Proteins are essential parts of living organisms that initiate and control almost all cellular processes. Despite the widely accepted belief that all functional proteins fold into stable and well-defined three-dimensional (3D) structures mandatory for protein activity, the existence of biologically functional disordered proteins has been increasingly recognized during past two decades. Proteins with inherent structural disorder, commonly known as intrinsically disordered proteins (IDPs), play many roles in a biological context. However, in contrast to their folded counterparts, they are dynamically unstructured and typically fluctuate among many conformations even while performing biological functions. In fact, it is this dynamical structural heterogeneity that that allows for IDPs to interact with other biological macromolecules in unique ways. Moreover, while a majority of proteins in eukaryotic proteomes have been found to have intrinsically disordered regions (IDR), the mechanisms by which protein disorder fives rise to biological functionality is still not well understood. Through a series of simulation studies on specific systems, this thesis probes several aspects of the emerging structure-function paradygm of IDPs, namely the mechanics, intermolecular assembly, and structural transitions occurring in these proteins. The lack of well-defined 3D structure in IDPs gives rise to distinct mechanical properties, the subject of the first study in the thesis on the elasticity of a elastomeric gluten-mimetic polypeptide with an intrinsically disordered character. This disordered polypeptide was shown to exhibit distinctively variable elastic response to a wide range of tensions, which a classical worm-like chain model failed to accurately describe, thus requiring a molecular-level analysis. IDPs frequently are frequently involved in protein-protein interactions, the focus of the second study on the propensity of an IDR, the B domain in dynamin-related protein 1 (Dpr1), to self-assemble into dimer structures while remaining disordered in all solution conditions. Despite a hypothesized auto-inhibitory role for this domain in Dpr1 that was assumed to be triggered by an disordered-to-order transition, the B domains in solution showed no tendency to form ordered structures even in the presence of order promoting osmolytes. Instead, self-association in the presence of osmolyte was found to occur by favorable intermolecular intereactions between specific region on the surface of the B-domains. Other IDPs do undergo a disorder-to-order transition in response to environmental cues, in ways that are unique disordered proteins, the focus of the last study on intermolecular ordering transitions in silk-like proteins. Factors such as protein sequence and physical tension were investigated, and results suggested that tyrosine residues in the key silk sequence motifs promote templating of beta structure from disordered precursors and that elongational stresses preferentialy stabilize antiparallel beta-sheet order. Together, these three computational studies provide insight into the nature of the structure-function mechanisms of IDPs.

This dissertation strives to analyze the role of the cultural route as an approach and evaluates its validity to foster regional cultural sustainability. The author has investigated the relationship between cultural route, cultural sustainability, and regional development through studying Swedish explorer Sven Hedin’s expedition heritage along the Silk Road. A qualitative approach was taken to study how practitioners in particular tourism subdivisions attempt to implanting Sven Hedin’s legacy into different practices in Northwest China. With the help of the Actor-Network Theory as a material-semiotic method, a significant finding is that evolutionary networks centered on Sven Hedin, as an internal drive to promote the development of cultural routes, are taking shape. Cultural route as an approach to foster regional development cannot be achieved independently by individuals and SMEs; an institutional dimension needs to be considered for integrated management. This approach offers a new participation model in regional construction to their recipients and provides a sustainable strength for inhabitants to understand their cultural identity and embrace their future.

