This degree project has been carried out on the commission of AB Borlänge Energi. The purpose of thisproject was to redesign the magazine Energitrycket. The magazine should inform about the current eventsat the company. The work consisted of redesign of the existing magazine and adjustment to copying andpublishing on the web.This project also contains a research about how paper and colour affect the print results. It shows thatthe maximum contrast and sharp image reproduction is best achieved on woodfree, coated, calenderedpaper with high whiteness. An uncoated, light yellow paper is however to recommend for a printed matterswith a lot of text.It also shows that every production unit reproduces colours differently. To get a good colour reproductionand a good communication between these units, they must be calibrated, and well-functioningICC-profiles must be created.

This project is a redesign of the magazine Vår Kommun, which is a magazine published by the municipality of UpplandsVäsby, Sweden. The redesign included a change of format from tabloid to a magazine format and the creating of adesign with a more modern look and feel of a magazine.

Todays travel trends go towards independence and self planning. If you need advice or help when performing your trip, there are several different series of guidebooks on the market and one of these series comes from the travel magazine Vagabond. This degree project concerns the redesigning of the travelguides of Vagabond, or to be precise: their cityguide over Istanbul. The purpose of the new design is to assure the resemblance between the guidebook and the magazine, as wanted by the Art Director of Vagabond Angelica Zander.Prior to the redesigning process preliminary studies that make up the fundamental ideas were made. Three other big titles of guidebooks on the market were analyzed, and in addition a great deal of focus – considering the final purpose – was put on the concept of magazine design. Some color psychology has also been studied to make out what a difference color makes in printed media and what power color can contribute with, when delivering the message. Finally redesign as a concept has been investigated to clarify why the way of expression should be renewed from time to time.The result is presented as spread examples from the cityguide over Istanbul. The new design is applied on the existing content and the result is supposed to appear as a miniature magazine.

<p>We present a computational structure-based redesign of the phenylalanine adenylation domain of the non-ribosomal peptide synthetase (NRPS) enzyme gramicidin S synthetase A (GrsA-PheA) for a set of non-cognate substrates for which the wild-type enzyme has little or virtually no specificity. Experimental validation of a set of top-ranked computationally-predicted enzyme mutants shows significant improvement in the specificity for the target substrates. We further present enhancements to the methodology for computational enzyme redesign that are experimentally shown to result in significant additional improvements in the target substrate specificity. The mutant with the highest activity for a non-cognate substrate exhibits 1/6 of the wild-type enzyme/wild-type substrate activity, further confirming the feasibility of our computational approach. Our results suggest that structure-based protein design can identify active mutants different from those selected by evolution.</p><p>Knowledge about the structures of individual domains and domain interactions can further our redesign of the NRPS enzymes for new bioactive nature product. So far, little structure information has been available for the auxiliary domains such as the epimerization domains and how they interact with the NRPS modules. Solution structure studies by nuclear magnetic resonance (NMR) provide advantages for understanding the dynamics of the domains and reveal active conformations that sometimes are not represented by the crystal structures. However, the large size of the NRPS proteins present challenges for structure studies in solution. In chapter 3, we study the solution structure of the 56 kDa epimerization domain of GrsA (GrsA-PheE) by NMR. We use multidimensional backbone resonance experiments as well as specific labeling strategy to assign the backbone resonances of GrsA-PheE. Secondary structures are determined by sets of residual dipolar couplings (RDCs) measured in multiple alignment media. To determine the global fold of the protein, we obtain long-range distance restraints by measuring the paramagnetic relaxation enhancements (PREs) from 15 site-directed spin labeling samples. </p><p>In chapter 4, we investigate the redox regulation of phosphatases. The activity levels of protein tyrosine phosphatases (PTPs) in cells are highly regulated in various ways including by phosphorylation, localization and protein-protein interaction. Additionally, redox-dependent modification has emerged as a critical part in attenuating PTPs activity in response to cellular stimuli. The tandem Src homology 2 domain-containing PTPs (SHPs) belong to the family of nonreceptor PTPs. The activity level of SHPs is highly regulated by interaction of SH2 domain, phosphorylation level of C-terminal tail and by reversible oxidation. In vivo evidence has shown the reversible oxidation of catalytic cysteine inhibits SHPs activity transiently as a result, affecting the phosphorylation level of its target proteins. In this chapter, we investigate in vitro the reversible oxidation of full-length and catalytic domain of SHP-1 and SHP-2 by using kinetic measurements and mass spectrometry. We have confirmed the susceptibility of the active site cysteines of SHPs to oxidative inactivation, with rate constants for oxidation similar to other PTPs (2-10 M-1s-1). Both SHP-1 and SHP-2 can be reduced and reactivated with the reductants DTT and gluthathione, whereas only the catalytic domain of SHP-2 is subject to reactivation by thioredoxin. Unlike PTPs whose oxidation contains a catalytic cysteine disulfide bonding to a backdoor cysteine or forms a sulfenylamide bonding to nearby backbone nitrogen, we have found that in the reversibly oxidized SHPs, the catalytic cysteines is re-reduced while two conserved backdoor cysteines form a disulfide linkage. Knocking out either of the backdoor cysteine preserves the reversibility of the oxidized SHPs with a disulfide formation between the catalytic cysteine and the remaining backdoor cysteine. However, removal of both backdoor cysteines leads to irreversible oxidative inactivation, demonstrating that these two cysteines are necessary and sufficient for ensuring reversible oxidation of the SHPs. Our results extend the mechanisms by which redox regulation of PTPs is used to modulate intracellular signaling pathways.</p> / Dissertation

