Enhanced anchorage of tissue-engineered cartilage using an osteoinductive approach

Articular cartilage injuries occur frequently in the knee joint. Several methods have been implemented clinically, to treat osteochondral defects but none have been able to produce a long term, durable solution. Photopolymerizable cartilage tissue engineering approaches appear promising; however, fundamentally, forming a stable interface between the tissue engineered cartilage and native tissue, mainly subchondral bone and native cartilage, remains a major challenge. The overall objective of this research is to find a solution for the current problem of dislodgment of tissue engineered cartilage at the defect site for the treatment of degraded cartilage that has been caused due to knee injuries or because of mild to moderate level of osteoarthritis. For this, an in-vitro model was created to analyze the integration of tissue engineered cartilage with the bone, healthy and diseased cartilage over time. We investigated the utility of hydroxyapatite (HA) nanoparticles to promote controlled bone-growth across the bone-cartilage interface in an in vitro engineered tissue model system using bone marrow derived stem cells. We also investigated the application of HA nanoparticles to promote enhance integration between tissue engineered cartilage and native cartilage both in healthy and diseased states. Samples incorporated with HA demonstrated significantly higher interfacial shear strength (at the junction between engineered cartilage and engineered bone and also with diseased cartilage) compared to the constructs without HA (p < 0.05), after 28 days of culture. These findings indicate that the incorporation of HA nanoparticles permits more stable anchorage of the injectable hydrogel-based engineered cartilage construct via augmented integration between bone and cartilage.^

Biocompatibility assessment of biosorbable polymer coated nitinol alloys

Owing to an increased risk of aging population and a higher incidence of coronary artery disease (CAD), there is a need for more reliable and safer treatments. Numerous varieties of durable polymer-coated drug eluting stents (DES) are available in the market in order to mitigate in-stent restenosis. However, there are certain issues regarding their usage such as delayed arterial healing, thrombosis, inflammation, toxic corrosion by-products, mechanical stability and degradation. As a result, significant amount of research has to be devoted to the improvement of biodegradable polymer-coated implant materials in an effort to enhance their bioactive response. ^ In this investigation, magneto-electropolished (MEP) and a novel biodegradable polymer coated ternary Nitinol alloys, NiTiTa and NiTiCr were prepared to study their bio and hemocompatibility properties. The initial interaction of a biomaterial with its surroundings is dependent on its surface characteristics such as, composition, corrosion resistance, work of adhesion and morphology. In-vitro corrosion tests such as potentiodynamic polarization and electrochemical impedance spectroscopic (EIS) studies were conducted to determine the coating stability and longevity. In-vitro hemocompatibility studies and HUVEC cell growth was performed to determine their thrombogenic and biocompatibility properties. Critical delamination load of the polymer coated Nitinol alloys was determined using Nano-scratch analysis. Sulforhodamine B (SRB) assays were performed to elucidate the effect of metal ions leached from Nitinol alloys on the viability of HUVEC cells. Scanning Electron Microscopy (SEM), X-ray Photoelectron Spectroscopy (XPS), contact angle meter and X-ray diffraction (XRD) were used to characterize the surface of the alloys. ^ MEP treated and polymer coated (PC) Nitinol alloys displayed a corrosion resistant polymer coating as compared to uncoated alloys. MEP and PC has resulted in reduced Ni and Cr ion leaching from NiTi5Cr and subsequently low cytotoxicity. Thrombogenicity tests revealed significantly less platelet adhesion and confluent endothelial cell growth on polymer coated and uncoated ternary MEP Nitinol alloys. Finally, this research addresses the bio and hemocompatibility of MEP + PC ternary Nitinol alloys that could be used to manufacture blood contacting devices such as stents and vascular implants which can lead to lower U.S. healthcare spending.^

A Cross-Generational Analysis of Spanish-to-English Lexico-Semantic Phenomena in Emerging Miami English

Sociolinguists have documented the substrate influence of various languages on the formation of dialects in numerous ethnic-regional setting throughout the United States. This literature shows that while phonological and grammatical influences from other languages may be instantiated as durable dialect features, lexical phenomena often fade over time as ethnolinguistic communities assimilate with contiguous dialect groups. In preliminary investigations of emerging Miami Latino English, we have observed that lexical forms based on Spanish lexical forms are not only ubiquitous among the speech of the first generation Cuban Americans but also of the second. Examples, observed in field work, casual observation, and studied formally in an experimental context include the following: “get down from the car,” which derives from the Spanish equivalent, bajar del carro instead of “get out of the car”. The translation task administered to thirty-one participants showed a variety lexical phenomena are still maintained at equal or higher frequencies.

