Malgré l’existence d’un vaccin préventif efficace, l’infection chronique par le virus de l’hépatite B (HBV) demeure un problème majeur de santé publique. La persistance de l’infection par HBV étant clairement associée à des réponses immunitaires insuffisantes, l’immunothérapie par le vaccin à base d’ADN nu, visant à stimuler les réponses humorales et cellulaires, apparaît comme particulièrement pertinente pour la thérapie des hépatites B chroniques. Toutefois, l’efficacité thérapeutique d’une telle stratégie reste limitée chez l’homme, d’où la nécessité d’optimiser cette approche vaccinale pour une utilisation ultérieure en clinique. Ainsi, l’objectif général de ce travail de thèse était d’explorer, avec le modèle du DHBV (« Duck Hepatitis B Virus »), étroitement apparenté au HBV humain, si l’administration du vaccin à ADN par électroporation (EP) pouvait davantage améliorer son efficacité prophylactique et thérapeutique. Nous avons montré, dans un 1er temps chez des canards naïfs, que l’administration du vaccin à ADN par EP permet de potentialiser le pouvoir neutralisant et d’élargir le répertoire épitopique de la réponse humorale dirigée contre la protéine d’enveloppe du DHBV, même avec des doses d’ADN relativement faibles. Dans un 2ème temps, nous avons montré chez des animaux chroniquement infectés par le DHBV, que l’administration par EP du vaccin à ADN ciblant les protéines structurales du DHBV et le DuIFN-γ améliore considérablement l’efficacité thérapeutique du vaccin, notamment au regard de la séroconversion et de la clairance virale. Les résultats ainsi obtenus confirment l’intérêt majeur de cette approche vaccinale pour la thérapie des hépatites B chroniques / Despite the existence of an effective prophylactic vaccine, chronic hepatitis B virus (HBV) infection remains a major public health problem. Since persistence of HBV infection is mostly associated with insufficient immune responses, therefore DNA vaccination capable of activating both humoral and cellular immune responses appears as a pertinent strategy for chronic hepatitis B therapy. However, the efficacy of such therapeutic approach remains limited in humans. Improvement of DNA vaccine efficacy is therefore needed for future therapeutic applications in clinic. The main objective of this thesis was to investigate in the duck hepatitis B virus (DHBV) model, whether the protective and therapeutic efficacy of DNA vaccine can be enhanced using EP-based delivery system. Firstly, we showed in naïve ducks that EP-based delivery was able to improve the dose efficiency of DNA vaccine and to maintain a highly neutralizing, multi-specific B-cell response even with relatively low DNA doses, suggesting that it may be an effective approach for chronic hepatitis B therapy at clinically feasible DNA dose. Secondly, we showed in chronic DHBV-carriers that in vivo EP is able to dramatically enhance the therapeutic potency of DNA vaccine targeting hepadnaviral proteins. Indeed, this approach was able to consistently restore humoral immune response and to sustainably decrease and even clear viral infection. Thus, these data strongly support the use of this approach for chronic hepatitis B therapy in humans

Pickling is a unit operation within stainless steel production, which means treating the steel with hydrofluoric acid (HF) and nitric acid (HNO3), also called mixed acid. The whole process generates waste water streams which have to be treated before released to recipient. The aim of this degree thesis was to make an evaluation of different possibilities for reduction of emissions from the pickling process with China as a possible future market. The work consisted of two different parts; the first was to describe and evaluate different treatment methods for waste pickling acid, with emphasis on denitrification technologies. The second and main part was to make a fundamental description of the neutralisation process and outline important parameters. The work was performed by gathering information from literature but also from industry in both Sweden and China. The work has been a collaboration between the Royal Institute of Technology (KTH), the Swedish Environmental Institute (IVL) and the company Scanacon. A review of the different acid recovery methods; ionic exchange, diffusion dialysis and extraction was made. The study showed that ionic exchange is a robust method with relatively low cost and therefore it has been largely implemented both in Swedish and Chinese industry. The outflow however still requires neutralisation. Nitrate reduction can be performed as “end of pipe”, those methods investigated in this study were; biological treatment, reverse osmosis and nanofiltration. Meanwhile, internal solutions such as evaporation and electro-dialysis are two interesting technologies which reduce nitrates in combination with acid recovery. It was found that slaked lime (Ca(OH)2) is the most suitable neutralisation agent for pickling waste and, besides the choice of chemicals, many important parameters influence the process, such as the optimal pH, mixing and conditions during lime slaking. Based on information from one of the visited sites in Sweden a mass balance of the neutralisation facility was made and from that the required amount of Ca(OH)2 was calculated. The calculations were verified by an experimental part performed by IVL, using pickling acids from the same site. The amount of metals in the outgoing water was calculated using software “Medusa” but also by equilibrium equations. However, the results differed somewhat; this is probably due to the fact that Medusa takes other complexes and their interaction, besides the formed metal