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Cardiovascular beta-adrenergic signaling : Maturation and programming effects of hypoxia in a chicken modelLindgren, Isa January 2010 (has links)
Despite the importance of β-adrenergic receptors (βARs) in cardiovascular disease, not much is known about how prenatal hypoxia effects βAR signaling in the postnatal animal. Thus, the aim of this thesis was to characterize the pre- and postnatal maturation of the cardiovascular βARs and the effects of chronic prenatal hypoxia on βAR signaling in the embryo and adult animal using the chicken as experimental model. βARs belong to the seven-transmembrane receptor family of G-protein coupled receptors and are crucial for cardiovascular development, growth and regulation. In the cardiovascular system there are two dominant subtypes, β1AR and β2AR, whose main ligands are the biogenic catecholamines epinephrine and norepinephrine. When stimulated, βARs primarily couple to the stimulatory G-protein (Gas) that stimulates adenylyl cyclase to convert ATP to cAMP. cAMP increases ino- and chronotropy of the heart and causes relaxation of blood vessels. β2ARs also have the ability to switch to inhibitory G-protein (Gi) signaling that decreases the cAMP production. To protect the cardiovascular system from overstimulation, the βARs desensitize and downregulate in the case of prolonged elevation of catecholamines. This blunts the cardiovascular response and the mechanisms behind desensitization/downregulation, including the β2AR switch to Gi signaling, are closely linked to cardiovascular disease and are of immense importance in medical therapeutics. Hypoxic stress releases catecholamines and thereby triggers βAR responses and desensitization/downregulation mechanisms. Hypoxia quite commonly occurs in utero and it is well known that prenatal insults, like malnutrition or hypoxia, are coupled to an increased risk of developing adult cardiovascular disease. This is referred to as developmental programming and constitutes an important and modern field of research. In this thesis, I show that; 1) the developmental trajectory for organ growth, especially the heart, is affected by hypoxia, 2) chronic prenatal hypoxia causes cardiac embryonic βAR sensitization, but causes desensitization postnatally suggesting that there is a hypoxia-induced “programming” effect on adult β-adrenoceptor function, 3) the adult βAR desensitization following prenatal hypoxia is linked to a decrease in β1AR/β2AR ratio, a decrease in cAMP following βAR stimulation with isoproterenol and an increase in Gas, 4) the chorioallantoic (CA) membrane arteries display hypoxic vasoconstriction, but lack 8-adrenergic reactivity and 5) hypotension of the chronically hypoxic chicken embryo is linked to a potent βAR relaxation of the CA vasculature and an increased AR sensitivity of the systemic arteries with no changes in heart rate. In conclusion, chronic prenatal hypoxia causes growth restriction, re-allocation and has programming effects on the βAR system in the adult. The latter indicates that the βAR system is an important factor in studying hypoxic developmental programming of adult cardiovascular disease.
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The search for sport-specific tests in boxing: Strength, power and anaerobic measurementsKhudair, Mohammed January 2017 (has links)
The sport of boxing is widely practiced around the world, and to compete internationally atthe World championships and the Olympic games, boxers need a high fitness level and one ofthe tools used to achieve a high fitness level is physical and physiological testing formethodological monitoring and planning of training. The aim of this thesis was to study therelationship between training time in boxers, as in the recalled number of weekly traininghours, and the results from four different tests, upper body Wingate anaerobic test (UWAnT),countermovement jump (CMJ), hand grip strength (HGS) and isometric mid-thigh pull(IMTP). The choice of each tests is discussed from a physiological perspective to show itsassociation to boxing performance. Testing consisted of one testing session, which was heldduring a competition period, and 16 male boxers (age=23±5 years) in the senior ranks wereincluded. The results showed that the number of weekly training hours had a weak correlationto HGS (r=0.236, r2=0.056), a strong correlation to CMJ(r=0.570. r2=0.325), a moderatecorrelation to peak isometric strength in IMTP (r=0.343, r2=0.118), a weak correlation torelative peak isometric strength in IMTP (r=0.189, r2=0.036) and a strong correlation to peakanaerobic power, relative peak anaerobic power and the fatigue index in UWAnT (r=0.574,r2=0.329; r=0.769, r2=0.591; r=0.641, r2=0.411 respectively). In the thesis, the appliedmethods and the group of participants included are also discussed to find a suitable way ofstudying the relationship between these and other tests that could be suitable to explaindifferent characteristics of boxing performance. Based on the findings in the thesis, it wasconcluded that HGS and IMTP do not explain strength in boxing performance and, therefore,should be studied further. Also, it was concluded that the different variables in UWAnT andCMJ do explain anaerobic power and capacity and lower body explosive strength in boxingperformance and could, therefore, be used as sport-specific test for boxing.