Race Relations & Politics in Venezuela during Punto Fijo (1958 – 1998)

In 1998, Hugo Chávez Frías’ presidential candidacy brought race to national discussion in Venezuela for first time since 1945. For long, the country’s politics had abided by the myth of racial harmony and racial democracy. This approach pointed to institutional separation in the United States and Africa as examples of true racism. Latin America was largely void of such atrocities. Nonetheless, Chávez claimed the present political parties (Acción Democrática, Copei and Unión Republicana Democrática) disenfranchised the common, colored Venezuelan. He continued to assert the opposition’s racism during his presidency. And his political fanbase agrees. A variety of scholars have studied the break from Punto Fijo politics to the Bolivarian Revolution. Yet, few have linked the obvious class struggle to race. Here, I seek to explain how racial identity has shaped class identity in Venezuela by closely examining the Punto Fijo era (1958-1998). The essay begins with an overview of historical race relations, moving to the period in focus. Then, I examine systematic and institutional exclusion under Punto Fijo politics. The object is to understand the merit of Chávez’s racial claims since 1998. Hence, the study also sees democracy in action and the consequences of racial exclusion. The study will be accomplished through secondary research, considering the limitations brought by working abroad. In the end, this study serves as first step in analyzing the fall of what was once considered Latin America’s most durable democracy.

Race Relations & Politics in Venezuela during Punto Fijo (1958 – 1998)

In 1998, Hugo Chávez Frías’ presidential candidacy brought race to national discussion in Venezuela for first time since 1945. For long, the country’s politics had abided by the myth of racial harmony and racial democracy. This approach pointed to institutional separation in the United States and Africa as examples of true racism. Latin America was largely void of such atrocities. Nonetheless, Chávez claimed the present political parties (Acción Democrática, Copei and Unión Republicana Democrática) disenfranchised the common, colored Venezuelan. He continued to assert the opposition’s racism during his presidency. And his political fanbase agrees. A variety of scholars have studied the break from Punto Fijo politics to the Bolivarian Revolution. Yet, few have linked the obvious class struggle to race. Here, I seek to explain how racial identity has shaped class identity in Venezuela by closely examining the Punto Fijo era (1958-1998). The essay begins with an overview of historical race relations, moving to the period in focus. Then, I examine systematic and institutional exclusion under Punto Fijo politics. The object is to understand the merit of Chávez’s racial claims since 1998. Hence, the study also sees democracy in action and the consequences of racial exclusion. The study will be accomplished through secondary research, considering the limitations brought by working abroad. In the end, this study serves as first step in analyzing the fall of what was once considered Latin America’s most durable democracy.

Efeito da moagem de alta energia na densificação e microestrutura do compósito AI2O3-Cu