Cette thèse porte sur le commerce de la soie entre la Chine et la France pendant le 19e siècle, avec l’ambition de clarifier certaines spécificités du commerce euro-asiatique dans le cadre du processus de globalisation. Nous avons choisi le commerce de la soie franco-chinois comme objet de recherche parce que, premièrement, au regard des archives et des documents historiques, nous découvrons que la croissance du commerce franco-chinois du 19e siècle provient et s'amplifie principalement avec celle de l’importation de la soie chinoise en France. L’échange de la soie est le plus essentiel et le plus typique dans les études du commerce entre les deux pays au 19e siècle. Deuxièmement, l’échange franco-chinois de la soie joue un rôle très important dans le commerce des matières premières du monde du 19e siècle. Précisément, cette thèse vise à répondre et approfondir des questions concernant le commerce franco-chinois de la soie et le commerce euro-asiatique de longue distance, notamment sur ses évolutions, ses impulsions, ses intermédiaires commerciaux et ses impacts industriels. Dans un premier temps, nous allons démontrer l’évolution de l’échange franco-chinois de la soie du 19e siècle, et analyser l’origine de sa prospérité au niveau de l'offre et la demande. Du côté de la demande, nous étudierons l’impact des changements de l’industrie française sur les importations de Chine. En particulier il s’agira de comprendre les raisons de la hausse limitée de la production séricicole française. Du côté de l’offre, la question consiste à comprendre plutôt ce qui rend possible la croissance importante de la production de soie grège en chine, mais aussi les raisons du développement limité de la demande intérieure. Dans un deuxième temps, nous allons discuter des rôles des différentes maisons commerciales reliant les marchés de soie situés des deux côtés du continent euro-asiatique. D’abord, comme la Grande Bretagne est le plus important point de distribution des matières premières et des produits semi-finis du monde pendant la période de la révolution industrielle, nous allons observer les rôles du marché de Londres et des marchands anglais dans le commerce indirect de la soie entre la France et la Chine. Ensuite, nous allons montrer les rôles des maisons françaises et des maisons étrangères dans le commerce direct de la soie entre la France et la Chine. Ce dernier démarre à partir des années 1850 et prospère à partir des années 1860, et nous allons étudier l’influence de la croissance de l’importation directe de la soie chinoise en France sur l’installation et le développement des maisons françaises en Chine, ainsi que leur rapport avec d’autres intermédiaires (maisons anglaises, allemandes et suisses), qui partagent le commerce de soie entre la France et la Chine. Enfin, nous allons analyser les rôles des différents groupes de négociants chinois, la relation entre ces groupes et ainsi que leurs relations avec des maisons étrangères. Finalement, comme la soie grège est une matière première pour la production industrielle, cette thèse évoquera l’impact industriel du commerce de la soie dans les deux pays. Nous choisirons un nouvel angle (inter- action des industrialisations) pour analyser la relation entre l’industrialisation et le commerce extérieur du 19e siècle : nous résumerons d’abord les discussions sur les impacts de l’industrialisation des pays occidentaux sur celle des pays asiatiques et ensuite, les effets du commerce de la soie sur les modalités de l’industrialisation en Chine et en France. Nous essayerons donc d’établir la liaison entre les révolutions industrielles orientales et occidentales par le biais du commerce international. / This book focuses on the silk trade between China and France in the 19th century, with the aim of clarifying certain specific Euro-Asian trade in the course of globalization in the 19th century. We chose the Franco-Chinese silk trade as the objective of research, because, first, the use of historical records and documents, we find that the Franco-Chinese trade in the 19th century and grew up mainly from the augmentation of the import of Chinese silk in France. The exchange of the silk is one of the most important and the most typical trade between the two countries in the 19th century. Secondly, the exchange of the Franco-Chinese silk plays a very important role in the trade in raw materials of the world in the 19th century. Precisely, this book is intended to address the issues and further discuss on the Franco-Chinese silk trade itself and the Eurasian business long distance, specifically on their evolutions, their impulses, their commercial intermediation and their industrial impacts. In the first step, we will show the development of Franco-Chinese silk trade of the 19th century, and analyze the causes of its prosperity, at the level of supply and demand. On the demand side, we will examine the impacts of changes in the French industry on imports from china. In particular, it relate to the decrease and the limited increase of the French silk production. On the supply side, the question is to understand what makes it possible for the growth of the production of raw silk in china, but also the reasons for the limited development of domestic demand. In a second step, we discuss the roles of the various silk trade corporations connecting two side of the Eurasian continent. First, the Great Britain is the most important country of distribution of raw materials and semi-finished products of the world during the period of the industrial revolution. We will observe the roles of the London market and English merchants in the indirect silk trade between France and china. Then, we show the roles of the French companies and foreign firms in the direct trade of silk between France and china, the prosperous of which starts from the 1850s and 1860s. In this part, we will discuss the influence of the growth of the direct import of Chinese silk in France to the installation and the development of French companies in china, and the relationship of these French companies with other intermediaries, especially the silks firms of England, Germany and Switzerland. Finally, we analyze the roles of different groups of Chinese merchants in the foreign trade of silk of china, the relationship between these groups and the relations between the Chinese traders and foreign firms. In the end, as the raw silk is a raw material for the production of silk, this book will also discuss the impact of the silk trade to the silk industry in the two countries. In this part, we will select a new angle – interaction of the industrializations in the two countries -- to analyze the relationship between foreign trade and industrialization in the 19th century. Firstly, there will be the discussions about the influence of the industrialization of western countries in the industrialization of the Asian countries. Secondly, we will also search for the effects of the dynamics of the silk trade between the two countries to their reactions of industrializations. In all these issues, we will try to link the eastern and western industrial revolutions to international trade together.

