A doença arterial coronária é importante e prevalente manifestação da aterosclerose. A avaliação da função diastólica pelos parâmetros mitrais obtidos com Doppler ecocardiográfico possui limitações nos coronariopatas com fração de ejeção do ventrículo esquerdo (FEVE) preservada. Nestes, a disfunção diastólica, independentemente da FEVE, associa-se a maior incidência de desfechos desfavoráveis. A elevação da pressão diastólica final (PD2) do ventrículo esquerdo (VE) é a principal consequência fisiológica da disfunção diastólica. A pesquisa por melhores formas de determinação da PD2 do VE estendeu-se às modernas técnicas ecocardiográficas de quantificação da mecânica cardíaca. O objetivo deste estudo é correlacionar as medidas de deformação miocárdica, obtidas pelo speckle-tracking ecocardiográfico bidimensional, com a medida invasiva da PD2 do VE em pacientes com insuficiência coronariana e FEVE preservada. Métodos: foram avaliados 81 coronariopatas (idade: 61 ±8 anos) com FEVE >50%, encaminhados para cineangiocoronariografia eletiva, 40 destes com PD2 elevada (>16 mm Hg). Todos os indivíduos foram submetidos à avaliação ecocardiográfica convencional imediatamente antes do cateterismo e subsequente avaliação offline, com ecocardiografia speckle tracking (EST) para obtenção de medidas sistólicas e diastólicas de strain e strain rate circunferenciais e longitudinais, e estudo rotacional do VE. Foram analisadas as variáveis diastólicas da EST, tanto de forma isolada, quanto combinada com a velocidade da onda E ao Doppler. Resultados: Comparativamente, os pacientes do grupo com PD2 do VE elevada (n=40) mostraram aumento do volume indexado do átrio esquerdo (22 ±6 mL vs 26 ±8,26 mL p=0,04), velocidade da onda E (65 ±15 cm/s vs 78 ±20 cm/s p=0,02), relação E/e\' médio (8,14 ±2,0 vs 11,54 ±2,7 p=0,03) e relação E/strain rate global circunferencial (SRGC) pico E (39 cm vs 46 cm p <0,01). Nos 81 pacientes a correlação de Spearman com a medida invasiva da PD2 do VE foi de 0,56 para a relação E/e\' (p=0,03) e de 0,43 para a relação E/ESRGC pico E (p<0,01). A área sob a curva ROC foi significativa em ambas, sendo 0,83 e 0,73 respectivamente (p<0,05). Conclusão: A relação E/SRGC pico E é capaz de identificar elevação da PD2 do VE em coronariopatas com FEVE preservada, com menor desempenho que a relação E/e\'. / Introduction: Coronary artery disease (CAD) is important and prevalent manifestation of atherosclerosis. The assessment of diastolic function by mitral Doppler echocardiographic parameters has limitations in patients with CAD and preserved left ventricular ejection fraction (LVEF). Diastolic dysfunction is associated with higher incidence of unfavorable outcomes in these patients, regardless of LVEF. The increase in left ventricle end-diastolic pressure (LVEDP) is the main physiological consequence of diastolic dysfunction. The search for better ways of determining the LVEDP extended to the quantitative evaluation of cardiac mechanics with the modern echocardiographic techniques. The aim of this study is to correlate the invasive mesures of LVEDP and myocardial deformation measurements obtained by the two-dimensional speckle-tracking echocardiography in patients with coronary artery disease and preserved LVEF. Methods: 81 CAD patients (age: 61 ± 8 years) with LVEF >50%, scheduled for elective coronary angiography were evaluated, 40 of these with high LVEDP (>16 mm Hg). All subjects underwent conventional echocardiography immediately before catheterization and subsequent offline assessment with speckletracking echocardiography (STE) to obtain systolic and diastolic values of circumferential and longitudinal strain and strain rate, and rotational LV study. Diastolic variables of EST were analyzed both isolated and combined with the speed of the transmitral Doppler E wave. Results: Patients in the group with the high LVEDP (n =40) showed increased left atrial volume index (22 ± 6 mL vs 26 ± 8.26 mL p =0.04), E wave velocity (65 ± 15 cm/s vs 78 ±20 cm/s p = 0.02), E/e\' (average) ratio ( 8.14 ± 2.0 vs 11.54 ± 2.7 p = 0.03) and E/global circumferential strain rate (GCSR) peak E (39 cm vs 46 cm p <0.01). In 81 patients, Spearman\'s correlation with the invasive measurement of LVEDP was 0,56 (p =0.03) for the E/e\' ratio and 0.43 for the E/GCSR peak E (p <0.01). The area under the ROC curve was significant for both (p < 0.05): 0.83 and 0.73 respectively. Conclusion: The E/GCSR peak E ratio is able to identify elevated LVEDP in CAD patients with preserved LVEF, with less performance than the E/e\' ratio.

