-vlak sektorale horing antenna, 'n X-band golfgeleier en die diffraksi op die rand van 'n plaat. Die praktiese implemcntering van die teorie word beklemtoon.

Made available in DSpace on 2014-10-09T12:34:00Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:01:05Z (GMT). No. of bitstreams: 0 / Tese (Doutoramento) / IPEN/D / Instituto de Pesquisas Energéticas e Nucleares - IPEN-CNEN/SP

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