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Thesis advisor: Cyril P. Opeil / The physiology of the vasculature in the central nervous system (CNS) which includes the blood-brain-barrier (BBB) and other factors, prevents the transport of most anticancer agents to the brain and restricts delivery to infiltrating brain tumors. The heterogeneous vascular permeability in tumor vessels (blood-tumor barrier; BTB), along with several other factors, creates additional hurdles for drug treatment of brain tumors. Different methods have been used to bypass the BBB/BTB, but they have their own limitations such as being invasive, non-targeted or requiring the formulation of new drugs. Magnetic Resonance Imaging guided Focused Ultrasound (MRIgFUS), when combined with circulating microbubbles, is an emerging noninvasive method to temporarily permeabilize the BBB and BTB. The purpose of this thesis was to use this alternative approach to deliver chemotherapeutic agents through the BBB/BTB for brain tumor treatment in a rodent model to overcome the hinderances encountered in prior approaches tested for drug delivery in the CNS. The results presented in thesis demonstrate that MRIgFUS can be used to achieve consistent and reproducible BBB/BTB disruption in rats. It enabled us to achieve clinically-relevant concentrations of doxorubicin (~ 4.8±0.5 µg/g) delivered to the brain with the sonication parameters (0.69 MHz; 0.55 MPa; 10 ms bursts; 1 Hz PRF; 60 s duration), microbubble concentration (Definity, 10 µl/kg), and liposomoal doxorubicin (Lipo-DOX) dose (5.67 mg/kg) used. The resulting doxorubicin concentration was reduced by 32% when the agent was injected 10 minute after the last sonication. Three weekly sessions of FUS and Lipo-DOX appeared to be safe in the rat brain, despite some minor tissue damage. Importantly, the severe neurotoxicity seen in earlier works using other approaches does not appear to occur with delivery via FUS-BBB disruption. The resuls from three weekly treatments of FUS and Lipo-DOX in a rat glioma model are highly promising since they demonstrated that the method significantly inhibits tumor growth and improves survival. Animals that received three weekly sessions of FUS + Lipo-DOX (N = 8) had a median survival time that was increased significantly (P<0.001) compared to animals who received Lipo-DOX only (N = 6), FUS only (N = 8), or no treatment (N = 7). Median survival for animals that received FUS + Lipo-DOX was increased by 100% relative to untreated controls, whereas animals who received Lipo-DOX alone had only a 16% improvement. Animals who received only FUS showed no improvement. No tumor cells were found in histology in 4/8 animals in the FUS + Lipo-DOX group, and only a few tumor cells were detected in two animals. Tumor doxorubicin concentrations increased monotonically (823±600, 1817±732 and 2432±448 ng/g) in the control tumors at 9, 14 and 17 days respectively after administration of Lipo-DOX. With FUS-induced BTB disruption, the doxorubicin concentrations were enhanced significantly (P<0.05, P<0.01, and P<0.0001 at days 9, 14, and 17, respectively) and were greater than the control tumors by a factor of two or more (2222±784, 3687±796 and 5658±821 ng/g) regardless of the stage of tumor growth. The transfer coefficient Ktrans was significantly (p<0.05) enhanced compared to control tumors only at day 9 but not at day 14 or 17. These results suggest that FUS-induced enhancements in tumor drug delivery for Lipo-DOX are relatively consistent over time, at least in this tumor model. These results are encouraging for the use of large drug carriers, as they suggest that even large/late-stage tumors can benefit from FUS-induced drug enhancement. Corresponding enhancements in Ktrans were found variable in large/late-stage tumors and not significantly different than controls, perhaps reflecting the size mismatch between the liposomal drug (~100 nm) and Gd-DTPA (molecular weight: 938 Da). Overall, this thesis research provides pre-clinical data toward the development of MRIgFUS as a noninvasive method for the delivery of agents such as Lipo-DOX across the BBB/BTB to treat patients with diseases of the central nervous system. / Thesis (PhD) — Boston College, 2014. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Physics.

