Development requires the acquisition of different cell fates. A major conserved pathway required for cell fate determination is the Notch signalling pathway. Neuralized is a key regulator of the Notch pathway and is essential for embryonic development in Drosophila melanogaster. I have been studying the role of Neuralized during Drosophila development, focusing on the regulation of this protein. Neuralized is an E3 ubiquitin ligase that targets Notch ligands for ubiquitination and endocytosis in the signal sending cell. This endocytic event is required for signal transduction, and cells lacking Neuralized fail to signal through Notch. I have identified a conserved interaction between Neuralized and phosphoinositides that is essential for the ability of Neuralized to promote ligand endocytosis and Notch signalling. Interactions between Neuralized and phosphoinositides are not required for ligand ubiquitination, identifying a role for Neuralized in downstream aspects of ligand trafficking. I have also determined that Neuralized is dynamically regulated through a combination of tissue specific expression, subcellular trafficking, protein interactions and posttranslational modification. Neuralized contains two related protein domains of unknown function called Neuralized homology repeats (NHR). To gain insight into the function of the NHR domain, I characterized another NHR containing protein, CG3894. CG3894 is required for development and preliminary data indicate that NHR domains dimerize, suggesting a possible interaction between Neuralized and CG3894. The study of Neuralized in Drosophila has contributed to our understanding of this essential protein both at a developmental and cellular level, and has provided a means through which to ask questions about regulation of Notch signalling in a relatively simple context. Given the importance of Notch signalling to development, and contributions that aberrations in signalling make to cancer and diseases of the nervous system, expanding our understanding of the regulation of Notch signalling is essential to understanding how this important pathway functions.

Urea is an important nitrogen fertilizer for plant nutrition, but is very susceptible to moisture sorption and caking even at low moisture contents, e.g. 0.25% w/w. When urea particles adsorb moisture followed by drying, crystal bridges form between urea particles. For particles in a bed, this process is called caking. Cakes in stored urea cause a degradation of its quality and value. Investigations of the moisture absorption in beds of manufactured urea particles and adsorption on the external and internal surfaces of urea particles are a necessary step if engineers are to recommend procedures to reduce caking and control inventories. Research on moisture adsorption and cake strength of urea fertilizer has not been sufficiently explored. Only recently have researchers started to devise tests to investigate the crystal bonding between two urea particles. Prior to this research, investigations of the moisture interactions in beds of urea were nearly non-existent. This thesis presents experimental, theoretical and numerical methods to investigate the coupled heat and moisture transfer processes in a bed of urea particles while the bed is exposed to ambient air with changing temperature and humidity.<p> Urea particles are nearly spherical with uniform particle size distribution. The particle size, its internal pore structure and rough crystalline external surface depend on the manufacturing process. In this thesis, two types of urea products are investigated, i.e. prill Georgia urea and granular Terico urea. The rough external surface and internal pore structure of each particle makes the total surface area exposed to water much larger than similar smooth and solid spherical particles. Although Georgia urea has higher external surface area than Terico urea, the latter type has larger total surface area and internal pore volume. For both Terico urea and Georgia, the internal surface area dominates the water sorption process but the external moisture sorption of Georgia urea is more important than that of Terico urea.<p> All the water vapor interaction experiments were carried out with air flow through a test bed because it shortens the duration of each experiment to a few hours in most cases. A series of experiments with step changes in inlet air temperature and humidity for air flow through a urea bed indicated that the measured outlet air temperature and humidity responses, each at a specific air flow rate, reveals a typical exponential or transient time change that can be characterized by a time constant. After formulating the theoretical problem for step changes in the inlet properties, the analytical solutions showed that the time constants of outlet response to whether a temperature step change or a humidity step change are functions of the convection coefficient and air velocity. The predicted outlet air temperature is determined by only one time constant for a temperature step change while it is determined by these two time constants for a humidity step change.<p> A new test cell with sampling test ports was developed to measure the transient moisture uptake of a urea particle bed and its distribution at any time without any interruption of the experiment. A novel particle sampling device, modified from a syringe and pistons, was designed to minimize the particle exposure to ambient air during the moisture content determination using a Karl Fischer titrator. Data from two continuous cyclic step changes in the inlet flow with relative humidities between 4% and 70% at room temperature showed a hysteresis in the isothermal moisture content for only the first cycle. After the second sorption- desorption cycle, the hysteresis disappeared. This implies that the internal pore and particle surface geometry changes are very slow after the first cycle.<p> A new theoretical porous media model was developed for a coupled heat and moisture transport process when humid air flowed uniformly through a large test bed in two coupled computational domains: internal domain (i.e., the particle phase) and the external domain (i.e., the interstitial air space). The moisture migration in two computational domains included: water vapor diffusion inside each particle, and water vapor convection and diffusion in the interstitial air space in the urea particle bed. For energy transport, the temperature was assumed to be uniform inside each particle, but heat convection and conduction between the urea particles and the interstitial air outside particles occurred throughout the bed. Both heat transfer and mass transfer in internal domain and external domain were coupled by the heat and mass convection at the gas-particle interface. The numerical simulation was compared with the data of moisture uptake and showed good agreement implying that the internal moisture diffusion that dominates the moisture uptake process is a very slow process.<p> These above experimental, theoretical and numerical research studies provide a set of information on how urea particles adsorb or desorb moisture from or to ambient air on the external and internal pore surface, which offers a useful suggestion for urea caking prevention and is also a first and necessary step to the study of further caking formation and strength.

