The increased interest in sustainability issues in recent years due to climate change has led to an increased interest among capital investors to invest more sustainably. In addition, there has been an increased interest among stakeholders, regulators and citizens to know more about the positive impact of sustainability reporting on business results. Sustainable investments are often followed by high costs, which makes it interesting from an investor perspective to investigate whether this investment can have a positive impact on a firm's financial result. Among the sectors that play a major role in sustainability investment is the real estate sector, as buildings currently account for 36 percent of CO2 emissions and 40 percent of energy consumption in the EU. Therefore, it is interesting to investigate how sustainability performance affects real estate firm performance. In this study, sustainability performance is measured using ESG scores while company performance is represented by ROA, ROE and Tobin's Q. Several regression analyses have been conducted using data from Eikon on real estate companies from 15 European countries. In addition to the overall ESG scores, the various ESG pillars were examined separately. The data analysis provides evidence of a positive significant impact of the overall ESG result on all three performance measures. Furthermore, we find that environmental disclosure has a positive impact on ROE and Tobin's Q, social disclosure has a positive effect on ROA and ROE and Governance disclosure has a positive effect on Tobin's Q. By applying these results to the shareholder- and the stakeholder theory, we can conclude that our study provides limited support for the stakeholder theory as most of our hypotheses are supported. This implies that the positive impact of sustainability investments on firm performance can lead to value creation for all stakeholders, not just the shareholders. / De senaste åren har vi sett ett ökat intresse för hållbarhetsfrågor vilket kan kopplas till klimatförändringarna. Detta har i sin tur drivit på intresset bland kapitalplacerare att investera mer hållbart. Parallellt med detta har intressenter, tillsynsmyndigheter och medborgare ökat sitt intresse för kopplingen mellan hållbarhet och finansiella resultat. Investeringar i hållbarhet medför ofta högre kostnader vilket gör det intressant ur ett investerarperspektiv att undersöka om det kan ha en positiv inverkan på ett det ekonomiska resultatet. Fastighetssektorn innehar en nyckelroll i omställningen till ett mer hållbart samhälle då byggnader ansvarar för 36 procent av CO2-utsläppen och 40 procent av energiförbrukningen inom EU. Givet denna nyckelroll och det kostsamma arbete som ligger framför fastighetssektorn är det således intressant att undersöka hur hållbarhetsarbete påverkar fastighetsbolagens finansiella resultat. I denna studie mäts fastighetsbolagens prestationer inom hållbarhet med hjälp av ESG-poängmedan det finansiella resultatet representeras av ROA, ROE och Tobins Q. Flertalet regressionsanalyser har utförts på data hämtad från databasen Eikon. Urvalet består av 111 fastighetsbolag från 15 olika länder inom Europa. Utöver den övergripande ESG-poängen undersöktes även de olika ESG-pelarna separat. Dataanalysen visar på en positiv signifikant inverkan av det övergripande ESG-resultatet på alla tre prestationsmätningar ROA, ROE och Tobin’s Q. Vidare finner vi att miljöpelaren (E) har en positiv inverkan på ROE och Tobins Q, den sociala pelaren (S) har en positiv effekt på ROA och ROE och ägarstyrning (G) har en positiv effekt på Tobins Q. Genom att analysera dessa resultat med hjälp av aktieägar- och intressentteorin kan vi dra slutsatsen att vår studie ger begränsat stöd för intressentteorin då en majoritet av våra hypoteser stöds. Detta betyder att investeringar i hållbarhet kan resultera i värdeskapande för fler intressenter än enbart aktieägarna.