Oocyte development in Xenopus laevis spans six morphologically distinct stages (stage I-VI), and is associated with a decrease in protein O-GlcNAc levels. As a first step in elucidating the role of O-GlcNAc in developing oocytes, initial efforts were focused on isolation and identification of fifteen modified proteins that decrease during oocyte development. Stage I oocytes due to their high amounts of these proteins, were used as starting material for purification. Multiple affinity and specific antibody based purification technique were initially used in an attempt to enrich the O-GlcNAc proteins. Due to the unique properties of the proteins ultimately identified, these techniques were unable to provide sufficient material for sequencing. However, differential centrifugation coupled with 2D-gel electrophoresis was highly successful. The majority of isolated proteins were strongly basic in nature with pIs 8-10. Coomassie stained bands from 2D-analysis were trypsin digested, and peptides were sequenced by mass spectroscopy (Finnigan LCQ). Mass data were interpreted by Bioworks software, and protein sequences were compared to multiple protein databases. Initially, six proteins were identified as Thesaurin a (42Sp50), cytoplasmic mRNA binding protein p54, y-box homolog, Xp 54 (ATP dependent RNA helicase p54), Vg1 RNA binding protein variant A, Zygote arrest 1(Zar1) and Poly (A) binding protein (PABP). Thesaurin a, the main component of 42S particle of previtellogenic oocytes (stages I-III) is involved in tRNA storage and possess low tRNA transfer activity; y-box factor homolog and Xp54 are present in oocyte mRNA storage ribonucleoprotein particles; Vg1 RBP variant A associates mVg1 RNA to microtubules in order to translocate to the vegetal cortex; Zar1 is involved in oocyte-to-embryo transition; and PABP initiates mRNA translation. This study is the first to characterize these oocyte specific proteins as O-GlcNAc modified proteins. Overall, the presence of several O-GlcNAc proteins in oocytes, the reduction in their levels/ O-GlcNAc levels, and the variation in maturation time in the presence of HBP-flux modulators in developing oocyte indicates O-GlcNAc may play important roles in metabolism, cell growth and cell division of X. laevis oocytes. Therefore, identifying the remainder of these proteins and elucidating the O-GlcNAc role in their function is a worthwhile pursuit.

<p>In the first part of this work, the influence of hydrogen on the structural and magnetic properties of Fe/V(001) superlattices was studied. The local structure of the vanadium-hydride layers was determined by extended x-ray absorption fine structure (EXAFS) measurements. The magnetic ordering in a weakly coupled Fe/V(001) superlattice was investigated using the magneto-optical Kerr effect (MOKE). The interlayer exchange coupling is weakened upon alloying with hydrogen and a phase with short-range magnetic order was observed.</p><p>The second part is concerned with first-principles calculations of magnetic materials, with a focus on magnetic recording applications. The uniaxial magnetic anisotropy energy (MAE) of Fe, Co, and Ni was calculated for tetragonal and trigonal structures. Based on an analysis of the electronic states of tetragonal Fe and Co at the center of the Brillouin zone, tetragonal Fe-Co alloys were proposed as a material that combines a large uniaxial MAE with a large saturation magnetization. This was confirmed by experimental studies on (Fe,Co)/Pt superlattices. The large uniaxial MAE of L1₀ FePt is caused by the large spin-orbit interaction on the Pt sites in connection with a strong hybridization between Fe and Pt. Furthermore, it was shown that the uniaxial MAE can be increased by alloying the Fe sublattice with Mn. The combination of the high-moment rare-earth (RE) metals with the high-<i>T</i>_C 3<i>d</i> transition metals in RE/Cr/Fe multilayers (RE = Gd, Tb, Dy) gives rise to a strong ferromagnetic effective exchange interaction between the Fe layers and the RE layer. The MAE of hcp Gd was found to have two principal contributions, namely the dipole interaction of the large localized 4<i>f</i> spins and the band electron magnetic anisotropy due to the spin-orbit interaction. The peculiar temperature dependence of the easy axis of magnetization was reproduced on a qualitative level.</p>