Bakgrund. Ordet eutanasi betyder dödshjälp och detta ämne väcker stor debatt världen över. Holland, Belgien, Luxemburg och delstaten Oregon i USA har legaliserat eutanasi. Riktlinjer som beskriver sjuksköterskors roll i eutanasiprocessen har utformats, dock syns stora skillnader länderna emellan. Syfte. Att belysa sjuksköterskors upplevelse av delaktigheten i eutanasiprocessen, samt hur omvårdnaden av patienten såg ut under denna process. Metod. En allmän litteraturstudie utfördes med induktiv innehållsanalys. Resultat. Studien belyser flera aspekter av sjuksköterskors upplevelser kring omvårdnaden av patienter under eutanasiprocessen. Kategorierna visar sjuksköterskors reaktioner på eutanasiförfrågan, vikten av ett gott samtal mellan patient och sjuksköterska, hur sjuksköterskor vårdar patienten under processen som leder fram till eutanasi samt hur hon finns som stöd för patienten och agerar patientens ”advokat”. Det framkom att sjuksköterskor åsidosätter sina egna åsikter om eutanasi och ställer upp för patienten samt hur de finner stöd i kollegor för att klara av den psykiskt påfrestande uppgift som eutanasiprocessen innebär. Slutsats. I flera studier anser sjuksköterskor det svårt att ge patienten bästa omvårdnad då riktlinjer som beskriver deras arbetsuppgifter under eutanasiprocessen är bristfälliga. / Background. Euthanasia can be translated into the meaning of helping a person to end his/her life. Holland, Belgium, Luxembourg and the State of Oregon (USA) have legalized euthanasia. Guidelines describing the nurses’ role in the process of euthanasia exists, though great differences can be seen between countries. Aim. To illuminate the nurses’ perception on their involvement in the euthanasiaprocess and what the care during this process looked like. Method. A general review of qualitative literature was conducted with analysis of the articles. Result. This study showed the nurses’ first reaction to the euthanasia request, the importance of in-depth conversations between the patient and the nurse, the nurses’ care for the patient during the process, how they stood by their patients’ side at all times and sometimes acted the role of the patients’ lawyer. This study raised issues about how nurses’ sometimes sat their negative thoughts about euthanasia aside to care for the patient and how they found support and comfort in their colleagues. Conclusion. Many nurses feel they cannot give the patient proper care due to failing guidelines describing their tasks during the euthanasia process.