Under början av 2010-talet populariserades en ny form av elektroniskt betalningsmedel, så kallade kryptovalutor. Dessa tillkom under slutet av 2000-talet, till stor del på grund av stora finanskrisen 2007, och fungerar som ett fristående valuta- och betalningssystem. Den första och mest välkända av dessa idag är bitcoin. Bitcoin, som många andra kryptovalutor men ingen i samma grad, genomgick en chockprishöjning under mitten 2010-talet ända fram tills 2018. Priset hade under denna tid rört sig från under $10 USD till över $20000 USD per bitcoin. En sådan ofantlig ökning av pris har skapat ett stort intresse hos många, från hobbyinvesterare till finanssektorns huvudanalytiker. En annan viktig händelse i bitcoins historia är åtalet mot Ross Ulbricht, som skapade en illegal digital handelsplats vid namn Silk Road som accepterade bitcoin. Då det fortfarande är ett nytt område har forskning kring fenomenet inte lämnat krubban än. Dock görs det uppenbart genom en snabb överblick att denna forskning främst ligger inom den ekonomiska sfären. Endast ett fåtal vetenskapliga artiklar som nämner den sociala kopplingen till bitcoin kan återfinnas, särskilt få med en kvalitativ forskningsansats. Det har därför gjort oss intresserade att göra ett tillägg till detta mer eller mindre outforskade fenomen. För att åstadkomma detta har vi valt att fokusera oss på en jämförelse av nyhetsartiklar skrivna från perspektivet av bitcoinvärlden med några av de största internationella mediepublikationer som har skrivit om bitcoin. Norman Faircloughs kritiska diskursanalys ligger till grund för teorin och metoden bakom denna analys. Det är genom hans forskningsansats som en textanalys av fenomenet möjliggörs. Detta ledde till att vi kunde urskilja ett antal olika diskurser från texterna, antagonistiska förhållanden mellan de och dess textuella konstruktion. Utifrån detta har vi härlett till vad vi tolkar vara en möjlig framkomst till sättet nyhetssidorna skriver om bitcoin.

Les patients atteints de cécité cornéenne résultant d'une maladie ou d'une blessure dans de nombreux pays ne seront probablement pas transplantés avec des cornées de donneurs humains en raison d'une grave pénurie mondiale de tissus de donneurs. Cependant, même si des cornées de donneurs étaient disponibles, les patients présentant une inflammation ou une maladie grave ne seraient pas aidés car ils courent un risque élevé de rejet des cornées de donneurs car celles-ci contiennent des cellules allogéniques. Les implants cornéens sans cellules qui ne déclenchent pas de rejet ont été développés comme alternatives à la transplantation de donneurs humains par le laboratoire Griffith, et ont montré dans un premier essai clinique chez l'homme qu'ils régénèrent de manière stable le tissu et les nerfs cornéens. Ces implants comprenaient du collagène humain recombinant, la principale protéine structurelle trouvée dans la cornée humaine. Cependant, les collagènes de pleine longueur sont difficiles et coûteux à produire et ne peuvent pas être personnalisés. Une grande variété de peptides plus courts qui imitent le collagène et d'autres molécules de la matrice extracellulaire ont été développés et testés. Cela comprend les peptides hybrides combinant le collagène et la soie (VBsilk). Le but de ma thèse est de confirmer les simulations de VBsilk d'un peptide hybride collagène-soie produit au Griffith Lab. Un autre objectif est de déterminer les conditions de production et de purification pour montrer que le peptide simulé peut être converti en un peptide réel. En bref, l'ADN codant pour une séquence de VBsilk a été cloné dans ClearColi, une souche d'E. Coli à faible endotoxine. Les bactéries ont été cultivées dans des cultures à grand volume. Le VBsilk a été extrait et purifié par FPLC. SDS-PAGE a montré que des bandes de protéines de taille appropriée étaient obtenues. Par conséquent, il est possible de produire le peptide VBsilk. / Patients with cornea blindness resulting from disease or injury in many countries are unlikely to be transplanted with human donor corneas due a worldwide severe shortage of donor tissues. However, even if donor corneas were available, patients with inflammation or severe disease would not be helped as they are at a high risk of rejecting donor corneas as these contain allogeneic cells. Cell-free corneal implants that do not trigger rejection were developed as alternatives to human donor transplantation by the Griffith lab, and shown in a first-in-human clinical trial to stably regenerate corneal tissue and nerves. These implants comprised recombinant human collagen, the main structural protein found in the human cornea. However, full-length collagens are difficult and expensive to produce, and cannot be customized. A wide variety of shorter peptides that mimic collagen and other extracellular matrix molecules have been developed and tested. This includes hybrid peptides combining collagen and silk (VBsilk). The aim of my thesis is to is to confirm simulations of VBsilk, a hybrid collagen-silk peptide that was produced in the Griffith Lab. A further aim is to determine the conditions for the production and purification to show that simulated peptide can be converted into an actual peptide. Briefly, the DNA coding for a VBsilk sequence was cloned into ClearColi, a strain of E. coli with low endotoxin. The bacteria were grown up in large volume cultures. The VBsilk was extracted and purified by FPLC. SDS-PAGE showed that appropriate-sized bands of protein were obtained. Hence, it is possible to produce VBsilk peptide.

