Investigating the Role of PDE4D1/2 in Vascular Smooth Muscle Cell Desensitization

Vascular smooth muscle cell (VSMC) behaviour and phenotypic modulation is critical to vessel repair following damage, and the progression of various cardiovascular diseases. The second messenger cyclic adenosine monophosphosphate (cAMP) plays a key role in VSMC function under the synthetic/activated phenotype, which is typically associated with unhealthy cell behaviour. Consequently, cAMP signaling is often targeted in attempts to impact several pathological diseases, including atherosclerosis, restenosis, and pulmonary arterial hypertension (PAH). The cyclic nucleotide phosphodiesterases (PDEs) catalyze hydrolysis of cAMP to an inactive form, and therefore directly regulate cAMP signaling. The PDE4D family dominates in synthetic VSMCs, and there is considerable interest in determining how distinct PDE4D isoforms affect cell function. Specifically, we are interested in the potential link between short isoforms of PDE4D and VSMC desensitization to pharmacological agents that impact cardiovascular disease via cAMP signaling. This study extends on previous work that assessed the expression of PDE4D splice variants in rat aortic VSMCs following prolonged challenge with cAMP-elevating agents. It was determined that PDE4D1 and PDE4D2 were uniquely expressed in synthetic VSMCs incubated with these agents, and that this upregulation impacted PDE activity and cAMP accumulation in these cells. Here, we report that PDE4D1 and PDE4D2 are markedly upregulated in synthetic human aortic smooth muscle cells (HASMCs) following prolonged challenge with cAMP-elevating agents. Using a combination of RNAi-based and pharmacological approaches, we establish that this upregulation is reflected in levels of cAMP PDE activity, and restricted to the cytosolic sub-cellular compartment. Our results suggest a role for localized PDE4D1 and PDE4D2 activity in regulating cAMP-mediated desensitization in HASMCs, and highlight their therapeutic potential in treating various cardiovascular diseases.

If People Were Kaleidoscopes: Sharpening the Resolution on Patient Engagement in Safety

Healthcare is unacceptably error prone. The question remains why, with 20 years of evidence, is error and harm reduction not being effective? While precise numbers may be debated, all stakeholders recognize the frequency of healthcare errors is unacceptable, and greater efforts to ensure safety must occur. In recent years, one of these strategies has been the inclusion of the patient and their family as partners in safety, and has been a required organizational practice of Accreditation Canada in many of their standard sets. Existing patient advisories created to encourage engagement, have typically not included patient perspectives in their development or been comprehensively evaluated. There are no existing tools to determine if and how a patient wants to be involved in safety engagement. As such, a multi-phased study was undertaken to advance our knowledge about the client’s and family’s role in promoting safety. Phase 1 of the study was a scoping review to methodically review the existing literature about patients’ and families’ attitudes, beliefs and behaviours about their involvement in healthcare safety. Phase 2 was designed to inductively explore how a group of patients in an Ontario, Canada, community hospital, describe healthcare safety and see their role in preventing error. The study findings, which include the narratives of 30 patients and 4 family members, indicate that although there are shared themes that influence a patient’s engagement in patient safety, every individual has unique, changing beliefs, experiences and reasons for involvement. Five conceptual themes emerged from their narratives: Personal Capacity, Experiential Knowledge, Personal Character, Relationships, and Meaning of Safety. These study results will be used to develop and test a pragmatic, accessible tool to enable providers a way to collaborate with patients for determining their personal level and type of safety involvement. The most ethical and responsible approach to healthcare safety is to consider every facet and potential way for improvement. This exploratory study provides fundamental insights into the complexity of patient engagement in safety, and evidence for future steps.

