883 resultados para patch clamp glioblastoma t98g pedot:pss


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Os objetivos a atingir em 2020 no que respeita ao processo de investigação e desenvolvimento de medicamentos estão claramente focados na redução em termos temporais na investigação pré-clínica e clínica e na diminuição da taxa de atrito entre as novas moléculas. De forma a atingir estes objetivos, um novo conceito tem sido desenvolvido e aplicado a este complexo e moroso processo, este é a Farmacologia Quantitativa e de Sistemas. Além disso, esta abordagem inovadora pode ser crucial para o tratamento de determinados tipos de tumores cerebrais letais – Glioblastoma Multiforme (GBM) – que permanecem um desafio terapêutico, e por tanto, uma doença com um destino fatal para os doentes. Por estas razões, esta dissertação de mestrado apresenta uma especial relevância, tendo por objetivos avaliar o potencial impacto e importância biológica da variação de parâmetros farmacológicos, para além da potência, no contexto da resposta celular ao fármaco, pela avaliação da perturbação induzida em células do GBM por inibidores do PDK1 e pela realização de uma caracterização multiparamêtrica dose-resposta destas novas moléculas. A presente dissertação assume em Portugal a vanguarda na área da Farmacologia Quantitativa e de Sistemas aplicada ao processo de investigação e desenvolvimento de medicamentos. Em última estância, esta dissertação poderá contribuir para uma melhor previsão dos fármacos durante este processo, significando assim possíveis vantagens para os utentes, indústrias farmacêuticas, institutos de investigação, governo e institutos superiores.

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

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Part 8: Business Strategies Alignment

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According to ecological theory, the coexistence of competitors in patchy environments may be facilitated by hierarchical spatial segregation along axes of environmental variation, but empirical evidence is limited. Cabrera and water voles show a metapopulation-like structure in Mediterranean farmland, where they are known to segregate along space, habitat, and time axes within habitat patches. Here, we assess whether segregation also occurs among and within landscapes, and how this is influenced by patch-network and matrix composition. We surveyed 75 landscapes, each covering 78 ha, where we mapped all habitat patches potentially suitable for Cabrera and water voles, and the area effectively occupied by each species (extent of occupancy). The relatively large water vole tended to be the sole occupant of landscapes with high habitat amount but relatively low patch density (i.e., with a few large patches), and with a predominantly agricultural matrix, whereas landscapes with high patch density (i.e.,many small patches) and low agricultural cover, tended to be occupied exclusively by the small Cabrera vole. The two species tended to co-occur in landscapes with intermediate patch-network and matrix characteristics, though their extents of occurrence were negatively correlated after controlling for environmental effects. In combination with our previous studies on the Cabrera-water vole system, these findings illustrated empirically the occurrence of hierarchical spatial segregation, ranging from withinpatches to among-landscapes. Overall, our study suggests that recognizing the hierarchical nature of spatial segregation patterns and their major environmental drivers should enhance our understanding of species coexistence in patchy environments.

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We present an isogeometric thin shell formulation for multi-patches based on rational splines over hierarchical T-meshes (RHT-splines). Nitsche’s method is employed to efficiently couple the patches. The RHT-splines have the advantages of allowing a computationally feasible local refine- ment, are free from linear independence, possess high order continuity and satisfy the partition of unity and non-negativity, properties. In addition, C 1 continuity of the RHT-splines obviates to use of rotational degrees of freedom. The good performance of the present method is demonstrated by a number of numerical examples.

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The basis of treatment for amblyopia (poor vision due to abnormal visual experience early in life) for 250 years has been patching of the unaffected eye for extended times to ensure a period of use of the affected eye. Over the last decade randomised controlled treatment trials have provided some evidence on how to tailor amblyopia therapy more precisely to achieve the best visual outcome with the least negative impact on the patient and the family. This review highlights the expansion of knowledge regarding treatment for amblyopia and aims to provide optometrists with a summary of research evidence to enable them to better treat amblyopia. Treatment for amblyopia is effective, as it reduces overall prevalence and severity of visual loss in this population. Correction of refractive error alone significantly improves visual acuity, sometimes to the point where further amblyopia treatment is not required. Atropine penalisation and patch occlusion are effective in treating amblyopia. Lesser amounts of occlusion or penalisation have been found to be just as effective as greater amounts. Recent evidence has highlighted that occlusion or penalisation in amblyopia treatment can create negative changes in behaviour in children and impact on family life. These complications should be considere when prescribing treatment because they can negatively affect compliance. Studies investigating the maximum age at which treatment of amblyopia can still be effective and the importance of near activities during occlusion are ongoing.

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It is unclear which theoretical dimension of psychological stress affects health status. We hypothesized that both distress and coping mediate the relationship between socio-economic position and tooth loss. Cross-sectional data from 2915 middle-aged adults evaluated retention of < 20 teeth, behaviors, psychological stress, and sociodemographic characteristics. Principal components analysis of the Perceived Stress Scale (PSS) extracted 'distress' (a = 0.85) and 'coping' (a =0.83) factors, consistent with theory. Hierarchical entry of explanatory variables into age- and sex-adjusted logistic regression models estimated odds ratios (OR) and 95% confidence intervals [95% CI] for retention of < 20 teeth. Analysis of the separate contributions of distress and coping revealed a significant main effect of coping (OR = 0.7 [95% CI = 0.7-0.8]), but no effect for distress (OR = 1.0 [95% CI = 0.9-1.1]) or for the interaction of coping and distress. Behavior and psychological stress only modestly attenuated socio-economic inequality in retention of < 20 teeth, providing evidence to support a mediating role of coping.

