Quantitative Magnetic Resonance Imaging of the Liver and Heart In Iron Overload

Systemic iron overload (IO) is considered a principal determinant in the clinical outcome of different forms of IO and in allogeneic hematopoietic stem cell transplantation (alloSCT). However, indirect markers for iron do not provide exact quantification of iron burden, and the evidence of iron-induced adverse effects in hematological diseases has not been established. Hepatic iron concentration (HIC) has been found to represent systemic IO, which can be quantified safely with magnetic resonance imaging (MRI), based on enhanced transverse relaxation. The iron measurement methods by MRI are evolving. The aims of this study were to implement and optimise the methodology of non-invasive iron measurement with MRI to assess the degree and the role of IO in the patients. An MRI-based HIC method (M-HIC) and a transverse relaxation rate (R2*) from M-HIC images were validated. Thereafter, a transverse relaxation rate (R2) from spin-echo imaging was calibrated for IO assessment. Two analysis methods, visual grading and rSI, for a rapid IO grading from in-phase and out-of-phase images were introduced. Additionally, clinical iron indicators were evaluated. The degree of hepatic and cardiac iron in our study patients and IO as a prognostic factor in patients undergoing alloSCT were explored. In vivo and in vitro validations indicated that M-HIC and R2* are both accurate in the quantification of liver iron. R2 was a reliable method for HIC quantification and covered a wider HIC range than M-HIC and R2*. The grading of IO was able to be performed rapidly with the visual grading and rSI methods. Transfusion load was more accurate than plasma ferritin in predicting transfusional IO. In patients with hematological disorders, the prevalence of hepatic IO was frequent, opposite to cardiac IO. Patients with myelodysplastic syndrome were found to be the most susceptible to IO. Pre-transplant IO predicted severe infections during the early post-transplant period, in contrast to the reduced risk of graft-versus-host disease. Iron-induced, poor transplantation results are most likely to be mediated by severe infections.

Emerging market patterns in recycled paper trade

The international recovered paper trade serves two important functions: increasing raw material availability in the paper and board industry and providing economic incentives to recycle. The purpose of this paper is to shed further light on emerging patterns in this trade by empirically analysing the changes in the bilateral trade flows of recycled paper between 1992 and 2008. According to our estimations, two important changes have taken place in the 1990s and 2000s. First, the growing importance of developing economies in global recycled paper trade plays a significant role in import demand as a determinant of trade flows. Second, the changes in global trade patterns necessitate investigating the transportation cost measures used in applied research.

To divide or differentiate? : nestin-mediated regulation of Cdk5 in cell fate decisions

The molecular functions of the non-cell cycle-related Cyclin-dependent kinase 5 (Cdk5) have been of primary interest within the neuroscience field, but novel undertakings are constantly emerging for the kinase in tissue homeostasis, as well as in diseases such as diabetes and cancer. Although Cdk5 activation is predominantly regulated by specific non-cyclin activator protein binding, additional mechanisms have proved to orchestrate Cdk5 signaling in cells. For example, the interaction between the intermediate filament protein nestin and Cdk5 has been proposed to determine cellular fate during neuronal apoptosis through nestin-dependent adjustment of the sensitive balance and turnover of Cdk5 activators. While nestin constitutes a crucial regulatory scaffold for appropriate Cdk5 activation in apoptosis, Cdk5 itself phosphorylates nestin with the consequence of filament reorganization in both neuronal progenitors and differentiating muscle cells. Interestingly, the two proteins are often found coexpressed in various tissues and cell types, proposing that nestin-mediated scaffolding of Cdk5 and its activators may be applicable to other tissue systems as well. In the literature, the molecular functions of nestin have remained in the shade, as it is mostly exploited as a marker protein for progenitor cells. In light of these studies, the aim of this thesis was to assess the importance of the nestin scaffold in regulation of Cdk5 actions in cell fate decisions. This thesis can be subdivided into two major projects: one that studied the nature of the Cdk5-nestin interplay in muscle, and one that assessed their role in prostate cancer. During differentiation of a myoblast cell line, the filament formation properties of nestin was found to be crucial in directing Cdk5 activity, with direct consequences on the process of differentiation. Also the genetic knockout of nestin was found to influence Cdk5 activity, although differentiation per se was not affected. Instead, the genetic ablation of nestin had broad consequences on muscle homeostasis and regeneration. While the nestin-mediated regulation of Cdk5 in muscle was found to act in multiple ways, the connection remained more elusive in cancer models. Cdk5 was, however, established as a significant determinant of prostate cancer proliferation; a behavior uncharacteristic for this differentiation-associated kinase. Through complex and simultaneous regulation of two major prostate cancer pathways, Cdk5 was placed upstream of both Akt kinase and the androgen receptor. Its action on proliferation was nonetheless mainly exerted through the Akt signaling pathway in various cancer models. In summary, this thesis contributed to the knowledge of Cdk5 regulation and functions in two atypical settings; proliferation (in a cancer framework) and muscle differentiation, which is a poorly understood model system in the Cdk5 field. This balance between proliferation and differentiation implemented by Cdk5 is ultimately regulated (where present) by the dynamics of the cytoskeletal nestin scaffold.

