A 50 MHz Frequency Modulated Continuous Wave (FMCW) radar system, developed at the University of Saskatchewan to provide improved spatial and temporal resolution measurements of auroral E-region plasma processes, introduces ambiguous spectral information, due to spectral ghosting, for scattering events in which multiple radar echoes are detected. This thesis identifies two Linearly Frequency Modulated (LFM) radar waveforms used by the FMCW system as the source of the ghosting. An analysis procedure designed to counteract the spectral ghosting problem is developed but is not an ideal solution, and therefore replacement of the LFM waveforms is recommended.<p> A detailed investigation of alternative radar waveforms using the Ambiguity Function and Ambiguity Diagram techniques is performed. A frequency coded continuous wave radar waveform based on a composite Costas sequence is proposed as a successor to the LFM waveforms. The composite Costas radar waveform will conserve the spatial and temporal resolutions extended by the LFM waveforms and preclude any spectral ghosting. Implementing the proposed radar waveform and avoiding receiver saturation issues with the mono-static FMCW radar system in which both the transmitting and receiving antenna arrays are simultaneously and continuously active and geographically co-located is also discussed.<p> In addition to this, two 50 MHz backscatter events are presented in this thesis to demonstrate the effectiveness of the FMCW system, notwithstanding the spectral ghosting complication. The first event from November 21, 2009 is identified as a Type 1 instability and the second from September 13, 2009 is identified as a Type 2 instability which lasted for ~ 16 minutes. Linear plasma fluid theory is used to provide a brief interpretation of both scattering events.

Flotillin-1 és una proteïna associada a membrana plasmàtica implicada en processos de trànsit de vesícules, reordenació del citoesquelet i transducció de senyals. Estudis previs en el laboratori han demostrat que Flotillin-1 és capaç de translocar-se a nucli en resposta a un estímul mitogènic i afavorir la proliferació de diverses línies cel·lulars. Els mecanismes mitjançant els quals provoca aquests efectes són desconeguts i objecte del present estudi.D'una banda demostrem que Flotillin-1 és un factor regulador de la cinasa Aurora B, una proteïna que intervé en el control de la mitosi i més concretament en el anaphase checkpoint. El knock-down de Flotillin-1 provoca events mitòtics aberrants, acompanyats del descens tant en l'expressió d'Aurora B com de la seva activitat mesurada com els nivells de fosforilació de la histona H3. Flotillin-1 interacciona amb Aurora B i evita la seva degradació per la via del proteasoma.D'altra banda, Flotillin-1 interacciona amb el receptor transmembrana Notch1, implicat en nombrosos processos de regulació de proliferació, diferenciació, apoptosi, etc. Flotillin-1 regula la localització subcel·lular de Notch1 així com la seva capacitat com activador transcripcional. La depleció o mutació de Flotillin-1 dificulta l'entrada de Notch1 a nucli i l'expressió dels gens diana de les famílies Hes/Hrt. En conjunt, es presenta a Flotillin-1 com una proteïna capaç d'actuar a diferents nivells i regular processos i vies de senyalització cel·lular que li confereixen un paper com a regulador de la proliferació cel·lular. / Flotillin-1 is a protein associated to plasma membrane involved in vesicle trafficking, cyotskeleton reorganization and signal transduction. Previous findings in our laboratory has shown that Flotillin-1 is able to translocate the nucleus under mitogenic stimulus and increase proliferation rates of several cell lines. The mechanisms of action are unknown and object of the present study.First, we show that Flotillin-1 is a regulator factor of the mitotic kinase Aurora B, a protein involved in control of mitosis and, specifically, in the anaphase checkpoint. The knock-down of Flotillin-1 causes aberrant mitotic events, decrease in Aurora B levels and its activity, measured as protein levels of phosporilated histone H3. Flotillin-1 interacts with Aurora B and avoid its degradation by the proteasome pathway.In addition, Flotillin-1 interacts with the transmembrane receptor Notch1, involved in many regulatory processes of proliferation, differentiation, apoptosis, etc. Flotillin-1 regulates the subcellular localization of Notch1 and its activity as transcriptional activator. The mutation or depletion of Flotillin-1 difficult the entry of Notch1 in the nucleus and the expression of its target genes Hes/ HRT. Overall, Flotillin-1 is a protein capable of acting at different levels, processes and signaling pathways in order to be a regulator of cell proliferation.