Min tanke med detta arbete var att hitta nya sätt att både skriva och producera låtar på, genom att använda mig av referenslåtar som inspirationskälla. Jag fokuserade på tre olika beståndsdelar från referenslåtarna, som sedan implementerades i tre nyskapade demolåtar. I låt 1 fokuserade jag på basen roll. I låt 2 fokuserade jag på solosångens relation till körsång och i låt 3 fokuserade jag på elpianot Fender Rhodes. När jag analyserade referenslåtarna så tog jag med mig vissa principer från respektive referenslåt och implementerade i mina egna låtar. Detta resulterade i att jag bland annat upptäckte nya spelsätt, sound och produktionstekniker att inspireras av till mina tre nyskrivna demolåtar. Att jobba med referenslåtar upplevde jag var ett bra startskott för att komma igång med låtskrivarprocessen. Samtidigt kunde jag stundtals känna mig begränsad och låst till referenslåtarna. Trots detta så var det en väldigt lärorik metod som hjälpte mig at vidga mina vyer och möjliggjorde för mig att skapa tre demolåtar som jag kanske inte annars hade skrivit.

Spiders produce a diverse number of silk proteins that are well-known for their extraordinary mechanical and biological properties. Dragline silk has been the most prominent focus of research because of its exceptional high tensile strength and extensibility. In our research, we have focused on the characterization of small molecular weight proteins found within dragline and tubuliform silks. Within the black widow spider, Lactrodectus hesperus, these proteins have been named Cysteine-Rich Protein (CRP) and determined to be a family of five individual proteins. The small protein identified within the tubuliform silks has been named Egg Case Protein 3 (ECP-3). In this study, recombinant expression of ECP-3 in the pET-19b-SUMO vector was to facilitate purification and development of an immunological reagent. Using western blot analysis, we have demonstrated that ECP-3 is efficiently expressed in bacteria. We also investigated CRP1 protein and its ability to bind MaSp1 components using pull down assays to determine potential interactions. No substantial biochemical evidence was produced to demonstrate protein-protein interactions between the two. Additionally, we show that using RT-PCR analysis from mRNAs collected from the major ampullate gland that transcript levels for CRP-family members from non-silked and a silked spider are different. CRP2 and CRP4 mRNA levels were shown to increase upon silking. Overall, the major findings of this thesis involved characterizing the ECP-3 protein found within tubuliform silks as well as determining the expression patterns for CRP-family members.