This study examined the effects of life experience information on the prediction of domain knowledge. Specifically, it was hypothesized that individuals with a higher level of experience within a domain would have a higher level of domain knowledge, and that attribution of experience (e.g., educational experience, extracurricular experience, etc) would influence the type of domain knowledge assessment on which an individual was most successful (e.g., open-ended scenarios vs. multiple-choice questions). In order to test these hypotheses, participants completed a biodata measure, various ability and non-ability measures, and a set of domain knowledge tests. Hypotheses were evaluated in the context of regressions and structural equation modeling. Results showed that biodata had significant predictive validity for domain knowledge.

In this thesis, we make automatic video categorization and summarization by using subtitles of videos. We propose two methods for video categorization. The first method makes unsupervised categorization by applying natural language processing techniques on video subtitles and uses the WordNet lexical database and WordNet domains. The method starts with text preprocessing. Then a keyword extraction algorithm and a word sense disambiguation method are applied. The WordNet domains that correspond to the correct senses of keywords are extracted. Video is assigned a category label based on the extracted domains. The second method has the same steps for extracting WordNet domains of video but makes categorization by using a learning module. Experiments with documentary videos give promising results in discovering the correct categories of videos. Video summarization algorithms present condensed versions of a full length video by identifying the most significant parts of the video. We propose a video summarization method using the subtitles of videos and text summarization techniques. We identify significant sentences in the subtitles of a video by using text summarization techniques and then we compose a video summary by finding the video parts corresponding to these summary sentences.

Herein are presented collective studies of amino acid-based surfactants, also known as lipoamino acids, at liquid interfaces. Chapter III describes an investigation of domain morphology of N-Stearoylglutamic acid (N-SGA) Langmuir monolayers at the air/water interface by epifluorescence microscopy. Anisotropic feather-like domains were observed in L-enantiomeric monolayers while symmetric circular domains were found in racemic N-SGA monolayers. At a surface pressure of 30 mN/m the enantiomeric domains melted at 31 ??C while the racemic domains melted at 27 ??C. This result is exactly opposite to the behavior found in bulk crystals where the racemate melts at a higher temperature. These results were explained in terms of different molecular packing and hydrogen bonding between bulk crystals and two-dimensional thin films for enantiomeric and racemic compounds. Chapter IV summarizes the investigations of hydrogen bonding in N-acyl amino acid monolayers by vibrational sum-frequency spectroscopy (VSFS). The intermolecular hydrogen bonding interaction between the adjacent molecules through amide-amide groups in N-stearoylalanine (N-SA) is characterized by an NH stretch peak at 3311 cm-1. This is the first time that the amide NH stretching signals have been detected with the VSFS technique. A similar peak was detected at 3341 cm-1on N-SGA monolayer. The higher frequency indicates that the H-bond strength is weaker due to the larger size of the glutamic acid residue. The NH stretch mode can thus be used as a fingerprint of hydrogen bonding among amide-amide groups. A peak at 3050 cm-1 due to hydrogen bonding among carboxyl groups was also resolved from the VSFS spectra. Molecular models of intermolecular hydrogen bonding were proposed.

The body-mind deterioration induced by speedy life style and working pressure is a common problem to the people in modern society. So it becomes more and more popular to take good care of one¡¦s health by exercising, which also promotes the development of professional sport and leisure business, for example, the aerobics club. But due to the economic depression, decrease in national income, and the impact of card debt, the operating conditions of many famous aerobic clubs are getting severe, even some of them close down. Therefore it is important to find the key success factors to manage aerobics clubs, so as to increase the probability of successful operation. The present study starts from collecting the relative references of sport and leisure business, aerobics, theory of decision-making management, and key success factors as well as their relative weighting. Then a Habitual Domains (HD) theory which is suitable to the characteristic of aerobics business is selected to analyze the key success factors. A multi-object decision-making method- Analytic Hierarchy Process (AHP) is also implemented to analyze the two questionnaires filled by professionals. Finally, the Expert Choice 2000 code is used to analyze the importance of key success factors and perform weighting calculation. Through the empirical analysis, the top priorities of key success factors of aerobics club operation are obtained, including the professionalism of coach, quality of service and software/hardware equipment. The operator of an aerobics club can follow the importance of priorities discussed in the present study to set up his own competitiveness, and then the aerobics club is assured to run permanently.

