Pharmacological and local toxicity studies of a liposomal formulation for the novel local anaesthetic ropivacaine

This study reports an investigation of the pharmacological activity, cytotoxicity, and local effects of a liposomal formulation of the novel local anaesthetic ropivacaine (RVC) compared with its plain solution. RVC was encapsulated into large unilamellar vesicles (LUVs) composed of egg phosphatidylcholine, cholesterol and a-tocopherol (4:3:0.07, mole %). Particle size, partition coefficient determination and in-vitro release studies were used to characterize the encapsulation process. Cytotoxicity was evaluated by the tetrazolium reduction test using sciatic nerve Schwann cells in culture. Local anaesthetic activity was assessed by mouse sciatic and rat infraorbital nerve blockades. Histological analysis was performed to verify the myotoxic effects evoked by RVC formulations. Plain (RVCPLAIN) and liposomal RVC (RVCLUV) samples were tested at 0.125%, 0.25% and 0.5% concentrations. Vesicle size distribution showed liposomal populations of 370 and 130 nm (85 and 15%, respectively), without changes after RVC encapsulation. The partition coefficient value was 132 26 and in-vitro release assays revealed a decrease in RVC release rate (1.5 fold, P < 0.001) from liposomes. RVCLUV presented reduced cytotoxicity (P < 0.001) when compared with RVCPLAIN Treatment with RVCLUV increased the duration (P < 0.001) and intensity of the analgesic effects either on sciatic nerve blockade (1.4-1.6 fold) and infraorbital nerve blockade tests (1.5 fold), in relation to RVCPLAIN. Regarding histological analysis, no morphological tissue changes were detected in the area of injection and sparse inflammatory cells were observed in only one of the animals treated with RVCPLAIN or RVCLUV at 0.5%. Despite the differences between these preclinical studies and clinical conditions, we suggest RVCLUV as a potential new formulation, since RVC is a new and safe local anaesthetic agent.

Applications of synchrotron x-ray powder diffraction in hydrated cements: high-resolution and high-pressure studies

The main aim of this study is to apply synchrotron radiation techniques for the study of hydrated cement pastes. In particular, the tetracalcium aluminoferrite phase, C4AF in cement nomenclature, is the major iron-containing phase in Ordinary Portland Cement (OPC) and in iron rich belite calcium sulfoaluminate cements. In a first study, the hydration mechanism of pure tetracalcium aluminoferrite phase with water-to-solid ratio of 1.0 has been investigated by HR-SXRPD (high resolution synchrotron X-ray powder diffraction). C4AF in the presence of water hydrates to form mainly an iron-containing hydrogarnet-type (katoite) phase, C3A0.84F0.16H6, as single crystalline phase. Its crystal structure and stoichiometry were determined by the Rietveld method and the final disagreement factors were RWP=8.1% and RF=4.8% [1]. As the iron content in the product is lower than that in C4AF, it is assumed that part of the iron also goes to an amorphous iron rich gel, like the hydrated alumina-type gel, as hydration proceeds. Further results from the high-resolution study will be discussed. In a second study, the behavior of pure and iron-containing katoites (C3AH6 and C3A0.84F0.16H6) under pressure have been analyzed by SXRPD using a diamond anvil cell (DAC) and then their bulk moduli were determined. The role of the pressure transmitting medium (PTM) has also been studied. In this case, silicone oil as well as methanol/ethanol mixtures have been used as PTM. Some “new peaks” were detected in the pattern for C3A0.84F0.16H6 as pressure increases, when using ethanol/methanol as PTM. These new peaks were still present at ambient pressure after releasing the applied pressure. They may correspond to crystalline nordstrandite or doyleite from the crystallization of amorphous aluminium hydroxide. The results from the high-pressure study will also be discussed.