The Cu-Al2O3 composite ceramic combines the phase of alumina, which is extremely hard and durable, yet very brittle, to metallic copper phase high ductility and high fracture toughness. These characteristics make this material a strong candidate for use as a cutting tool. Al2O3-Cu composite powders nanocrystalline and high homogeneity can be produced by high energy milling, as well as dense and better mechanical structures can be obtained by liquid phase sintering. This work investigates the effect of high-energy milling the dispersion phase Al2O3, Cu, and the influence of the content of Cu in the formation of Cu-Al2O3 composite particles. A planetary mill Pulverisatte 7 high energy was used to perform the experiments grinding. Al2O3 powder and Cu in the proportion of 5, 10 and 15% by weight of Cu were placed in a container for grinding with balls of hard metal and ethyl alcohol. A mass ratio of balls to powder of 1:5 was used. All powders were milled to 100 hours, and powder samples were collected after 2, 10, 20, 50 and 70 hours of grinding. Composite powders with compact cylindrical shape of 8 mm diameter were pressed and sintered in uniaxial matrix resistive furnace to 1200, 1300 to 1350 °C for 60 minutes under an atmosphere of argon and hydrogen. The heating rate used was 10°C/min. The powders and structures of the sintered bodies were characterized by XRD, SEM and EDS. Analysis TG, DSC and particle size were also used to characterize the milled powders, as well as dilatometry was used to observe the contraction of the sintered bodies. The density of the green and sintered bodies was measured using the geometric method (mass / volume). Vickers microhardness with a load of 500 g for 10 s were performed on sintered structures. The Cu-Al2O3 composite with 5% copper density reached 61% of theoretical density and a hardness of 129 HV when sintered at 1300 ° C for 1h. In contrast, lower densities (59 and 51% of the theoretical density) and hardness (110 HV and 105) were achieved when the copper content increases to 10 and 15%.

The importance of realistic dispersal models in planning for conservation : application of a novel modelling platform to evaluate management scenarios in an Afrotropical biodiversity hotspot

Funded by European Union's Horizon 2020 Marie Sklodowska-Curie. Grant Number: 661211 Research Foundation Flanders (FWO). Grant Numbers: G.0055.08, G.0149.09, G.0308.13 FWO Research Network on Eco-Evolutionary dynamics French Ministère de l'Energie de l'Ecologie du Développement Durable et de la Mer through the EU FP6 BiodivERsA Eranet NERC. Grant Number: NE/J008001/1

L'application de l'analyse de cycle de vie simplifiée à la pratique du design industriel pour la conception de produits ou services à moindre impact environnemental

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Défis et perspectives de l'expansion aquacole en Thaïlande

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Redeeming Faustus: Tracing the pacts of Mariken and Faust from the 1500s to the present

This dissertation uncovers and analyzes the complicated history of the devil’s pact in literature from approximately 1330 to 2015, focusing primarily on texts written in German and Dutch. That the tale of the pact with the devil (the so-called Faustian bargain) is one of the most durable and pliable literary themes is undeniable. Yet for too long, the success of Johann Wolfgang von Goethe’s Faust I (1808) decisively shaped scholarship on early devil’s pact tales, leading to a misreading of the texts with Goethe’s concerns being projected onto the earliest manifestations. But Goethe’s Faust really only borrows from the original Faust his name; the two characters could not be more different. Furthermore, Faustus was not the only early pact-maker character and his tale was neither limited to the German language nor to the Protestant faith. Among others, tales written in Dutch about a female, Catholic, latemedieval pact-maker, Mariken van Nieumeghen (1515), illustrate this. This dissertation seeks to redeem the early modern Faustus texts from its misreading and to broaden the scholarship on the literature of the devil’s pact by considering the Mariken and Faust traditions together.

The first chapter outlines the beginnings of pact literature as a Catholic phenomenon, considering the tales of Theophilus and Pope Joan alongside Mariken of Nijmegen. The second chapter turns to the original Faust tale, the Historia von D. Johann Fausten (1587), best read as a Lutheran response to the Catholic pact literature in the wake of the Reformation. In the third chapter, this dissertation offers a new, united reading of the early modern Faust tradition. The fourth and fifth chapters trace the literary preoccupation with the pacts of both Mariken and Faustus from the late early modern to the present.

The dissertation traces the evolution of these two bodies of literature and provides an in-depth analysis and comparison of the two that has not been done before. It argues for a more global literary scholarship that considers texts across multiple languages and one that takes into consideration the rich body of material of the pact tradition.

Development and Characterization of Monovalent and Bivalent RNA Aptamers Targeting the Common Pathway of Coagulation

Anticoagulant agents are commonly used drugs to reduce blood coagulation in acute and chronic clinical settings. Many of these drugs target the common pathway of coagulation because it is critical for thrombin generation and disruption of this portion of the pathway has profound effects on the hemostatic process. Currently available drugs for these indications struggle with balancing desired activity with immunogenicity and poor reversibility or irreversibility in the event of hemorrhage. While improvements are being made with the current drugs, new drugs with better therapeutic indices are needed for surgical intervention and chronic indications to prevent thrombosis from occurring.