O aumento expressivo nos níveis de ruído, principalmente nas áreas urbanas próximas aos aeroportos, tem contribuído de forma preocupante para os já elevados e atuais níveis de poluição sonora registrados nos grandes centros urbanos. Além do fato dos incômodos e desconfortos no cotidiano das pessoas provocados por esse fato, as autoridades que tratam desse assunto alertam para os danos causados a saúde humana e dos seres vivos em geral. Alguns países europeus que estudam este assunto se dizem preocupados com os impactos negativos em suas economias na questão do desequilíbrio orçamentário no setor da saúde. A tese motivada pela utilização ampla de barreiras acústicas no setor de transporte rodoviário, ferroviário convencional e de alta velocidade, e, prioritariamente aéreo, pôde construir por intermédio desses contextos o conhecimento necessário e um cenário de expectativas promissoras com o objetivo de colaborar com a atenuação do ruído aeronáutico com uma proposta acadêmica de implantação de barreiras acústicas articuladas posicionadas nas cabeceiras da pista principal do Aeroporto de Congonhas em São Paulo no momento da decolagem, tendo como paradigma conceitual e operacional o uso similar dos defletores de energia que são utilizados nos conveses dos porta-aviões no momento das suas decolagens. / The significant increase in noise levels, especially in urban areas close to airports, has contributed to the alarmingly high already and current noise pollution levels recorded in major urban centers. Besides the fact of annoyances and discomforts in the everyday life of people caused by this fact, the authorities dealing with this subject warn of the damage to human health and living creatures in general. Some European countries who study this issue claim to be concerned about negative impacts on their economies on the question of the budget imbalance in the health sector. Some European countries who study this issue claim to be concerned about negative impacts on their economies on the question of the budget imbalance in the health sector. The thesis motivated by wide use of noise barriers in the road transport sector, conventional and high-speed rail, and, as a matter of priority air could build through these contexts the knowledge necessary and a promising expectations scenario with the objective of collaborating with the aeronautical noise attenuation with an academic proposal to implement noise barriers at the headwaters of the track positioned hinged main from Congonhas Airport in Sao Paulo at the time of takeoff with the conceptual and operational paradigm using similar energy deflectors that are used on the decks of the carrier at the time of their landings.

Thesis (M. Arch. A.S.)--Massachusetts Institute of Technology, Dept. of Architecture, 1980. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND ROTCH. / Includes bibliographical references (p. 127-133). / Designing environments to accommodate people in wheelchairs is far more than ramps and wide toilet stalls built according to the state building code. This study attempts to illuminate the functional imperatives behind certain standards (especially relating to spinal cord injuries) and to show how families with chair-bound members actually use their homes. There are seven case studies in the body of this work ranging from a situation where both parents are disabled to the typical nuclear family with only one disabled parent to 'families' composed of unrelated individuals sharing a home. Use of each house is illustrated via a diary-generated daily routine as well as by a house evaluation showing the adapted and unadapted features. The case studies are heavily illustrated with photographs. The final chapters discuss the issues and themes that emerged from the study and propose a model of individual competence that is based on an equilibrium among various options for adapting behavior and/ or physical surroundings. Prioritized standards are proposed, parallel to ANSI A117.1-1977, that advocate broad application of minimum accessibility standards, narrower application of acceptable accessibility standards and specialized application of adaptive accessibility standards. This proposal is made in order that a wider range of housing choices be made available to families with chair-bound member(s). In general it was found that most requirements for accessibility did not interfere with the needs of the ambulatory - except in the requirements for counter heights in the kitchen. / by Donna P. Duerk. / M.Arch.A.S.