Olefin metathesis is arguably the most versatile catalytic route yet developed for the assembly of carbon-carbon bonds. Metathesis methodologies are attractive from both synthetic and ecological standpoints, because they employ unactivated double bonds. This reduces the total number of synthetic steps, and the associated generation of chemical wastes. The drive to deploy olefin metathesis in highly demanding contexts, including pharmaceutical manufacturing and chemical biology, puts severe pressure on catalyst lifetime and productivity. Understanding the relevant decomposition pathways is critical to achieve essential performance goals, and to enable informed catalyst redesign. This thesis work expands on significant prior advances that identified and quantified critical decomposition pathways for ruthenium catalysts stabilized by N-heterocyclic carbene (NHC) ligands. Because pristine catalyst materials are essential for mechanistic study, it focuses first on methods aimed at improving efficiency and purity in catalyst synthesis. Merrifield iodide resins were shown to function as efficient, selective phosphine scavengers in the production of clean second-generation catalysts from PCy3- stabilized precursors. The thesis then turns to mechanistic examination of decomposition pathways that underlie success and failure for leading NHC catalysts, for comparison with a new family of catalysts stabilized by cyclic (alkyl)(amino) carbene (CAAC) ligands. These represent the first in-depth mechanistic studies of the CAAC catalysts, which have attracted much attention for their breakthrough productivities in challenging metathesis reactions. The remarkable productivity of the CAAC catalysts is shown to originate in their resistance to decomposition of the key metallacyclobutane intermediate via b-elimination, and (to a lesser extent) in their resistance to attack by nucleophiles and Bronsted bases. Importantly, however, they are more susceptible to bimolecular decomposition. The latter behaviour, as well as their resistance to b-elimination, is traced to the strong trans influence of the CAACs relative to NHC ligands. This insight significantly advances our understanding of the fundamental properties governing both productivity and decomposition. Finally, two new catalysts are developed, building on the principle that nucleophilic stabilizing ligands should be avoided in the precatalysts. In the first of these complexes, an o-dianiline ligand is employed to stabilize the precatalyst. This flexible, H-bonding chelate serves the further purpose of accelerating macrocyclization of flexible dienes that bear polar functionalities. As its H-bonding capacity also increases its sensitivity to trace water, however, an alternative catalyst architecture was pursued. The latter consists of a dimer bearing bulky Ru-indenylidene centers, in which a dative bond from a bridging chloride affords the fifth ligand essential to stabilize the precatalyst.

The caspase family of proteins is critical to biological understanding, because they serve as the final arbiters of life and death, being the initiators and executioners of cell death. Specifically, caspase-7 plays a key role in apoptosis, however its full complement of targets within the cell has not yet been elucidated, nor has its function been targeted by drug design efforts. These factors stem from the lack of fundamental understanding of the structural dynamics of the protein, including the mobile loops that constitute the active site binding groove of caspase-7, and their ability to modulate the function of the protein. In this work, we describe the importance of the entire loop bundle for catalysis, demonstrate a novel approach for allosteric control using loop movement, develop computational methods to engineer a new binding site for an allosteric effector and discover a hereunto unseen native disulfide within caspase-7 that may contribute to specificity and catalysis. The information obtained within this study is applicable for not only the study of caspase-7, but also the greater field of apoptosis research.

The study and design of light-weight automobiles has emerged as an important area of interest in the government, academia, and the manufacturing industry. Significant advances in vehicle weight reduction technologies have taken place in almost all fields of transportation. Weight reduction is identified as a key factor to achieving fuel-economy, energy efficiency and environmental safety. The main objective of this thesis is to investigate cost effective design methodologies that enable fabrication of light weight structures, which subsequently result in a fuel saving. A few important techniques and trends of weight reduction in the automotive industry over the past few years are studied as part of the thesis. A summary from the survey of various approaches to weight reduction is presented in the literature review. This thesis is based on the theory of semi-tension fields, which was originally applied towards the design of structures in the aircraft industry. A semi-tension field is a post buckling phenomenon in which the load is continued to be carried even after the web has buckled. The advantage of semi-tension fields is twoold: first, by using this theory the structural stability of the original structure is retained; and secondly, its application replaces a comparatively heavy-weight shear resistant web with a thin web, potentially resulting in reduced weight. The semi-tension field theory is applied to the redesign of back panel of a prototype Ford F-150 pick up truck, which was modeled and analyzed using IDEAS Master Series 8 FEA software. The literature review also consists of the survey of several advances in the Semi-tension fields theory, and the corresponding trends in weight reduction. Analytical theories related to semi-tension field-based design and the respective mathematical formulations have also been described. Finite element analyses of the design that resulted from the application of the theory were carried out and results were validated using analytical theories. A technical paper demonstrating the redesign of a door beam was also studied and results are presented as an appendix.