<p>Uvod: Nespecifičnost kliničke slike sepse, velike individualne razlike u odgovoru organizma na infekciju kao i neophodnost adekvatne inicijalne procene težine kliničke slike, toka i ishoda bolesti, čine istraživanja biomarkera koji bi doprineli pravovremenom postavljanju dijagnoze i adekvatnoj prognozi bolesti izuzetno značajnim. Do sada je ispitivano preko 200 biomarkera od kojih ni jedan nije pokazao zadovoljavajuću senzitivnost i specifičnost. Uloga B limfocita u patogenezi sepse pri tome je nedovoljno istražena. Članovi superfamilije tumor-nekrozis faktora alfa: A proliferation inducing ligand (APRIL), Bcell activating factor (BAFF) i solubilni transmembrane activator and calcium modulator cyclophilin ligand interactor (sTACI) su citokini koji imaju ključnu ulogu u homeostazi B limfocita. Cilj istraživanja bio je da se ispita dijagnostički i prognostički značaj citokina članova superfamilije tumor nekrozis faktora alfa (APRIL, BAFF, sTACI) za procenu težine kliničke slike, razvoja multiorganske disfunkcije (MODS) u prvih 48h hospitalizacije i letalnog ishoda sepse. Ispitanici i metode: Istraživanjem je obuhvaćeno 150 obolelih od sepse lečenih na Klinici za infektivne bolesti i Odeljenju anestezije i reanimacije Kliničkog centra Vojvodine i 30 zdravih dobrovljnih davalaca krvi. Kod svih bolesnika evidentirani su demografski i ostali podaci iz istorije bolesti kao i laboratorijske analize u okviru rutinske dijagnostike sepse. Iz dodatnih 5ml venske krvi svim ispitanicima određene su koncentracije APRIL-a, BAFF-a, sTACI-ja ELISA metodom komercijalnim testovima proizvođača R&amp;D Systems. Rezultati pokazuju da su koncentracije sva tri citokina (APRIL, BAFF i sTACI) statistički značajno povi&scaron;ene kod obolelih od sepse u odnosu na zdravu populaciju (p&lt;0.001), pri čemu APRIL pokazuje najveću senzitinvost (99%) i specifičnost (97%). Najveći dijagnostički značaj BAFF-a ogleda se u sposobnosti distinkcije između sepsi uzrokovanih Gram pozitivnim i Gram negativnim bakterijama (p=0,03). U predikciji razvoja MODS-a i letalnog ishoda sepse multivarijantnom regresionom analizom kao nezavisni prediktori pokazali su se jedino antiinflamatorni biomarker sTACI receptor i klinička procena pacijenta iskazana kroz APACHE II i SOFA skor. Senzitivnost i specifilnost sTACI receptora u predikciji razvoja MODS-a i letalnog ishoda daleko nadma&scaron;uje do sada rutinski kori&scaron;ćen prokalcitonin. Zaključak: Dobijeni rezultati ukazuju na to da su citokini koji učestvuju u regulaciji funkcije B limfocita značajni dijagnostički i prognostički parametri u sepsi. Predominacija antiinflamatornog odgovora na koju ukazuju povi&scaron;ene koncentracije sTACI receptora pokazala se pored APACHE II i SOFA skora kao jedini nezavisni prediktor razvoja MODS-a i letalnog ishoda septičnih bolesnika. Neophodna su dalja istraživanja u pravcu određivanja momenta kada u imunskom odgovoru organizam prelazi iz stanja dominacije proniflamatornog u dominaciju antiinflamatornog odgovora radi pravovremenog reagovanja imunomodulatornom terapijom.</p> / <p>Introduction: The nonspecific clinical presentation of sepsis and great individual response variations, as well as huge significance of adequate early prognosis of its clinical course and outcome made sepsis biomarkers research extremely significant. The properties of more than 200 biomarkers have been evaluated for prognostic value, but none have adequate specificity and sensitivity. The role of the B cells in sepsis pathogenesis also remains unclear. Tumor necrosis factor alpha (TNF-&alpha;) superfamily members: A proliferation inducing ligand (APRIL), Bcell activating factor (BAFF) and soluble transmembrane activator and calcium modulator cyclophilin ligand interactor (sTACI) are key factors in B cell biology. The aim of the study was to evaluate the diagnostic and prognostic significance of determining the concentrations of tumor necrosis factor alpha superfamily members for the prediction of MODS development in the first 48h of hospitalization as well as outcome prediction.