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Avrinningsmodell i MIKE Urban och parameteranalys av ett extremregn i området Brynäs, GävleRydin, Johan January 2021 (has links)
Med klimatförändringar kommer alla sorters väderlekar bli extremare och därmed intensivare regn oftare. En avrinningsmodell kan bidra med en värdefull insikt på var problem kan uppstå i förväg samt testa olika klimatscenarion och lösningar. Fram till år 2100 räknar man med att volymen nederbörd kan öka mellan 10 % till 40 %. Syftet med arbetet var att skapa en avrinningsmodell för området Brynäs i Gävle och att även ta reda på parameterkänsligheten för Mannings tal, genomsläppsarea för brunnar och höjddatats gridstorlek. Modelleringsverktyget MIKE Urban användes för att upprätta en kopplad modell mellan höjddata och ledningsnätsdata (2D/1D koppling). Modellen belastades med en konstruerad regnserie kallad Chicago design storm (CDS) med en återkomsttid på 100 år och varaktighet på 6 timmar. Resultaten är hämtad från de två utlopp inom modellområdet genom flödeskurvor.Resultatet visade att ledningsnätet inte klarar av att hantera ett 100 års regn och att ledningsnätet är så belastat att parameteranalysen inte heller kunde påvisa några större skillnader mellan olika manningstal och genomsläppsareor, skillnad på mindre än 1 %. Parametern gridstorlek hade störst skillnad i resultat där man kan se att den största gridstorleken på 25m avvek mycket från de resterande fyra lägre gridstorlekarna på 2m, 3m, 4m och 10m. Resultatet påvisade också stor översvämning (över en meter) vid områden nära utloppen där det är lågpunkter i området med känd problematik sedan tidigare.
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HiPIMS-based Novel Deposition Processes for Thin FilmsAijaz, Asim January 2012 (has links)
In this research, high power impulse magnetron sputtering (HiPIMS) based new deposition processes are introduced to address; the issue of low degree of ionization of C in magnetron sputtering discharges, and the difficulty encountered in thin film deposition on complex-shaped surfaces. The issue of low degree of C ionization is addressed by introducing a new strategy which is based on promoting the electron impact ionization ofC by increasing the electron temperature in the plasma discharge using Ne, instead of conventionally used Ar. The Ne-based HiPIMS process provides highly ionized C fluxes which are essential for the synthesis of high-density and sp3 rich amorphous carbon (a-C) thin films such as diamond-like carbon (DLC) and tetrahedral a-C (ta-C). The feasibility of coating complex-shaped surfaces is demonstrated by using the dual-magnetron approach in an open-field (magnetic field of the magnetrons) configuration and performing sideways deposition of Ti films. The HiPIMS-based open-field configuration process enhances the sideways transport of the sputtered flux — an effect which is observed in the case of HiPIMS. The characterization of the Ne-HiPIMS discharge using a Langmuir probe and mass spectrometry shows that it provides an increase in the electron temperature resulting in an order of magnitude decrease in the mean ionization length of the sputtered C as compared to the conventional Ar-HiPIMS discharge. The C1+ ion energy distribution functions exhibit the presence of an energetic C1+ ion population and a substantial increase in the total C1+ ion flux. The higher C1+ ion flux facilitates the growth of sp3 rich carbon films with mass densities, measured by x-ray reflectometry, reaching as high as approx. 2.8 gcm-3. The dual-magnetron open-field configuration process is operated in DCMS as well as in HiPIMS modes. The plasma characterization, performed by Langmuir probe measurements and optical emission spectroscopy, shows that the plasma density in the Ti-HiPIMS discharge is higher than that of the Ti-DCMS discharge. This results in the higher ionized fraction of the sputtered Ti in the case of HiPIMS. The film uniformity and the deposition rate of the film growth, obtained by employing scanning electron microscopy, demonstrate that the sideways deposition approach can be used for depositing thin films on complex-shaped surfaces.
