PEGylation of protein side-chains has been used for more than 30 years to enhance the pharmacokinetic properties of protein drugs, and has been enabled by the recent development of many chemoselective reactions for protein side-chain modification. However, there are no structure- or sequence-based guidelines for selecting sites that provide optimal PEG-based pharmacokinetic enhancement with minimal loss to biological activity. Chapter 1 is a brief introduction to protein PEGylation. In chapter 2 we use the WW domain of the human protein Pin 1 (WW) as a model system to probe the impact of PEG on protein conformational stability. Using a combination of experimental and theoretical approaches, we develop a structure-based method for predicting which sites within WW are most likely to experience PEG-based stabilization, and show that this method correctly predicts the location of a stabilizing PEGylation site within the chicken Src SH3 domain. PEG-based stabilization in WW is associated with enhanced resistance to proteolysis, is entropic in origin, and likely involves disruption by PEG of the network of hydrogen-bound solvent molecules that surround the protein. Chapter 3 shows that PEG-based stabilization of the WW domain depends strongly on the identity of the PEG-protein linker, with the most stabilizing linkers involving conjugation of PEG to an Asn side-chain amide nitrogen. Chapter 4 investigates the interplay between structure-based guidelines for PEG-base stabilization developed in chapter 2 and the different chemistries explored in chapter 3.

Presented here are the results from the steady state flow boiling of R245FA in a laboratory scale horizontal stainless-steel test tube with an inner diameter of 8.5 mm and a length of 900 mm at a saturation temperature of 35 °C and 40 °C. Experiments were conducted at mass fluxes ranging between 200 and 300 kg/m²s at inlet vapour qualities from 0.2 to 0.7 under uniform, and non-uniform imposed heat flux cases that are expected to exist in horizontal parabolic trough solar collectors. Nine (9) different heat flux distributions were investigated. Local and average heat transfer coefficients (HTC’s) were determined based on wall temperature measurements taken along the length and around the circumference of the test section. Through the choice of the fluid being linked to the possible usage of DSG technology in organic Rankine cycles, the qualitative trends and observed performance variations can be used to predict the same for a working fluid such as water. It was found that the non-uniformity of the heat flux greatly alters the HTC’s of the fluid undergoing boiling but has no effect on the pressure drop characteristics of the fluid undergoing boiling. Heating only on the sides of the tube yielded HTC’s that were 46 % lower than achieved under uniform heating. Heating only from the top proved to be more effective in heat transmission to the fluid than heating only from the bottom (as is the case on PTC solar fields), by only a slight margin, and both these cases yielded HTC’s that were 30 % lower than the uniform heating case. Applying a bell curve heat flux distribution over the tube walls yielded overall HTC’s that differed from the uniform case by a maximum of 5 %, even as the peak heat flux position changes around the circumference of the tube. A further study may be done to quantify the degree to which the non-uniformity of the heat flux influences the local HTC’s, and to develop correlations that may aid in predicting these cases. An integration with flow pattern mapping may also be done to solidify the understanding of the phenomenon governing these observations. / Dissertation (MEng)--University of Pretoria, 2021. / Department for International Development (DFID) through Royal Society-DFID Africa Capacity Building Initiative. / The UK Engineering and Physical Sciences Research Council (EPSRC) [grant numbers EP/T03338X/I and EP/P004709/1]. / Russian Government "Megagrant" project 075-15-2019-1888. / Mechanical and Aeronautical Engineering / MEng / Unrestricted

Orientador: João Ruggiero Neto / Banca: Fernando Luís Barroso da Silva / Banca: Amando Siuti Ito / Resumo: Em força iônica e concentração de polímero neutro adequadas, moléculas de DNA transitam da conformação dispersa em solução para uma forma compacta de alta densidade numérica de segmentos. Tal transição é denominada transição-psi (ou transição Ψ). Nesse trabalho, usamos espectroscopia de dicroísmo circular para monitorar a transição Ψ multimolecular e estimar os valores críticosdas concentrações do polímero neutro como função da concentração do sal NaCl necessárias para induzir a transição-Ψ em soluções de DNA de baixo peso molecular. Essas estimativas foram realizadas para PEGs de diferentes graus de polimeração. As concentrações críticas necessárias para induzir o decolapso também foram estimadas. Os resultados experimentais para as concentrações críticas foram comparados com os valores teórico obtidos usando um modelo recentemente proposto por de Vries (de Vries, 2001) para explicar a condensação de DNA / Abstract: in adequate conditions of ionic strenght and neutral polymer concentration, DNA undergoes a transition from its random-coil state to a compact form of high density of numerical segments of chain. Such transition is often called psi-transition ( or transition-Ψ). In this work, we used the circular dichroism spectroscopy to monitor the multimolecular transition-Ψ of DNA and estimate the critical values of the neutral polymer concentration (PEG) as a function of the NaCl molar concentration to induced the transition-Ψ in the DNA of low molecular weight. This estimation has been carried out for PEG of different degree of polimerization. It was estimated the critical PEG and NaCl concentration for the DNA decollapse. The experimental results of the critical concentrations were compared with theoretical values obtained using a model recently proposed by the compared with theoretical values obtained using a model recently proposed by de Vries (de Vries, 2001) to explain the DNA condensation / Mestre