<br />Subjects and methods: The study included 150 patients suffering from sepsis treated at the Clinic for infectious diseases and Department for anesthesiology and reanimatology of the Clinical center of Vojvodina, and 30 healthy volunteer blood donors. The demographic and other data regarding routine blood analysis performed during sepsis treatment of the patients has been acquired from their hospitalization documentation. Additional 5 ml of venous blood was taken from the patients and the concentrations of APRIL, BAFF and sTACI have been determined using the ELISA method by using R&amp;D Systems commercial kit&rsquo;s. Results: There is a statistically significant difference in concentrations of APRIL, BAFF and sTACI between healthy blood donors and septic patients (p&lt;0.001). APRIL showed the highest sensitivity (99%) and specificity (97%) in distinguishing sepsis from healthy subjects. BAFF showed statistically significant higher concentrations in Gram positive than in Gram negative sepsis (p=0,03). In the multivariate logistic regression analysis, only anti-inflammatory cytokine sTACI and APACHE II or SOFA score remained significant predictors of MODS and lethal outcome. sTACI showed greater sensitivity and specificity for MODS and outcome prediction then the widely used procalcitonin.&nbsp; Conclusions: The concentrations of TNF superfamily members, the main regulators of B cell function, have a significant diagnostic and prognostic value in predicting sepsis course and outcome. The predomination of the anti-inflammatory response, as being pointed out by elevated concentrations of sTACI receptors, has proved to be the only independent predictor, besides APACHE II and SOFA score, in MODS and lethal outcome development in sepsis. Further research is needed in order to accurately determine the exact moment when the immunological response shifts from the predominance of the pro-inflammatory response to the predominance of the anti-inflammatory response, so as to ensure the timely application of therapy that modulates the immunological response.</p>

Charles University in Prague Faculty of Natural Sciences Summary of Ph.D. thesis The role of LIF gene mutations and the relative distribution of NK cells, NKT and T lymphocytes in follicular fluid and blood of women with different history of infertility Jiří Křížan Prague 2010 1 | P a g e Doctoral degree programs in biomedicine Charles University in Prague and the Academy of Sciences of the Czech Republic Programme: Biomedicine Chairman of the Subject Board: Doc. RNDr. Vladimír Holáň, Dr.Sc. Place of study: Institute of Microbiology, v.v.i., Academy of the Czech Sciences Vídeňská 1083, 142 20 Prague 4 phone: +420 296 442 318 Autor: Mgr. Jiří Křížan Supervisor: RNDr. Petr Šíma, CSc. The dissertation can be found at Dean's Office Faculty of Charles University in Prague 2 | P a g e CONTENTS Contents 2 Summary 3 1. Introduction 5 2. Hypotheses and aims 6 3. Material and methods 7 Material: 7 Methods: 8 4. Results 10 5. Discussion 12 6. Conclusion 15 7. References 16 Bibliography of Autor: 18 1. papers in extenso (thesis background) 18 2. papers in extenso (without regard to thesis) 19 3 | P a g e SUMMARY The aim of the dissertation thesis "The role of LIF gene mutations and the relative distribution of NK cells, NKT, and T lymphocytes in follicular fluid and blood of women with different history of infertility"...