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Physical Vapor Deposition of Yttria-Stabilized Zirconia and Gadolinia-Doped Ceria Thin Films for Fuel Cell ApplicationsSønderby, Steffen January 2012 (has links)
In this thesis, reactive sputter deposition of yttria-stabilized zirconia (YSZ) and cerium gadolinium oxide (CGO) thin films for solid oxide fuel cell (SOFC) applications have been studied. All films have been deposited under industrial conditions. YSZ films were deposited on silicon wafers as well as commercial NiO-YSZ fuel cell anodes. The texture, morphology, and composition of the deposited films were investigated with respect to deposition parameters such as bias voltage which was identified as a key parameter to tailor the texture of the film and promote less columnar coatings when depositing on Si. In contrast, films grown on NiO-YSZ fuel cell anodes were seen to be randomly orientated when deposited at low substrate bias voltages. When the bias voltage was increased the film took over the orientation of underlying substrate due to substrate template effects. The deposited coatings were found to be homogeneous large areas within the coating zone, which is highly important for industrial applications. The performance of sputtered CGO thin films as diffusion barriers for stopping Sr diffusion between SOFC cathodes and electrolytes was also studied. This was done by introducing the sputtered CGO films in a metal-based SOFC setup. The performance depended on the density of the barrier layer, signifying that Sr diffusion and SrZrO3 formation is an issue. Area specific resistances down to 0.27 Ωcm2, corresponding to a maximum power density up to 1.14 W cm−2 at 650 °C could be obtained with sputtered CGO barrier layers in combination with Sr-doped lanthanum cobalt oxide cathodes which is a significant improvement compared conventional ceramic SOFCs. The diffusion mechanism of Sr through sputtered CGO films was investigated. For this purpose, a model system simulating a SOFC was prepared by depositing CGO and YSZ on cathode material. This setup allowed observation of Sr diffusion by observing SrZrO3 formation using X-ray diffraction while annealing. Electron microscopy was subsequently performed to confirm the results. It was found that Sr diffused along column/grain boundaries in the CGO films but by modifying the film thickness and microstructure the breaking temperature of the barrier could be increased.
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Me-Si-C (Me= Nb, Ti or Zr) : Nanocomposite and Amorphous Thin FilmsTengstrand, Olof January 2012 (has links)
This thesis investigates thin films of the transition metal carbide systems Ti-Si-C, Nb-Si-C, and Zr-Si-C, deposited at a low substrate temperature (350 °C) with dc magnetron sputtering in an Ar discharge. Both the electrical and mechanical properties of these systems are highly affected by their structure. For Nb-Si-C, both the ternary Nb-Si-C and the binary Nb-C are studied. I show pure NbC films to consist of crystalline NbC grains embedded in a matrix of amorphous carbon. The best combination of hardness and electrical resistivity are for ~15 at.% a-C phase. The properties of nc-NbC/a-C are similar to films consisting of nc-TiC/a-C. I further show that in a model system of epitaxial TiCx (x ~0.7) up to 5 at.% Si can be incorporated. At higher Si content, Si starts segregate out from the TiCx to the grain boundaries causing a loss of epitaxy. Higher amounts of Si into the Nb-Si-C and Zr-Si-C systems make them become amorphous. These amorphous structures are unstable under electron irradiation were they crystallize. I show that the cause of crystallization is driven by atomic displacement events.
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Exploring the SPR methodology for monitoring of critical attributes in toxicity testing and bioproductionBergström, Gunnar January 2012 (has links)
Analysis of biological components is central in bioprocess monitoring, process control, product quality control and cell based toxicity assaying. One of these themes that is pursued in this thesis is the use of biosensors for monitoring of molecular markers, exploiting the natural selectivity of biomolecules. Another is the use of glycoconjugates to monitor the activity of biomolecules in a flu vaccine process is studied and were the sensor is based on the concept of weak affinity giving fast response time for the sensor. A third theme is monitoring of cell cultures used for toxicity testing different protein markers is of interest. When developing biosensor surfaces for new antigens commercial preparations of antibodies are often used. In this work we have chosen to look at lactate dehydrogenase (LDH) and describe the preparation and characterisation of antibody used in biosensor surface development. The design of a sensor surface is important for the characteristics of a sensor. By binding antibodies in an oriented manner to the surface a better control of the properties of the antibodies is achieved. The demonstrated method also has the advantage of in situ purification and provides a flexible platform for antibody evaluation and sensor development. In one sentence this thesis explores the possibility of utilizing recognition elements of a biosensor surface. In particular, surface plasmon resonance (SPR) is used as the primary biosensing tool, however most findings in are relevant for other biosensors. Moreover, the thesis approaches existing bioanalytical impediments, such as purity and accessibility of the recognition elements on the sensor surface and preparation strategies to achieve this.