Determinants of capital expenditures: Evidence from oil and mining sectors in Russia

This master’s thesis investigates the significant macroeconomic and firm level determinants of CAPEX in Russian oil and mining sectors. It also studies the Russian oil and mining sectors, its development, characteristics and current situation. The panel data methodology was implemented to identify the determinants of CAPEX in Russian oil and mining sectors and to test derived hypotheses. The core sample consists of annual financial data of 45 publicly listed Russian oil and mining sector companies. The timeframe of the thesis research is a six year period from 2007 to 2013. The findings of the master’s thesis have shown that Gross Sales, Return On Assets, Free Cash Flow and Long Term Debt are firm level performance variables along with Russian GDP, Export, Urals and the Reserve Fund are macroeconomic variables that determine the magnitude of new capital expenditures reported by publicly listed Russian oil and mining sector companies. These results are not controversial to the previous research paper, indeed they confirm them. Furthermore, the findings from the emerging countries, such as Malaysia, India and Portugal, are analogous to Russia. The empirical research is edifying and novel. Findings from this master’s thesis are highly valuable for the scientific community, especially, for researchers who investigate the determinant of CAPEX in developing countries. Moreover, the results can be utilized as a cogent argument, when companies and investors are doing strategic decisions, considering the Russian oil and mining sectors.

Making home rules for mother tongues : the legal implications of linguistic diversity in the design of autonomy regimes

Principen om nationalismen där det politiska och det nationella är samspelt kan vara av markant betydelse för uppbyggande av autonomiska regimer. Likaså tillåter decentralicering och delegering av befogenheter för språk och utbildning (officiellt erkännande av språk, standardisering av språk, undervisningsspråk och relaterade läroplaner) formning av identiteter inom dessa autonomiska regimer. Resultatet är en ofullkomlig cirkulär relation där språk, samfund och politiska institutioner ömsesidigt och kontinuerligt formar varandra: lingvistiskt mångfald prägar och formger autonomiska ordningar och vice-versa. De juridiska implikationerna av territoriella och icke-territoriella former av autonomi är dock av en annan art. Emedan territoriell autonomi bygger på idéen om ett eventuellt inkluderande hemland för lingvistiska grupper, vars vistelseort är avgörande, förstärker den icke-territoriella autonomin idéen om ett exclusivt samfund bestående av själv-identifierade medlemmar som är kapabla till självstyre oavsett territoriella gränser. Denna avhandling utgör an analys av sådana juridiska implikationer genom komparativa och institutionella analyser. Avhandlingen föreslår som resultat en serie av normativa och pragmatiska rekommendationer inriktade på att främja demokratiseringsprocesser i linje med principer om multikulturalism.