<p>This thesis focuses on peptides derived from the Prion, Doppel and Influenza haemagglutinin proteins in the context of bilayer interactions with model membranes and live cells. The studies involve spectroscopic techniques like fluorescence, fluorescence correlation spectroscopy (FCS), circular and linear dichroism (CD and LD), confocal fluorescence microscopy and NMR.</p><p>The peptides derived from the Prion and Doppel proteins combined with their subsequent nuclear localization-like sequences, makes them resemble cell-penetrating peptides (CPPs). mPrPp(1-28), corresponding to the first 28 amino acids of the mouse PrP, was shown to translocate across cell membranes, concomitantly causing cell toxicity. Its bovine counterpart bPrPp(1-30) was demonstrated to enter live cells, with and without cargo, mainly via macropinocytosis. The mPrPp(23-50) peptide sequence overlaps with mPrPp(1-28) sharing the KKRPKP sequence believed to encompass the driving force behind translocation. mPrPp(23-50) was however found unable to cross over cell membranes and had virtually no perturbing effects on membranes.</p><p>mDplp(1-30), corresponding of the first 30 N-terminal amino acids of the Doppel protein, was demonstrated to be almost as membrane perturbing as melittin. NMR experiments in bicelles implied a transmembrane configuration of its alpha-helix, which was corroborated by LD in vesicle bilayers. The positioning of the induced alpha-helix in transportan was found to be more parallel to the bilayer surface in the same model system.</p><p>Positioning of the native Influenza derived fusion peptide in bilayers showed no pH dependence. The glutamic acid enriched variant however, changed its insertion angle from 70 deg to a magic angle alignment relative the membrane normal upon a pH drop from 7.4 to 5.0. Concomitantly, the alpha-helical content dramatically rose from 18% to 52% in partly anionic membranes, while the native peptide’s helicity increased only from 39% to 44% in the same conditions.</p>

The aim of the work presented in this thesis is to contribute to a fundamental understanding of polarizing phenomena in some scarab beetles. The aim is also to study the beetle structures as inspiration in fabrication of artificially sculptured films. The three investigated species Cetonia aurata, Potosia cuprea and Liocola marmorata are of the family Scarabaediae and subfamily Cetoniianae (Guldbaggar). They were all collected at Swedish locations and are the only species of Cetoniinae scarabs in Sweden. This work reports on their optical properties represented by Mueller matrix elements, degree of polarization data and trace curves in the Cartesian complex plane representation of polarized light. From these results we verifyan earlier structural model for the Cetonia aurata and make way for similar models of the other two species. The ellipsometer used in this work is of dual rotating compensator type from which the complete Mueller-matrix for the medium examined can be obtained. The ellipsometric measurements were conducted on the scutellum for four different angles of incidence, 45°, 55°, 65° and 75° over a wave-length range of 245-1000 nm. Common for all examined species is that left polarization is observed in the wavelength range of 400 800 nm. For most of these species the polarization state is close to circular at some wavelengths especially at smaller angles of incidence. In general the degree of polarization is high (above 50%) when the polarization is near-circular. The degree of polarization also shows a clear dependence on the angle of incidence. The earlier model for Cetonia aurata shows a good agreement with the experimental data of this work. The model is also found as a good basis to work from to create models for the other two species.

