Cerebral small vessel disease (SVD) is a vascular neurodegenerative disease which is the leading cause of vascular dementia and causes 20% of strokes. 20-30% of those over 80 show signs of the disease as white matter hyperintensities on MRI scans, doubling their risk of stroke and trebling their risk of dementia. Sporadic SVD is thought to be caused by hypertension but 30% of sufferers are normotensive and an alternative hypothesis implicates loss of integrity of the blood brain barrier (BBB). To investigate this, I studied brains from normotensive people with early stage SVD and found reduced capillary endothelial claudin-5 (a BBB tight junction protein), more oligodendrocyte precursor cells (OPCs; the precursors to myelinating oligodendrocytes), and more microglia/macrophages compared to controls. Furthermore, in a relevant rat model of spontaneous SVD, the Stroke Prone Spontaneously Hypertensive Rat (SHRSP; disease model; DM) I found that reduced endothelial claudin-5 was the earliest change, appearing at 3 weeks of age, followed by OPC proliferation, appearing at 4 weeks, and then increased number of microglia/macrophages, appearing at 5 weeks. Importantly, all these changes occurred at a young age (< 5 weeks), before any measurable hypertension. These changes were confirmed in an ex vivo slice culture model (i.e. removing blood flow), ruling out direct damage by leakage of blood components through an impaired BBB and suggesting an inherent endothelial cell dysfunction as the primary cause, with secondary BBB defects. This hypothesis of endothelial dysfunction is supported by increased endothelial cell proliferation in both human SVD tissue and the DM rats, and lower levels of endothelial nitric oxide synthase (eNOS) in brains of DM rats. To study this further I isolated primary brain microvascular endothelial cells (BMECs) from DM and control rats and found that those from DM rats formed less mature tight junctions (less membranous claudin-5) than control BMECs. I also found that conditioned media (CM) from DM BMECs causes OPCs in culture to proliferate more and mature less. This indicates that the endothelial dysfunction is inherent to the endothelial cells, rather than induced by other cell types, and through secreted factors causes OPC changes mirroring what is seen in vivo. Using an antibody array, I identified HSP90α as a candidate secreted factor and showed that it is necessary (by blocking the protein in CM) and sufficient (by adding recombinant HSP90α) to induce the maturation phenotype in OPCs, but not the proliferation phenotype. The idea that endothelial dysfunction causes SVD begs the question of what causes endothelial dysfunction, especially in our inbred DM rat strain. To establish this, I reanalysed sequencing data of the DM and control rats from a previously published study, searching for mutations which lead to truncated proteins in genes expressed in brain endothelial cells. We confirmed the candidate gene Atp11b, a phospholipid flippase, was mutated as predicted. I found that knocking down Atp11b using siRNA in a control endothelial cell line caused endothelial dysfunction and a loss of tight junction maturity, and that CM from these cells causes OPCs to proliferate more and mature less, mirroring what we see in primary DM BMECs and suggesting that Atp11b has a key function in promoting normal endothelial function. Furthermore, I showed that knocking down Atp11b causes cells to secrete increased levels of HSP90α. I propose a mechanism whereby ATP11B regulates the retention of HSP90α within endothelial cells, which in turns regulates eNOS levels and activity, as has been shown previously. In summary, this work shows that there are many pre-symptomatic changes which occur in the brain in the development of SVD in DM rats, and that these are ultimately caused by endothelial dysfunction. As these changes are similar to those found in spontaneous human SVD, I propose that endothelial dysfunction is a key mechanism of human SVD, which may in the future lead to new therapies.