A class of therapeutics known as aptamers may be able to meet the need for safer anticoagulant agents. Aptamer are short single-stranded RNA oligonucleotides that adopt specific secondary and tertiary structures based upon their sequence. They can be generated to both enzymes and cofactors because they derive their inhibitory activity by blocking protein-protein interactions, rather than active site inhibition. They inhibit their target proteins with a high level of specificity and bind with high affinity to their target. Additionally, they can be reversed using two different antidote approaches, specific oligonucleotide antidotes, or with cationic, “universal” antidotes. The reversal of their activity is both rapid and durable.

The ability of aptamers to be generated to cofactors has been conclusively proven by generating an aptamer targeting the common pathway coagulation cofactor, Factor V (FV). We developed two aptamers with anticoagulant ability that bind to both FV and FVa, the active cofactor. Both aptamers were truncated to smaller functional sizes and had specific point mutant aptamers developed for use as controls. The anticoagulant activity of both aptamer-mutant pairs was characterized using plasma-based clotting assays and whole blood assays. The mechanism of action resulting in anticoagulant activity was assessed for one aptamer. The aptamer was found to block FVa docking to membrane surfaces, a mechanism not previously observed in any of our other anticoagulant aptamers.

To explore development of aptamers as anticoagulant agents targeting the common pathway for surgical interventions, we fused two anticoagulant aptamers targeting Factor X and prothrombin into a single molecule. The bivalent aptamer was truncated to a minimal size while maintaining robust anticoagulant activity. Characterization of the bivalent aptamer in plasma-based clotting assays indicated we had generated a very robust anticoagulant therapeutic. Furthermore, we were able to simultaneously reverse the activity of both aptamers with a single oligonucleotide antidote. This rapid and complete reversal of anticoagulant activity is not available in the antithrombotic agents currently used in surgery.

Essays in Macro Finance

I study the link between capital markets and sources of macroeconomic risk. In chapter 1 I show that expected inflation risk is priced in the cross section of stock returns even after controlling for cash flow growth and volatility risks. Motivated by this evidence I study a long run risk model with a built-in inflation non-neutrality channel that allows me to decompose the real stochastic discount factor into news about current and expected cash flow growth, news about expected inflation and news about volatility. The model can successfully price a broad menu of assets and provides a setting for analyzing cross sectional variation in expected inflation risk premium. For industries like retail and durable goods inflation risk can account for nearly a third of the overall risk premium while the energy industry and a broad commodity index act like inflation hedges. Nominal bonds are exposed to expected inflation risk and have inflation premiums that increase with bond maturity. The price of expected inflation risk was very high during the 70's and 80's, but has come down a lot since being very close to zero over the past decade. On average, the expected inflation price of risk is negative, consistent with the view that periods of high inflation represent a "bad" state of the world and are associated with low economic growth and poor stock market performance. In chapter 2 I look at the way capital markets react to predetermined macroeconomic announcements. I document significantly higher excess returns on the US stock market on macro release dates as compared to days when no macroeconomic news hit the market. Almost the entire equity premium since 1997 is being realized on days when macroeconomic news are released. At high frequency, there is a pattern of returns increasing in the hours prior to the pre-determined announcement time, peaking around the time of the announcement and dropping thereafter.