Magister Educationis - MEd / Learners in mainstream schools have diverse learning needs and experience a variety of learning barriers. Many of the learners struggle to read and write, and are therefore in need of assistance to enhance their academic performance. In addition, schools and teachers tend to assess leaners predominantly through writing methods and prefer text-based approaches in the form of writing over numerous other forms of assessment methods prescribed in the National Policy Pertaining to the Programme and Promotion Requirements (NPPR) (DBE: 2012). However, there are other ways through which learners can be assessed. This study explored the use of scribes as an alternative method to assist learners with learning barriers. The study examined the challenges relating to alternative methods of assessment within the inclusive education paradigm which seeks to accommodate different learning needs in South African schools. The study investigated factors that influence the implementation of alternative assessment to assist learners with diverse learning barriers. This study was conducted within the framework of a qualitative case study research methodology. Data collection methods included the use of questionnaires, document analysis and semi-structured interviews with teachers in Cape Town at a primary school (which constituted the case). The research eek answers to the following research question to understand why the phenomena exist; What factors influence the use of alternative assessment methods such as the use of scribes? The research also aimed to understand teachers‟ views and perceptions regarding the implementation and processes of alternative assessment methods.

There is a growing body of literature recognizing the benefits of Open Data. However, many potential data providers are unwilling to publish their data and at the same time, data users are often faced with difficulties when attempting to use Open Data in practice. Despite various barriers in using and publishing Open Data still being present, studies which systematically collect and assess these barriers are rare. Based on this observation we present a review on prior literature on barriers and the results of an empirical study aimed at assessing both the users' and publishers' views on obstacles regarding Open Data adoption. We collected data with an online survey in Austria and internationally. Using a sample of 183 participants, we draw conclusions about the relative importance of the barriers reported in the literature. In comparison to a previous conference paper presented at the conference for E-Democracy and Open Government, this article includes new additional data from participants outside Austria, reports new analyses, and substantially extends the discussion of results and of possible strategies for the mitigation of Open Data barriers.

Two-dimensional (2D) materials have attracted extensive research interest in recent years. Among them, graphene and the semiconducting transition metal dichalcogenides (TMDs) are considered as promising candidates for future device applications due to their unique atomic thickness and outstanding properties. The study on graphene and TMDs has demonstrated great potential to further push the scaling of devices into the sub-10 nanometer regime and enable endless opportunities of novel device architectures for the next generation. In this thesis, crucial challenges facing 2D materials are investigated from material synthesis to electronic applications. A comprehensive review of the direct synthesis of graphene on arbitrary substrates with an emphasis on the metal-catalyst-free synthesis is given, followed by a detailed study of the contact engineering in TMDs with a focus on the strategies to lower the contact resistance. Effective approaches have been demonstrated to solve these issues. These include: (1) metal-catalyst-free synthesis of graphene on various insulating substrates; (2) Fermi level pinning observed in TMDs and integration of graphene contact to lower the contact resistance; and (3) application of metal-insulator-semiconductor (MIS) contact in TMD field-effect transistors (FETs). First, a direct low-temperature synthesis of graphene on insulators without any metal catalysts has been realized. The effects of carbon sources, NH3/H2 concentrations, and insulating substrates on the material synthesis have been systematically investigated. Graphene transistors based on the as-grown material have been fabricated to study the electronic properties, which can further confirm the nitrogen-doped graphene has been synthesized from the electrical characterizations. Then electronic devices focusing on the semiconducting TMDs has been studied. The Fermi level pinning has been observed and studied in WS2 FETs with four metal materials. A novel method of using graphene as an insertion layer between the metal and TMDs has been proven to effectively reduce the contact resistance. Owing to the benefit of tuning the graphene work function via the electric field, the contact resistance can further be reduced. Finally, the effectiveness of MIS contacts in WS2 FETs has been demonstrated. A thickness dependence research has been conducted to find the optimal thickness of the inserted insulator. Moreover, the possible physical mechanism of how this MIS contact reduces the contact resistance in 2D materials has been discussed.