It is predicted that by 2050 there will be 10 million deaths annually due to super-resistant bacterial infections. Antimicrobial resistance (AMR) is already responsible for nearly 5 million deaths a year. Ribosomes serve as an ideal drug target being frequently targeted by antibiotics and having a highly conserved structure with few options for resistance. However, computer aided drug design (CADD) using ribosome crystal structures presents several challenges and is underutilized in the field. In this work we establish a successful protocol for antibiotic redocking and docking within the high interest sites of the peptidyl transferase center (PTC). Molecular visualization and interaction mapping were used to atomistically delineate binding patterns in the ribosomal PTC that could be used for CADD. Eleven ribosome crystal structures were validated for computational testing, which revealed derivative binding patterns in the A-site and P-site that can be used to increase antibiotic efficacy. Ribosome overlays revealed high interaction frequency nucleotides that were widely conserved throughout the different species and could be used to inform bidentate design to target two pockets at once. This work serves as a basis for methods to computationally explore drug optimization on ribosome targeting antibiotics to help combat the rapid expansion of AMR. / Master of Science in Life Sciences / Antimicrobial resistance (AMR) to antibiotics by bacteria is a rapidly increasing problem. Current trends predict that there will be more death due to super-resistant bacterial strains than cancer by 2050. Ribosomes are essential cellular machinery for bacteria and make an ideal antibiotic target. Using computational tools to optimize antibiotics with available ribosome crystal structural data presents several challenges and is underutilized throughout the field. In this work we establish a successful protocol for determining and exploiting antibiotic binding patterns within the functional center of the ribosome, the peptidyl transfer center (PTC). Nearly a dozen ribosome crystal structures were validated for computational testing, and binding patterns were revealed within the PTC that allowed antibiotic derivatives with increased efficacy to be developed. Ribosome validation also helped inform new drug class design so that multiple drug sites could be targeted at once, which were docked sharing high frequency nucleotide interactions with both parent antibiotics. This work serves as a basis for methods to computationally explore drug optimization on ribosome targeting antibiotics to help combat the rapid expansion of AMR.

The concept of sustainable development has been pervasive in recent years and many organizations choose to implement sustainability and adapt their activities accordingly. The purpose of this study have been to explore how a collaboration on the use of waste materials may look to analyze what influences cooperation. A case study has been carried out examining a Swedish state regional project aimed at creating partnerships between actors and utilizing textile waste with the help of design. The study was conducted using qualitative methods and the collection of data has been done through interviews and by examining documents. The results show that there are seven key factors that affect cooperation: expectations, commitment, internal communication, a strong non-profit actor, individual treatment, personal networks and the diversity of actors. The discussion addresses that the project has been publicly funded and suggests that further research may focus on the logistics and marketing of redesign.

<h1>Sammanfattning</h1><p>Detta examensarbete är baserat på ett uppdrag från AB Mälarplast, en plasttillverkare i Eskilstuna, med syftet att designa en serie med tre olika glastyper. Ett vin-, champagne- och grogglas skulle ges förslag på, som alla innehöll en gemensam nämnare som kopplade de alla glastyperna. Uppdragsgivaren hade redan före arbetet skapa kontakt med en kund som importerade en glasserie från Nya Zeeland. På grund av att den långa transportvägen innebär en hög kostnad försöker Mälarplast ta över den utländska leverantörens plats, och därigenom kunna erbjuda ett bättre pris. Examensarbetet är ett stöd för tillverkningen som kommer starta innan årets slut.</p><p>Arbetet kom att baseras på en bakgrundsundersökning av vinkultur, materiallära och produktionsteknik för att sedan genom olika verktyg och modeller komma fram till en konkurrenskraftig lösning för AB Mälarplasts situation. De nämnda verktygen behandlar följande områden: marknad, kvalitet och design för att nå fram till ett koncept som uppfyller kraven från uppdragsgivaren och lämpar sig bäst enligt egna observationer.</p><p>Materialalternativen och ekonomiska faktorer beskrivs i arbetet men behandlas inte djupgående eftersom de av AB Mälarplast redan fastsällts och därmed mer eller mindre lämnats låsta för mig. Dessutom var begränsningar nödvändiga och dessa delar fick stå utanför. Större fokus lades istället på det som uppdragsgivaren bad om hjälp med dvs. designen och basera detta på en vetenskaplig grund genom olika designrelaterade verktyg som lärts ut på Mälardalens högskola. Det har varit viktigt att inte lägga fram ogrundade förslag när man som designer kontra VD haft olika syn på vad som bör prioriteras: försäljning genom design eller högre intäkter genom ekonomistyrning.</p><p>Uppdragsgivaren granskade det slutgiltiga förslaget i form av en fysisk modell av typen vinglas, då denna är huvudprodukten. Därefter resulterade den slutliga designen i en CAD-fil.  Detta är grunden till framtida produktion av glasserien.</p><p> </p>