<p>Chronically implanted recording electrode arrays linked to prosthetics have the potential to make positive impacts on patients suffering from full or partial paralysis [1;2]. Such arrays are implanted into the patient's cortical tissue and record extracellular potentials from nearby neurons, allowing the information encoded by the neuronal discharges to control external devices. While such systems perform well during acute recordings, they often fail to function reliably in clinically relevant chronic settings [3]. Available evidence suggests that a major failure mode of electrode arrays is the brain tissue reaction against these implants (termed the glial scar), making the biocompatibility of implanted electrodes a primary concern in device design. Previous studies have focused on modifying the form factor of recording arrays, implanting such arrays in experimental animals, and, upon explantation, evaluating the glial scarring in response to the implant after several weeks in vivo. Because of a lack of information regarding the mechanisms involved in the tissue reaction to implanted biomaterials in the brain, it is not surprising that these in vivo studies have met with limited success. This dissertation describes the development of a simple, controlled in vitro model of glial scarring and the utilization of that model to probe the cellular and molecular mechanisms behind glial scarring.</p><p>A novel in vitro model of glial scarring was developed by adapting a primary cell-based system previously used for studying neuroinflammatory processes in neurodegenerative disease [4]. Midbrains from embryonic day 14 Fischer 344 rats were mechanically dissociated and grown on poly-D-lysine coated 24 well plates to a confluent layer of neurons, astrocytes, and microglia. The culture was injured with either a mechanical scrape or foreign-body placement (segments of 50 mm diameter stainless steel microwire), fixed at time points from 6 h to 10 days, and assessed by immunocytochemistry. Microglia invaded the scraped wound area at early time points and hypertrophied activated astrocytes repopulated the wound after 7 days. The chronic presence of microwire resulted in a glial scar forming at 10 days, with microglia forming an inner layer of cells coating the microwire, while astrocytes surrounded the microglial core with a network of cellular processes containing upregulated GFAP. Neurons within the culture did not repopulate the scrape wound and did not respond to the microwire, although they were determined to be electrically active through patch clamp recording. </p><p>This initial model recreated many of the hallmarks of glial scarring around electrodes used for recording in the brain; however, the model lacked the reproducibility necessary to establish a useful characterization tool. After the protocol was amended to resemble protocols typically used to culture neural stem/precursor cells, an intense scarring reaction was consistently seen [5]. To further optimize and characterize the reaction, six independent cell culture variables (growth media, seeding density, bFGF addition day, serum concentration in treatment media, treatment day, and duration of culture) were varied systematically and the resulting scars were quantified. The following conditions were found to give the highest level of scarring: Neurobasal medium supplemented with B27, 10% fetal bovine serum at treatment, 10 ng/ml b-FGF addition at seeding and at treatment, treatment at least 6 days after seeding and scar growth of at least 5 days. Seeding density did not affect scarring as long as at least 500,000 cells were seeded per well, but appropriate media, bFGF, and serum were essential for significant scar formation. </p><p>The optimized in vitro model was then used to help uncover the underlying molecular and cellular mechanisms behind glial scarring. A microwire coating that mimics the basal lamina present within glial scars was developed that allows cells responding to the coated microwire to be isolated and evaluated (i.e. through cell counting or cell staining). A panel of soluble factors known to be involved in glial scar formation was added to the media and the cellular response was recorded. The extent of cell accumulation on the coated microwires was significantly increased by titration of the culture with serum, the pleotropic growth factor bFGF, the inflammatory cytokines IL-1&alpha; and IL-1&beta;, and the growth factors PDGF and BMP-2. The other fourteen soluble factors tested had little to no effect on the number of cells that attached to the coated microwires, although a specific blocker of the bFGF receptor was able to abrogate the effect of bFGF. This study proposes essential roles in glial scarring of serum, which infiltrates brain tissue upon disruption of the blood-brain barrier, and bFGF, which is a necessary growth and survival factor for the neural precursor cells that respond to injury. These insights suggest repeated rounds of implant micromotion-induced cellular damage, with the resultant neuronal death, serum release, and bFGF deposition may thicken the glial scar and lead to recording signal loss.</p> / Dissertation