A 50 MHz Frequency Modulated Continuous Wave (FMCW) radar system, developed at the University of Saskatchewan to provide improved spatial and temporal resolution measurements of auroral E-region plasma processes, introduces ambiguous spectral information, due to spectral ghosting, for scattering events in which multiple radar echoes are detected. This thesis identifies two Linearly Frequency Modulated (LFM) radar waveforms used by the FMCW system as the source of the ghosting. An analysis procedure designed to counteract the spectral ghosting problem is developed but is not an ideal solution, and therefore replacement of the LFM waveforms is recommended.<p> A detailed investigation of alternative radar waveforms using the Ambiguity Function and Ambiguity Diagram techniques is performed. A frequency coded continuous wave radar waveform based on a composite Costas sequence is proposed as a successor to the LFM waveforms. The composite Costas radar waveform will conserve the spatial and temporal resolutions extended by the LFM waveforms and preclude any spectral ghosting. Implementing the proposed radar waveform and avoiding receiver saturation issues with the mono-static FMCW radar system in which both the transmitting and receiving antenna arrays are simultaneously and continuously active and geographically co-located is also discussed.<p> In addition to this, two 50 MHz backscatter events are presented in this thesis to demonstrate the effectiveness of the FMCW system, notwithstanding the spectral ghosting complication. The first event from November 21, 2009 is identified as a Type 1 instability and the second from September 13, 2009 is identified as a Type 2 instability which lasted for ~ 16 minutes. Linear plasma fluid theory is used to provide a brief interpretation of both scattering events.

Det började faktiskt redan hösten 2004, när jag satt och arbetade med ett av de otaliga projekt man gör under sin skolgång. Projektet gick ut på att skapa en hemsida med en digital katalog, och voilá, där föddes idén. Sedan fortsatte jag att fundera, vända och vrida på idén, ett system för att skapa digitala kataloger och mindre presentationer som vemsomhelst skulle kunna använda. Just detta att inte exkludera de som inte kan ”Flash” från de som skall kunna redigera systemet har varit en av mina stora grundpelare, ett slags digital demokratitanke. För att skapa systemet har jag använt ”Macromedia Flash MX” och dess inbyggda programmeringsspråk ”ActionScript”. Programmeringsspråket är inte ursprungligen tänkt att användas för att göra system, men jag tycker personligen att jag lyckats bevisa att det fungerar även för det ändamålet. Jag har även använt 3d- modelleringsprogrammet ”Alias Wavefront Maya 6.0” för att skapa viss grafik i en av systemets demonstratorer, detta för att visa på systemets potential. Under projektet har jag försökt att hela tiden tänka enkelt och utveckla ett stabilt system med stor potential. Slutprodukten har blivit mycket mer än bara ett system, det är lika mycket en vision om en framtid där fler kan använda sig av den digitala teknologin för att synas. / Detta är en reflektionsdel till en digital medieproduktion.

Muscle stem cells self-renew to maintain the long-term capacity for skeletal muscles to regenerate. However, the homeostatic regulation of muscle stem cell self-renewal is poorly understood. By utilizing high-throughput screening and transcriptomic approaches, we identify the critical function of dystrophin, the epidermal growth factor receptor (EGFR), and fibronectin in the establishment of cell polarity and in determining symmetric and asymmetric modes of muscle stem cell self-renewal. These findings reveal an orchestrated network of paracrine signaling that regulate muscle stem cell homeostasis during regeneration and have profound implications for the pathogenesis and development of therapies for Duchenne muscular dystrophy.

No description available.