Ph.D. / Molecular Microbiology and Immunology / Both poxviruses and γ2-herpesviruses share the K3-family of viral immune evasion proteins. These proteins are characterized by an amino-terminal RING-CH domain followed by two transmembrane domains. We analyzed several human homologues of the K3-family termed membrane-associated RING-CH (MARCH) proteins. All MARCH proteins localized to subcellular membranes while several reduced surface levels of known K3-family substrates. Thus, MARCH proteins appear to be structurally and functionally homologous to viral K3 proteins. One of the major challenges in determining the function of this family is the identification of their physiological substrates. To overcome this we created a quantitative proteomics approach which can be used to identify novel substrates for both the K3- and MARCH-families. Using stable isotope labeling by amino acids in cell culture, we compared the proteome of plasma membrane, golgi, and endoplasmic reticulum membranes in the presence and absence of K5 and MARCH-VIII. Quantitative mass spectrometric protein identification from these fractions revealed that CD316 (bone marrow stromal antigen 2), CD166 (activated leukocyte cell adhesion molecule) and syntaxin-4 were consistently underrepresented in the plasma membrane of K5 expressing cells, while CD44, CD81 (TAPA-1) and B-cell receptor-associated protein 31kDa (Bap31) were consistently underrepresented in the plasma membrane of MARCH-VIII expressing cells. Furthermore, downregulation of each of these proteins was independently confirmed. Our results both identify and characterize a novel family of human ubiquitin ligase enzymes and elucidate a novel technique which can analyze this family and be easily adapted to the analysis of other cellular enzymes viral immune modulators.

Polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), two groups of struc-turally related chlorinated aromatic hydrocarbons, generally referred to as “dioxins” are of great concern due to their extreme toxicity and presence in all compartments of the environment. Since they occur at very low levels, their analysis is complex and challenging, and there is a need for cost-efficient, reliable and rapid analytical alternatives to the expensive methods in-volving use of gas chromatography high-resolution mass spectrometry (GC-HRMS). It is im-portant to routinely monitor food and feed items to detect contaminations at an early stage. For the regulation of dioxins and dioxin-like PCBs in food and feed according to current legis-lation, large numbers of samples have to be analysed. Furthermore, soils at many industrial sites are also contaminated with dioxins and need remediation. In order to optimize the cost-efficiency of reclamation activities it is important to acquire information about the levels and distribution of dioxins in the contaminated areas. The aim of the studies underlying this thesis was to investigate the potential of comprehen-sive two-dimensional gas chromatography with a micro-electron capture detector (GC × GC-µECD) as a cost-effective method for analysing dioxins and dioxin-like PCBs in food, feed, fly ash and contaminated soils. Quantification studies of dioxins and dioxin-like PCBs were con-ducted and results were compared with GC-HRMS reference data. Generally, there was good agreement between both the congener-specific results and data expressed as total toxic equiva-lents (TEQs). The developed GC × GC-µECD method meets the European Community (EC) requirements for screening methods for control of dioxins and dioxin-like PCBs in food and feed. The presented results also indicate that GC × GC-µECD has potential to be used as a routine method for the congener-specific analysis of 2,3,7,8-PCDD/Fs and dioxin-like PCBs in matrices such as food and feed, fly ash and soil. However, to fully exploit the potential of the GC × GC-µECD technique, it should be combined with a fast and cost-efficient sample preparation procedure. Therefore, a number of certified reference materials (CRMs) were extracted using a new shape-selective pressurized liquid extraction technique with integrated carbon fractionation (PLE-C), and the purified extracts were analysed for PCDD/Fs using GC × GC-µECD. The results compared well with the certified values of a fly ash and a sandy soil CRM, but they were much too high for a com-plex clay soil CRM. It was concluded that this combination of techniques was very promising for screening ash and highly permeable soils. Further assessments and method revisions are still required before GC × GC-µECD can be used on a routine basis, and available software packages need to be refined in order to accelerate the data-handling procedures, which currently restrict the sample throughput.

No description available.

The purpose of this study is to examine the geothermal potential, sustainability, and reinjection possibility of Edremit geothermal field. In order to investigate this, a numerical model consisting of a hot and cold water aquifer system is established. A two dimensional cross sectional model is set to simulate this geothermal system. Different pressure and temperature values are applied to the nodes at the boundaries to perform a steady state calibration which minimizes the computed results and observed values obtained from the near well logs. After the calibration, three alternative scenarios are proposed and the response of the pressure and temperature to these conditions is evaluated. At first the water is pumped from the wells of Yagci, Derman, Entur and ED-3 seperately at a mass rate of 5 kg/s and energy rate of 4.182 x 105 J/s. Then, in scenario 2 the water is pumped at the same rate from all the wells mentioned in the first scenario together. For the third scenario another well is opened to the geothermal system and 80% of the pumped water (temperature being 200C) is injected to the system from the wells while all the wells mentioned are working. The results of these scenarios are utilized to evaluate the reservoir in terms of its response to different production and reinjection conditions. Interpretation of the reservoir response in view of the pressure and temperature declines emphasize that such a simulation study can be applied to assess potential and sustainability of the geothermal systems.

