Watson and Crick’s double-helical model of DNA is considered to be one of the great discoveries in biology. However, in 1976, two groups of scientists, one in New Zealand, the other in India, independently published essentially the same radical alternative to the double helix. The alternative, Side-By-Side (SBS) or ‘warped zipper’ conformation for DNA is not helical. Rather than intertwine, as do Watson and Crick’s helices, its two exoskeletal strands are topologically independent. Thus, unlike the double helix, they may separated during replication without unwinding. This dissertation presents, but does not arbitrate among scientific arguments. Its concerns are meta-scientific; in particular, why and how the individuals who invented the & ‘warped zipper’ came to do so. Against Popper and most recent philosophers of science, it is taken to be “the business of epistemology to produce what has been called a ‘rational reconstruction’ of the steps that have led the scientist to a discovery [Popper (1972), p.31, emphasis in the original].” On the received view, the invention of the ‘warped zipper’ must be irrational or, at best, non-rational thereby excluding from philosophical investigation. I establish that this philosophical dogma is not true a priori, as is usually supposed, and, in the case of the SBS structure of DNA, false a posteriori. The motivation for, and development of the SBS structure for DNA reveals a process best characterized as significantly, though not entirely, rational.

<p>The major aim of the studies that this thesis is based on has been to better define the topological determinants of the formation of so-called helical hairpins during membrane protein assembly in the ER membrane.</p><p>The helical hairpin is a basic folding unit in membrane proteins. It is composed of two closely spaced transmembrane helices with a short connecting loop and it is believed to be inserted into the membrane as one compact unit. It is becoming increasingly clear that the helical hairpin is a very common structural element in membrane proteins and a detailed understanding of its properties is of central importance.</p><p>We demonstrate that the efficiency of formation of helical hairpins depends both on the overall length of the hydrophobic segment, on the amino acids flanking the transmembrane segment, and on the identity of the central, potentially turn-forming residues. We also show that interhelical hydrogen bonds between pairs of Asn or Asp residues can induce helical hairpin formation.</p><p>A detailed topology mapping is also reported for the <i>Escherichia coli </i>inner membrane chloride channel YadQ, a protein for which the X-ray structure is known. Our results provide a critical test of the reporter fusion approach and offer new insights into the YadQ folding pathway.</p><p>In summary, the results present in this thesis have increased our understanding of the determinants of membrane protein topology and structure. Furthermore, the information obtained can be used to improve current models for predictions of membrane protein topology.</p>

The major aim of the studies that this thesis is based on has been to better define the topological determinants of the formation of so-called helical hairpins during membrane protein assembly in the ER membrane. The helical hairpin is a basic folding unit in membrane proteins. It is composed of two closely spaced transmembrane helices with a short connecting loop and it is believed to be inserted into the membrane as one compact unit. It is becoming increasingly clear that the helical hairpin is a very common structural element in membrane proteins and a detailed understanding of its properties is of central importance. We demonstrate that the efficiency of formation of helical hairpins depends both on the overall length of the hydrophobic segment, on the amino acids flanking the transmembrane segment, and on the identity of the central, potentially turn-forming residues. We also show that interhelical hydrogen bonds between pairs of Asn or Asp residues can induce helical hairpin formation. A detailed topology mapping is also reported for the Escherichia coli inner membrane chloride channel YadQ, a protein for which the X-ray structure is known. Our results provide a critical test of the reporter fusion approach and offer new insights into the YadQ folding pathway. In summary, the results present in this thesis have increased our understanding of the determinants of membrane protein topology and structure. Furthermore, the information obtained can be used to improve current models for predictions of membrane protein topology.

The importance for companies in knowledge or technology intensive industries to take part in research partnerships has been thoroughly researched, and the gain of collaboration with external parties has been proven. One of these most influential collaboration types is the one between academia and industry, where the US Bayh-Dole Act provided a break-through policy change for the transfer, conversion and commercialization of knowledge and innovations. To counter this, the European Union has implemented a policy around a facilitating, user-centered milieu for innovation called Living Labs. In this article, the purpose is to identify potential collaboration barriers in the university-industry collaboration when implemented in this milieu. This is done by using a multiple case study where the respondents are seven individuals, from three Living Lab entities and two companies. The findings show that the inclusion of users give the setting its advantage, but also gives additional management needs, something that applies to all participants in the setting – the company representatives must have a diverse set of abilities, the researchers should be standalone and independent from the Living Labs management, the management must establish a shared physical context for all parties to interact within and there must be a very clear agreement between all parties what there are expecting from the collaboration regarding outcomes, process and structure.

The following study investigates the intramolecular and intermolecular interactions responsible for invoking stereoselectivity and stereospecificity in the synthesis of a chiral original species and amino acid receptor. The former commences with a brief overview of the nature, scope and applications of helical chirality, and culminates in the formation of a permanent helix via the synthesis of a novel chiral lactone. The latter is discussed as an extension of a naturally occurring cofactor whose identity is modulated to furnish a tailored receptor selective to the binding of amino-acid enantiomers. The study and analysis is executed via both synthetic and computational methods.

