CEO Characteristics and Firm Performance

CEOs of large companies have a lot of power in the company-wide hierarchy and their actions are followed closely by the news media, financial analysts and private investors, for instance. For this reason, they are interesting targets for further investigation in the academic world as well. Especially, the influence of various characteristics related to the CEOs are of special interest. Previous academic research shows that different characteristics connected to the CEO can influence a firm’s financial performance either in a positive or negative manner. This study examines the relationship between these CEO characteristics and firm financial performance through six individual measures: age, gender, experience, CEO/Chairman duality, salary and firm ownership. Firm financial performance is proxied through the profitability indicator ROA and the valuation measure Tobin’s q. It is expected that certain characteristics have significant influence on firm performance. The study examines a panel data of 291 individual S&P 500 companies and 482 CEOs of those companies through a period of seven years, 2010-2016. The individual variables are obtained from Execucomp and Datastream. Panel regressions with period-, cross-section- and industry-fixed effects are utilized in the study to form the results. The empirical findings of the study show that female CEOs tend to affect firm performance positively. CEO experience, measured as the time the individual has held the position in the company, and CEO/Chairman duality are also shown to have a positive relationship with the financial performance of the sample firms. The remaining characteristics yield inconclusive or insignificant results in regard to firm financial performance. Due to the issue of endogeneity affecting most corporate governance studies, the results of the study should be treated as rather tentative.fi=Opinnäytetyö kokotekstinä PDF-muodossa.|en=Thesis fulltext in PDF format.|sv=Lärdomsprov tillgängligt som fulltext i PDF-format

Metabolic alterations in immune cells associate with progression to type 1 diabetes

Aims/hypothesis Previous metabolomics studies suggest that type 1 diabetes is preceded by specific metabolic disturbances. The aim of this study was to investigate whether distinct metabolic patterns occur in peripheral blood mononuclear cells (PBMCs) of children who later develop pancreatic beta cell autoimmunity or overt type 1 diabetes. Methods In a longitudinal cohort setting, PBMC metabolomic analysis was applied in children who (1) progressed to type 1 diabetes (PT1D, n = 34), (2) seroconverted to >= 1 islet autoantibody without progressing to type 1 diabetes (P1Ab, n = 27) or (3) remained autoantibody negative during follow-up (CTRL, n = 10). Results During the first year of life, levels of most lipids and polar metabolites were lower in the PT1D and P1Ab groups compared with the CTRL group. Pathway over-representation analysis suggested alanine, aspartate, glutamate, glycerophospholipid and sphingolipid metabolism were over-represented in PT1D. Genome-scale metabolic models of PBMCs during type 1 diabetes progression were developed by using publicly available transcriptomics data and constrained with metabolomics data from our study. Metabolic modelling confirmed altered ceramide pathways, known to play an important role in immune regulation, as specifically associated with type 1 diabetes progression. Conclusions/interpretation Our data suggest that systemic dysregulation of lipid metabolism, as observed in plasma, may impact the metabolism and function of immune cells during progression to overt type 1 diabetes. Data availability The GEMs for PBMCs have been submitted to BioModels (), under accession number MODEL1905270001. The metabolomics datasets and the clinical metadata generated in this study were submitted to MetaboLights (), under accession number MTBLS1015.Peer reviewe

Simultaneous determination of perfluoroalkyl substances and bile acids in human serum using ultra-high-performance liquid chromatography-tandem mass spectrometry

There is evidence of a positive association between per- and polyfluoroalkyl substances (PFASs) and cholesterol levels in human plasma, which may be due to common reabsorption of PFASs and bile acids (BAs) in the gut. Here we report development and validation of a method that allows simultaneous, quantitative determination of PFASs and BAs in plasma, using 150 mu L or 20 mu L of sample. The method involves protein precipitation using 96-well plates. The instrumental analysis was performed with ultra-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS), using reverse-phase chromatography, with the ion source operated in negative electrospray mode. The mass spectrometry analysis was carried out using multiple reaction monitoring mode. The method proved to be sensitive, robust, and with sufficient linear range to allow reliable determination of both PFASs and BAs. The method detection limits were between 0.01 and 0.06 ng mL(-1) for PFASs and between 0.002 and 0.152 ng mL(-1) for BAs, with the exception of glycochenodeoxycholic acid (0.56 ng mL(-1)). The PFAS measured showed excellent agreement with certified plasma PFAS concentrations in NIST SRM 1957 reference serum. The method was tested on serum samples from 20 healthy individuals. In this proof-of-concept study, we identified significant associations between plasma PFAS and BA levels, which suggests that PFAS may alter the synthesis and/or uptake of BAs.Graphica