This thesis deals with Large Eddy Simulation (LES) of impinging air jets. The impinging jet configuration features heated circular jets impinging onto a flat plate. The problem addressed here is of generic nature, with applications in many engineering devices, such as cooling of components in gas turbines, in cars and electronic devices. The flow is inherently unsteady and contains relatively slowly varying coherent structures. Therefore, LES is the method of choice when the Reynolds number is large enough to exclude Direct Numerical Simulations (DNS). The present LES model is a basic model without explicit Sub-Grid-Scale (SGS) modeling and without explicit filtering. Instead, the numerical scheme is used to account for the necessary amount of dissipation. By using the computational grid as a filter the cutoff wavenumber depends explicitly on the grid spacing. The underlying computational grid is staggered and constructed in a Cartesian coordinate system. Heat transfer is modeled by the transport equation for a passive scalar. This is possible due to the negligible influence of buoyancy which implies constant density throughout the flow field. The present method provides accurate results for simple geometries in an efficient manner. A great variety of inlet conditions have been considered in order to elucidate how the dynamics of the flow and heat transfer are affected. The considered studies include top-hat and mollified mean velocity profiles subjected to random and sinusoidal perturbations and top-hat profiles superimposed with solid body rotation. It has been found that the shape of the mean inlet velocity profile has a decisive influence on the development of the flow and scalar fields, whereas the characteristics of the imposed artificial disturbances (under consideration) have somewhat weaker effect. In order to obtain results unequivocally comparable to experimental data on turbulent impinging jets both space and time correlations of the inflow data must be considered, so also the spectral content. This is particularly important if the region of interest is close to the velocity inlet, i.e. for small nozzle-to-plate spacings. Within this work mainly small nozzle-toplate spacings are considered (within the range of 0.25 and 4 nozzle diameters), which emphasizes the importance of the inflow conditions. Thus, additional to the basic methods also turbulent inflow conditions, acquired from a precursor pipe simulation, have been examined. Both for swirling and non-swirling flows. This method emulates fully developed turbulent pipe flow conditions and is the best in the sense of being well defined, but it demands a great deal of computing power and is also rather inflexibility. In case of the basic randomly perturbed methods the top-hat approach has been found to produce results in closest agreement with those originating from turbulent inlet conditions. In the present simulations the growth of individual instability modes is clearly detected. The character of the instability is strongly influenced by the imposed boundary conditions. Due to the lack of correlation random superimposed fluctuations have only a weak influence on the developing flow field. The shape of the mean profile, on the other hand, influences both the growth rate and the frequency of the dominant modes. The top-hat profile yields a higher natural frequency than the mollified. Furthermore, for the top-hat profile coalescence of pairs of vortices takes place within the shear-layer of the axial jet, whereas for the mollified profile (for the considered degree of mollification) it takes place within the wall jet. This indicates that the transition process is delayed for smoother profiles. The amount of wall heat transfer is directly influenced by the character of the convective vortical structures. For the mollified cases wall heat transfer originates predominantly from the dynamics of discrete coherent structures. The influence from eddy structures is low and hence Reynolds analogy is applicable, at least in regions of attached flow. The top-hat and the turbulent inflow conditions yield a higher rate of incoherent small scale structures. This strongly affects the character of wall heat transfer. Also the applied level of swirl at the velocity inlet has significant influence on the rate of heat transfer. The turbulence level increases with swirl, which is positive for heat transfer, and so also the spreading of the jet. The latter effect has a negative influence on wall heat transfer, particularly in the center most regions. This however depends also on the details of the inflow data. / QC 20100831

G-quadruplex structures are found in important regions of the eukaryotic genome, such as telomeres and regulatory sequences of genes, and are likely to play important roles in regulation of biological events. The significant structural differences with duplex DNA make quadruplex DNA a very attractive target for anticancer drug design. The purpose of this study is to explore conformational space in a series of heterocyclic cations to discover novel structural motifs that can selectively bind and stabilize specific G-quadruplex arrangements. A variety of biophysical techniques such as thermal melting experiments, biosensor surface plasmon resonance, circular dichroism, fluorescence displacement assay and mass spectrometry were employed to evaluate the affinity of the compounds and their recognition properties. The screening of the molecules allowed the identification of not only selective G-quadruplex ligands but also potential quadruplex groove binders. These results can be useful for the development of new efficient telomerase inhibitors which are endowed with pharmacological activity.

There is a high demand for quadruplex-specific compounds that not only bind preferentially to quadruplex DNA over duplex DNA, but also bind to one quadruplex motif over other motifs. Quadruplex structures are recognized as common occurrences in cancer cells, and if a compound could stabilize this structure, it may serve as an effective anti-cancer treatment with minimal side effects. In this study, cyanine dyes’ interactions with DNA were analyzed with fluorescence titrations, UV-Vis thermal studies, circular dichroism titrations, and surface plasmon resonance (SPR) analysis. With these techniques, binding affinity, DNA stabilization, and conformational shifts were analyzed to determine if cyanine dyes could act as quadruplex-specific binding compounds for possible cancer treatments.