Several different laser remote sensing techniques related to the detection of trace chemical species were studied. In particular, a Differential-Absorption lidar (DIAL), a Laser-Induced-Breakdown Spectroscopy (LIBS) lidar, and a Raman lidar were studied. Several of the laser spectroscopic techniques that were used were common throughout these different studies. More precisely, 10.6 μm CO2 laser related spectroscopy was common for the DIAL and LIBS studies, and 266 nm Nd:YAG laser related spectroscopy was used for the LIBS and Raman studies. In the first system studied a tunable CO2 DIAL system was developed for the first time to our knowledge for the potential detection of the explosive Triacetone Triperoxide (TATP) gas clouds. The system has been used to measure gas samples of SF6, and has shown initial absorption measurements of samples of TATP contained within an enclosed optical absorption cell. DIAL/Lidar returns from a remote retroreflector target array were used for the DIAL measurements after passage through a laboratory cell containing the TATP gas. DIAL measured concentrations agreed well with those obtained using a calibrated Ion Mobility Spectrometer. DIAL detection sensitivity of the TATP gas concentration in the cell was about 0.5 ng/μl for a 0.3 m path-length. However, the concentration of TATP was found to be unstable over long periods of time possibly due to re-absorption and crystallization of the TATP vapors on the absorption cell windows. A heated cell partially mitigated these effects. In the second set of studies, a Deep UV LIBS system was developed and studied for the remote detection of solid targets, and potentially chemical, biological, and explosive substances. A 4th harmonic Q-Switched Nd:YAG laser operating at 266 nm was used for excitation of the LIBS plasma at standoff ranges up to 50 m . The LIBS plasma emission covering the range of 240 – 800 nm was enhanced by use of a nearly simultaneous 10.6 μm CO2 laser that increased the LIBS plasma emission by several orders of magnitude. The emission spectrum was used to detect and identify the species of interest. Plasma temperatures on various solid substrates were measured. An increase in the plasma temperature of about 5000 K was measured and analyzed, for the first to our knowledge, due to the addition of the CO2 laser pulse to the LIBS plasma generated by the Nd:YAG laser. An optimum temporal overlap of the two laser pulses was found to be important for the enhancement. Finally, in a third related lidar system, initial 266 nm Raman lidar studies were conducted at detection ranges of 15 m. However, significant spectroscopic background interferences were observed at these wavelengths and additional optical filtering is required.

Colloidal, metallic nanoparticles have myriad applications, but they are most ideal when they are monodisperse, and demonstrate maximum catalytic utility when they are small (< 5 nm) and uncoated; because their surface area is accessible and maximized. Laser- assisted metal nanoparticle synthesis is a ‘green’ method that has become a topic of active research because it is able to produce uncoated or ‘naked’ products. The nanoparticles synthesized in this work were formed through the reduction of metal salts in aqueous solutions; but the reducing agent is an electron-dense microplasma generated by the laser pulse interacting with the media. Because no chemical reducing agents or stabilizers are needed, the products have no surfactants. The underlying reaction mechanisms that drive this type of synthesis are generally understood, however, there is insufficient detail that would allow control over the formation of ultimate product morphologies and size distributions. The metals examined in this thesis are: gold, whose formation follows an autocatalytic rate law; and silver, whose formation follows a first-order rate law. Through my research, I was able to explore the effects that physical parameters (such as laser pulse settings) and chemical parameters (such as radical scavenger addition) have on laser-assisted gold or silver nanoparticle synthesis. My research, outlined in this thesis, is therefore focused on elucidating such details and distilling them into methods of control in order to better predict and tune nanoparticle products.

Thesis (Ph. D.)--Ohio State University, 2006. / Title from first page of PDF file. Includes bibliographical references (p. 195-202).

Neurotransmitter receptor types mediating the generation of intracellular signals are of two types; ligand-gated ion channels and G protein coupled receptors. The effector enzyme phosphoinositide-specific phospholipase C (PLC) is modulated by stimulation of G protein coupled receptors, leading to an increased breakdown of inositol phospholipids ("Ptdlns breakdown").In recent years, the receptors in the brain coupled to PLC and modulation of such receptor-mediated Ptdlns breakdown have been characterised. One such modulation is the "potassium effect", whereby an increase in the assay [K+] from 6 to 18 mM potentiates the Ptdlns breakdown response to the muscarinic agonist carbachol in the rat brain. It has been speculated that this effect is one way of enhancing the signal :noise ratio of muscarinic neurotransmission. The mechanisms responsible for the potassium effect have been studied in this thesis.Initial methodological studies indicated that the temperature of the Krebs buffer used after tissue dissection was an important factor regulating the Ptdlns response to receptor stimulation. Expressing the Ptdlns breakdown response as a fraction of the total labelled phosphoinositides was more useful than other ways of expressing the data. Acid extraction of the Lipid fraction was also superior to neutral extraction.Miniprismspreparedfrompig striatum and hippocampus showed qualitative (but not quantitative) similarities with the rat with respect to stimulation by carbachol, noradrenaline and the potassium effect. Dopamine also stimulated Ptdlns breakdown, though probably via a noradrenergic mechanism.The enhancing actions of potassium appeared to be selective for muscarinic Ml-type receptors. Thus glutamate, quisqualate and NaF-stimulated Ptdlns breakdown are not affected by raised [K+].The potassium effect is brought about by two mechanisms. In calcium-free Krebs buffer, the effect could be mimicked by the calcium channel agonist BAY K-8644 and partially antagonised by verapamil. At an assay [Ca2*] of 2.52 mM, however, modulation of calcium uptake had little effect on carbachol-stimulated Ptdlns breakdown at either normal or raised [K+]. The synergy between potassium and carbachol at252 mM Ca?+ is not dependent upon tissue depolarisation perse, since other ways of depolarising the tissue did not enhance the response to carbachol. It is suggested that potassium might have a direct effect on the muscarinic Ml-type receptor - G protein - PLC complex.In order to investigate this possibility, the effect of fluoride ions (which activate G proteins via formation of AlF4) on basal and carbachol-stimulated Ptdlns breakdown was investigated. Fluoride ions inhibited the enhanced breakdown response to carbachol found at raised [K+]. However, this effect is secondary to effects of fluoride on PLC substrate availibility rather than on G protein function. / digitalisering@umu