Die Phospholipid-Hydroperoxid Glutathion-Peroxidase (phGPx) ist ein monomeres Selenoprotein, welches innerhalb der Familie der Glutathion-Peroxidasen aufgrund seiner breiten Substratspezifität und der Fähigkeit Proteinthiole zu modifizieren eine Sonderstellung einnimmt. Vom Gen der phGPx werden nach heutigem Kenntnisstand drei verschiedene Protein-Isoformen gebildet. Die mitochondriale Isoform enthält am N-Terminus ein mitochondriales Insertionssignal und wird bevorzugt im Testis exprimiert. Von einem im Leserahmen stromabwärts liegenden Startkodon wird die kürzere, ubiquitär exprimierte zytosolische Isoform synthetisiert. Eine dritte phGPx-Isoform besitzt eine N-terminale nukleäre Lokalisationssequenz (kodiert von einem alternativen Exon 1) und wird vornehmlich in den Kernen post-meiotischer Zellen der Spermatogenese gefunden. Aufgabe dieser Arbeit war es, die molekularen Mechanismen zu untersuchen, die am Zustandekommen des vielfältigen Expressionsmusters der phGPx-Isoformen beteiligt sind. Im ersten Teil der Arbeit wurden transkriptionelle Regulationsmechanismen der phGPx-Expression untersucht. Im proximalen Promotorbereich (-100 bp – +228 bp) des phGPx-Gens wurden unter in vitro (Supershift-Assay) und in vivo (Chromatin-Immunopräzipitation) Bedingungen die Transkriptionsfaktoren Sp1 und NF-Y identifiziert, die an drei GC-reiche Motive beziehungsweise zwei inverse CCAAT-Boxen binden. Darüber hinaus konnten in kompetetiven Gelshift-Assays im proximalen Promotorbereich zwei Bindungssequenzen identifiziert werden, die von Faktoren der Smad-Familie gebunden werden. Funktionelle in vitro Promotorstudien mit mutierten Promotorkonstrukten zeigten, dass die Mutagenesen der Sp1- und NF-Y Bindestellen einen starken Einfluss auf die Reportergenaktivität hatten. Im zweiten Teil der Arbeit wurden durch Untersuchungen von Protein-RNA-Interaktionen post-transkriptionelle Mechanismen der Expressionsregulation studiert. Mit Hilfe des in vivo Ansatzes des Hefe Drei-Hybrid Systems wurde der Guanin-reiche Sequenz bindende Faktor 1 (GRSF1) identifiziert, der in der 5’-untranslatierte Region der mitochondrialen phGPx-mRNA bindet. In RNA Gelshift-Assays wurde die Spezifität dieser Interaktion bestätigt und näher charakterisiert. Schließlich wurden für GRSF1 und die phGPx Expressionsprofile in murinen Gewebe erstellt sowie die zeitabhängige Expression beider Proteine während der Embryogenese verfolgt. Die auffällig ähnlichen Expressionsmuster lassen ähnliche Regulationsmechanismen vermuten. Die in dieser Arbeit identifizierten trans-regulatorischen Proteine Sp1, NF-Y, Smad und GRSF1 sollten an der differentiellen Expression der phGPx-Isoformen beteiligt sein. / The Phospholipid Hydroperoxide Glutathione Peroxidase (phGPx) is a monomeric selenoprotein that is unique in the family of Glutathione Peroxidases due to its low substrate specificity and its ability to oxidise protein thiols. Three different isoforms are known to derive from one common gene. The mitochondrial Isoform contains an N-terminal mitochondrial insertion sequence and is preferentially expressed in postpubertal testis. The shorter, ubiquitously expressed, cytosolic isoform is expressed from an in-frame start codon. A third isoform contains an N-terminal nuclear localization signal coded for by an alternative exon 1 and is preferentially expressed in the nuclei of post-meiotic spermatides. The aim of the present study is to investigate the molecular mechanisms leading to the different isoforms and causing their tissue specific expression pattern. In the first part of this work transcriptional regulatory mechanisms will be analysed. Within the proximal promoter region (-100 to +228 bp) of the phGPx gene the transcription factors SP1 and NF-Y were identified to bind to three GC-boxes and two CCAAT-boxes respectively using in vitro methods (Supershift Assays) and in vivo methods (Chromatine immunoprecipitation). Moreover, performing competitive gel shift assays two binding elements for the smad family of transcription factors could be identified. Functional in vitro reporter gene assays provided evidence that the mutagenesis of the binding sequences for NF-Y and Sp1 has a strong impact on promoter activity. In the second part of this work post-transcriptional events in the expression regulation of the phGPx were analysed on the basis of protein/RNA interactions. Applying the in vivo approach of the yeast three hybrid system the Guanin-riche sequence binding factor 1 (GRSF1) could be identified binding to the 5’-untranslated region of the mitochondrial phGPx messenger. RNA mobility shift assays were performed to further characterize the specificity of this protein/RNA interaction. Eventually, the tissue distribution of GRSF1 and phGPx was studied in murine tissues and their expression kinetics were followed during murine embryogenesis. The obvious parallel expression kinetics for mitochondrial phGPx and GRSF1 suggest common regulatory mechanisms for these two genes. All the identified trans-regulatory elements are very likely to be involved in the differential expression regulation of the phGPx isoforms.

