Targeted Proteomics and Biochemical Fractionation: New Tools for Deciphering the Synapse in Schizophrenia

Schizophrenia is a chronic and debilitating psychiatric illness affecting approximately 1% of the world\u27s population for which there is no cure and treatment options are limited. Poor understanding of disease pathology and the difficulty in modeling psychiatric symptoms in animal models has hindered the search for a cure. Despite these difficulties great progress has been made on several fronts. Genetic studies have identified risk genes for disease, while fMRI and histology experiments have located brain regions with altered activity and cytoarchitecture. Pharmacology, molecular and immunology studies have identified receptor signaling pathways that are perturbed as well. One of the biggest challenges currently facing the field is elucidating the mechanisms linking genetic and environmental risk to the altered processes observed in the brains of schizophrenic patients. One approach to this question may be to investigate the postmortem brain tissues of patients. The goal of this thesis is to use mass spectrometry based proteomics to investigate the expression and partitioning of postsynaptic density proteins in these tissues. The postsynaptic density is implicated in disease pathology by genetic, cytoarchitecture and molecular studies. Thus, there is a good possibility that its protein composition reflects the crossroads of genetic risk and dysregulated molecular and developmental processes. A qualitative analysis of the human postsynaptic density was performed to catalog the proteins therein. Data from this experiment was harnessed to develop a mass spectrometry method for the targeted quantification of over 200 synaptic proteins. This method was then used to validate subcellular fractionation of human postmortem brain tissue to capture synaptic microdomains. Finally, this targeted mass spectrometry method was utilized to quantify synaptic protein expression and PSD partitioning in postmortem brain tissues of subjects and patients. The enrichment of PSD proteins was elevated in tissue from schizophrenic subjects compared to controls, while total protein expression was unaltered. This data suggests that partitioning, not expression, of postsynaptic proteins is altered in schizophrenia. The results of this study demonstrate the power of a targeted mass spectrometry approach and provide an important context in which to study the dysregulation of synaptic processes in schizophrenia

Roots of Social Enterprise : Entrepreneurial Philanthropy, England 1600-1908

Purpose: Insights into the roots of social enterprise from before the term was adopted are provided by examining histories of charitable service and comparing current understandings of social enterprise. Social enterprise models of welfare provision are evidenced from the 17th Century onwards. Persistent themes are identified that provide insights for current practice and understanding. Design/Methodology/Approach: This historiography examines interpretations from 1905 to the present day of examples of welfare provision between two watershed points: 1600, just prior to the Poor Laws and 1908, when the Old Age Pensions Act shifted emphasis in public sector provision. Findings: Activities that would nowadays be termed social enterprise are evidenced in histories of charitable philanthropy covering each Century since 1600. Prevailing attitudes uncritically demarcated deserving and undeserving poor. Histories contributed to a heroic narrative of social entrepreneurs, describing activities dependent on wellnetworked, politically active individuals that rarely continued beyond their involvement. The political environment was recognised to influence the types of organisations, governance and resourcing. Research limitations/Implications: The historiography takes examples from three centuries between 1600 and 1908 but is not comprehensive. Recurrent themes are identified for further research. Originality/Value: Social enterprise is a 21st Century label but not a new phenomenon. Identification of prevailing themes provides insights for the understanding of social enterprises in the 21st Century

Participatory Local Governance and Social Enterprise: Exploring the links between social entrepreneurial behaviour and democratic resource allocation through participatory budgeting

Participatory Budgeting (PB) is an innovation in participatory democracy. Inspired by social and political movements for citizen participation in Brazil in the 1980s which aimed to tackle democratic deficits and target public funds at the most marginalised communities (Abers et al. 2018; Novy & Leubolt, 2005). It has since evolved, with over 3000 reported experiences globally (Shah, 2007). PB is now expanding rapidly in Europe and the USA. With that shift it can be argued that it has moved away from primarily promoting equity and re-distribution of resources towards a focus on public participation in public service delivery (Sintomer et al., 2012), with the legitimacy that brings for government. We explored the extent to which PB can and does support the development of the local social economy, in particular the development of social enterprises and cooperatives. Through reflecting on the longitudinal qualitative learning of some key actors in the development of Participatory Budgeting in the UK, viewed through a social economy lens, we found that Participatory Budgeting, in and of itself, stimulates the development of new cooperatives and sustained social action, but mostly in instances where this was the specific intent. There are clear indications that Participatory Grant Making, and neighbourhood based Participatory Budgeting does stimulate civic action, build new social capital and develop agency within participating individuals, particularly in the unique form of Participatory Grant Making most common in the UK. Participatory Budgeting may generate socially entrepreneurial behaviours, and express values commonly held within social economy organisations. If a specific intention behind Participatory Budgeting was to promote a vibrant autonomous social economy it may become a useful addition to existing models to stimulate social entrepreneurship, and thus create the right conditions for the social economy to flourish