The following study investigates the intramolecular and intermolecular interactions responsible for invoking stereoselectivity and stereospecificity in the synthesis of a chiral original species and amino acid receptor. The former commences with a brief overview of the nature, scope and applications of helical chirality, and culminates in the formation of a permanent helix via the synthesis of a novel chiral lactone. The latter is discussed as an extension of a naturally occurring cofactor whose identity is modulated to furnish a tailored receptor selective to the binding of amino-acid enantiomers. The study and analysis is executed via both synthetic and computational methods.

Knowledge production has changed considerably in the past few decades. This transformation has notably affected universities both as unique institutions and citadels of knowledge. These changes are being brought by a number of factors, such as the globalization of the economy, the rise of technologies based on generic forms of knowledge, and the ability of universities to hold and exploit patents. In both scale and intensity, these alterations have led policy makers to reflect more on how scientific and technological innovation can and should be enhanced by policy decisions that would improve university-industry and government cooperation. This new fusion of three complementary societal sectors has been described by sociologists as the triple helix. As an analytical and normative concept, the triple helix is derived from the changing role of government in different societies in relation to academia and industry. Its basis is the recognition that the interaction among university-industry-government as relatively independent, yet inter-dependent institutional spheres is critical to improving the conditions for innovation in a knowledge-based society. The study reveals that commercial research funding significantly affects the perceptions of university-industry collaboration and academic knowledge capitalization. The analysis showed that academic scientists who received commercial research funding have relatively positive views about university-industry relations than those who do not receive such funds. However, one cannot conclude that commercial activities of academic scientists are harming the core functions of the university or that intellectual autonomy is being surrendered to industrial partners. Based on the findings of the study, and the contours of the triple helix model, it is argued that the growth of university-industry-government collaboration is not necessarily pre-determined in favour of either private corporations or the state, nor is it necessarily at the expense of universities. It is further contended that the growing notion that academic capitalism is harming the core functions of the university is perhaps a bit simplistic in that the issue is more complex and multifaceted than usually acknowledged. <p>In light of the above, the study asserts that the future viability of policies encouraging universities to be entrepreneurial may, if approached strategically, be catalysts for the science-based knowledge economy. For that to be realistic there is the need to understand the university as a differentiated social system rather than a unified whole. This will avoid the situation whereby all university activities are subordinated under a homogenous policy of one size fits all. In the context of triple helix relations, conceptualizing the university as a differentiated social system means a deep-seated and continually growing purposeful specialization such as the adoption of an economic development function in addition to teaching, research and community engagement.

The work describes the development of a new class of synthetic metallopeptides that features a dirhodium metal center. Combination of peptide and dirhodium properties leads to unique effects on peptide structure, peptide-protein interactions, and metal catalytic activity aimed at small molecule as well as protein substrates. Dirhodium is directly bound to carboxylate side chains of aspartate or glutamate yielding kinetically inert coordination complexes. This improves stability, allows purification and provides enhanced biocompatibility. Bridging of two side chains in the same sequence enables control of the peptide secondary structure. Dirhodium metallopeptides are applied to regulate coiled coil dimerization, stabilize and induce helical secondary structure, catalyze enantioselective organometallic transformation, and serve as ligands for proteins. These results lead to the development of hybrid organic-inorganic therapeutic agents, biological probes for study of protein-protein interactions, and enantioselective metallopeptide catalysis.

Europe is arguably in need of a more offensive approach towards theencouragement of entrepreneurship and research based product development.Several European initiatives have been initiated towards this aim, one ofwhich is the Knowledge and Innovation Communities (KICs); an initiativeultimately taken by the European Commission. The main purpose of the KICsis to foster innovation and commercialization in Europe by combining forcesof industry and university, much in line with the theory of the TripleHelix. This master’s thesis is a follow up report of a previously conductedRemotely Operated Vehicle (ROV) market analysis, which was a deliverable inthe OTS project; a KIC InnoEnergy initiated project, aiming towards productdevelopment within the ocean energy sector. The purpose of this thesis hasbeen to, on the one hand evaluate how such a multidisciplinary projectworks in practice, the consequences of its design and the coping of theseconsequences, and on the other hand to identify and map prerequisites for asituation regarding if, and how, the project should invite anotherparticipant from industry into a collaboration. Based on a qualitativeanalysis of seven interviews with representatives from both academia andindustry, the conclusions indicated that the structure and future of theOTS/ROV project is perceived as unclear, best remedied by strongermanagement, additional funding, and invitation of a new collaborator. Thedemands for such collaboration mainly include an explicit project plan fromthe external ROV supplier’s point of view, and the sharing of knowledge andequipment of the supplier from the internal members’ point of view.

This thesis addresses the opportunities and difficulties that can occur in the creation of an innovation arena concerning sustainable city solutions. A case study was conducted of the Stockholm Royal Seaport project and a model for the management of an innovation arena was created. Three critical factors were discovered which were commitment, collective risk taking and trust and their connection to the overall common vision for an innovation arena. Conclusions after analyzing the critical factors was that clear contracts needs to be established and that third party involvement in the process of searching, qualifying and coaching of involved actors can be helpful in the process of developing an innovation arena.