In this thesis, we study the shape analysis problem and propose new methods for shape description, similarity and recognition. Firstly, we introduce a new shape descriptor in a two-step method. In the first step, the 2-D shape information is mapped into a set of 1-D functions. The mapping is based on the beams, which are originated from a boundary point, connecting that point with the rest of the points on the boundary. At each point, the angle between a pair of beams is taken as a random variable to define the statistics of the topological structure of the boundary. The third order statistics of all the beam angles is used to construct 1-D Beam Angle Statistics (BAS) functions. In the second step, we apply a set of feature extraction methods on BAS functions in order to describe it in a more compact form. BAS functions eliminate the context-dependency of the representation to the data set. BAS function is invariant to translation, rotation and scale. It is insensitive to distortions. No predefined resolution or threshold is required to define the BAS functions. Secondly, we adopt three different similarity distance methods defined on the BAS feature space, namely, Optimal Correspondence of String Subsequences, Dynamic Warping and Cyclic Sequence Matching algorithms. Main goal in these algorithms is to minimize the distance between two BAS features by allowing deformations. Thirdly, we propose a new Hidden Markov Model (HMM)topology for boundary based shape recognition. The proposed topology called Circular HMM is both ergodic and temporal. Therefore, the states can be revisited in finite time intervals while keeping the sequential information in the string, which represents the shape. It is insensitive to size changes. Since it has no starting and terminating state, it is insensitive to the starting point of the shape boundary. Experiments are done on the dataset of MPEG 7 Core Experiments Shape-1. It is observed that BAS descriptor outperforms all the methods in the literature. The Circular HMM gives higher recognition rates than the classical topologies in shape analysis applications.