A Restorative Theory of Criminal Justice

In this project, I defend a restorative theory of criminal justice. I argue that the response to criminal wrongdoing in a just society should take the form of an attempt to heal the damage done to the community resulting from crime. I argue that the moral responsibilities of wrongdoers as wrongdoers ought to provide the framework for how a just society should respond to crime. Following the work of R.A. Duff, I argue that wrongdoers incur second-order duties of moral recognition. Wrongdoers owe it to others to recognize their wrongdoing for what it is, i.e. wrongdoing, and to shoulder certain burdens in order to express their repentant recognition to others via a meaningful apology. In short, wrongdoers owe it to their victims and others in the community to make amends. What I will deny, however, is the now familiar claim in the restorative justice literature that restoring the normative relationships in the community damaged by criminal forms of wrongdoing requires retributive punishment. In my view, how we choose to express the judgement that wrongdoers are blameworthy should flow from an all things considered judgment that is neither reducible to the judgement that the wrongdoer is culpably responsible for wronging others, nor the judgement that the wrongdoer in some basic sense “deserves to suffer” (or “deserves punishment,” etc.).

Communication-efficient decentralized sequential detection

The problem of decentralized sequential detection is studied in this thesis, where local sensors are memoryless, receive independent observations, and no feedback from the fusion center. In addition to traditional criteria of detection delay and error probability, we introduce a new constraint: the number of communications between local sensors and the fusion center. This metric is able to reflect both the cost of establishing communication links as well as overall energy consumption over time. A new formulation for communication-efficient decentralized sequential detection is proposed where the overall detection delay is minimized with constraints on both error probabilities and the communication cost. Two types of problems are investigated based on the communication-efficient formulation: decentralized hypothesis testing and decentralized change detection. In the former case, an asymptotically person-by-person optimum detection framework is developed, where the fusion center performs a sequential probability ratio test based on dependent observations. The proposed algorithm utilizes not only reported statistics from local sensors, but also the reporting times. The asymptotically relative efficiency of proposed algorithm with respect to the centralized strategy is expressed in closed form. When the probabilities of false alarm and missed detection are close to one another, a reduced-complexity algorithm is proposed based on a Poisson arrival approximation. In addition, decentralized change detection with a communication cost constraint is also investigated. A person-by-person optimum change detection algorithm is proposed, where transmissions of sensing reports are modeled as a Poisson process. The optimum threshold value is obtained through dynamic programming. An alternative method with a simpler fusion rule is also proposed, where the threshold values in the algorithm are determined by a combination of sequential detection analysis and constrained optimization. In both decentralized hypothesis testing and change detection problems, tradeoffs in parameter choices are investigated through Monte Carlo simulations.

Polymer Light-Emitting Electrochemical Cells with Embedded Bipolar Electrodes: Visualizing Bipolar Electrochemistry in Solid State

The work presented in this thesis examines the properties of BPEs of various configurations and under different operating conditions in a large planar LEC system. Detailed analysis of time-lapsed fluorescence images allows us to calculate the doping propagation speed from the BPEs. By introducing a linear array of BPEs or dispersed ITO particles, multiple light-emitting junctions or a bulk homojunction have been demonstrated. In conclusion, it has been observed that both applied bias voltages and sizes of BPEs affected the electrochemical doping from the BPE. If the applied bias voltage was initially not sufficiently high enough, a delay in appearance of doping from the BPE would take place. Experiments of parallel BPEs with different sizes (large, medium, small) demonstrate that the potential difference across the BPEs has played a vital role in doping initiation. Also, the p-doping propagation distance from medium-sized BPE has displayed an exponential growth over the time-span of 70 seconds. Experiments with a linear array of BPEs with the same size demonstrate that the doping propagation speed of each floating BPE was the same regardless of its position between the driving electrodes. Probing experiments under high driving voltages further demonstrated the potential of having a much more efficient light emission from an LEC with multiple BPEs.

How the Pershore Plum Won the Great War

The First World War was won not just on the battlefields but on the Home Front, by the men, women and children left behind. This book explores the lives of the people of Pershore and the surrounding district in wartime, drawing on their memories, letters, postcards, photographs, leaflets and recipes to demonstrate how their hard work in cultivating and preserving fruit and vegetables helped to win the Great War. Pershore plums were used to make jam for the troops; but ensuring these and other fruits and vegetables were grown and harvested required the labour of land girls, Boy Scouts, schoolchildren, Irish labourers and Belgian refugees. When submarine warfare intensified, food shortages occurred and it became vital for Britain to grow more and eat less food. Housewives faced many challenges in feeding their families and so in 1916 the Pershore Women’s Institute was formed, providing many women with practical help and companionship during some of Britain’s darkest hours in history.