A SCR Model based on Reactor and Engine Experimental Studies for a Cu-zeolite Catalyst

A NOx reduction efficiency higher than 95% with NH3 slip less than 30 ppm is desirable for heavy-duty diesel (HDD) engines using selective catalytic reduction (SCR) systems to meet the US EPA 2010 NOx standard and the 2014-2018 fuel consumption regulation. The SCR performance needs to be improved through experimental and modeling studies. In this research, a high fidelity global kinetic 1-dimensional 2-site SCR model with mass transfer, heat transfer and global reaction mechanisms was developed for a Cu-zeolite catalyst. The model simulates the SCR performance for the engine exhaust conditions with NH3 maldistribution and aging effects, and the details are presented. SCR experimental data were collected for the model development, calibration and validation from a reactor at Oak Ridge National Laboratory (ORNL) and an engine experimental setup at Michigan Technological University (MTU) with a Cummins 2010 ISB engine. The model was calibrated separately to the reactor and engine data. The experimental setup, test procedures including a surrogate HD-FTP cycle developed for transient studies and the model calibration process are described. Differences in the model parameters were determined between the calibrations developed from the reactor and the engine data. It was determined that the SCR inlet NH3 maldistribution is one of the reasons causing the differences. The model calibrated to the engine data served as a basis for developing a reduced order SCR estimator model. The effect of the SCR inlet NO2/NOx ratio on the SCR performance was studied through simulations using the surrogate HD-FTP cycle. The cumulative outlet NOx and the overall NOx conversion efficiency of the cycle are highest with a NO2/NOx ratio of 0.5. The outlet NH3 is lowest for the NO2/NOx ratio greater than 0.6. A combined engine experimental and simulation study was performed to quantify the NH3 maldistribution at the SCR inlet and its effects on the SCR performance and kinetics. The uniformity index (UI) of the SCR inlet NH3 and NH3/NOx ratio (ANR) was determined to be below 0.8 for the production system. The UI was improved to 0.9 after installation of a swirl mixer into the SCR inlet cone. A multi-channel model was developed to simulate the maldistribution effects. The results showed that reducing the UI of the inlet ANR from 1.0 to 0.7 caused a 5-10% decrease in NOx reduction efficiency and 10-20 ppm increase in the NH3 slip. The simulations of the steady-state engine data with the multi-channel model showed that the NH3 maldistribution is a factor causing the differences in the calibrations developed from the engine and the reactor data. The Reactor experiments were performed at ORNL using a Spaci-IR technique to study the thermal aging effects. The test results showed that the thermal aging (at 800°C for 16 hours) caused a 30% reduction in the NH3 stored on the catalyst under NH3 saturation conditions and different axial concentration profiles under SCR reaction conditions. The kinetics analysis showed that the thermal aging caused a reduction in total NH3 storage capacity (94.6 compared to 138 gmol/m3), different NH3 adsorption/desorption properties and a decrease in activation energy and the pre-exponential factor for NH3 oxidation, standard and fast SCR reactions. Both reduction in the storage capability and the change in kinetics of the major reactions contributed to the change in the axial storage and concentration profiles observed from the experiments.

Blessed are the Peacemakers: Transnational Alliance, Protective Accompaniment and the Presbyterian Church of Colombia

The purpose of this thesis was to explore how Christian networks enable strategies of transnational alliance, whereby groups in different nations strive to strengthen one another’s leverage and credibility in order to resolve conflicts and elaborate new possibilities. This research does so by analyzing the case of the Presbyterian Church of Colombia (IPC). The project examines the historical development of the IPC from the initial missionary period of the 1850s until the present. Specifically, the purpose of the study was to consider how the historical struggle to articulate autonomy and equality vis-à-vis the U.S. Presbyterians (PCUSA) and paternalist models of ecclesial relations has affected recent political strategies pursued by the IPC. Despite the paternalism of the early missionary model, changing conceptions of social transformation during the 60s contributed to a shift in relations. Over time the IPC and PCUSA negotiated relationships in which groups both acknowledge a problematic history and insist upon an ethnic of partnership and respect. Today, PCUSA groups, in concert with the IPC, collaborate on a range of transnational political strategies aimed at strengthening the IPC’s leverage in local struggles for justice and peace. A review of this case suggests that long-established Christian networks may have an advantage over other civil society groups such as NGOs in facilitating strategies of transnational alliance. Although civil society organizations often have better access to important resources needed for international advocacy initiatives, Christian networks, such as the one established between the IPC and U.S. Presbyterian communities, rely on a history of negotiating power-disparity in order to elaborate relationships based on listening and partnership. Such findings prove important not only to how we conceptualize transnational alliance but also to the ways that we think about the history and future of Christian networks.