Araneoid spiders use specialized sets of abdominal silk glands to produce up to seven different types of silks, each with diverse functional properties. At the time of these studies, fibroin eDNA sequences that encode egg case silk had not been reported in the literature. This study used conventional nucleic acid-nucleic acid screening of a eDNA library to isolate a novel gene, named tubuliform spidroin 1 , from the black widow spider Latrodectus hesperus. TuSp 1 was demonstrated to be selectively expressed in the tubuliform gland (the gland suspected for egg case silk production), and examination of the amino acid sequence revealed highly homogeneous repeats (184 amino acid ensemble repeats), a characteristic feature of fibroin sequences. Analyses of the ensemble repeats within the amino acid sequence of TuSp 1 revealed the lack of long stretches of polyalanine and glycine-alanine sub-repeats, which are commonly found in minor ampullate and major ampullate silks. Polyserine blocks and short polyalanine stretches were highly represented in the TuSp 1 amino acid sequence. Our data support the assertion that TuSp 1 represents the main constituent within egg case silk. This supposition is supported by the observation that the amino acid composition of raw egg case silk was strikingly similar to the amino acid composition predicted from the translated TuSp1 eDNA. Two additional constituents identified in black widow egg case, egg case protein 1 (ECP-1) and egg case protein 2 (ECP-2), were also partially characterized in this study. Using immunohistochemical approaches, we demonstrate that ECPs predominantly localize to the exterior of the large diameter fibers of egg cases. Additionally, these studies revealed smaller amounts of ECPs localized to the interior portion of the fibers. Collectively, these results support TuSp1 as the predominant fibroin within egg sacs as well as reveal a structural role for the ECPs, providing clues regarding the supramolecular structure of egg case fibers.

Spider silk is one of the most remarkable materials produced in the natural world and its strength and extensibility are legendary. To date, the majority of studies have been performed on the following silks: dragline, capture spiral, and eggcase silk. The primary goal of this study was to characterize a lesser known silk type, called wrapping (swathing) silk, from Latrodectus hesperus. My research focused on elucidating the fibroins that make up the swathing silk. Perfonning MS/MS analyses on solubilized wrapping silk fibroins digested with trypsin, we demonstrate that a novel fibroin named AcSp !-like is present within wrapping silk. Consistent with this finding, SEM analyses reveal that wrapping silk is a composite material, containing at least three different diameter silk fibers. By using scanning electron micrographs, along with amino acid composition analyses and MS/MS analyses, we demonstrate wrapping material contains the fibroins AcSp1-like, MiSp1-like, MaSp1 and MaSp2. These are the first studies to reveal that minor, major and acinifonn silks are constituents of wrapping material.

Forskningsområdet för bärbar elektronik är fortfarande relativt ungt och det finns ett stort behov av utveckling av nya material inom området. Olika typer av kompositer är mycket intressanta och de ska uppvisa såväl hög hållfasthet som goda ledande egenskaper. I detta avseende är silkes fibroin och MXene mycket intressanta utgångsmaterial eftersom silkestrådarna kan ge en struktur med god jonledningsförmåga och god flexibilitet och MXene kan bidra med hög styvhet och god elektrisk ledningsförmåga. Med detta som bakgrund beslöts att undersöka om kompositer av silkestrådar och MXene kan användas i kompositer som kan användas i bärbar elektronik. 3 olika typer av hydrogeler studerades och de innehöll silkes fibroin med 0, 1 och 5% MXene. De egenskaper som utvärderades var struktur, mekaniska egenskaper, stabilitet i vatten, bionedbrytbarhet och både statisk och dynamisk ledningsförmåga. Resultaten visar att de tillverkade nanokompositerna har lovande förutsättningar inom området eftersom en kombination av silkes fibroin med 5 % MXene har god stabilitet, konduktivitet och en hög och stabil Gauge-faktor. / As the research area of wearable electronics is still relatively new, material science with this focus opens plenty of unexplored fields. That is why a study characterizing the unexplored composite system of silk fibroin and MXene (Silk/MXene) was conducted. These two biocompatible materials are complementary with regard to the requirements for wearable electronics materials. Silk fibroin dispose an ionic conductivity and solid flexibility, while MXene brings mechanical strength and significant increase of electrical conductivity. The reinforced hydrogel materials were studied at two concentrations of fillers, 1% and 5% and compared to pristine silk fibroin. All three materials were studied from the point of view of their structure, mechanical properties, behaviour in aqueous environment, biodegradability and electrical conductivity, both static and dynamic. Nanocomposite systems of silk fibroin and MXene have shown a potential for being used in the intended application area, as Silk/MXene 5% film displays good stability, conductivity with high andstable Gauge factor.