The purpose of this thesis is to develop a model that will guide a company towards a decision of whether to change the current due date of work orders or not. The model will help the company to reveal the technical and financial factors that will be affected and how these factors can be assessed. After accomplishing a thorough literature review, we found no existing practical models in this specific area. We developed a model to cover this gap in the existing theories. A case study approach was used to test the developed model on our case company Elitfönster in Lenhovda who manufactures windows. We applied our model at the processing department and the change concerned going from a weekly to a daily due date of work orders. The technical factors that would be affected by the change of the due date are; setup times, lead time and output of components. The financial factors that will be affected are the tied-up capital and the manning. We found that a change could not be carried through without a purchase of an extra plane. The model also showed that the financial benefits that the change generated could not surpass the costs that an extra plane would cause. Thereby, our recommendations to the case company are to keep the current due date of work orders until the rest of the company can handle the extra components that can be produced after the change. / Syftet med denna uppsats är att utveckla en modell som ska vägleda ett företag mot ett beslut om man ska ändra den nuvarande tidpunkt när en arbetsorder ska vara färdigställd, eller inte. Modellen kommer att hjälpa företaget att påvisa de tekniska och finansiella faktorer som kommer att påverkas och hur dessa kan bedömas. Efter att ha gjort en grundlig litteraturstudie kunde vi inte hitta några existerande modeller inom detta specifika område. Vi utvecklade en modell för att täcka denna brist i den existerande teorin. Vi använde oss av en fallstudie för att testa vår utvecklade modell på Elitfönster i Lenhovda som tillverkar fönster. Vi applicerade vår modell på maskinverkstaden och förändringen handlade om att gå från att färdigställa arbetsorder på en vecka till att färdigställa dem på en dag. De tekniska faktorer som skulle påverkas av en förändring är; ställtiderna, ledtiden och mängden producerade komponenter. De finansiella faktorerna som kommer att påverkas är mängden bundet kapital samt bemanningen. Vi kom fram till att en förändring inte kunde genomföras utan att köpa in en extra hyvel. Modellen visade också att de finansiella fördelarna som en förändring skulle generera inte skulle motsvara de kostnader som den extra hyveln skulle orsaka. Våra rekommendationer till företaget är således att fortsätta med den nuvarande tidpunkt när en arbetsorder ska vara färdigställd tills resten av företaget kan hantera de extra komponenter som skulle kunna bli producerade efter förändringen.

<p>The purpose of this thesis is to develop a model that will guide a company towards a decision of whether to</p><p>change the current due date of work orders or not. The model will help the company to reveal the technical and</p><p>financial factors that will be affected and how these factors can be assessed. After accomplishing a thorough</p><p>literature review, we found no existing practical models in this specific area. We developed a model to cover this</p><p>gap in the existing theories. A case study approach was used to test the developed model on our case company</p><p>Elitfönster in Lenhovda who manufactures windows. We applied our model at the processing department and the</p><p>change concerned going from a weekly to a daily due date of work orders. The technical factors that would be</p><p>affected by the change of the due date are; setup times, lead time and output of components. The financial</p><p>factors that will be affected are the tied-up capital and the manning. We found that a change could not be carried</p><p>through without a purchase of an extra plane. The model also showed that the financial benefits that the change</p><p>generated could not surpass the costs that an extra plane would cause. Thereby, our recommendations to the</p><p>case company are to keep the current due date of work orders until the rest of the company can handle the extra</p><p>components that can be produced after the change.</p> / <p>Syftet med denna uppsats är att utveckla en modell som ska vägleda ett företag mot ett beslut om man ska</p><p>ändra den nuvarande tidpunkt när en arbetsorder ska vara färdigställd, eller inte. Modellen kommer att hjälpa</p><p>företaget att påvisa de tekniska och finansiella faktorer som kommer att påverkas och hur dessa kan bedömas.