A Phenomenological Exploration of Black Male Law Enforcement Officers' Perspectives of Racial Profiling and Their Law Enforcement Career Exploration and Commitment

This phenomenological study explored Black male law enforcement officers’ perspectives of how racial profiling shaped their decisions to explore and commit to a law enforcement career. Criterion and snow ball sampling was used to obtain the 17 participants for this study. Super’s (1990) archway model was used as the theoretical framework. The archway model “is designed to bring out the segmented but unified and developmental nature of career development, to highlight the segments, and to make their origin clear” (Super, 1990, p. 201). Interview data were analyzed using inductive, deductive, and comparative analyses. Three themes emerged from the inductive analysis of the data: (a) color and/or race does matter, (b) putting on the badge, and (c) too black to be blue and too blue to be black. The deductive analysis used a priori coding that was based on Super’s (1990) archway model. The deductive analysis revealed the participants’ career exploration was influenced by their knowledge of racial profiling and how others view them. The comparative analysis between the inductive themes and deductive findings found the theme “color and/or race does matter” was present in the relationships between and within all segments of Super’s (1990) model. The comparative analysis also revealed an expanded notion of self-concept for Black males – marginalized and/or oppressed individuals. Self-concepts, “such as self-efficacy, self-esteem, and role self-concepts, being combinations of traits ascribed to oneself” (Super, 1990, p. 202) do not completely address the self-concept of marginalized and/or oppressed individuals. The self-concept of marginalized and/or oppressed individuals is self-efficacy, self-esteem, traits ascribed to oneself expanded by their awareness of how others view them. (DuBois, 1995; Freire, 1970; Sheared, 1990; Super, 1990; Young, 1990). Ultimately, self-concept is utilized to make career and life decisions. Current human resource policies and practices do not take into consideration that negative police contact could be the result of racial profiling. Current human resource hiring guidelines penalize individuals who have had negative police contact. Therefore, racial profiling is a discriminatory act that can effectively circumvent U.S. Equal Employment Opportunities Commission laws and serve as a boundary mechanism to employment (Rocco & Gallagher, 2004).

Language policy and critical discourse studies:towards an integrated approach

This chapter offers a framework for combining critical language policy with critical discourse studies (CDS) to analyse language policy as a process in the context of minority language policy in Wales. I propose a discursive approach to language policy, which starts from the premise that language policy is constituted, enacted, interpreted and (re)contextualised in and through language. This approach extends the critical language policy framework provided by Shohamy (Language policy: hidden agendas and new approaches. Routledge, London, 2006) and integrates perspectives from the context-sensitive discourse-historical approach in CDS. It incorporates discourse as an essential lens through which policy mechanisms, ideologies and practices are constituted and de facto language policy materialises. This chapter argues that conceptualising and analysing language policy as a discursive phenomenon enables a better understanding of the multi-layered nature of language policy that shapes the management and experience of corporate bilingualism in Wales.

EU-North Africa relations in cross-border law enforcement: new legal challenges for the EU in the post-Lisbon and post-Stockholm era

