A alveolite seca é uma das complicações pós-operatórias mais comuns e sintomáticas na exodontia, porém, até o momento não possui um protocolo de tratamento definido. A oxitetraciclina (OTC) é um antibiótico de amplo espectro utilizado no tratamento de múltiplas infecções. Entretanto, nos últimos anos as tetraciclinas de primeira geração, tais como a OTC, têm sido evitadas devido ao surgimento de microrganismos resistentes. Afortunadamente, nos últimos anos tem se observado uma tendência contrária graças às medidas de controle no uso de antibióticos. Sistemas de liberação controlada podem evitar o desenvolvimento de resistência bacteriana e diminuir o risco de efeitos adversos. Este estudo teve como objetivo preparar uma nanofibra polimérica de policaprolactona e oxitetraciclina (PCL/OTC), e ainda avaliar suas propriedades físicas e biológicas in vitro e in vivo, visando seu futuro uso no tratamento da alveolite seca. As nanofibras poliméricas carregadas com OTC foram preparadas pelo sistema de eletrofiação, caracterizadas através da microscopia eletrônica de varredura (MEV) e avaliadas sobre seu perfil de liberação do fármaco. A atividade antibacteriana da nanofibra sobre um biofilme misto de Porphyromonas gingivalis, Prevotella intermédia, Fusobacterium nucleatum, Eikenella corrodens, Streptococcus sanguis e Aggregatibacter actinomycetemcomitans foi analisada mediante a contagem das unidades formadoras de colônias viáveis após os tempos de contato de 1, 4, 24, 30 e 48 h. O processo de reparo alveolar induzido pela nanofibra PCL/OTC foi avaliado de forma histomorfológica e histomorfométrica após o tratamento da alveolite seca em molares de ratos, e comparado ao tratamento com nanofibras de PCL pura e Alvogyl®, 7, 14 e 21 dias após a exodontia. Finalmente, foi realizada a identificação e contagem de osteoclastos através da marcação da fosfatase ácida resistente ao tartarato (TRAP), nos mesmos tempos de avaliação. As nanofibras PCL/OTC apresentaram orientação randômica em camadas e morfologia multiforme. O perfil de liberação do sistema apresentou um efeito de explosão nas primeiras 8 horas, seguido por um período de liberação lenta e prolongada da OTC. A nanofibra PCL/OTC (132 ?g de OTC/mL) reduziu mais de 50% das colônias do biofilme nas primeiras horas de liberação, seguido por um período de manutenção em que a porcentagem de colônias bacterianas permaneceu baixa. O grupo tratado com PCL/OTC apresentou a maior porcentagem de tecido conjuntivo no 7º dia (p<0,05) e maior porcentagem de osso neoformado no 14º e 21º dias após a exodontia (p<0,05), em comparação aos outros grupos. O tratamento de alveolite seca com a fibra PCL/OTC permitiu a regeneração tecidual do alvéolo quase em sua totalidade até o 21º dia, sendo que a cronologia de regeneração tecidual com este material foi mais rápida do que com a fibra de PCL pura, e esta última mais rápida que do que o controle positivo Alvogyl®. O grupo PCL/OTC apresentou uma quantidade menor (p<0,05) de osteoclastos por área em relação aos outros grupos nos três tempos experimentais. O perfil de liberação prolongando de OTC e as propriedades biológicas relevantes apresentadas pela nanofibra PCL/OTC, sugerem que esta poderia ser considerada uma alternativa para o tratamento da alveolite seca. / Dry socket is one of the most common and symptomatic postoperative complications in tooth extraction, however, to date, it does not have an established treatment protocol. Oxytetracycline (OTC) is a broad-spectrum antibiotic, employed in the treatment of multiple infections. Nevertheless, in the last few years, first-generation tetracyclines such as OTC, have been avoided due to the development of resistant microorganisms. Fortunately, in recent years there has been a contrary trend thanks to control measures in the use of antibiotics. Controlled release systems can prevent the development of bacterial resistance and decrease the risk of adverse effects. This study aimed to prepare a polymeric nanofiber of polycaprolactone and oxytetracycline (PCL/OTC), and to evaluate its physical and biological properties in vitro and in vivo, aiming its use in the treatment of dry socket at the future. The OTC-charged polymeric nanofibers were prepared by electrospinning, and characterized by scanning electron microscopy (SEM) and drug release profile evaluation. The antibacterial activity of the nanofiber over a mixed biofilm containing Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum, Eikenella corrodens, Streptococcus sanguis, and Aggregatibacter actinomycetemcomitans was analyzed by counting the viable colony-forming units after 1, 4, 24, 30 and 48 h of contact. The alveolar repair process induced by the PCL/OTC nanofiber was evaluated histomorphologically and histomorphometrically after the treatment of dry socket in rat molars, and compared to the treatment with plain PCL nanofibers and AlvogylTM, 7, 14 and 21 days after extraction. Finally, the identification and counting of osteoclasts were performed through the tartrate resistant acid phosphatase (TRAP) staining, at the same evaluation time points. PCL/OTC nanofibers presented random orientation in layers and multiform morphology. The release profile of the PCL/OTC system showed a burst effect within the first 8 hours, followed by a prolonged slow release period. The PCL/OTC nanofiber at a concentration of 132 ?g OTC/mL reduced more than 50% of the biofilm colonies in the first few hours of release, followed by a maintenance period in which the percentage of bacterial colonies remained low. The PCL/OTC group presented the highest percentage of connective tissue on the 7th day (p<0.05), and of newly formed bone on the 14th and 21st days (p<0.05) after dental extraction, compared to the other groups. The treatment of dry socket with the PCL/OTC fiber allowed almost complete tissue regeneration up to the 21st day, and the chronology of tissue regeneration with this material was faster than with the plain PCL fiber, and the latter was more rapid than the positive control AlvogylTM. The PCL/OTC group presented a lower amount (p<0.05) of osteoclasts per area than the other two groups in the three experimental periods. The prolonged release profile of OTC and the relevant biological properties presented by the PCL/OTC nanofibers suggest that these may be considered as an alternative treatment of dry socket.