The aim of this project is to model current volt-age characteristic curves for different plasma conditions (i.eelectron density, electron temperature, ion temperature andplasma potential) that can be found in active auroras. This isdone by simulating the charging of a FFU with a connectedLangmuir probe in the software SPIS. These I-V curves wereused to determine the plasma properties of the auroras in whichthe sounding rockets SPIDER-1 and SPIDER-2 were launched.Through the simulations it was also studied how the differentparameters effects the I-V curves.The results showed that the plasma SPIDER-1 was launchedin most likely had properties close to nominal conditions and forSPIDER-2 there was colder electrons in the plasma. A conclusionthat only the electron temperature affects the shape of the I-Vcurves for the values simulated in this project can be drawnas well as the conclusion that the geometry of the probe doesnot affect the shape of the I-V curves. Another result showsthat electron temperature also affect how the hull of the FFUcharges. A higher electron temperature gives the hull a morenegative charge. / Syftet med detta projekt är att modellera ström-pänningskaraktäristisk kurvor för olika plasmatillstånd som finns i aktiva auroror. Detta görs genom att simulera laddning på en FFU med en ansluten Langmuir-prob i SPIS. Dessa I-V-kurvor används för att bestämma plasma egenskaperna för aurororna sondraketerna SPIDER-1 och SPIDER- 2 skjöts upp i. I-V kurvorna används också för att bestämma hur plasma parametrarna elektron temperatur, jon temperatur och elektrondensitet samt hur probens geometri påverkar I-V- kurvornas utseende. Resultaten visade att den plasma SPIDER-1 blev uppskjuten i troligen hade nominella förhållanden och att den SPIDER-2 blev uppskjuten i troligtvis hade kallare elektroner. En slutsats om att endast elektron temperaturen påverkar formen på IV- kurvorna kan dras, såväl som slutsatsen att probens geometri inte påverkar formen på IV-kurvorna. Ett annat resultat visar att elektron temperaturen också påverkar ytpotentialen på FFUn. En högre elektron temperatur ger FFUn en mer negativ laddning. / Kandidatexjobb i elektroteknik 2020, KTH, Stockholm

Both technological and experimental advancements in the field of biotechnology have allowed scientists to make leaps in areas such nucleic acid, antibody, and recombinant protein technologies. Here we focus on the use of recombinant proteins as molecular recognition motifs, wound healing biomaterials, and agents for cell cycle pathway elucidation are discussed. The author's primary project is described in chapters 2 and 3, and is focused on designed leucine-rich repeat proteins which offer increased stability, modularity, and surface area for binding interactions. These proteins bind at least two muramyl dipeptide ligands with picomolar to nanomolar affinity (Kd1 = 0.04 – 3.5 nM); as measured by fluorescence quenching experiments and ITC. The longest designed repeat, CLRR8, has a Kd app value of 1.0 nM which is comparable to full length native NOD2 protein. Molecular docking simulations revealed the locations of two potential binding sites and their respective interactions. The series of proteins represents a foundation for a high affinity and highly specific molecular recognition scaffold that has the potential to bind a variety of ligands. Previously the author contributed to the design of recombinant keratin proteins, and the work in Chapter 4 builds on the original design to allow for controlled degradation in wound healing systems. Site-directed mutagenesis was utilized to introduce these degradation sites, and modified keratin proteins were expressed with no differences to native recombinant keratin proteins. Success in engineering a variation of native keratin protein with no issues in expression lay the foundation for further engineering of native keratin or other relevant proteins for improved functionality. Chapter 5 describes steps towards producing human Aurora borealis (Bora) protein, an important substrate in cell cycle regulation, by in vitro transcription-translation with locked Ser–Pro analogues. This will allow for the elucidation of the active isomerization form to ensure proper cell division. Site-directed mutagenesis successfully introduced the amber codon to relevant Ser-Pro sites at positions 274 and 278. These mutated Bora genes along with modified ribosomes and aminoacyl tRNA will allow for the incorporation of locked dipeptide analogues. Expression of native Bora was carried out as a control, and appeared to express in dimeric form. The experiments carried out in Chapter 5 describe and outline all the molecular biology work completed and to be completed for this novel method of studying cis-trans isomerization in living cells. / Doctor of Philosophy / Sequencing of the human genome and the rapid development of gene editing and recombinant DNA technologies paved the way for a massive shift in the pharmaceutical industry. The first pharmaceutical companies in the 19th century started as fine chemicals businesses. The discovery of penicillin introduced antibiotics, and improved synthetic techniques led to the giants we know as big pharma today. Today, in the 21st century both computing and biotechnology has allowed for great leaps forward in precision medicine. Biotechnology refers to the manipulation of living organisms or their components to produce useful commercial products. In the pharmaceutical industry this refers to genetic engineering for novel pharmaceuticals. Here, we focus on the use of recombinant technology to create proteins for use in biomedical applications. Recombinant proteins are proteins formed by laboratory methods of molecular cloning. Through this technology, we are able to elucidate sequence-structure-function relationships of proteins, and determine their specific functions. Additionally, recombinant methods allow us to fine tune or modify the sequences of natural proteins to be more effective scaffolds or reagents. Chapter 3 focuses on the development of synthetic proteins for medical diagnostics. We designed a protein scaffold, based on natural innate immunity proteins, to detect bacteria cell wall components. Chapter 4 focuses on the engineering of keratin protein with applications in wound healing. We introduce controlled degradation of the biomaterial for use in potential drug delivery systems at the wound site. Chapter 5 focuses on the use of recombinant technologies aiding in the elucidation of a regulatory protein's function in cell division.