The Stockholm Programme, allied to the Lisbon Treaty, heralds a new era of development of the EU provisions on cross-border law enforcement. The focus is shifting from the ongoing internal EU developments to the external relations of the EU. Many North African countries have had long legal relationships with the EU through the Euro-Mediterranean Partnerships. A number of these partnership agreements make express references, at the political level, to the development of cross-border law enforcement provision, as is the case of Morocco and Algeria with regard to drug trafficking and manufacture, or the lengthy references by Egypt to many of the crimes of interest to the EU’s own law enforcement legal framework. Algeria is currently focusing on modernising their own police forces, with both Algeria and Tunisia, reforming their criminal judicial frameworks. Another key player, Libya, currently has no legal agreements with the EU, and at least until the recent conflict, maintained an observer status in the Euro-Mediterranean process. At a practitioner level, the European Police College (CEPOL) is currently involved in the Euromed Police II programme. Clearly momentum is developing, both within the EU and from a number of Euro-Med North African countries to develop closer law enforcement co-operation. This may well develop further with the recent changes in governments of a number of North African countries. The EU approach in the Police and Judicial Cooperation in Criminal Matters (PJCCM) policy area is to develop a legal framework upon which EU cross-border law enforcement will be based. The current EU cross-border law enforcement framework is the product of many years of multi-level negotiations. Challenges will arise as new countries from different legal and policing traditions will attempt to engage with already highly detailed legal and practice frameworks. The shared European legal traditions will not necessarily be reflected in the North African countries. This chapter critically analyses, from an EU legal perspective the problems and issues that will be encountered as the EU’s North African partner countries attempt to articulate into the existing, and still developing EU cross-border law enforcement framework.

Antioxidant activity and cholinesterase inhibition studies if four flavoring herb from Alentejo.

In Alzheimer’s disease, the most common form of dementia, the loss of cholinergic neurons leads to the progressive reduction of acetylcholine in the brain, resulting cognitive impairment. Inhibition of the hydrolysis of acetylcholine by blocking acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) has been considered as a potential target in the treatment of Alzheimer’s disease. Essential oils and extracts of aromatic plants may have an important role in the oxidative stress protection. Traditionally, in Alentejo (Portugal), aromatic herbs Calamintha nepeta, Foeniculum vulgare, Mentha spicata and Thymus mastichina are often used by local population as condiments in food preparations. In this study, essential oils (EOs) and aqueous extracts (decoction waters) of these flavouring herbs were selected in order to evaluate its antioxidant potential and ability to inhibit AChE and BChE activities. Results suggest the potential use of EOs and extracts as nutraceutical or pharmaceutical preparations in the prevention of the oxidative stress and degenerative diseases.

Quantum computing and post-quantum cryptography

One of the main practical implications of quantum mechanical theory is quantum computing, and therefore the quantum computer. Quantum computing (for example, with Shor’s algorithm) challenges the computational hardness assumptions, such as the factoring problem and the discrete logarithm problem, that anchor the safety of cryptosystems. So the scientific community is studying how to defend cryptography; there are two defense strategies: the quantum cryptography (which involves the use of quantum cryptographic algorithms on quantum computers) and the post-quantum cryptography (based on classical cryptographic algorithms, but resistant to quantum computers). For example, National Institute of Standards and Technology (NIST) is collecting and standardizing the post-quantum ciphers, as it established DES and AES as symmetric cipher standards, in the past. In this thesis an introduction on quantum mechanics was given, in order to be able to talk about quantum computing and to analyze Shor’s algorithm. The differences between quantum and post-quantum cryptography were then analyzed. Subsequently the focus was given to the mathematical problems assumed to be resistant to quantum computers. To conclude, post-quantum digital signature cryptographic algorithms selected by NIST were studied and compared in order to apply them in today’s life.

Quantitative analysis of pre- and post-operative valvular annulus deformations following valvular insufficiency

Valvular insufficiency is a growingly common valvular heart disease that frequently is associated with regurgitation. Atrioventricular incompetency can lead to overall ventricular and atrial enlargement, volume overload, heart impairment and, if not treated, can culminate in heart failure. With the advances in technology and the increasing interest in devices that have lower post-operative burden on patients, transcatheter mitral and tricuspid valve repair systems are going through a phase of rapid development and growing use. In this work, we aimed to quantitatively assess the morphology of mitral and tricuspid annuli in patients who underwent transcatheter valve repair with MitraClip/TriClip, before and after the intervention, using three-dimensional transoesophageal echocardiography images, in order to evaluate the geometrical changes of the annulus following the intervention. For our purposes, firstly, we implemented a tool for the visualization and navigation of the volumetric data across the cardiac cycle. Then, in order to track the annulus over the cardiac cycle, we extracted five rotational slices from the volume data, selected two initial points on each slice, and tracked these points across the cardiac cycle using KLT algorithm. In a first stage we led a parameters optimization for the tracking method, and we studied the sensitivity of the KLT algorithm to the initialization points, that are manually chosen by the user. In a second stage, we analysed 10 subjects (5 for mitral regurgitation and 5 for tricuspid regurgitation), tracking their annulus before and after valve repairment. In conclusion, we found in all our 10 subjects that immediately after the intervention there is a shortening of the major diameters of the valves, mainly the shortest diameter, due to the clip application, that leads to a reduction of the perimeter and the area of the annulus.