Nanocrystalline beta-silicon carbide (ß-SiC) was synthesized at relatively low temperature (<1300C) by carbothermal reduction (CTR) reaction in fine scale carbon/silica mixtures. The fine scale mixing of the reactants (i.e., carbon and silica) was achieved by solution-based processing and subsequent heat treatment. The mechanism of the CTR reaction in the current system was investigated from different aspects. The condensates of the volatile species generated during the CTR reaction was collected and analyzed. The results supported previous investigations which suggested that the CTR reaction is a multi-step process that involves silicon monoxide (SiO) vapor as a reaction intermediate. The kinetics of the CTR reaction was investigated by isothermal weight loss study and by the study which determined the amount of SiC formed via quantitative X- ray diffraction (QXRD) analysis. The results of kinetic study were consistent with the "shrinking-core" model, in which the reaction between SiO vapor and carbon at the carbon surface to produce SiC is the rate-controlling step. In addition, several techniques, including XRD, gas adsorption analysis, laser diffraction particle size analysis, SEM, TEM, etc., had been used to study the structural evolutions of the reaction product of CTR. It was demonstrated that the evolutions of product structure characteristics such as crystallite size, specific surface area, specific pore volume, pore size distribution, particle size distribution, and powder morphology, etc. were consistent with each other and provided support to the reaction mechanism proposed.

Lead (Pb) is one of the most well known toxic heavy metals in human beings and animals, which leads to toxic neurological disorders, cognitive problems, learning and memory disabilities. Epidemiological studies revealed that chronic lead exposure is one of the environmental risk factors which may cause Alzheimer¡¦s Disease, which were speculated for the observation of cellular necrosis, apoptosis, and £]-amyloid deposition frequently occuring altogether after chronic lead exposure. Recent studies have shown that the £]-amyloid formed during autophagic turnover of APP-rich organelles supplied by both autophagy and endocytosis. Therefore, we will conduct the new perspective for studying the possible role of autophagy on amyloidogensis disorders after lead exposure. SH-SY5Y human neuroblastoma cells, used in this study, were differentiated to a neuronal phenotype by retinoic acid (RA) to the culture medium at 10 £gM for 1, 2, 3 and 4 days. Doses of lead acetate with of lead acetate were 5 £gM and applied to the neuronal culture and then cell viability measurement by MTT assay. The apoptotic effect of non-differentiation and differentiation neuroblastoma cells after lead exposure was determined by cleaved DNA fragments. Furthermore, APP, intracellular A£]1-40 and A£]1-42 expression were quantified by Real-time PCR and ELISA, respectively. The autophagy process and variation of total and phosphorylated mammalian target of rapamycin (mTOR) forms were determined after lead exposure in non-differentiation and differentiation neuroblastoma cells by western blot. The results indicate that lead exposure enhances autophagy response in both non-differentiation and differentiation SH-SY5Y cells, which might cause neuronal apoptosis associated with £]-amyloidgenesis. Otherwise, lead exposure resulted in the inhibition of mTOR signaling, which correlated with the autophagic process. Besides, in our studies, non-differentiated cells exhibited more toxic vulnerability than RA induced differentiated neuron is congruous to previous finding that lead exposure during fetal development might be a potential risk factor for AD in the adulthood.

Title from PDF of title page. / Document formatted into pages; contains 73 pages. / Thesis (M.S.E.E.)--University of South Florida, 2003. / Includes bibliographical references. / Text (Electronic thesis) in PDF format. / ABSTRACT: The goals of this research project were the design and construction of a carbon nanotube (CNT) reactor based on the plasma enhanced chemical vapor deposition (PECVD) principle and the development of a method for directed assembly of CNTs by catalyst patterning. PECVD was selected as the growth method due to the requirement of a catalyst for the growth process, thereby facilitating directed assembly and controlled diameter CNT growth at well-defined locations. The reactor was built in accord with horizontal flow design using standard ultra high vacuum components. The controllable parameters of the reactor include sample temperature, DC plasma intensity, chamber pressure, gas flow ratios, and total gas flow. The most favorable parameters for growing CNTs of well defined length, diameter, and separation were obtained by initially using parameter values obtained from literature, then optimized by changing a parameter and noting the effect on CNT growth. / ABSTRACT: Catalyst patterns for the directed assembly of CNTs were prepared by electron-beam lithography (EBL). Experiments were performed that demonstrated the feasibility of using lithographic methods to achieve directed assembly of carbon nanotubes for the manufacture of CNT devices. Experiments focusing on growth interruption and regrowth of CNTs were conducted to investigate methods of introducing tailored branching points into carbon nanotubes during the growth process. These experiments clearly demonstrate that growth interruption increases the occurrence of CNT branching. An analysis of the relationships between CNT diameter, branching points, and the number of growth steps was conducted. / System requirements: World Wide Web browser and PDF reader. / Mode of access: World Wide Web.