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Amphibian is an 10’00’’ musical work which explores new musical interfaces and approaches to hybridising performance practices from the popular music, electronic dance music and computer music traditions. The work is designed to be presented in a range of contexts associated with the electro-acoustic, popular and classical music traditions. The work is for two performers using two synchronised laptops, an electric guitar and a custom designed gestural interface for vocal performers - the e-Mic (Extended Mic-stand Interface Controller). This interface was developed by one of the co-authors, Donna Hewitt. The e-Mic allows a vocal performer to manipulate the voice in real time through the capture of physical gestures via an array of sensors - pressure, distance, tilt - along with ribbon controllers and an X-Y joystick microphone mount. Performance data are then sent to a computer, running audio-processing software, which is used to transform the audio signal from the microphone. In this work, data is also exchanged between performers via a local wireless network, allowing performers to work with shared data streams. The duo employs the gestural conventions of guitarist and singer (i.e. 'a band' in a popular music context), but transform these sounds and gestures into new digital music. The gestural language of popular music is deliberately subverted and taken into a new context. The piece thus explores the nexus between the sonic and performative practices of electro acoustic music and intelligent electronic dance music (‘idm’). This work was situated in the research fields of new musical interfacing, interaction design, experimental music composition and performance. The contexts in which the research was conducted were live musical performance and studio music production. The work investigated new methods for musical interfacing, performance data mapping, hybrid performance and compositional practices in electronic music. The research methodology was practice-led. New insights were gained from the iterative experimental workshopping of gestural inputs, musical data mapping, inter-performer data exchange, software patch design, data and audio processing chains. In respect of interfacing, there were innovations in the design and implementation of a novel sensor-based gestural interface for singers, the e-Mic, one of the only existing gestural controllers for singers. This work explored the compositional potential of sharing real time performance data between performers and deployed novel methods for inter-performer data exchange and mapping. As regards stylistic and performance innovation, the work explored and demonstrated an approach to the hybridisation of the gestural and sonic language of popular music with recent ‘post-digital’ approaches to laptop based experimental music The development of the work was supported by an Australia Council Grant. Research findings have been disseminated via a range of international conference publications, recordings, radio interviews (ABC Classic FM), broadcasts, and performances at international events and festivals. The work was curated into the major Australian international festival, Liquid Architecture, and was selected by an international music jury (through blind peer review) for presentation at the International Computer Music Conference in Belfast, N. Ireland.

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Decision support systems (DSS) have evolved rapidly during the last decade from stand alone or limited networked solutions to online participatory solutions. One of the major enablers of this change is the fastest growing areas of geographical information system (GIS) technology development that relates to the use of the Internet as a means to access, display, and analyze geospatial data remotely. World-wide many federal, state, and particularly local governments are designing to facilitate data sharing using interactive Internet map servers. This new generation DSS or planning support systems (PSS), interactive Internet map server, is the solution for delivering dynamic maps and GIS data and services via the world-wide Web, and providing public participatory GIS (PPGIS) opportunities to a wider community (Carver, 2001; Jankowski & Nyerges, 2001). It provides a highly scalable framework for GIS Web publishing, Web-based public participatory GIS (WPPGIS), which meets the needs of corporate intranets and demands of worldwide Internet access (Craig, 2002). The establishment of WPPGIS provides spatial data access through a support centre or a GIS portal to facilitate efficient access to and sharing of related geospatial data (Yigitcanlar, Baum, & Stimson, 2003). As more and more public and private entities adopt WPPGIS technology, the importance and complexity of facilitating geospatial data sharing is growing rapidly (Carver, 2003). Therefore, this article focuses on the online public participation dimension of the GIS technology. The article provides an overview of recent literature on GIS and WPPGIS, and includes a discussion on the potential use of these technologies in providing a democratic platform for the public in decision-making.