</p><p>Efter att ha gjort en grundlig litteraturstudie kunde vi inte hitta några existerande modeller inom detta specifika</p><p>område. Vi utvecklade en modell för att täcka denna brist i den existerande teorin. Vi använde oss av en</p><p>fallstudie för att testa vår utvecklade modell på Elitfönster i Lenhovda som tillverkar fönster. Vi applicerade vår</p><p>modell på maskinverkstaden och förändringen handlade om att gå från att färdigställa arbetsorder på en vecka</p><p>till att färdigställa dem på en dag. De tekniska faktorer som skulle påverkas av en förändring är; ställtiderna,</p><p>ledtiden och mängden producerade komponenter. De finansiella faktorerna som kommer att påverkas är</p><p>mängden bundet kapital samt bemanningen. Vi kom fram till att en förändring inte kunde genomföras utan att</p><p>köpa in en extra hyvel. Modellen visade också att de finansiella fördelarna som en förändring skulle generera</p><p>inte skulle motsvara de kostnader som den extra hyveln skulle orsaka. Våra rekommendationer till företaget är</p><p>således att fortsätta med den nuvarande tidpunkt när en arbetsorder ska vara färdigställd tills resten av företaget</p><p>kan hantera de extra komponenter som skulle kunna bli producerade efter förändringen.</p>

NOVEL METABOLIC REGULATORS AND PROINFLAMMATORY FACTORS IN THE ETIOPATHOGENESIS OF TYPE 2 DIABETES MELLITUS AND OBESITY: THE INFLUENCE OF PHARMACOLOGICAL AND DIETARY INTERVENTIONS MUDr. Miloš Mráz Doctoral Thesis ABSTRACT (EN) Identifying novel factors involved in the etiopathogenesis of obesity, diabetes mellitus and their complications has become one of the primary scopes of metabolic research in the last years. The aim of the present study was to evaluate the role of recently discovered metabolic and inflammatory regulators including fibroblast growth factors 19 and 21 and chemotactic cytokines in the development of obesity and type 2 diabetes mellitus (DM2). A total number of 182 patients were included into the study. They were divided into 3 groups - patients with obesity but without type 2 diabetes mellitus, individuals with obesity and type 2 diabetes mellitus and healthy control normal-weight subjects. Selected interventions included 2 to 3 weeks of very-low-calorie diet (VLCD - energy content 2500 kJ/day), 3 months of administration of PPARα receptor agonist fenofibrate and acute hyperinsulinemia during hyperinsulinemic isoglycemic clamp. Our results indicate that the increase of circulating FGF-21 levels after VLCD and fenofibrate treatment could contribute to positive metabolic effects of these...

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The thesis consists of three parts. The first part is a Russian translation of selected excerpts from Jan Zábrana's diaries Celý život. The second part is a commentary on the translation, which includes three chapters: translation analysis of the source text, description of the overall approach to the translation and the translation strategy, a typology of the particular translation problems and ways of solving them.

This thesis describes methods of high frequency noise and vibrations computation of cabin part of EV–55M (aircraft developed by Evektor Kunovice). There is a brief summary of methods used for determining high frequency noise and vibrations in the first part of the thesis. Detailed explanation is given for Statistical Energy Analysis (SEA) which is nowadays the most dominant method in this area. The energy balance equation is derived in this chapter and SEA parameters such as modal density, damping loss factor, coupling loss factor and power input are introduced here. Next part deals with main noise sources of propeller driven and jet aircraft and passive and active noise controls are discussed. Practical part of this thesis deals with modeling aircraft EV–55M fuselage using VA One SEA module. Two models were created. First of them is only an outside fuselage with aircraft flooring and the second one is extended by interior trim panels and is applicable for simulation of noise control treatments. Computational modeling is accompanied by experimental measurement of passive noise control material characteristics. Postprocessing of information obtained from impedance tube measurement was performed in FOAM – X. Determined characteristics of porous material were used as inputs to VA One and reduction of sound pressure level in fuselage cavities by using noise control treatment was found. In conclusion there is a summary of noise transmission paths from sources to interior cavity and some treatments of them are simulated