Design methods for side shear of drilled shafts, including the resistance factors that should be applied, do not account for any specific construction procedure. Instead, design often relies on analysis of case studies which include all construction methods used in each geomaterial type (e.g. clays, sands and rocks), or on parametric analysis. Nonetheless, literature suggests that different construction procedures result in varying side shear. This research investigated 2 types of construction: (1) slurry stabilization in sandy soils using bentonite and polymer products that are commonly used on the field, with exposure times from near 0h to 96h, and (2) temporary casing stabilization in simulated limestone using 3 different methods for installation and extraction of the casings which included: driven, coarse-tooth rotated and fine-tooth rotated. All specimens were 1/10th scale in relation to the most common shafts sizes constructed in the field. The results showed that bentonite slurry causes a significant reduction on the side shear within relatively short periods of time (between 2h and 4h of open excavation), whereas polymer slurry did not show appreciable variations up to 96h. The driven and coarse-tooth rotated temporary casing exhibited lower side shear resistance than the fine-tooth rotated casings, which can be attributed to the larger annulus outside the casing and the additional crumbled pieces of rock that degrades the contact interface with the socket concrete. Construction-based resistance factors are suggested for each construction procedure investigated in this study and clearly show the effects from different methods.

Magister Scientiae Dentium - MSc(Dent) / The purpose of this study is to evaluate the need for prophylactic antibiotic treatment in third molar surgery and to establish specific guidelines for antibiotic prophylaxis in the department of Maxillo-Facial and Oral Surgery (MFOS) at Tygerberg Academic, Groote Schuur and Mitchells Plain Hospitals.

This master thesis describes the development of an application for control and management of smart sockets at home. The first part describes the software that was used in creating this application. Specifically, the Qt application platform and the SQLite relational database system. The second part describes the structure and function of this application. The next part describes the application used to test the functionality of the created application and the designed communication protocol. The last part of the work describes the testing and evaluation of the created application.

The thesis deals with the design of a transtibial prosthesis by additive manufacturing technology. Based on walking biomechanics and the current situation of knowledge a prosthetic foot has been designed for a patient with low level of physical activity. Furthermore, the thesis describes the design of an individual socket for the patient. The socket has been designed by reverse engineer procedure based on the three-dimensional geometry of patient´s stump obtained by 3D scanning. Testing samples of the foot and the socket have been made for the check of functionality of both the devices and then subjected to mechanical tests in accordance to the methodology regulation ISO 10328. Finally, the thesis depicts the FDM technology used for the production of functional samples of the designed devices; assembly of modular transtibial prosthesis and its testing by the patient.

It has been shown that the interface between the prosthetic socket and residual limb (S-RL) interface is an important factor in determining acceptance and outcomes of upper limb prostheses. [1] Among the most common complaint from amputees is that the prosthesis is uncomfortable due to developing skin irritation which is usually attributed to poor fit (Nielson 1990). In order to understand why skin irritations can and do occur it is imperative to examine the biomechanical properties of the S-RL interface. A primary reason behind the development of skin irritation is instability of the socket upon the residuum. Alley (2009) asserts that excess slip, axial rotation, and translation are the facets of instability that cause skin irritations due to friction and shear. Measuring the motion at the S-RL interface is not commonly done and therefore there is still no valid and reliable method to quantify the motion clinically. A licensed prosthesis fabricated a transhumeral residual limb model to fit within a typical, harness suspended transhumeral prosthesis. A custom testing apparatus was built to hold the residual limb model and prosthesis for testing. Eight infrared markers were placed on the prosthesis and residual limb model: Two each respectively on the "wrist", elbow axis, socket, and on the residual limb model. The model consists of 3 rigid segments, the forearm, socket, and residual limb. Pearson r correlations were done to see how strongly correlated the motion analysis calculated values were to the accepted values. All results were significant with a r < = .95 and p < .05.