Development and scale-up studies of bio-based poly(ester-amide)s

Plastics are polymers of conventional and extensive use in our day-to-day life. This is due to their light weight, adaptability to different uses and low prices. A downside of such extensive use is the environmental pollution arising from plastic production and disposal. Indeed, many commodity polymers are produced from non-renewable resources while other do not bio-degrade after their end-of-life disposal. Consequently, the ideal polymer comes from renewable raw materials and bio-degrades after its disposal, meaning that it would do little or no harm to the environment from the beginning to the end of its life cycle. In this thesis project a class of bio-based and bio-degradable co-polymers, namely poly(ester-amide)s, was investigated because of their tunable mechanical and bio-degradation properties as well as their renewable origin. Such polymers were synthetized and characterized thermically and mechanically. Furthermore, a scale-up procedure was developed and applied to one polymer and processing trials were made with the material obtained after scale-up.

Quality controls for the Mu2e electromagnetic calorimeter and R&D studies for the muon capture rate determination

According to the SM, while Lepton Flavour Violation is allowed in the neutral sector, Charged Lepton Flavour Violation (CLFV) processes are forbidden. The Mu2e Experiment at Fermilab will search for the CLFV process of neutrinoless conversion of a muon into an electron within the field of an Al nucleus. The Mu2e detectors and its state-of-the-art superconducting magnetic system are presented, with special focus put to the electromagnetic crystal calorimeter. The calorimeter is composed by two annular disks, each one hosting pure CsI crystals read-out by custom silicon photomultipliers (SiPMs). The SiPMs are amplified by custom electronics (FEE) and are glued to copper holders in group of 2 SiPMs and 2 FEE boards thus forming a crystal Readout Unit. These Readout Units are being tested at the Quality Control (QC) Station, whose design, realization and operations are presented in this work. The QC Station allows to determine the gain, the response and the photon detection efficiency of each unit and to evaluate the dependence of these parameters from the supply voltage and temperature. The station is powered by two remotely-controlled power supplies and monitored thanks to a Slow Control system which is also illustrated in this work. In this thesis, we also demonstrated that the calorimeter can perform its own measurement of the Mu2e normalization factor, i.e. the counting of the 1.8 MeV photon line produced in nuclear muon captures. A specific calorimeter sub-system called CAPHRI, composed by four LYSO crystals with SiPM readout, has been designed and tested. We simulated the capability of this system on performing this task showing that it can get a faster and more reliable measurement of the muon capture rates with respect to the current Mu2e detector dedicated to this measurement. The characterization of energy resolution and response uniformity of the four procured LYSO crystals are llustrated.

A Infância na latitude zero: as brincadeiras da criança 'global' africana

Tese de Doutoramento em Estudos da Criança (área de especialização em Sociologia da Infância).

Edgar Rice Burroughs' Martian Novels as an Early Paradigm of Racial Toleration

The Martian novels of Edgar Rice Burroughs (ERB) provide an early paradigm of racial toleration by displacing the heterogeneous race conflicts of the U. S. to an interplanetary location. There, the protagonist John Carter, representing Burroughs himself, introduces a level of racial acceptance and integration almost unheard of on the Earth of that era (the early twentieth century).

Dispelling the Mascot Myth: The Misuse of Indigenous Peoples as Mascots in American Schools

This workshop details the deculturalization process that takes place when Indigenous Peoples are used as mascots in school-related activities; examines the arguments(s) and defensive tactics used by sports fans and school officials to maintain these hegemonic images; and offers successful strategies for developing policy toward the elimination of Indigenous Peoples as mascots.