hydroxides, into consideration. Within the mining industry research has been made on different methods for neutralisation and some have been tested in field. An example is the High Density Sludge process (HDS), were an amount of sludge is recycled back to the neutralisation tank. It was shown that this gave improved sludge properties and decreased lime consumption. This could perhaps also be implemented for waste water in the stainless steel industry, and the method was also tested during the experimental part of this project. The dry content increased after a number of cycles but further investigation is required before any conclusion can be drawn. / Betning är en enhetsprocess inom tillverkningen av rostfritt stål då godset behandlas med fluorväte syra (HF) och salpetersyra (HNO3), också kallad blandsyra. Betningen ger upphov till vatten strömmar som måste behandlas innan de släpps ut till recipienten. Syftet med det här examensarbetet var att göra en utvärdering av olika tekniker för att reducera utsläpp till vatten från betningen med Kina som potentiell framtida marknad. Arbetet bestod av två delar; den första delen var att beskriva och utvärdera olika behandlingsmetoder av förbrukade betbad med betoning på denitrifikationstekniker. Den andra och största delen var att göra en grundläggande beskrivning av neutralisationsprocessen. Studien utfördes genom att inhämta information från litteratur samt från industrin i både Sverige och Kina. Arbetet har varit ett samarbetsprojekt mellan Kungliga Tekniska Högskolan (KTH), Svenska miljöinstitutet (IVL) och företaget Scanacon.    Arbetet behandlar syraåtervinningsystemen; jonbytare, diffusions dialys samt extraktion. Nitrat reduktion kan ske internt eller externt där de externa åtgärder som behandlas i denna rapport är biologisk rening, omvänd osmos och nanofiltrering. De interna metoderna avdunstning och elektrodialys är intressanta eftersom de återvinner syran samtidigt som de reducerar nitraterna avsevärt. Studien visade att jonbyte, på grund av dess robusthet och relativt låga kostnad är den mest implementerade metoden för syraåtervinning i både svensk och kinesisk industri idag. Restprodukten från jonbytaren kräver dock fortsatt behandling, där det traditionella valet är neutralisation. Studien visade att släckt kalk (Ca(OH)2) är det mest passande kemikalien för neutralisation av betsyror. Förutom kemikalieval så finns det många parametrar som påverkar effektiviteten hos processen så som pH, omrörning och förhållanden under kalksläckningen. Baserat på information ifrån ett av de besökta stålverken i Sverige, gjordes en massbalans över dess neutralisationanläggning. Utifrån de flöden som denna gav kunde den teoretiska mängden kalk som krävdes för utfällning räknas ut. Beräkningarna verifierades med en experimentell del som utfördes av IVL på betsyror från samma verk. Resthalterna av metall i utgående vatten beräknades med programmet ”Medusa” men också med jämviktsekvationer. Resultaten mellan de två skiljde sig, detta beror förmodligen på att Medusa förutom hydroxidutfällning tar hänsyn till andra utfällningskomplex och dess interaktioner. Inom gruvvatten industrin har det forskats en del kring olika neutralisationsmetoder, en i litteraturen föreslagen sådan är ”High Density Sludge process (HDS)”. Här återförs en del av slammet tillbaka till neutralisationssteget, vilket visade sig ge förbättrade slamegenskaper och minskad kalkåtgång. Det var intressant att undersöka om denna metod också gick att implementera på förbrukade betbad och därför prövades metoden i den experimentella delen av detta projekt. Detta gav efter ett antal återföringscykler högre torrhalt på slammet, dock krävs fortsatta undersökningar innan någon slutsats kan dras.

Cellulose is the most abundant biopolymer on Earth as it is found in every plant cell wall; therefore, it represents one of the most promising natural resources for the fabrication of sustainable materials. In plants, cellulose is mainly used for structural integrity, however, some species organise cellulose in helicoidal nano-architectures generating strong iridescent colours. Recent research has shown that cellulose nanocrystals, CNCs, isolated from natural fibres, can spontaneously self-assemble into architectures that resemble the one producing colouration in plants. Therefore, CNCs are an ideal candidate for the development of new photonic materials that can find use to substitute conventional pigments, which are often harmful to humans and to the environment. However, various obstacles still prevent a widespread use of cellulose-based photonic structures. For instance, while the CNC films can display a wide range of colours, a precise control of the optical appearance is still difficult to achieve. The intrinsic low thermal stability and brittleness of cellulose-based films strongly limit their use as photonic pigments at the industrial scale. Moreover, it is challenging to integrate them into composites to obtain further functionality while preserving their optical response. In this thesis, I present a series of research contributions that make progress towards addressing these challenges. First, I use an external magnetic field to tune the CNC films scattering response. Then, I demonstrate how it is possible to tailor the optical appearance and the mechanical properties of the films as well as to enhance their functionality, by combining CNCs with other polymers. Finally, I study the thermal properties of CNC films to improve the retention of the helicoidal arrangement at high temperatures and to explore the potential use of this material in industrial fabrication processes, such as hot-melt extrusion.