Metabolic alterations in immune cells associate with progression to type 1 diabetes

Aims/hypothesisPrevious metabolomics studies suggest that type 1 diabetes is preceded by specific metabolic disturbances. The aim of this study was to investigate whether distinct metabolic patterns occur in peripheral blood mononuclear cells (PBMCs) of children who later develop pancreatic beta cell autoimmunity or overt type 1 diabetes.MethodsIn a longitudinal cohort setting, PBMC metabolomic analysis was applied in children who (1) progressed to type 1 diabetes (PT1D, n = 34), (2) seroconverted to ≥1 islet autoantibody without progressing to type 1 diabetes (P1Ab, n = 27) or (3) remained autoantibody negative during follow-up (CTRL, n = 10).ResultsDuring the first year of life, levels of most lipids and polar metabolites were lower in the PT1D and P1Ab groups compared with the CTRL group. Pathway over-representation analysis suggested alanine, aspartate, glutamate, glycerophospholipid and sphingolipid metabolism were over-represented in PT1D. Genome-scale metabolic models of PBMCs during type 1 diabetes progression were developed by using publicly available transcriptomics data and constrained with metabolomics data from our study. Metabolic modelling confirmed altered ceramide pathways, known to play an important role in immune regulation, as specifically associated with type 1 diabetes progression.Conclusions/interpretationOur data suggest that systemic dysregulation of lipid metabolism, as observed in plasma, may impact the metabolism and function of immune cells during progression to overt type 1 diabetes.</p

Quantitative genome-scale metabolic modeling of human CD4+ T cell differentiation reveals subset-specific regulation of glycosphingolipid pathways

T cell activation, proliferation, and differentiation involve metabolic reprogramming resulting from the interplay of genes, proteins, and metabolites. Here, we aim to understand the metabolic pathways involved in the activation and functional differentiation of human CD4+ T cell subsets (T helper [Th]1, Th2, Th17, and induced regulatory T [iTreg] cells). Here, we combine genome-scale metabolic modeling, gene expression data, and targeted and non-targeted lipidomics experiments, together with in vitro gene knockdown experiments, and show that human CD4+ T cells undergo specific metabolic changes during activation and functional differentiation. In addition, we confirm the importance of ceramide and glycosphingolipid biosynthesis pathways in Th17 differentiation and effector functions. Through in vitro gene knockdown experiments, we substantiate the requirement of serine palmitoyltransferase (SPT), a de novo sphingolipid pathway in the expression of proinflammatory cytokines (interleukin [IL]-17A and IL17F) by Th17 cells. Our findings provide a comprehensive resource for selective manipulation of CD4+ T cells under disease conditions characterized by an imbalance of Th17/natural Treg (nTreg) cells.</p

Protein production and purification of type II transmembrane protease Tmprss2 in Pichia pastoris (Komagataella phaffii)