Els serveis de telecomunicacions i sistemes radar estan migrant a freqüències mil•limètriques (MMW), on es disposa d 'una major amplada de banda i conseqüentment d'una major velocitat de transmissió de dades. Aquesta migració requereix de l'ús de diferents tecnologies amb capacitat d'operar a la banda de freqüències mil•limètriques (30 a 300 Ghz), i més concretament en les bandes Ka (26,5 - 40GHz), V (50 – 75GHz) i W (75 – 110GHz). En moltes aplicacions i sobretot en aquelles on l'antena forma part d'un dispositiu mòbil, es cerca poder utilitzar antenes planes, caracteritzades per tenir unes dimensions reduïdes i un baix cost de fabricació. El conjunt de requeriments es pot resumir en obtenir una antena amb capacitat de reconfigurabilitat i amb un baix nivell de pèrdues en cada una de les bandes de freqüència. Per tal d'afrontar aquests reptes, les dimensions de les antenes mil•limètriques, juntament amb els tipus de materials, toleràncies de fabricació i la capacitat de reconfigurabilitat ens porten a l'ús de processos de microfabricació. L'objectiu d'aquesta tesis doctoral és l'anàlisi dels conceptes mencionats, tipus de materials, geometries de línia de transmissió i interruptors, en el context de les freqüències mil•limètriques, així com la seva aplicació final en dissenys d'antenes compatibles amb els processos de microfabricació. Finalment, com a demostració s'han presentat dissenys específics utilitzables en tres aplicacions a freqüències mil•limètriques: Sistemes de Comunicació per Satèl•lit (SCS) a la banda Ka, Xarxes d'àrea personal inalàmbriques (WPAN) a la banda V i sistemes radar per l'automoció a la banda W. La primera part d'aquesta tesis consisteix en l'anàlisi d'algunes tecnologies circuitals a freqüències mil•limètriques. S'han presentat els materials més utilitzats a altes freqüències (Polytetrafluoroethylene or Teflon (PTFE), Quartz, Benzocyclobuten polymer (BCB) i Low Temperature Co-fired Ceramic (LTCC)) i s'han comparat en termes de permitivitat i tangent de pèrdues. També s'inclou un estudi de pèrdues a altes freqüències en les principals línies de transmissió (microstrip, stripline i CPW). Finalment, es presenta un resum dels interruptors RF-MEMS i es comparen amb els PIN diodes i els FET. En la segona part, es presenten diferents agrupacions d'antenes amb la capacitat de reconfigurar la polarització i la direcció d'apuntament. S'han dissenyat dos elements base reconfigurables en polarització: CPW Patch antena i 4-Qdime antena. La primera antena consisteix en un element singular amb interruptors RF-MEMS, dissenyada per operar a les bandes Ka i V. La segona antena consisteix en una arquitectura composta on la reconfigurabilitat en polarització s'obté mitjançant variant la fase d'alimentació de cada un dels quatre elements lineals. La fase és controlada mitjançant interruptors RF-MEMS ubicats en la xarxa de distribució. L'antena 4-Qdime s'ha dissenyat per operar en les bandes V i W. Ambdós elements base s'han utilitzat posteriorment pel disseny de dues agrupacions d'antenes amb capacitat de reconfigurar l'apuntament del feix principal. La reconfigurabilitat es dur a terme utilitzant desfasadors de fase d'1 bit. La part final de la tesis es centra en les toleràncies de fabricació i en els processo de microfabricació d'agrupacions d'antenes mil•limètriques. Les toleràncies de fabricació s'han estudiat en funció dels error d'amplitud i fase en cada element de l'agrupació, fixant-se en les pèrdues de guany, error d'apuntament, error en l'amplada de feix, errors en el nivell de lòbul secundari i en l'error en la relació axial. El procés de microfabricació de les diferents antenes dissenyades es presenta en detall. Els dissenys de l'antena CPW Patch reconfigurable en polarització i apuntament operant a les bandes Ka i V, s'han fabricat en la sala blanca del Cornell NanoScale Science & Technology Facility (CNF). Posteriorment, s'han caracteritzat l'aïllament i el temps de resposta dels interruptors RF-MEMS, i finalment, el coeficient de reflexió, el diagrama de radiació i la relació axial s'han mesurat a les bandes Ka i V per les antenes configurades en polarització lineal (LP) i circular (CP). / Telecommunication services and radar systems are migrating to Millimeter-wave (MMW) frequencies, where wider bandwidths are available. Such migration requires the use of different technologies with the capability to operate at the MMW frequency band (30 to 300GHz), and more specifically at Ka- (26.5 to 40GHz), V- (50 to 75GHz) and W-band (75 to 110GHz). For many applications and more concretely those where the antenna is part of a mobile device, it is targeted the use of planar antennas for their low profile and low fabrication cost. A wide variety of requirements is translated into a reconfiguration capability and low losses within each application frequency bandwidth. To deal with the mentioned challenges, the MMW antenna dimensions, together with the materials, fabrication tolerances and reconfigurability capability lead to microfabrication processes. The aim of this thesis is the analysis of the mentioned concepts, materials, transmission lines geometries and switches in the MMW frequencies context and their final application in antenna designs compatible with microfabrication. Finally, specific designs are presented as a demonstration for three MMW applications: Satellite Communication Systems (SCS) at Ka-band, Wireless Personal Area Network (WPAN) at V-band and Automotive Radar at W-band. The first part of this thesis consist to analyze some MMW circuit technologies. The four most used materials at MMW frequencies (Polytetrafluoroethylene or Teflon (PTFE), Quartz, Benzocyclobuten polymer (BCB) and Low Temperature Co-fired Ceramic (LTCC)) have been presented and compared in terms of permittivity (εr) and loss tangent (tanδ). An study of the main transmission lines attenuation (microstrip, stripline and CPW) at high frequencies is included. Finally, an overview of the RF-MEMS switches is presented in comparison with PIN diodes and FETS switches. The second part presents different polarization and beam pointing reconfigurable array antennas. Two polarization-reconfigurable base-elements have been designed: CPW Patch antenna and 4-Qdime antenna. The first consists of a single reconfigurable element with integrated RF-MEMS switches, designed to operate at Ka- and V-band. The second antenna presented in this thesis has a composed architecture where the polarization reconfigurability is obtained by switching the phase feeding for each of the four linear polarized elements in the feed network with RF-MEMS switches. The 4-Qdime antenna has been designed to operate at V- and W-band. The two base-elements have been used to design two beam pointing reconfigurable antenna arrays. Using phased array techniques, beamsteering is computed and implemented with 1-bit discrete phase-shifter. The final part of the thesis is focused into the fabrication tolerances and microfabrication process of Millimeter-wave antenna arrays. The fabrication tolerances have been studied as a function of the amplitude and phase errors presented at each elements array, focusing on the gain loss, beam pointing error, Half-Power Beamwidth (HPBW) error, sidelobe level error and axial ratio error. The microfabrication process for the designed antennas is presented in detail. Polarization- and pointing- reconfigurable CPW Patch antenna operating at Ka- and V- band have been fabricated in a clean-room facility at Cornell NanoScale Science & Technology Facility (CNF). The RF-MEMS switches isolation and time response have been characterized. Finally, the reflection coefficient, radiation pattern and axial ratio have been measured at Ka- and V-band for the fabricated antennas configured in Linear Polarization (LP) and Circular Polarization (CP).