There are 209 PCB congeners, 136 of which have been found in technical PCB mixtures and hence may be found in the environment as a result of either intentional or unintentional release. The identification and quantification of the congeners are difficult due to analytical bias from coeluting PCBs and other persistent organic pollutants. Among the 209 possible PCB congeners, 19 tri- and tetra-ortho chlorinated congeners exist in stable atropisomeric conformations. The racemization barrier were determined for twelve of the nineteen atropisomers and was found to be between 176-185 kJ × mol-1 and ca. 250 kJ × mol-1 for tri- and tetra-ortho PCB, respectively. Further, a buttressing effect of 6.4 kJ × mol-1 was observed for congeners with vicinal ortho-meta chlorines. Comprehensive two-dimensional gas chromatography (GC×GC) was used to analyze the atropisomers and other PCBs. A Longitudinally Modulated Cryogenic System (LMCS) was used with liquid CO2 as cryogen. The LMCS was optimized for semi-volatile organic substances, primarily PCBs. The trap temperature was shown to be an important factor for the trapping and desorption efficiency, as was the thermal mass of the column used in the modulator region. A number of column sets were tested and the separation efficiency, congener resolution and analysis time was evaluated. Good separation of non- and mono-ortho PCBs and “bulk” PCBs (in a technical PCB) was obtained within 8 min using a smectic liquid crystal column (LC50) as the first and a nonpolar column as the second dimension column. Using a second column, an efficient nonpolar (DB-XLB) column, which separates many PCB congeners, were combined with a polar (cyanopropyl) or shape selective (LC50) second dimension column. As a maximum, 181 of the 209 congeners and 126 of the 136 Aroclor PCBs were resolved. The seven frequently measured PCBs (PCBs 28, 52, 101, 118, 138, 153 and 180) and all WHO-PCBs were separated from all other Aroclor PCBs. Chiral PCBs are released into the environment as racemic mixtures. However, organisms have been shown to enantiomerically enrich many of the atropisomers, suggesting that enantioselective biotransformations occur. Non-racemic PCB enrichment has also been seen in mammalians including humans, which is of particular concern because of the potential health risk. An analytical procedure were therefore developed and used to determine the levels of atropisomeric PCBs, planar-PCBs (WHO-PCBs) and total PCBs in seals with different health status. GC×GC was used to separate the target PCBs from other PCBs and potential interferences. A chiral column (permethylated â-cyclodextrin) was used in combination with a polar or shape selective column and enantiomeric fractions (EFs) were determined for five atropisomeric PCBs, i.e. CBs 91, 95, 132, 149 and 174. Some atropisomers had EF that deviated largely from racemic. The deviation was larger in liver than blubber, indicating enantioselective metabolism. However, there was no selective passage of the studied atropisomeric PCBs across placenta and no selective blood-brain barrier. Similarly, no correlation between EFs and health status was observed, although there was a correlation between total PCBs and health status.