Hydrological response unit-based blowing snow modelling over mountainous terrain

Wind transport and sublimation of snow particles are common phenomena across high altitude and latitude cold regions and play important roles in hydrological and atmospheric water and energy budgets. In spite of this, blowing snow processes have not been incorporated in many mesoscale hydrological models and land surface schemes. A physically based blowing snow model, the Prairie Blowing Snow Model (PBSM), initially developed for prairie environments was used to model snow redistribution and sublimation by wind over two sites representative of mountainous regions in Canada: Fisera Ridge in the Rocky Mountain Front Ranges in Alberta, and Granger Basin in the Yukon Territory. Two models were used to run PBSM: the object-oriented hydrological model, Cold Regions Hydrological Modelling Platform (CRHM) and Environment Canada’s hydrological-land surface scheme, Modélisation Environmentale Communautaire – Surface and Hydrology (MESH). PBSM was coupled with the snowcover energy and mass-balance model (SNOBAL) within CRHM. Blowing snow algorithms were also incorporated into MESH to create MESH-PBSM. CRHM, MESH and MESH-PBSM were used to simulate the evolution of snowcover in hydrological response units (HRUs) over both Fisera Ridge and Granger Basin. To test the models of blowing snow redistribution and ablation over a relatively simple sequence of mountain topography, simulations were run from north to south over a linear ridge in the Canadian Rocky Mountains. Fisera Ridge snowcover simulations with CRHM were performed over two winters using two sets of wind speed forcing: (1) station observed wind speed, and (2) modelled wind speed from a widely applied empirical, terrain-based windflow model. Best results were obtained when using the site meteorological station wind speed data. The windflow model performed poorly when comparing the magnitude of modelled and observed wind speeds. Blowing snow sublimation, snowmelt and snowpack sublimation quantities were considerably overestimated when using the modelled wind speeds. As a result, end-of-winter snow accumulation was considerably underestimated on windswept HRUs. MESH and MESH-PBSM were also used to simulate snow accumulation and redistribution over these same HRUs. MESH-PBSM adequately simulated snow accumulation in the HRUs up until the spring snowmelt period. MESH without PBSM performed less well and overestimated accumulation on windward slopes and the ridge top whilst underestimating accumulation on lee slopes. Simulations in spring were degraded by a large overestimation of melt by MESH. The early and overestimated melt warrants a detailed examination that is outside the scope of this thesis. To parameterize snow redistribution in a mountain alpine basin, snow redistribution and sublimation by wind were calculated for three winters over Granger Basin using CRHM. Snow transport fluxes were distributed amongst HRUs using inter-HRU snow redistribution allocation factors. Three snow redistribution schemes of varying complexity were evaluated. CRHM model results showed that end-of-winter snow accumulation can be most accurately simulated when the inter-HRU snow redistribution schemes take into account wind direction and speed and HRU aerodynamic characteristics, along with the spatial arrangement of HRUs in the catchment. As snow transport scales approximately with the fourth power of wind speed (u4), inter-HRU snow redistribution allocation factors can be established according to the predominant u4 direction over a simulation period or can change at each time step according to an input measured wind direction. MESH and MESH-PBSM were used to simulate snow accumulation and ablation over these same HRUs. MESH-PBSM provided markedly better results than MESH without blowing snow algorithms. That snow redistribution by wind can be adequately simulated in computationally efficient HRUs over mountainous terrain has important implications for representing snow transport in large-scale hydrology models and land surface schemes. Snow redistribution by wind caused mountain snow accumulation to vary from 10% to 161% of seasonal snowfall within a headwater catchment in the Canadian Rocky Mountains, and blowing snow sublimation losses ranged from 10 to 37% of seasonal snowfall

The Relationship Between Equity Dependence and Environmental Performance

How does a corporation’s dependence on its shareholders affect the sustainability of its commitment to environmental performance? Although the literature has investigated how the financial markets respond to environmental and green initiatives, it has yet to examine the relationship between a firm’s commitment to the environment and its dependence on the equity markets. In this research, we explore the relationship between equity dependence and environmental performance and find equity dependence is significantly related to corporations’ environmental concerns but not their environmental strengths

Graphene: Kinks, Superlattices, Landau levels, and Magnetotransport

We review recent work on superlattices in monolayer and bilayer graphene. We highlight the role of the quasiparticle chirality in generating new Dirac fermion modes with tunable anisotropic velocities in one dimensional (1D) superlattices in both monolayer and bilayer graphene. We discuss the structure of the Landau levels and magnetotransport in such superlattices over a wide range of perpendicular (orbital) magnetic fields. In monolayer graphene, we show that an orbital magnetic field can reverse the anisotropy of the transport imposed by the superlattice potential, suggesting possible switching-type device applications. We also consider topological modes localized at a kink in an electric field applied perpendicular to bilayer graphene, and show how interactions convert these modes into a two-band Luttinger liquid with tunable Luttinger parameters. The band structures of electric field superlattices in bilayer graphene (with or without a magnetic field) are shown to arise naturally from a coupled array of such topological modes. We briefly review some bandstructure results for 2D superlattices. We conclude with a discussion of recent tunneling and transport experiments and point out open issues.Comment: Invited Review Article for Special Issue on Graphene, References added, Typos correcte

Applications of the quasi-steady-state photoconductance technique

The main applications of photoconductance measurements of silicon wafers are the determination of implicit device voltages, bulk minority carrier lifetimes, emitter recombination currents and surface recombination velocities. These applications are illustrated with selected experiments. Multicrystalline and single crystal silicon wafers are used with different surface conditions. The practical situations considered here range from industrial process control to advanced research. Interpreting photoconductance in terms of implicit device voltage is particularly useful: the swept illumination conditions used in a quasi-steady-state photoconductance measurement permit the determination of complete I-V characteristic curves, ideality factors and saturation currents. The more classical interpretation in terms of an effective lifetime teff allows to discriminate different recombination mechanisms. Shockley-Read-Hall bulk recombination with a large asymmetry between the fundamental electron and hole lifetimes is found to explain the strong variation of teff at low injection level observed in some samples. Measurements in the high injection range permit the determination of the emitter saturation current density. This saturation current can impose quite restrictive limits on the measurable minority carrier lifetimes at low injection, particularly for low resistivity wafers. The surface recombination velocity of the Si/SiO2 interface can also be a source of variability of teff