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The Effect of Mg Doping on Optical and Structural Properties of GaNKhromov, Sergey January 2012 (has links)
Mg is the most commonly used p-type dopant for GaN, however the impact of Mg incorporation on structural, morphological and optical properties of GaN is still not fully understood. Another research challenge is to understand and improve the properties of nonpolar GaN as it allows the fabrication of more efficient optoelectronic devices due to the absence of polarization fields. Thus, the aim of this thesis was to explore the effect of Mg doping on polar c-plane GaN in Paper 1 and nonpolar m-plane GaN in Paper 2. The samples were grown by metal-organic vapor phase epitaxy with varying Mg content on free-standing GaN substrates. The studies were done by transmission electron microscopy (TEM) and low temperature cathodoluminescence (CL) with the aim to correlate the optical and structural data obtained by these techniques. Polar c-plane GaN:Mg layers exhibit such structural defects as stackingfaults (SF) of a small size (5-10 nm). The basal plane SF (BSF)density was estimated to be ~ 105 − 106 cm−1 increasing with Mgconcentrations. Comparison between as-grown and annealed sampleshas not shown significant difference in structural or optical properties.Characteristic broad emission lines observed in CL in the rangeof 3.29 − 3.41 eV have been attributed to SF-related emissions byanalogy with nonpolar undoped GaN films grown heteroepitaxially.Acceptor bound exciton (ABE) emission and SF-related peaks havedemonstrated metastability. CL mapping performed on the TEMsamples at the energies corresponding to SF-related peaks has confirmedthat the origin of these lines is associated with Mg-doped GaNlayers. In nonpolar m-plane GaN:Mg layers similar BSFs have been observed. In addition more extended BSFs and prismatic SFs wereidentified at the interface with the GaN substrate. For the m-planesamples with Mg concentration of ~ 1019 cm−3 a number of fine CLlines have been detected in the region of 3.3-3.4 eV. Their shape andappearance were unlike the SF-related emissions in the case of c-planeGaN discussed in Paper 1. These peaks are not likely to be associatedwith donor-acceptor pair (DAP) recombination as has been proved byestimation of the separated DAP energies and by CL mapping experiment.A tentative explanation is given to these peaks as being relatedto excitons bound to some low symmetry acceptor defect centers.
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The Alzheimer Aβ Peptide : Identification of Properties Distinctive for Toxic Prefibrillar SpeciesGöransson, Anna-Lena January 2012 (has links)
Proteins must have specific conformations to function correctly inside cells. However, sometimes they adopt the wrong conformation, causing dysfunction and disease. A number of amyloid diseases are caused by misfolded proteins that form amyloid fibrils. One such disease is Alzheimer’s disease (AD). The protein involved in this deadly disease is the amyloid β (Aβ) peptide. The formation of soluble prefibrillar oligomeric Aβ species has been recognized as an important factor in the development of AD. The aim of work described in this thesis was to investigate which properties of these oligomeric species can be linked to toxicity. We approached this task by comparing the aggregation behavior and biophysical properties of aggregates formed by variants of the Aβ peptide that have been shown to differ in neurotoxicity when expressed in the central nervous system (CNS) of Drosophila melanogaster. A combined set involving different fluorescent probes was used in parallell with transmission electron microscopy. The toxicity of species formed during the aggregation process was examined by exposing human SH-SY5Y neuroblastoma cells to Aβ aggregates. We deduced that there is a correlation between cell toxicity and the propensity of the Aβ peptide to form small prefibrillar assemblies at an early stage of aggregation in vitro. Moreover, these prefibrillar species were characterized by their ability to be recognized by pentamer formyl thiophene acetic acid (p-FTAA) and the presence of exposed hydrophobic patches. We also found that larger aggregates did not induce cell death.
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Thin Film Synthesis and Characterization of New MAX Phase AlloysMockutė, Aurelija January 2012 (has links)
The objective of this Thesis is synthesis and characterization of new MAX phase alloys (M = early transition metal, A = A-group element, and X = C or N) based on incorporation of M and X elements previously not used in any known MAX phases. This is motivated by a search for optimized and unique materials properties, such as different magnetic states. Two synthesis routes have been used to attain Ti2AlC1-xOx: deposition of Ti2AlCy under high vacuum conditions with residual gas acting as O source, and solid-state reactions following deposition of understoichiometric TiCy on Al2O3. Detailed local quantification by analytical transmission electron microscopy (TEM) including electron energy loss spectroscopy (EELS) shows up to 13 at.% O within high quality MAX phase structure. According to previous theoretical work, the range of experimentally obtained O content is enough to observe drastic changes in the materials anisotropic electronic properties. Calculations on effect of substitutional O on shear deformation have also been performed. In a recent theoretical study by Dahlqvist et al., (Cr,Mn)2AlC has been predicted as a new stable magnetic nanoscale laminate. Inspired by this work, thin films of (Cr,Mn)2AlC, as well as of a neighboring system (Cr,Mn)2GeC, have been synthesized by magnetron sputtering. Incorporation of 8 and 12.5 at.% of Mn, respectively, has been detected by analytical TEM including EELS and energy dispersive X-ray spectroscopy (EDX). The total saturation moment of 0.36μB per Mn atom at 50 K has been measured by vibrating sample magnetometry (VSM) for a (Cr,Mn)2GeC sample, providing the first experimental evidence of a magnetic MAX phase. The experimental results obtained in this Thesis provide a base for expanding the MAX phase definition and materials characteristics into new areas, towards further fundamental understanding and functionalization.
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