Applications of accuracy certificates for problems with convex structure   This dissertation addresses the efficient generation and potential applications of accuracy certificates in the framework of “black-box-represented” convex optimization problems - convex problems where the objective and the constraints are represented by  “black boxes” which, given on input a value x of the argument, somehow (perhaps in a fashion unknown to the user) provide on output the values and the derivatives of the objective and the constraints at x. The main body of the dissertation can be split into three parts.  In the first part, we provide our background --- state of the art of the theory of accuracy certificates for black-box-represented convex optimization. In the second part, we extend the toolbox of black-box-oriented convex optimization algorithms with accuracy certificates by equipping with these certificates a state-of-the-art algorithm for large-scale nonsmooth black-box-represented problems with convex structure, specifically, the Non-Euclidean Restricted Memory Level (NERML) method. In the third part, we present several novel academic applications of accuracy certificates. The dissertation is organized as follows: In Chapter 1, we motivate our research goals and present a detailed summary of our results. In Chapter 2, we outline the relevant background, specifically, describe four generic black-box-represented generic problems with convex structure (Convex Minimization, Convex-Concave Saddle Point, Convex Nash Equilibrium, and Variational Inequality with Monotone Operator), and outline the existing theory of accuracy certificates for these problems. In Chapter 3, we develop techniques for equipping with on-line accuracy certificates the state-of-the-art NERML algorithm for large-scale nonsmooth problems with convex structure, both in the cases when the domain of the problem is a simple solid and in the case when the domain is given by Separation oracle. In Chapter 4, we develop  several novel academic applications of accuracy certificates, primarily to (a) efficient certifying emptiness of the intersection of finitely many solids given by Separation oracles, and (b) building efficient algorithms for convex minimization over solids given by Linear Optimization oracles (both precise and approximate). In Chapter 5, we apply accuracy certificates to efficient decomposition of “well structured” convex-concave saddle point problems, with applications to computationally attractive decomposition of a large-scale LP program with the constraint matrix which becomes block-diagonal after eliminating a relatively small number of possibly dense columns (corresponding to “linking variables”) and possibly dense rows (corresponding to “linking constraints”).

Magnetic shape memory (MSM) materials are a new class of smart materials which exhibit shape deformation under the influence of an external magnetic field. They are interesting for various types of applications, including actuators, displacement/force sensors, and motion dampers. Due to the huge strain and the magnetic field-driven nature, MSM materials show definite advantages over other smart materials, e.g. conventional thermal shape memory materials, in terms of displacement and speed. The principle behind the magnetic field induced strain (MFIS) is the strong coupling between magnetization and lattice structure. The investigation of both static and dynamic magnetic domain structures in MSM materials is a key step in optimizing the properties for future possible devices. In this work, optical polarization microscopy is applied to investigate the twin boundary and magnetic domain wall motion in bulk NiMnGa single crystals. Surface magnetic domain patterns on adjacent sides of bulk crystals are revealed for the first time providing comprehensive information about the domain arrangement inside the bulk and at the twin boundary. The tilting of the easy axis with respect to the sample surface determines the preferable domain size and leads to spike domain formation on the surface. Out-of-plane surface domains extend into the bulk within a single variant, while a twin boundary mirrors the domain pattern from adjacent variants. Furthermore, magnetic domain evolution during twin boundary motion is observed. The partial absence of domain wall motion throughout the process contradicts currently proposed models. The magnetic state alternates along a moving twin boundary. With the abrupt nucleation of the second variant this leads to the formation of sections of magnetically highly charged head-on domain structures at the twin boundaries. On the other hand, a dynamic actuation experimental setup, which is capable to provide high magnetic fields in a wide range of frequency, was developed in the course of this study. The observation of reversible twin boundary motion up to 600 Hz exhibits the dependence of strain, hysteresis, and twin boundary velocity on the actuation speed. MFIS increases with frequency, while the onset field is similar in all observed cases. Twin boundary mobility enhancement by fast twin boundary motion is proposed to explain the increase in MFIS. The twin boundary velocity is shown to be inversely proportional to the twin boundary density. No limit of twin boundary velocity is observed in the investigated frequency range.