The purpose of this Bachelor’s thesis “Protein production and purification of type II transmembrane protease Tmprss2 in Pichia pastoris (Komagataella phaffii)” is to assess optimization possibilities for production and purification methods of mouse Tmprss2 in Pichia pastoris. The aim of the thesis was to develop upstreaming and downstreaming strategies capable of producing 2 mg amounts of properly folded and active Tmprss2 for crystallization experiments. Solving the crystal structure of Tmprss2 and the enzyme-substrate interaction surface in combination with Hemagglutinin 1 could lead to determining the process of proteolytic activation of Hemagglutinin 1 by Tmprss2.Therefore producing Tmprss2 for crystallization is an essential step for structure-based drug design for Hemagglutinin 1. This thesis is specifically concerned with the cultivation of recombinant Pichia pastoris cell lines in 2 L scale using a bioreactor to demonstrate the potential of iterative methanol induction cultivation mode for Tmprss2 production. The initial hypothesis was that the production of Tmprss2 could be increased with optimized cultivation methods and NiSepharose™ Excel resin material could be utilized in optimizing direct immobilized metal ion affinity chromatography(IMAC) of Tmprss2. It is important to note that for IMAC fusing Tmprss2 with a histidine-tag is required, consequently recombinant expression is necessary for preforming IMAC. The iterative methanol induction cultivation mode has been previously used in Tmprss2 production in flask scale successfully. Based on previous studies advanced strategies for upscaling the iterative methanol induction cultivation mode to reactor scale were developed and tested to meet production goals for crystallization. The scope of the experiments was limited to developing optimized cultivation strategies for previously developed recombinant Pichia pastoris cell lines and exploring the potential of NiSepharose™ Excel resin material in immobilized metal ion affinity chromatography of Tmprss2. The previously developed cell lines used in this thesis work were “Tmrss2-Mut” (P. pastoris KM71H/pPICZα-Tmprss2-D343Nopt clone o108 MutS) and “Tmprss2-WT” (P. pastoris Wild type jackpot clone KM71H-pPICZα-Tmprss2-WTopt o20). The research was carried out in five experimentation Cycles over the period of 11 weeks in “Recombinant Protein Expression"-research group in Helmholtz-Centre for Infection Research, Braunschweig, Germany. The outcome of this research into protein production and purification of type II transmembrane protease Tmprss2 in Pichia pastoris was a strategy for optimized cultivation of Pichia pastoris cell lines in 2 L scale using a bioreactor in iterative methanol induction cultivation mode. The initial hypothesis was also confirmed as NiSepharose™ Excel resin material could be utilized in direct immobilized metal ion affinity chromatography of Tmprss2 without issues with 4 column stripping common in similar IMAC materials designed for histidine tagged proteins. Tmprss2 was produced in the target amount for crystallization experiments in a single iteration using the Tmprss2-Mut cell line. However, the fast 48 h production Cycle in iterative methanol induction mode would allow pooling the produced Tmprss2 from several successive iterations to reach higher amounts. Pooling the products of several iterations would make reaching sufficient amounts for crystallization of the desired autocatalyzed form of Tmprss2 produced by the Tmprss2-WT possible. The issue with the lowered Hemagglutinin 1 cleaving activity of Tmprss2 D343N produced by the Tmprss2-Mut expression cassette could potentially be countered by coincubation with processed Tmprss2 produced with the WT-Tmprss2 expression cassette. Autocatalyzing the uncleaved Tmprss2 D343N to process it to the truncated form with higher activity would reduce the amount of iterations required to reach ample amounts of active Tmprss2 for crystallization. The limitations of the developed upstreaming and downstreaming strategies were also recognized. The main issues encountered were loss of Tmprss2 in concentration and through degradation over time. The purification using IMAC was prone to issues with precipitation of the culture supernatant interfering with the process. The iterative methanol induction cultivation mode requires removing the cell culture from the reactor in between iterations causing increased risk of contamination. Further development for countering these limitations were suggested in the form of modified techniques. Loss of protein during concentration might be avoided using a more sophisticated concentration technique i.e. repeated IMAC, diafiltration or TCA precipitation. The degradation of Tmprss2 could be limited by conducting IMAC in 4 °C instead of room temperature. The precipitation problems may be addressed by monitoring and adjusting the concentration of media components throughout the cultivation to prevent building up of materials in successive iterations. Risk of contamination and degradation of Tmprss2 during cultivation could be decreased by implementing continuous cultivation with perfusion membrane for harvesting. The cultivation strategy could also be shifted from aiming to shorten the glycerol growth phase to aiming to run the reactor in ultra-high cell density conditions. Running the reactor in the range of OD> 500; WCW >400 g/L would be a trade-off for increased Tmprss2 total yields at the cost of longer process time for a single batch of Tmprss2. The increased total yields could be reached by upscaling the reactor cultivation based on the methods developed for a 2 L scale bioreactor in iterative methanol induction cultivation mode

The correlation between dividend policy measures and share price volatility on OMX Helsinki

