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Coming dissertations at Uppsala university

  • Magma generation and formation of continental crust in the Izu arc Author: Haochen Duan Link: Publication date: 2022-01-18 13:09

    The Izu oceanic arc is produced by the subduction of the Pacific Sea Plate beneath the Philippine Sea Plate. The proto-Izu oceanic arc was initially formed at ca. 50 Ma, then it was separated into the Kyushu-Palau and Izu arc by the extension of the Shikoku basin from ca. 25 Ma. After the formation of the Shikoku basin, volcanism initiated in the Izu rear-arc at ca. 17 Ma. Nowadays, arc volcanism has built up a thick crust observed by seismic velocities that extends from the Izu fore-arc to rear-arc and the upper crust has felsic compositions. The bimodal mafic-felsic volcanism in the Izu arc-front displays depleted light rare earth elements whereas in the Izu rear-arc the volcanic rocks display enriched light rare earth elements. International Ocean Discovery Program (IODP) Site U1437 is the first scientific drill site in the Izu rear-arc, which drilled 1.8 km into the volcaniclastic successions between the Manzi and Enpo seamount chains. Site U1437 is divided into seven stratigraphic units that range in age from 0 to ca. 16 Ma. This thesis aims to investigate the magma generation and the formation of continental crust in the Izu rear-arc using boron (δ11B) and oxygen (δ18O) isotopes. 

    The felsic melt inclusions from Unit II and Unit IV show that felsic volcanic rocks are formed by partial melting of the pre-existing altered and fresh oceanic crust. Meanwhile, fractional crystallization of mafic magmas affects the diverse compositions of the oceanic crust protolith. Therefore, partial melting of oceanic crust and fractional crystallization of mantle-derived mafic magmas both influence the formation of felsic continental crust in the Izu rear-arc. These findings indicate that extensional settings, like the Izu rear-arc, should be considered as potential locations for the formation of continental crust in the Phanerozoic, Archean and even in the Hadean.

    The basaltic melt inclusions in Unit VII show that the mafic volcanic rocks in the Izu rear-arc are not derived from the mantle wedge that is metasomatized by slab-derived fluids. Instead, primary magmas in the Izu rear-arc are formed by mélange diapirs ascending into the mantle wedge. This could explain the across arc mantle heterogeneity observed in the Izu arc, with the arc front volcanic rocks are associated with slab-derived fluids and the Izu rear-arc compositions are influenced by mélange. Mélange compositions generated in the rear-arc may be recycled into the upper mantle forming the upper mantle heterogeneity observed in MORB globally.

  • A pharmacokinetic approach to intra-brain distribution with a focus on cyclic peptides Author: Erik Melander Link: Publication date: 2022-01-18 09:18

    When designing treatments for disorders of the central nervous system (CNS) reaching the site of action is a major hurdle in the development process. Regardless if the target is extra- or intracellular, precise measurements to understand the distribution within the CNS are required. There is however a lack of understanding of differences in blood-brain barrier transport and intra-brain distribution of both small and large molecules. In this thesis the regional Blood-Brain Barrier transport of antipsychotic agents, along with their brain tissue binding and regional cellular accumulation was quantified. Furthermore, a novel LC-MS/MS method was developed for the quantitative analysis of the cyclic peptide kalata B1 was developed for analysis of brain tissue and plasma samples. The Blood-Brain Barrier transport, permeability, intra-brain distribution and cellular accumulation were assessed for two cyclic peptides, SFTI-1 and kalata B1. 

    The antipsychotics exhibited clear differences in their regional BBB transport as well as their brain tissue binding, with the most dramatic spatial differences in BBB transport being observed for the p-glycoprotein substrates risperidone and paliperidone. The highest level of transporter mediated protection was observed in the cerebellum, with pronounced efflux for several of the antipsychotics. The development of a quantitative method for the cyclic peptide kalata B1 was successfully validated and applied to measure low concentration of the peptide in biological matrices. The BBB transport of SFTI-1 was markedly higher than that of kalata B1 whereas both peptides exhibited similar permeability across an in vitro BBB model. It was also shown that SFTI-1 resides mainly within the interstitial fluid within the brain, but that kalata B1 readily enters the cells of the brain parenchyma. The cellular accumulation of kalata B1 was abolished under cold conditions, and was not observable in lung tissue, suggesting an active process that is tissue specific. It was also shown that both peptides are taken up into cell cultures of neurons and astrocytes.

    In conclusion this thesis and the studies herein contribute to a better understanding of distribution patterns of both antipsychotics and cyclic peptides and provides valuable lessons in terms of what types of studies should be prioritized for the development of such molecules into therapeutic agents.

  • Rättslig operationalisering av företags samhällsansvar : Om avtalsrättsligt, köprättsligt, marknadsföringsrättsligt och aktiebolagsrättsligt genomdrivande av företags samhällsansvar Author: Lovisa Halje Link: Publication date: 2022-01-18 08:43

    The main objective of this thesis is to explore and describe the possibilities for legal operationalization of CSR in contract law, sales law and consumer sales law, marketing law and company law. A supplementary aim is to identify regulation on and illustrate the regulatory context of CSR. The illustration provides a background and a framework for the main objective of the study, as well as confirms the legal relevance of CSR.

    Legal operationalization of CSR requires that CSR is anchored in law and that there are mechanisms for enforcement available. In contract law, CSR is legally anchored when a CSR condition follows from a contract. In a Swedish sales law context, legal anchoring takes place when a buyer’s expectation regarding CSR is not met and this is considered a defect, fel. From a marketing law point of view, the possibilities to consider a CSR statement an unfair commercial practice are relevant. In a company law context, CSR is legally anchored when included in the articles of association, in an instruction from the general meeting or the board, in the board’s internal guidelines or in the remuneration guidelines of the company. In all, contract parties, shareholders and the board are “strong” legal subjects, in that they are able to proactively formulate and anchor CSR norms in law. In company law, the understanding of the company’s interest and purpose, as well as the business case for CSR and the understanding of profit create borders within which the company law operationalization of CSR functions. Sales law and marketing law offer retroactive tools to market actors. The possibilities to anchor CSR in marketing law are vast, whereas the applicability of the sales law rules to a large extent is dependent on the connection between the (failed) CSR expectation and the sold goods. The remedies in the explored areas of law typically do not protect the CSR interest in question directly.