The aim of this dissertation is to investigate the incidence of instability in out-of-home care for children and how children experience this instability. The dissertation consists of two studies. The quantitative study is based on an examination of social work case files of 213 children who began 317 placements in 2005 and 2006. Every placement was followed for a maximum of two years. The qualitative study used interpretive phenomenology as method and is based on interviews with 12 purposively selected children who had experienced placement breakdown at some point during 2011 or 2012.   The quantitative study shows that the majority of children had experienced problems in their home environments prior to placement. Most commonly reported was parents’ substance abuse or mental health problems. Preschool and schoolchildren were more often placed in care due to neglect whereas adolescents were placed because of their own behavior problems or relational problems. Children in the qualitative study described that the problems they experienced prior to coming into care continued to influence them during their time in care. The quantitative study indicates that different types of instability are associated with children’s ages. That is, breakdown was most common for adolescents whereas preschool children more often experienced planned placements changes. Children in the qualitative study gave similar descriptions of planned placement changes and placement breakdown. The difficulty with which these children experienced the move from a foster family or group home depended on their relationship to caregivers. Therefore, planned placement changes from foster homes or institutional settings in which children reported being happy were described as more difficult than breakdown in placements from which children wanted to move. In children’s views, breakdown was caused by mismatches between them and caregivers, mistreatment in care settings, and their own behavior problems. However, children explained that when social workers did not listen to them, behavior problems in the form of running away, self-harming or behaving badly, were the only way of ending placements in which they were miserable. All children in the qualitative study described a wish for close relationships with consistent adults and an opportunity to feel that they belong somewhere. These fundamental needs were difficult for them to have satisfied due to their parents’ problematic life histories, instability in care which repeatedly placed children in new care situations, and a lack of continuity of social workers.

No description available.

L'objectiu d'aquest estudi és el d'investigar sobre l'ús de matèria orgànica per part dels fongs i bacteris que colonitzen diferents substrats bentònics en rius Mediterranis i analitzar l'efecte dels factors ambientals i antròpics sobre l'estabilitat estructural i funcional de les comunitats del biofilm. La metodologia emprada en aquest estudi consisteix en: i) anàlisi de la biomassa bacteriana i fúngica, ii) anàlisi de la composició de les comunitats bentòniques (identificació d'hifomicets aquàtics i anàlisi del 16S rDNA bacterià), i iii) anàlisi de l'activitat enzimàtica extracel·lular relacionada amb el reciclatge de matèria orgànica en rius. / This study aimed to investigate on the use of organic matter by fungi and bacteria inhabiting different benthic substrata and to analyze the effect of environmental and anthropogenic perturbations on the structural and functional stability of biofilms. The following methodologies has been used in this study: i) analysis of fungal and bacterial biomass, ii) analysis of benthic community composition (identification of hyphomycete taxa, analysis of the bacterial 16S rDNA), and iii) analysis of extracellular enzyme activities involved in organic matter recycling in rivers.

No description available.

Laser Induced Breakdown Spectroscopy (LIBS) which is used to determine the elemental content of various samples, inspects the emission spectroscopy of samples of interest for searching certain elements or identifying the unknown content. In this study, spectroscopic analyses of various kinds of metals, namely, Cu, Fe, Mo, Ti, W, some compounds such as CuBe, ZnSe, ZnS, GaSe, some semimetals like Si, Ge and even gases were investigated by means of a compact-commercial portable LIBS system and an independently constructed experimental set-up consisting of a single pulse system and various kinds of double pulse configurations using Nd:YAG lasers. The contributions of this thesis to the LIBS community can be classified into two main groups- which are experimental and code development. One of the experimental contributions was the investigation of the different crystal surfaces of silicon in which dangling bond density were taken into account for a more precise comparison of atomic emissions. The second experimental contribution was the polarization experiments by which polarization dependency, to some extent, was demonstrated. The third and final one was the orthogonal double pulse configuration with a 45 o incidence angle for both lasers in opposite directions by which it was shown that the positioning becomes straightforward yielding the desired reproducible results. The second major contribution was to develop a basic code for analyzing the experimental data more accurately. In conclusion, by means of the different experimental approaches, factors relating to the enhancement in intensity were investigated and as a result of developing the code, flexibility in upgrading the constraints of element searching was obtained and the updating of the database was accomplished.