Amyloid-proteins are among the most actively researched biological topics today, because they have been associated with many serious human diseases, such as Alzheimer's disease and type II diabetes. In particular the deposition of protein aggregates on cell membranes has been suspected as the causes of the diseases, although the proof is still elusive. Studying the interactions of amyloid-forming peptides with lipid-bilayer membranes may clarify the pathway of the β-aggregate formation and provide new insights into the amyloid hypothesis of diseases. In this thesis, I investigate how three peptides, penetratin, amylin, and LL-37, interact with lipid membranes by using several techniques well-developed in our lab. In the study of penetratin interacting with lipid membranes, we were able to clarify the energy pathway of amyloid formation mediated by membrane-binding. This provides the sole experimental proof for the Jarrett-Lansbury theory of β- amyloid formation. Our investigation on amylin-membrane interaction clarifies how amylin in different forms damage bilayer membranes. Between penetratin and amylin we have clarified the complicated pattern of interactions between amyloid-forming peptides and lipid bilayers. The third peptide LL-37 studied in my thesis turned out to a pore forming peptide. I found the mistake made by previous investigators in several different laboratories that made them erroneously conclude that LL-37 was not a pore forming peptide. The results of these three peptides show that methods we used are a comprehensive set of tools that can reveal a broad range of peptide properties. Both the formation of amyloid aggregates and formation of membrane pores can be explained by a two-state model proposed by Huang describing peptide-membrane interactions. For LL-37, the second state is a pore in membrane. But for penetratin and amylin the second state is an aggregation in the β form. We found that β-aggregates have low affinity within a lipid bilayer, and therefore exit from the bilayer structure. However, this exit process extracts lipid molecules from the bilayer and incorporates them in the peptide aggregates. We suggest that this is the molecular process of how amylin might damage of the membranes of β-cells.

The error analysis is made for the simple annular domain with the circular boundaries having the same origin. The error bounds are derived, and the optimal convergence rates can be archived. For circular domains with circular boundaries, the same convergence rates can be achieved by strict proof. Moreover, the NFM algorithms and its conservative schemes can be applied to very small holes, which are difficult for other numerical methods to handle. Both the NFM and the collocation Trefftz method(CTM) are used for very small circular holes, the CTM is superior to the NFM in accuracy and stability.

The collocation Trefftz method (CTM) proposed in [36] is employed to annular shaped domains, and new error analysis is made to yield the optimal convergence rates. This popular method is then applied to the special case: the Dirichlet problems on circular domains with circular holes, and comparisons are made with the null field method (NFM) proposed , and new interior field method (IFM) proposed in [35], to find out that both errors and condition numbers are smaller. Recently, for circular domains with circular holes, the null fields method (NFM) is proposed by Chen and his groups. In NFM, the fundamental solutions (FS) with the source nodes Q outside of the solution domains are used in the Green formulas, and the FS are replaced by their series expansions. The Fourier expansions of the known or the unknown Dirichlet and Neumann boundary conditions on the circular boundaries are chosen, so that the explicit discrete equations can be easily obtained by means of orthogonality of Fourier functions. The NFM has been applied to elliptic equations and eigenvalue problems in circular domains with multiple holes, reported in many papers; here we cite those for Laplace¡¦s equation only (see [18, 19, 20]). For the boundary integral equation (BIE) of the first kind, the trigonometric functions are used in Arnold [4, 5], and error analysis is made for infinite smooth solutions, to derive the exponential convergence rates. In Cheng¡¦s Dissertation [21, 22], for BIE of the first kind, the source nodes are located outside of the solution domain, the linear combination of fundamental solutions are used, and error analysis is made only for circular domains. This fact implies that not only can the CTM be applied to arbitrary domains, but also a better numerical performance is provided. Since the algorithms of the CTM is simple and its programming is easy, the CTM is strongly recommended to replace the NFM for circular domains with circular holes in engineering problems.