Les facteurs de transcription STAT3 sont activés et impliqués dans le développement tumoral par leurs effets sur la prolifération et la survie cellulaire. Lorsque STAT3 est phosphorylé sur la tyrosine 705, il semble impliqué dans la transformation cellulaire et dans l'échappement aux traitements classiques de chimiothérapie. Un second site de phosphorylation sur la sérine 727 a été décrit mais son implication dans la régulation de l'activité de STAT3 en réponse aux traitements a été peu étudiée. Nous nous sommes donc intéressés au rôle de la phosphorylation de la sérine 727 de STAT3 dans la réponse de lignées cellulaires colorectales aux agents génotoxiques et plus particulièrement aux inhibiteurs de topoisomérases de type I. Le traitement entraine une perte de la transcription de la cycline D1 et de myc, gènes cibles de STAT3 phosphorylée sur tyrosine 705 et une activation de la kinase cdk5. Cette dernière va phosphoryler STAT3 sur son résidu sérine 727 ce qui va lui permettre de se fixer sur le promoteur du gène de la protéine de réparation Eme1, pour activer sa transcription. Ceci permet la réparation des dommages de l'ADN induits par le Sn38 et entraine une diminution de la sensibilité au traitement. D'autre part, l'inhibition des topoisomérases entraine une perte de la protéine myc normalement liée au promoteur d'Aurora A en phase G2/M et qui, associée au recrutement des répresseurs mad et miz aboutit à l'inhibition de la transcription de la kinase Aurora A. Une inhibition de la séparation des centrosomes est alors observée et entraine un arrêt en phase G2/M. En plus de la régulation de l'activité transcriptionnelle de STAT3 phosphorylée sur la sérine, nous nous sommes intéressés aux partenaires protéiques du facteur de transcription en réponse à sa phosphorylation. Par l'intermédiaire de la technique du double hybride et de la spectrométrie de masse, nous avons pu mettre en évidence deux nouveaux partenaires potentiels de STAT3. D'abord DDB2, protéine impliquée dans l'entrée en sénescence et dans la méthylation de l'ADN. Puis, ASPP2, une protéine qui confère à p53 une meilleure affinité de fixation à certains de ses promoteurs. Nous pensons que la phosphorylation de STAT3 sur la sérine 727 pourrait être impliquée dans l'induction de la sénescence et dans la réparation des dommages de l'ADN et que la cellule tumorale détournerait ces processus de protection pour réparer son ADN afin de résister au traitement. Les cellules pourraient alors proliférer avec un matériel génétique abimé, ce qui rendrait ces cellules instables sur le plan génomique. La détection de cette phosphorylation de STAT3 pourrait etre utilisée comme un marqueur de résistance aux inhibiteurs de topoisomérase. Ceci pourrait ainsi permettre de mieux prédire la réponse des patients à ce traitement.

El debate sobre la violencia y las víctimas ha cobrado mayor protagonismo en los últimos años, así como la producción cultural que se hace alrededor de esta categoría. Pero esta centralidad de la víctima se ha vuelto problemática, como ya lo han señalado otros estudios, en cuanto encasilla a los sujetos en roles pasivos o los inserta como meros objetos. Es por esta razón que me ha interesado analizar la novela La sangre de la aurora, pues si bien mantiene a la víctima como una categoría central y remanente de la violencia, su visión va más allá de ella y no permite limitarla a un estereotipo determinado. Considero que esta tesis rescata esos elementos que la novela de Salazar Jiménez visibiliza sobre la violencia y los tipos de violencia que sufren las víctimas y cómo se diferencia de otras narrativas al representarla, dándole una nueva configuración al término. Asimismo con la ayuda de la teoría psiconalítica determino que la novela ahonda en el pasado traumático de las víctimas y construye una noción de trauma que se ve reflejado en la forma narrativa fragmentada y caótica. Todo ello, dentro de una perspectiva de género que nos revela una potencialidad de lo femenino. De este modo, la novela va más allá de las víctimas al devolverles a éstas su condición de sujetos políticos, otorgándoles una voz y agencia propias, recogiendo todas sus complejidades y experiencias y, además, problematizando el término al incluir al perpetrador en dicha categoría. / Tesis