Dividend policy refers to the decision whether a firm decides to distribute some of its earnings as dividends to shareholders or not. Two significant variables are related to it: dividend yield and payout ratio. The former indicates how much a firm pays out in dividends each year relative to its share price, whereas the latter refers to the percentage of earnings paid to shareholders in dividends. Dividend policy is seen as one indicator of share price volatility, which measures the dispersion of returns and price changes for a certain security. The purpose of this study is to analyze these two dividend -related variables together with share price volatility and examine if there is any correlation between them. If a correlation is found, what kind of a correlation is it? The study only examines Finnish public companies listed on OMX Helsinki. The approach used is quantitative because of the numerical material gathered. The needed variables are gathered from different sources, mainly from Kauppalehti’s and Mornigstar’s website, but also official financial statements of the firms are used to retrieve information. The Pearson Correlation Coefficient is used in SPSS to measure and determine the correlation of the three variables. The results of the research clearly show that there is a negative correlation between dividend policy measures (yield & ratio) and share price volatility among the examined companies. The correlation of -0,508 between share price volatility and dividend yield, as well as the correlation of -0,185 among share price volatility and dividend payout ratio tell us that as one variable increases, the other tends to decrease, and vice versa. In addition to the negative correlation found, the author also found a positive correlation of 0,232 within the relationship between dividend yield and dividend payout ratio. All in all, the study aims to give its reader a comprehensive view about the effects of dividend policy on share price volatility in the Finnish markets by examining the relationship between the three formerly mentioned variables

Simultaneous Determination of Per- and Polyfluoroalkyl Substances and Bile Acids in Human Serum Using Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry

There is evidence of a positive association between per- and polyfluoroalkyl substances (PFAS) and cholesterol levels in human plasma, which may be due to common reabsorption of PFAS and bile acids (BAs) in the gut. Here we report development and validation of a method that allows simultaneous, quantitative determination of PFAS and BAs in plasma, using 150 uL or 20 uL of sample. The method involves protein precipitation using 96-well plates. The instrumental analysis was performed with ultra-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS), using reverse-phase chromatography, with the ion source operated in negative electrospray mode. The mass spectrometry analysis was carried out using multiple reaction monitoring mode. The method proved to be sensitive, robust and with sufficient linear range to allow reliable determination of both PFAS and BAs. The method detection limits were between 0.01 and 0.06 ng⋅mL-1 for PFAS and between 0.002 and 0.152 ng⋅mL-1 for BAs, with the exception of glycochenodeoxycholic acid (0.56 ng⋅mL-1). The PFAS measured showed excellent agreement with certified plasma PFAS concentrations in NIST SRM 1957 reference plasma. The method was tested on serum samples from 20 healthy individuals. In this proof-of-concept study, we identified significant associations between plasma PFAS and BA levels, which suggests that PFAS may alter the synthesis and/or uptake of BAs

Links between central CB1-receptor availability and peripheral endocannabinoids in patients with first episode psychosis

There is an established, link between psychosis and metabolic abnormalities, such as altered glucose metabolism and dyslipidemia, which often precede the initiation of antipsychotic treatment. It is known that obesity-associated metabolic disorders are promoted by activation of specific cannabinoid targets (endocannabinoid system (ECS)). Our recent data suggest that there is a change in the circulating lipidome at the onset of first episode psychosis (FEP). With the aim of characterizing the involvement of the central and peripheral ECSs, and their mutual associations; here, we performed a combined neuroimaging and metabolomic study in patients with FEP and healthy controls (HC). Regional brain cannabinoid receptor type 1 (CB1R) availability was quantified in two, independent samples of patients with FEP (n = 20 and n = 8) and HC (n = 20 and n = 10), by applying three-dimensional positron emission tomography, using two radiotracers, [11C]MePPEP and [18F]FMPEP-d2. Ten endogenous cannabinoids or related metabolites were quantified in serum, drawn from these individuals during the same imaging session. Circulating levels of arachidonic acid and oleoylethanolamide (OEA) were reduced in FEP individuals, but not in those who were predominantly medication free. In HC, there was an inverse association between levels of circulating arachidonoyl glycerol, anandamide, OEA, and palmitoyl ethanolamide, and CB1R availability in the posterior cingulate cortex. This phenomenon was, however, not observed in FEP patients. Our data thus provide evidence of cross talk, and dysregulation between peripheral endocannabinoids and central CB1R availability in FEP.</p