Resumo: Nas últimas décadas, um grande número de peptídeos antimicrobianos tem sido isolado de várias espécies de seres vivos, fazendo parte da sua imunidade inata. Estes peptídeos possuem algumas características em comum: 1) apresentam carga positiva (grande ocorrência de aminoácidos básicos); 2) possuem um porcentual considerável de aminoácidos hidrofóbicos e 3) apresentam grande tendência de adotarem estruturas secundárias anfipáticas. Devido à sua propriedade de permeabilizar e destruir membranas bacterianas, levando-as à morte, estes peptídeos são um foco de interesse no desenvolvimento de novos antibióticos. Um modo de estudo destas moléculas é por meio da adição de marcadores na seqüência peptídica, permitindo relacionar as propriedades conformacionais com a atividade biológica envolvida. Desta forma, este trabalho teve como objetivo sintetizar e avaliar 3 análogos de um novo peptídeo antimicrobiano extraído da pele da rã Hypsiboas albopunctatus de seqüência GWLDVAKKIGKAAFNVAKNF( I/L), denominado de hilina C (hyC), a fim de obter informações a respeito do seu mecanismo de ação e estruturação frente a miméticos de membrana. Os análogos possuem o composto paramagnético ácido 2,2,6,6-tetrametilpiperidina-N-oxil-4- amino-4-carboxílico (TOAC) substituindo os aminoácidos alanina na posição 13 e triptofano na posição 2, ou adicionado na extremidade N-terminal do peptídeo. Os peptídeos foram sintetizados por Síntese Peptídica em Fase Sólida (SPFS) utilizando a estratégia química Fmoc. As propriedades conformacionais dos peptídeos e as suas dinâmicas foram investigadas por dicroísmo circular (CD) e ressonância paramagnética eletrônica (RPE) em água, trifluoretanol (agente indutor de estrutura secundária), micelas zwitteriônicas (lisofosfatidilcolina - LPC) e em dois tipos de lipossomas de composições lipídicas diferentes:... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: In recent decades, a large number of antimicrobial peptides have been isolated from several species of microorganisms as part of their innate immunity. These peptides have some particular features: 1) positive charges (high occurrence of basic amino acids), 2) a considerable percentage of hydrophobic amino acids and 3) greater tendency to adopt amphipatic secondary structures. Due to the property of permeabilizing and destroying bacterial membranes, causing cell death, these peptides are interesting regarding the development of new antibiotics. To study these molecules, markers were added in the peptide sequence, allowing conformational properties to relate with the biological activity involved. Thus, this work aimed to synthesize and evaluate 3 analogues of a new antimicrobial peptide extracted from the skin secretion of the frog Hypsiboas albopunctatus, whose sequence is GWLDVAKKIGKAAFNVAKNFI/L, called Hilina C (hyC) in order to obtain information of the mechanism of action and structure of this peptide, using membrane mimetics. The analogues have the compound paramagnetic amino acid 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid (TOAC) replacing the alanine at position 13 and triptofan in position 2, or added to the end of the Nterminal peptide. The peptides were synthesized by Solid Phase Peptide Synthesis (SPPS) using the Fmoc chemistry strategy. The conformational properties of peptides and their dynamics were investigated by electronic paramagnetic resonance (EPR) and circular dichroism (CD) in water, trifluorethanol (TFE) (secondary structure inducer agent), zwitterionics micelles (lysophosphatidylcholine - LPC) and two types of liposomes in different lipid compositions: PE:PA:PC and SM:PA:PC. The biological activities were examined by determining the minimal inhibitory concentration (MIC) in bacteria (two Gram-positive and two Gram-negative) and the minimal... (Complete abstract click electronic access below) / Orientador: Eduardo Maffud Cilli / Coorientador: Reinaldo Marchetto / Banca: Antonio José da Costa Filho / Banca: Clovis Ryuichi Nakaie / Mestre