This thesis is based on four papers dealing with two different areas of mathematics.Paper I–III are in combinatorics, while Paper IV is in mathematical physics.In combinatorics, we work with design theory, one of whose applications aredesigning statistical experiments. Specifically, we are interested in symmetric incompleteblock designs (SBIBDs) and triple arrays and also the relationship betweenthese two types of designs.In Paper I, we investigate when a triple array can be balanced for intersectionwhich in the canonical case is equivalent to the inner design of the correspondingsymmetric balanced incomplete block design (SBIBD) being balanced. For this we derivenew existence criteria, and in particular we prove that the residual designof the related SBIBD must be quasi-symmetric, and give necessary and sufficientconditions on the intersection numbers. We also address the question of whenthe inner design is balanced with respect to every block of the SBIBD. We showthat such SBIBDs must possess the quasi-3 property, and we answer the existencequestion for all know classes of these designs.As triple arrays balanced for intersections seem to be very rare, it is natural toask if there are any other families of row-column designs with this property. In PaperII we give necessary and sufficient conditions for balanced grids to be balancedfor intersection and prove that all designs in an infinite family of binary pseudo-Youden designs are balanced for intersection.Existence of triple arrays is an open question. There is one construction of aninfinite, but special family called Paley triple arrays, and one general method forwhich one of the steps is unproved. In Paper III we investigate a third constructionmethod starting from Youden squares. This method was suggested in the literaturea long time ago, but was proven not to work by a counterexample. We show interalia that Youden squares from projective planes can never give a triple array bythis method, but that for every triple array corresponding to a biplane, there is asuitable Youden square for which the method works. Also, we construct the familyof Paley triple arrays by this method.In mathematical physics we work with solitons, which in nature can be seen asself-reinforcing waves acting like particles, and in mathematics as solutions of certainnon-linear differential equations. In Paper IV we study the non-commutativeversion of the two-dimensional Toda lattice for which we construct a family ofsolutions, and derive explicit solution formulas. / Denna avhandling baseras på fyra artiklar som behandlar två olika områden avmatematiken. Artikel I-III ligger inom kombinatoriken medan artikel IV behandlarmatematisk fysik.Inom kombinatoriken arbetar vi med designteori som bland annat har tillämpningardå man ska utforma statistiska experiment.I artikel I undersöker vi när en triple array kan vara snittbalanserad vilket i detkanoniska fallet är ekvivalent med den inre designen till den korresponderandesymmetriska balanserade inkompletta blockdesignen (SBIBD) är balanserad. För dettapresenterar vi nya nödvändiga villkor. Speciellt visar vi att den residuala designentill den korresponderande SBIBDen måste vara kvasi-symmetrisk och ger nödvändigaoch tillräckliga villkor för dess blockskärningstal. Vi adresserar ocksåfrågan om när den inre designen är balanserad med avseende på alla SBIBDensblock. Vi visar att en sådan SBIBD måste ha den egenskap som kallas kvasi-3 ochsvarar på existensfrågan för alla kända klasser av sådana designer.Eftersom snittbalanserade triple arrays verkar vara väldigt sällsynta är detnaturligt att fråga om det finns andra familjer av rad-kolumn designer som hardenna egenskap. I artikel II ger vi nödvändiga och tillräckliga villkor för att enbalanced grid ska vara snittbalanserad och visar att alla designer i en oändlig familjav binära pseudo-Youden squares är snittbalanserade.Existensfrågan för triple arrays är öppen fråga. Det finns en konstruktionsmetodför en oändlig men speciell familj kallad Paley triple arrays och så finns det enallmän metod för vilken ett steg är obevisat. I artikel III undersöker vi en tredjekonstruktionsmetod som utgår från Youden squares. Denna metod föreslogs i litteraturenför länge sedan men blev motbevisad med hjälp av ett motexempel. Vivisar bland annat att Youden squares från projektiva plan aldrig kan ge en triplearray med denna metod, men att det för varje triple array som korresponderartill ett biplan, så finns det en lämplig Youden square för vilken metoden fungerar.Vidare konstruerar vi familjen av Paley triple arrays med denna metod.Inom matematisk fysik arbetar vi med solitoner som man i naturen kan få sesom självförstärkande vågor vilka beter sig som partiklar. Inom matematiken ärde lösningar till vissa ickelinjära differentialekvationer. I artikel IV studerar vi dettvådimensionella Toda-gittret för vilken vi konstruerar en familj av lösningar ochäven explicita lösningsformler.

The soil-structure interface is fundamental to the performance of many geotechnical engineering systems; including penetration test devices, deep foundations, and retaining structures. In geotechnical engineering structures, the counterface may range from a polymer in the case of a geosynthetically reinforced earth retaining structure to steel for cone penetration testing or pile foundations. Interface strength is affected by many factors, among which surface roughness is the most dominant. To date common practice has been to characterize counterface surface roughness by a roughness parameter based on only its spatial properties and soil roughness separately by various incompatible means resulting in two roughness values unrelated to each other. The vast number of analyzing methods and developed parameters reveal the general confusion regarding this concept. Rather than analyzing the particulate and continuum media separately, it is compulsory to coalesce the analysis and quantify the relative nature of interface behavior. This can be accomplished by examining the particulate and continuum media through the same powerful tools. The motive of this study is to develop a unified approach to determining the index properties of particles and surfaces in a particle-surface interface. This is accomplished by examining several particle shape and surface roughness parameters in terms of their ability to uniquely describe and distinguish particulate medium and continuum roughness, respectively. In this study, surfaces are analyzed as derived particles by wrapping surface profiles and particles are evaluated as derived surfaces via unrolling particle outlines. In addition, particle shape parameters are modified to allow surface roughness analysis and surface roughness parameters are modified to characterize particle shape. A unified approach for particulate shape and continuum roughness would ultimately lead to a better understanding of micro-scale interaction mechanism and better quantification of macro-scale mobilized resistance for soil and engineering surface interaction.