Attack simulation based software protection assessment method

Software protection is an essential aspect of information security to withstand malicious activities on software, and preserving software assets. However, software developers still lacks a methodology for the assessment of the deployed protections. To solve these issues, we present a novel attack simulation based software protection assessment method to assess and compare various protection solutions. Our solution relies on Petri Nets to specify and visualize attack models, and we developed a Monte Carlo based approach to simulate attacking processes and to deal with uncertainty. Then, based on this simulation and estimation, a novel protection comparison model is proposed to compare different protection solutions. Lastly, our attack simulation based software protection assessment method is presented. We illustrate our method by means of a software protection assessment process to demonstrate that our approach can provide a suitable software protection assessment for developers and software companies.

Estudo de caso: minimização e reúso de água em shopping center da região sul do Brasil

The main issues related to water conservation in urban centers are the increase in water supply cost, demand growth, pollution and differences in the distribution of water resources. Water conservation, the controlled and efficient use of water, includes both measures as reasonable means of water reuse. Thus, conservation practices are an effective way to meet demand and supply water to new activities and users without jeopardizing the supplying water bodies and preserving the natural environment. This study aims to examine the water management of a shopping mall and the use of rainwater harvesting combined with greywater reuse. For buildings in general, water loss is common due to leaks in the hydraulic and restroom equipment. These losses, which are caused by a high volume of water used and wasted in the system, are often the result of design errors, incorrect maintenance procedures and users' bad habits In southern Brazil, where there is rainfall almost all year long, water shortages occasionally occur, particularly in some winter mouths. One difficulty that appears on rainwater studies is the proper determination of rainwater volume that can be used to address water supply systems. In this work, the simulation method was used to determine this volume. Thus, simulations with the following variables: rainfall, catchment area and water consumption were performed. For mall's hydraulic systems, segmented alternatives are adopted. That is, focusing on the use of rainwater or greywater reuse. Other alternatives of effluent reuse have been slightly discussed due to sanitary issues, those are effluents from toilets and kitchen sinks. The adoption of greywater may be feasible if there is a significant flow of greywater to comply water demand for toilet flushing. The inspections made in this study found that the quantity of sinks was insufficient to supply an adequate amount of water to toilets and urinals. The greywater reuse system was found to be infeasible in terms of demand and supply of water. Conversely, the rainwater harvesting system was entirely feasible and easily supplied water to all restrooms and contributed to the cooling of the air conditioning system with a short payback period. One of the challenges of this work was the need to compare the actual water consumption with a water consumption parameter used in buildings. Thus, a method that addresses the generation of specific consumption indexes for specific activity (like a mall) was used. The water consumption indices showed that this mall has a satisfactory water management program.

El desarrollo de capacidades y la gestión del conocimiento en los potenciales de cambio y competitividad universitaria

El presente artículo se centra en la consideración de que hay empresas que desconocen los mecanismos necesarios para preservar y dinamizar los conocimientos que se generan en sus interacciones cotidianas a través de los roles y perfiles profesionales de quienes forman parte de ellas. Se parte del supuesto que estas empresas, por estar atentas a las cadenas de producción, no centran su mirada en la gestión del conocimiento, posibilitando la fuga del mismo hacia otros sectores, lo que constituye una pérdida irreparable respecto al potencial humano y al capital cognitivo. Con el objetivo de adquirir conocimiento sobre cómo se puede mejorar y desarrollar la capacidad profesional en lo que respecta al aprendizaje, las TIC y las estrategias de comunicación dentro de un marco de una organización competitiva se realizó el proyecto a partir de un estudio de caso en la Universidad de Medellín y su Departamento de Ciencias Básicas bajo una metodología cualitativa y usando el método etnográfico. Entre los resultados se puede resaltar: 1. Si la gestión que implica evaluar el desempeño de los docentes no funciona bien, existe la posibilidad de que se sientan desmotivados para realizar cambios profesionales; 2. El proyecto Permanencia con Calidad muestra un proceso de cambio y con ello un desarrollo de capacidades profesionales y una nueva práctica, lo cual se manifiesta en la manera en que los docentes se expresan sobre su rol profesional