Orientador: Lourdes Campaner dos Santos / Banca: Luciana Polese / Banca: Clélia Akiko Hiruma Lima / Banca: Daniel Rinaldo / Banca: Marcelo Aparecido da Silva / Resumo: Terminalia catappa Linn. pertence à Família Combretaceae e é comumente chamada amendoeira-da-praia ou chapéu de sol. A família Combretaceae reúne numerosas espécies que têm sido estudadas por seu uso pela população para fins medicinais. É originária da Malásia, mas, muitas vezes, cultivada e muito característica da costa brasileira. A partir do extrato hidroalcoólico das folhas, foram detectados como constituintes principais a substância majoritária punicalagina (anômeros α e β), o composto punicalina, ácido galágico e ácido elágico. Identificouse, também, as substâncias 1,2,3-Tri-O-galoil-β-D-glicose e possíveis isômeros, 1,6- Di-O-galoil-β-D-glicose, HHDP-acetilglicosídeo, HHDP-hexosídeo, ácido elágico hexosídeo, ácido galágico e apigenina 8-C-(2'-galoil)-β-D-glicopiranosil. Estes metabolitos foram confirmados por experimentos FIA-ESI-IT-MSn (Direct Flow Analysis-Electrospray ionization-Íon Trap-Tandem Mass Spectrometry) and High Performance Liquid Chromatography (HPLC) acoplada a arranjo de fotodiodos (PDA). Ácido elágico, ácido gálico e galato de metila foram confirmados por experimentos de co-injecção de padrão. Punicalagina foi detectada e isolada da fração hidrometanólica como uma mistura de anômeros e confirmada por experimentos de RMN 1H e 13C, mono e bidimensionais. O fracionamento da fração acetato proveniente do extrato hidroalcoólico por MPLC (Medium Pressure Liquid Chromatography) permitiu o isolamento dos metabólitos ácido galágico e apigenina 8-C-(2'-galoil)-β-D-glicopiranosil. A configuração absoluta dos anômeros da punicalagina e do composto apigenina 8-C-(2'-galoil)-β-D-glicopiranosideo foi estabelecida por experimentos de dicroísmo circular (DC). A determinação quantitativa dos principais metabolitos secundários foi realizada por HPLC-PDA, possibilitando, assim, a determinação da concentração e teor (%) de... / Abstract: Terminalia catappa Linn. belongs to Combretaceae family and is commonly called almond-the-beach or sun hat.The Combretaceae family gathers numerous species that has been studied for its use by the population for medicinal purposes. It is from Malaysia, but often cultivated and very characteristic of the Brazilian coast. From the alcoholic extract of the leaves were detected as main constituents the major substance punicalagin (α and β anomers), the punicalin compound, gallagic acid and ellagic acid. It was identified as well, the 1,2,3-Tri-O-galloyl-β-D-glucose substances, and possible isomers, 1,6-Di-O-galloyl-β-D-glucose, HHDP acetilglicoside, HHDPhesoside, ellagic acid hexoside, gallagic acid and apigenin 8-C (2 '-galloyl)-β-Dglucopyranosyl. These metabolites were confirmed by FIA-ESI-IT-MSn experiments (Direct Flow Analysis Electrospray ionization-Ion-Trap Tandem Mass Spectrometry) and High Performance Liquid Chromatography (HPLC) coupled with diode array (PDA). Ellagic acid, gallic acid and methyl gallate were confirmed by standard coinjection experiments. Punicalagin was detected and isolated from the hydromethanol fraction as a mixture of anomers experiments and confirmed by 1H and 13C NMR, mono- and bi-dimensional. The ethyl acetate fraction from fractionation of the hydroalcoholic extract by MPLC (Medium Pressure Liquid Chromatography) allowed the isolation of galágico acid metabolites and 8 apigenin-C (2'- galloyl) -β-Dglucopyranosyl. The absolute configuration of anomers of the compound of punicalagin and apigenin 8-C (2'-galloyl) -β-D- glucopyranosyl was established by experiments circular dichroism (CD). Quantitative determination of the main secondary metabolites was performed by HPLC-PDA, thus allowing the determination of concentration and content (%) of metabolites present in the alcoholic extract. They were first quantified in hydroalcoholic extract of this species, the... / Doutor

Circular words, also known as necklaces, are combinatorial objects closely related to linear words. A brief history of circular words is given, from their early conception to present results. We introduce the concept of a level word, that being a word containing a equal or roughly equal amount of each letter. We characterize exactly the lengths for which level square free circular words on three letters exist. This is accomplished through a modification of Shur’s construction of square-free circular words. A word on two letters is called a Frankel-Simpson word if the only squares it contains are 00, 11, and 0101. Using the result mentioned above and several computer searches, we characterize exactly the lengths for which circular Frankel-Simpson words exist, and give an example or construction for each. / Graduate