<p>The recent development of methods for constructing andhandling large collections (libraries) of proteins, from whichvariants with desired traits can be isolated, hasrevolutionized the field of protein engineering. Key elementsof such methods are the various ways in which the genotypes(the genes) and the phenotypes (the encoded proteins) arephysically linked during the process. In one section of thework underlying this thesis, one such technique (phagedisplay), was used to isolateand identify protein librarymembers based on their catalytic or target molecule-bindingproperties.</p><p>In a first study, phage display libraries of the lipolyticenzyme Lipolase from Thermomyces lanuginosa were constructed,the objective being to identify variants with improvedcatalytic efficiency in the presence of detergents. Toconstruct the libraries, nine positions were targeted for codonrandomization, all of which are thought to be involved in theconformational change-dependent enzyme activation that occursat water-lipid interfaces. The aim was to introduce two tothree amino acid mutations at these positions per lipase gene.After confirming that the wt enzyme could be functionallydisplayed on phage, selections with the library were performedutilizing a mechanism-based biotinylated inhibitor in thepresence of a detergent formulation. According to rhodamineB-based activity assays, the fraction of active clonesincreased from 0.2 to 90 % over three rounds of selection.Although none of the variants selected using this approachshowed increased activity, in either the presence or absence ofdetergent compared to the wild type enzyme, the resultsdemonstrated the possibility of selecting variants of theenzyme based on catalytic activity.</p><p>In the following work, phage libraries of the StaphylococcalProtein A (SPA)-derived Z-domain, constructed by randomizationof 13 surface-located positions, were used to isolate Z domainvariants (affibodies) with novel binding specificities. Astargets for selections, the parental SPA domains as well as twopreviously selected affibodies directed against two unrelatedtarget proteins were used. Binders of all three targets wereisolated with affinities (KD) in the range of 2-0.5 µM.One SPA binding affibody (Z_SPA-1) was shown to bind to each of the fivehomologous native IgG-binding domains of SPA, as well as theZdomain used as the scaffold for library constructions.Furthermore, the Z_SPA-1affibody was shown to compete with one of thenative domains of SPA for binding to the Fc part of humanantibodies, suggesting that the Z_SPA-1affibody bound to the Fc-binding surface ofthe Z domain. The majority of the affibodies isolated in theother two selections using two different affibodies as targets,showed very little or no binding to unrelated affibodies,indicating that the binding was directed to the randomizedsurface of their respective targets, analogously toanti-idiotypic antibodies.</p><p>The structure of the wild type Z domain/Z_SPA-1affibody co-complex was determined by x-raycrystallography, which confirmed the earlier findings in thatthe affibody Z_SPA-1affibody was shown to bind to the Fc bindingsurface of the Z domain. Further, both the Z domain and the Z_SPA-1affibody had very similar three helix-bundletopologies, and the interaction surface involved ten out of thethirteen randomized residues, with a central hydrophobic patchsurrounded by polar residues. In addition, the interactionsurface showed a surprisingly high shape complementarity, giventhe limited size of the library used for selections. The Z_SPA-1affibody was further investigated for use invarious biotechnological applications. In one study, the Z_SPA-1affibody was successfully recruited as a novelaffinity gene fusion partner for production, purification anddetection of cDNA-encoded recombinant proteins using anSPA-based medium for affinity chromatography. Further, the SPAbinding capability of the Z_SPA-1affibody was employed for site-specific andreversible docking of Z_SPA-1affibody-tagged reporter proteins onto an SPAfusion protein anchored to a cellulose surface via acellulose-binding moiety. These generated protein complexesresembles the architecture of so-called cellulosomes observedin cellulolytic bacteria. The results suggest it may bepossible to use anti-idiotypic affibody-binding protein pairsas modules to build other self-assembling types of proteinnetworks.</p><p><b>Keywords:</b>phage display, selection, mechanism-basedinhibitor, affinity domains, crystal structure, Staphylococcusaureus protein A, affinity chromatography, anti-idiotypicbinding pairs, affibody, combinatorial, protein engineering,lipase, cellulosome, assembly.</p>