Experimental and Theoretical Models to Probe Mechanisms of Biological Charge Flow

Nature is challenged to move charge efficiently over many length scales. From sub-nm to μm distances, electron-transfer proteins orchestrate energy conversion, storage, and release both inside and outside the cell. Uncovering the detailed mechanisms of biological electron-transfer reactions, which are often coupled to bond-breaking and bond-making events, is essential to designing durable, artificial energy conversion systems that mimic the specificity and efficiency of their natural counterparts. Here, we use theoretical modeling of long-distance charge hopping (Chapter 3), synthetic donor-bridge-acceptor molecules (Chapters 4, 5, and 6), and de novo protein design (Chapters 5 and 6) to investigate general principles that govern light-driven and electrochemically driven electron-transfer reactions in biology. We show that fast, μm-distance charge hopping along bacterial nanowires requires closely packed charge carriers with low reorganization energies (Chapter 3); singlet excited-state electronic polarization of supermolecular electron donors can attenuate intersystem crossing yields to lower-energy, oppositely polarized, donor triplet states (Chapter 4); the effective static dielectric constant of a small (~100 residue) de novo designed 4-helical protein bundle can change upon phototriggering an electron transfer event in the protein interior, providing a means to slow the charge-recombination reaction (Chapter 5); and a tightly-packed de novo designed 4-helix protein bundle can drastically alter charge-transfer driving forces of photo-induced amino acid radical formation in the bundle interior, effectively turning off a light-driven oxidation reaction that occurs in organic solvent (Chapter 6). This work leverages unique insights gleaned from proteins designed from scratch that bind synthetic donor-bridge-acceptor molecules that can also be studied in organic solvents, opening new avenues of exploration into the factors critical for protein control of charge flow in biology.

The Resurgence of Gaelic power in Ireland and Scotland and its wider impact, c.1350-1513

Over the course of the later Middle Ages nearly half the landmass of the British Isles fell under the control of a handful of Gaelic dynasties in Ireland and Scotland. The impact of this profound geopolitical recasting of much of the Atlantic Archipelago has however, received very little scholarly attention. Instead, historians have tended to view events within this expanding Gaelic world, or Gàidhealtachd, as peripheral to the political development of the British Isles and the course of Anglo-Scottish relations during the later Medieval period. Drawing upon a comprehensive range of sources from Ireland, Scotland, and England, as well as significant archival research, this thesis challenges the concept of the so-called 'Celtic fringe' and illustrates how developments within the Gàidhealtachd impacted upon the course of 'British' politics during the period c.1350-1513. The thesis centres on an examination of how two competing Gaelic alliance systems came to dominate much of the Gàidhealtachd from the late fourteenth century through to the early 1500s. The first of these alliance blocs was controlled chiefly by the O'Neills of Tyrone, the O'Briens of Thomond, and MacDonalds of the Hebrides; in the other network the O'Donnells of Tyrconnell, the Burkes of Mayo and the Campbells of Argyll held sway. By tracing the interconnectivity of the lordships in each respective network, the thesis investigates how these alliance systems became a durable force not only within the Gàidhealtachd but also on the broader 'British' stage. The thesis is structured in a manner that makes the intricate, lineage-based world of the Gàidhealtachd more accessible. Each chapter shifts between the various regions of the Gaelic world and examines how developments in one region impacted upon corresponding territory. Ultimately, this provides historians with a new model for exploring what has previously been a majorly neglected area of Irish and British history.

La mesure alternative d’hostilité dans les relations de rivalité interacteur.

Le présent travail explore le phénomène de la rivalité interétatique1 et les mesures de son intensité. Chacune des définitions existantes de la rivalité fait la lumière sur l’une de ses caractéristiques. La rivalité durable met l’accent sur la compétition militarisée, la rivalité stratégique accorde une importance particulière à la perception de l’ennemi, tandis que la rivalité interétatique est axée sur les questions autour desquelles la compétition se déroule. Ces visions différentes du phénomène de la rivalité laissent leur empreinte sur son opérationnalisation et sur le choix des paramètres visant à le capter. Nous réunissons ces trois interprétations dans une seule définition de rivalité interacteur, en proposant une nouvelle classification des actions hostiles, ainsi que la mesure alternative d’hostilité fondée sur la fréquence de ces dernières. Les quatre études de cas suivantes nous ont permis d’atteindre ces objectifs : les relations de rivalité entre l’Afghanistan et le Pakistan, entre l’Arménie et l’Azerbaïdjan, entre le Bélize et le Guatemala, ainsi qu’entre la Somalie et l’Éthiopie.