Comparison of five popular normalization methods using a spike-in proteomics data set

Mass spectrometry (MS)-based proteomics has seen significant technical advances during the past two decades and mass spectrometry has become a central tool in many biosciences. Despite the popularity of MS-based methods, the handling of the systematic non-biological variation in the data remains a common problem. This biasing variation can result from several sources ranging from sample handling to differences caused by the instrumentation. Normalization is the procedure which aims to account for this biasing variation and make samples comparable. Many normalization methods commonly used in proteomics have been adapted from the DNA-microarray world. Studies comparing normalization methods with proteomics data sets using some variability measures exist. However, a more thorough comparison looking at the quantitative and qualitative differences of the performance of the different normalization methods and at their ability in preserving the true differential expression signal of proteins, is lacking. In this thesis, several popular and widely used normalization methods (the Linear regression normalization, Local regression normalization, Variance stabilizing normalization, Quantile-normalization, Median central tendency normalization and also variants of some of the forementioned methods), representing different strategies in normalization are being compared and evaluated with a benchmark spike-in proteomics data set. The normalization methods are evaluated in several ways. The performance of the normalization methods is evaluated qualitatively and quantitatively on a global scale and in pairwise comparisons of sample groups. In addition, it is investigated, whether performing the normalization globally on the whole data or pairwise for the comparison pairs examined, affects the performance of the normalization method in normalizing the data and preserving the true differential expression signal. In this thesis, both major and minor differences in the performance of the different normalization methods were found. Also, the way in which the normalization was performed (global normalization of the whole data or pairwise normalization of the comparison pair) affected the performance of some of the methods in pairwise comparisons. Differences among variants of the same methods were also observed.

Educação, criação e autoria nas manifestações tradicionais das culturas populares : as manifestações da Festa do Divino de Pirenópolis – GO

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Educação, Programa de Pós-Graduação em Educação, 2015.

Avaliação térmica dos resíduos da destilação atmosférica das blendas - biodiesel/diesel

The worldwide concern regarding the use of sustainable energy and preserving the environment are determining factors in the search for resources and alternative sources of energy and therefore fuel less aggressive nature. In response to these difficulties Biodiesel has emerged as a good solution because it is produced from renewable sources, produces burns cleaner and is easily reproducible. This work was synthesized with biodiesel oil, sunflower via homogeneous catalysis in the presence of KOH, with and without the use of BHT and subsequently added to the blends BX (a proportion of biodiesel X = 5, 10, 15 and 20 %). Atmospheric distillation of the analysis, performed in blends with and without BHT were collected residue generated by each sample and performed a study heat from the thermogravimetric analysis at a heating rate of 10 °C*min-1, nitrogen atmosphere and heating to 600 °C. According to the specifications of Resolution N 7/2008 for biodiesel, it was found that the synthesized material was in accordance with the specifications. For blends showed that the samples are in accordance with the Resolution of ANP N 42/2009. From the TG / DTG curves of the samples of biodiesel, blends and waste can be seen that these show a single loss of thermal decomposition concerning constituents present in each sample. The blends without BHT with ratios of 5%, 10% and 15% biodiesel showed a lower amount of waste (1,07%; 1,09% e 1,10%) to mineral diesel (1,15%). Therefore, it is concluded that the addition of biodiesel with diesel mineral can improve some physico-chemical parameters, but also, depending on the added amount, decreasing the amount of waste generated. This fact is of great importance because the carbonaceous residue can cause problems in mechanical equipment and parts for vehicles, causing more frequent maintenance, and this is not desirable

An Integrative Case Study of Positive Youth Development in a Recreational Community Sport Program

Thesis (Ph.D, Kinesiology & Health Studies) -- Queen's University, 2016-07-21 14:22:50.954

Vicarious Power: The Interpersonal Transference of Power

Thesis (Ph.D, Psychology) -- Queen's University, 2016-07-29 15:58:26.695

Medium-Chain-Length Poly (3-Hydroxyalkanoate) Nanoparticle Suspensions

Thesis (Master, Chemical Engineering) -- Queen's University, 2016-08-16 04:58:55.749