CdTe/CdS thin film solar cells are the most promising cost-effective solar cells. The goal of this project is to improve the performance for CdS/CdTe devices by improving the open circuit voltage Voc and current density Jsc. Efforts focused on increasing the Voc, which include increasing the doping concentration by introducing Phosphorus and Antimony, finding and testing new back contact materials, and varying the ambient of CSS CdTe. In addition, the effect of Zn2SnO4 on the cells' performance was also studied. Electrical characterization of the thin films and completed devices were carried out by Current-Voltage (J-V), Capacitance-Voltage (C-V), and Spectral Response (SR) measurements. Structural/chemical characterization was done by SEM, XRD and EDS analysis. The ambient of CSS CdTe affects the growth rate, the grain size and electronic properties of CdTe. The N2/O2 mixture with varied ratio (N2/O2=9/1, 7/3, 5/5 and 1/9) was used in this study. The cells' performance and the net carrier concentration were studied as a function of the N2/O2 ratio. The net carrier concentration increases with the increasing O2 concentration. The extrinsic impurities (P and Sb) were incorporated into CdTe layer. Phosphorus was directly introduced into CSS CdTe source. The Sb was incorporated into CdTe by a diffusion process. The effects of the annealing parameters, the excess Sb on CdTe surface, the CdCl2 treatment and the depth of Sb in CdTe were studied. Higher doping concentration up to 1016 cm-3 has been achieved, however, Voc is still in the range of 830 mV.

Purpose: The aim of this study was to assess the outcome of treatment of teeth with open apices managed by the orthograde placement of a bioceramic apical barrier as well as to identify potential outcome factors for this type of treatment. Methods: Patient records were pooled from graduate resident cases completed at Virginia Commonwealth University between January 1, 2010 and May 31, 2018. A total of 515 patients were identified using relevant ADA codes and a key word search within the patient record database. A total of 104 patients (119 teeth) had an open apex that had NSRCT utilizing a bioceramic apical barrier, with 32 of the patients (36 teeth) returning for follow-up. Results: Of the 36 examined teeth (30.8% recall rate),72% were considered healed. 92% were considered healed or healing. No predictive variable analyzed had a significant effect on the outcome. Conclusion: Overall, these results indicate that a bioceramic apical barrier technique is a promising treatment option for obturating teeth with open apices during NSRCT.

A major product of HIV-infected and cytokine-stimulated monocytic-lineage cells is quinolinic acid (QUIN), a neurotoxic metabolite of the kynurenine pathway (KP) of L-tryptophan (L-Trp) metabolism. Despite the large number of neurotoxins found in HIV patients with AIDS Dementia Complex (ADC), only QUIN correlates with both the presence and severity of ADC. With treatment, cerebrospinal fluid (CSF) QUIN concentrations decrease proportionate to the degree of clinical and neuropsychological improvement. As endothelial cells (EC) of the blood-brain barrier (BBB) are the first brain-associated cell that a bloodborne pathogen would encounter, this project examined the BBB response to KP metabolites, as these are implicated in damage of the CNS associated with ADC. Using RT-PCR and HPLC/gas chromatographymass spectrometry (GC-MS), I found that cultured primary human BBB EC and pericytes constitutively expressed the KP. EC synthesised kynurenic acid (KA) constitutively, and after immune activation, kynurenine (KYN). Pericytes produced small amounts of picolinic acid and after immune activation, KYN. An SV40-transformed BBB EC showed no KP expression. By contrast, human umbilical vein EC only expressed low levels of KA after immune activation, however human dermal microvascular EC showed a similar constitutive and inducible KP to that in BBB EC. As T cells are central to primary HIV infection, I also examined KP expression in two CD4+ and one CD4- cell lines, but none showed either constitutive or inducible KP expression. I next examined how QUIN might interact with BBB EC. There was no binding of 3H-QUIN to cultured primary human BBB EC, however a biologically relevant concentration of QUIN induced changes in gene expression which adversely affected EC function, possibly mediated by lipid peroxidation and oxidative stress. The upregulated genes were of the heat shock protein family, and the downregulated genes were associated with regulation of cell adhesion, tight junction and cytoskeletal stability, metalloproteinase (MMP) regulation, apoptosis and G protein signaling. Immunofluorescence showed that QUIN induced morphological changes in BBB EC consistent with the changes in gene expression. Gelatin zymography showed that this was not mediated by MMPs, as constitutive MMP expression was unchanged. These data provide strong evidence for QUIN directly damaging the BBB in the context of HIV infection.