TESIS PARA OPTAR AL GRADO DE MAGÍSTER EN TRIBUTACIÓN / Cattaneo Escobar, Isaías Daniel, [Parte I], Moscoso Iturra, Sebastián, [Parte II] / En una economía global, los actores económicos privilegian aquellos países que prueben ser más estables económicamente (Araneda, 1969, p.8), aumentando su actividad económica en estos (Rodríguez, 2002, p.44). Desde el inicio de la década de 1990, en el contexto del retorno a la democracia y la apertura económica chilena al extranjero (Villalobos, 2001, p. 417) que dicho cambio político conllevó, Chile ha experimentado un proceso paulatino y constante, no libre de contracciones, de crecimiento económico. En las palabras de la González, “Chile, en lo referente al ambiente para hacer negocios, se encuentra primero en América Latina y en un lugar privilegiado en el mundo” (González, 2010, p. 99)1. Así, las consecuencias jurídico-tributarias de que un agente económico realice actividades en otro Estado adquieren importancia central. En este contexto, dos de los principales mecanismos de inversión son: - Llevar a cabo una inversión en una compañía existente, como socio o accionista. - Invirtiendo como sí mismo en otro país, es decir, mediante un “establecimiento permanente” en el exterior. En el desarrollo de este AFE nos enfocaremos en la segunda de estas alternativas. Ahora bien, el objetivo general del presente AFE es analizar la institución del establecimiento permanente de una empresa extranjera en Chile, a la luz de la actual legislación chilena, el otrora planteamiento histórico del Servicio de Impuestos Internos y su actual interpretación establecida en la Circular 57 de 07 de diciembre de 2017, mostrando un cambio de forma sobre fondo a uno de fondo sobre forma. Adicionalmente, cabe destacar que para efecto del análisis objeto de esta AFE, las hipótesis de “Agenciamiento” en Chile, derivado de la suscripción de un mandato comercial con un agente en Chile no será considerada, limitándose el análisis la hipótesis arriba describa. Como se analizará, el otrora planteamiento histórico del Servicio de Impuestos Internos se enfocaba principalmente en aspectos formales para determinar la existencia de un Establecimiento Permanente de una empresa extranjera en Chile, como lo era la mera comprobación de que el ente chileno pudiera cerrar negocios en Chile.

This theses presents a discussion on the symbiotic relationship between the economic development and environmental protection. The presentation is based upon an extensive literature overview with a strong focus on Chinese research publications.

More resources are being defined as critical, which can be attributed to the linear economy of ‘take, make and dispose’. An alternative is to implement the circular economy (CE) which could reduce several negative effects, among other things resource depletion. The aim of this thesis is to identify what current sustainability indicators are lacking to assess a resource with the CE concept. This is done by developing CE core indicators, which then are compared with sustainability indicators. The life cycle of rare earth elements (REE) is used as a case study to validate the CE core indicators. To achieve this literature studies and comparative analysis will be performed. Existing definitions and indicators of CE were studied to compile a complete set of core indicators. These compiled CE core indicators were then compared with adapted United Nation (UN) sustainability indicators. The UN indicators were chosen after analysing several different sustainability indicator system and their compatibility with the resource perspective. The main differences between the UN indicators and CE core indicators is that the UN indicators does not include economic aspects such as market diversity and social aspects such as consumption behaviour. However, the UN indicator system includes transportation and governance that could be beneficial to include into the CE concept. The economic viability to perform the CE analysis and non-existing CE indicators for companies and countries were identified as two barriers that could hinder development and efficient use of a CE indicator system. A way to increase the economic viability is to use already generated data for the CE indicator analysis, though the economical aspect has to be studied further. The non-existing CE indicators for companies and countries are counted as a barrier due to the risk of sub-optimisation of one resource. Additionally, the CE indicator results could be misinterpreted to blame a few for the problems of the resource instead of using the results to improve all parts of the life cycle. Further research is also needed to investigate how, or even if, social aspects such as culture and society could be indicated within a CE indicator system. In conclusion, the UN indicator system could be a good baseline to develop a CE indicator system for a resource though further research is needed.

This study aims to account for the potential of algae as future innovative foods in the Swedish market. The methods for collecting the empirical material were quantitative content analysis and mapping of how many food companies there are in the Swedish market that have algae in their products. The second method was a qualitative interview survey in which the respondents were allowed to express their opinions and perceptions about circular design, food technology and algae as alternative foods. Through results and analysis, it has been shown that there are only a couple of food companies with a focus on algae on the Swedish market, but that the market is in its infancy. A lot of research is done on the subject and large investments are made on algae research in Sweden. This in turn shows that there is interest and potential for these innovative and more climate-friendly foods. Unfortunately, it has been difficult to establish innovative food companies, as Sweden is a country that has valued the safety and development of existing foods. On the other hand, Swedes are proving to be the most open consumers to new trends and embrace new foods. This is good for the development of testing new foods in the Swedish market before export. Through the Government's action plan for the 2030 agenda, innovation is a cornerstone that opens up better conditions for food innovation. It is obvious that it is necessary to invest in innovation in the food chain in order for Sweden to be globally competitive and achieve these goals to reach a sustainable future. The global goals that will form this study are the following, 2 - zero hunger, 12 - responsible consumption and production, 13 - climate action, 14 - life below water.