Vor dem Hintergrund der in der Mikroelektronik-Fertigung heute verbreiteten Kupfertechnologie werden in der vorliegenden Arbeit drei neuartige metallorganische Verbindungen, nämlich phosphitstabilisierte Kupfer(I)-Trifluoracetat-Komplexe vorgestellt und hinsichtlich ihrer Anwendbarkeit für die chemische Gasphasenabscheidung (CVD) von Kupfer untersucht. Im einzelnen handelt es ich um die Substanzen Tris(trimethylphosphit)kupfer(I)trifluoracetat (METFA), Tris(triethylphosphit)kupfer(I)trifluoracetat (ETTFA) und Tri(tris(trifluorethyl)phosphit)kupfer(I)trifluoracetat (CFTFA). Mit den Substanzen erfolgen CVD-Experimente auf TiN und Cu bei Temperaturen &lt;400&deg;C. Die Precursoren werden dabei mittels eines Flüssigdosiersystems mit Verdampfereinheit der Reaktionskammer zugeführt. Während METFA wegen seiner ausreichend geringen Viskosität unverdünnt verwendet werden kann, kommen für ETTFA und CFTFA jeweils Precursor-Acetonitril-Gemische zum Einsatz. Mit keinem der Neustoffe können auf TiN geschlossene Kupferschichten erzeugt werden, während dies auf Kupferunterlagen in Verbindung mit Wasserstoff als Reduktionsmittel gelingt. Die Abscheiderate beträgt hierbei 2-3nm/min; der spezifische Widerstand der Schichten bewegt sich zwischen 4&mu;&Omega;cm und 5&mu;&Omega;cm. Mit allen Substanzen werden besonders an dünnen, gesputterten Kupferschichten Agglomerationserscheinungen und Lochbildung beobachtet. Im Fall von CFTFA treten zusätzlich Schäden am darunterliegenden TiN/SiO₂-Schichtstapel auf. Vergleichende Untersuchungen mit der für die Cu-CVD etablierten Substanz (TMVS)Cu(hfac) ergeben sowohl auf Cu als auch auf TiN geschlossene Kupferschichten. Dabei liegen die Abscheideraten bei Temperaturen zwischen 180&deg;C und 200&deg;C im allgemeinen deutlich über 100nm/min. Ein Vergleich dieser Resultate mit den Ergebnissen für die Neustoffe legt nahe, dass den untersuchten Kupfer(I)-Trifluoracetaten keine ausreichende Tauglichkeit für Cu-CVD-Prozesse in der Mikroelektronik-Technologie bescheinigt werden kann. Die im Vergleich zu (TMVS)Cu(hfac) höhere thermische Stabilität der Precursoren und ihre Fähigkeit, mit Wasserstoff als Reaktionspartner auf Cu geschlossene Kupferschichten erzeugen zu können, deutet jedoch auf ihre eventuelle Eignung für ALD-Prozesse hin. Daher widmet sich die Arbeit in einem abschließenden Kapitel dem Thema der Atomic Layer Deposition (ALD), wobei nach einem allgemeinen Überblick besonders auf für die Mikroelektronik relevante ALD-Prozesse eingegangen wird.

Diss. (sammanfattning) Uppsala : Univ., 2009. / Härtill 4 uppsatser.

Thesis (Ph. D.)--University of Hong Kong, 2001. / Includes bibliographical references (leaves 150-191).

Thesis (Ph.D.)--University of Central Florida, 2008. / Adviser: Sic L. Chan. Includes bibliographical references (p. 74-84).

Thesis (Ph.D.)--University of Central Florida, 2009. / Adviser: Kiminobu Sugaya. Includes bibliographical references (p. 45-50).

Thesis (Ph. D.)--University of Washington, 2003. / Vita. Includes bibliographical references (leaves 114-145).