Programmed death-ligand 1 (PD-L1) is a type 1 transmembrane protein that has been reported to play a vital role in mediating suppressed immunity. The interaction between PD-L1 and PD-1 delivers a negative signal that reduces the proliferation of these T cells and induces apoptosis at the same time. Antibodies that can block the Programmed death-ligand 1 (PD-L1) on tumor cells have been shown to alleviate cancer-induced immunosuppression. While antibodies have a great potential in various therapeutic uses, many drawbacks such as the high cost of production, huge molecular size, and poor permeability impose restrictions on the extensive use of full-length antibodies. These limitations have necessitated research for finding alternatives to antibodies, such as peptides, that have lower molecular weight and similar properties as antibodies but do not have the lengthy and complicated approach of producing antibodies. In this study, a novel approach based on molecular interactions of the PD1-PD-L1 complex was developed to design peptides against PD-L1 using Knob-Socket model as basis. Three generations of peptides, α-helix, over-packed and salt bridge function peptides, were designed. All designed peptides were docked in the Molecular Operating Environment (MOE) and the AutoDock Vina software for the docking energy and the detail interaction information. Synthesis and characterization of selected peptides were performed after simulation studies. Surface Plasmon Resonance (SPR) studies showed that α-helix and over-packed peptides can’t bind to the PD-L1 protein with no response on sensorgrams, while peptides with salt bridge function had a higher binding response than those two generations of peptides. In confocal microscopic studies, PD-L1 positive breast cancer cell line MDA-MB-231 was used to determine the binding specificity of the salt bridge function peptides to PD-L1 in vitro, while another breast cancer cell line (MCF-7, without PD-L1) was used as a control. After incubation with peptides, significant fluorescence intensities were detected on the MDA-MB-231 cells, while only background fluorescence was observed on MCF-7 cells. In conclusion, this study demonstrated that peptides against PD-L1 designed using the Knob-Socket model and molecular interaction between PD-L1-PD1 complex showed feasibility to bind specifically with PD-L1 receptors.

To investigate whether higher order packing interactions confer protein-DNA specificity, a modified Knob-Socket (KS) model was used to analyze the interface of bZIP-DNA crystal structures. The KS analysis identified a nine-residue quadripartite recognition core consisting of four contiguous KS pockets P1, P2, N3, and N4 that each pack one of the four DNA half-site bases in the target sequence. Only one base per base pair packs, and these interactions are split across the DNA strands: the first two positive strand positions 1p and 2p pack into P1 and P2 while the last two negative strand positions 3n and 4n pack into N3 and N4. Amino acid sequence analysis of the four KS pocket regions indicates that the primary mechanism recognition is packing or non-packing of the 5-methyl group of dT as well as 5-methylcytosine. P1 shows little packing of dT; P2 packs dT but including two Asn residues in this pocket seems to block packing in this region; N3 also packs dT, but including a Phe also blocks packing; N4 consistently packs dT. This analysis demonstrates that there is an amino acid code to DNA recognition, allowing for multi-residue recognition and packing of the 5-methyl group.

Cancer has been a pervasive and deadly problem for many years. No treatments have been developed that effectively destroy cancer cells while also keeping healthy cells safe. In this work, the knob-socket construct is used to analyze two systems involved in cancer pathways, the PDZ domain and the Bcl-BH3 complex. Application of the knob-socket model in mapping the packing surface topology (PST) allows a direct analysis of the residue groups important for peptide specificity and affinity in both of these systems. PDZ domains are regulatory proteins that bind the C-terminus of peptides involved in the signaling pathway of cancer progression. The domain includes five -strands, two -helices, and six coils/turns. In this study, the PST of all eight solved crystal structures of T-cell lymphoma invasion and metastasis 1 (Tiam1) PDZ domains are mapped to reveal details of ligand-domain binding pockets and packing interactions. Four main interactions were identified in the comparison of the PST maps and a consensus sequence was calculated using knob-socket interaction data. In the case of the Bcl-BH3 complex, binding of these two proteins prevents an unhealthy cell from undergoing apoptosis. In the knob-socket mapped protein-ligand interactions, the helical ligand consists of 8 to 10 residues that specifically interact with four helices on the binding protein: the N-terminus of Helix2, the main bodies of Helix3 and Helix4 and the C-terminus of Helix5. Among all of the interactions that were analyzed, there were three amino acids from the ligand, glycine, leucine, and isoleucine, that always packed into the hydrophobic groove that is key for ligand recognition. By using knob-socket analysis to map quaternary packing structure, it was possible to identify the quaternary-level protein interactions that define ligand specificity and binding strength. From this analysis, possible protein mimetics can be developed that could be used as cancer treatments.

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