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Within the Australian wet tropics bioregion, only 900 000 hectares of once continuous rainforest habitat between Townsville and Cooktown now remains. While on the Atherton Tableland, only 4% of the rainforest that once occurred there remains today with remnant vegetation now forming a matrix of rainforest dispersed within agricultural land (sugarcane, banana, orchard crops, townships and pastoral land). Some biologists have suggested that remnants often support both faunal and floral communities that differ significantly from remaining continuous forest. Australian tropical forests possess a relatively high diversity of native small mammal species particularly rodents, which unlike larger mammalian and avian frugivores elsewhere, have been shown to be resilient to the effects of fragmentation, patch isolation and reduction in patch size. While small mammals often become the dominant mammalian frugivores, in terms of their relative abundance, the relationship that exists between habitat diversity and structure, and the impacts of small mammal foraging within fragmented habitat patches in Australia, is still poorly understood. The relationship between foraging behaviour and demography of two small mammal species, Rattus fuscipes and Melomys cervinipes, and food resources in fragmented rainforest sites, were investigated in the current study. Population densities of both species were strongly related with overall density of seed resources in all rainforest fragments. The distribution of both mammal species however, was found to be independent of the distribution of seed resources. Seed utilisation trials indicated that M.cervinipes and R.fuscipes had less impact on seed resources (extent of seed harvesting) than did other rainforest frugivores. Experimental feeding trials demonstrated that in 85% of fruit species tested, rodent feeding increased seed germination by a factor of 3.5 suggesting that in Australian tropical rainforest remnants, small mammals may play a significant role in enhancing germination of large seeded fruits. This study has emphasised the role of small mammals in tropical rainforest systems in north eastern Australia, in particular, the role that they play within isolated forest fragments where larger frugivorous species may be absent.

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An algorithm to improve the accuracy and stability of rigid-body contact force calculation is presented. The algorithm uses a combination of analytic solutions and numerical methods to solve a spring-damper differential equation typical of a contact model. The solution method employs the recently proposed patch method, which especially suits the spring-damper differential equations. The resulting semi-analytic solution reduces the stiffness of the differential equations, while performing faster than conventional alternatives.

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In recent years, multilevel converters are becoming more popular and attractive than traditional converters in high voltage and high power applications. Multilevel converters are particularly suitable for harmonic reduction in high power applications where semiconductor devices are not able to operate at high switching frequencies or in high voltage applications where multilevel converters reduce the need to connect devices in series to achieve high switch voltage ratings. This thesis investigated two aspects of multilevel converters: structure and control. The first part of this thesis focuses on inductance between a DC supply and inverter components in order to minimise loop inductance, which causes overvoltages and stored energy losses during switching. Three dimensional finite element simulations and experimental tests have been carried out for all sections to verify theoretical developments. The major contributions of this section of the thesis are as follows: The use of a large area thin conductor sheet with a rectangular cross section separated by dielectric sheets (planar busbar) instead of circular cross section wires, contributes to a reduction of the stray inductance. A number of approximate equations exist for calculating the inductance of a rectangular conductor but an assumption was made that the current density was uniform throughout the conductors. This assumption is not valid for an inverter with a point injection of current. A mathematical analysis of a planar bus bar has been performed at low and high frequencies and the inductance and the resistance values between the two points of the planar busbar have been determined. A new physical structure for a voltage source inverter with symmetrical planar bus bar structure called Reduced Layer Planar Bus bar, is proposed in this thesis based on the current point injection theory. This new type of planar busbar minimises the variation in stray inductance for different switching states. The reduced layer planar busbar is a new innovation in planar busbars for high power inverters with minimum separation between busbars, optimum stray inductance and improved thermal performances. This type of the planar busbar is suitable for high power inverters, where the voltage source is supported by several capacitors in parallel in order to provide a low ripple DC voltage during operation. A two layer planar busbar with different materials has been analysed theoretically in order to determine the resistance of bus bars during switching. Increasing the resistance of the planar busbar can gain a damping ratio between stray inductance and capacitance and affects the performance of current loop during switching. The aim of this section is to increase the resistance of the planar bus bar at high frequencies (during switching) and without significantly increasing the planar busbar resistance at low frequency (50 Hz) using the skin effect. This contribution shows a novel structure of busbar suitable for high power applications where high resistance is required at switching times. In multilevel converters there are different loop inductances between busbars and power switches associated with different switching states. The aim of this research is to consider all combinations of the switching states for each multilevel converter topology and identify the loop inductance for each switching state. Results show that the physical layout of the busbars is very important for minimisation of the loop inductance at each switch state. Novel symmetrical busbar structures are proposed for multilevel converters with diode-clamp and flying-capacitor topologies which minimise the worst case in stray inductance for different switching states. Overshoot voltages and thermal problems are considered for each topology to optimise the planar busbar structure. In the second part of the thesis, closed loop current techniques have been investigated for single and three phase multilevel converters. The aims of this section are to investigate and propose suitable current controllers such as hysteresis and predictive techniques for multilevel converters with low harmonic distortion and switching losses. This section of the thesis can be classified into three parts as follows: An optimum space vector modulation technique for a three-phase voltage source inverter based on a minimum-loss strategy is proposed. One of the degrees of freedom for optimisation of the space vector modulation is the selection of the zero vectors in the switching sequence. This new method improves switching transitions per cycle for a given level of distortion as the zero vector does not alternate between each sector. The harmonic spectrum and weighted total harmonic distortion for these strategies are compared and results show up to 7% weighted total harmonic distortion improvement over the previous minimum-loss strategy. The concept of SVM technique is a very convenient representation of a set of three-phase voltages or currents used for current control techniques. A new hysteresis current control technique for a single-phase multilevel converter with flying-capacitor topology is developed. This technique is based on magnitude and time errors to optimise the level change of converter output voltage. This method also considers how to improve unbalanced voltages of capacitors using voltage vectors in order to minimise switching losses. Logic controls require handling a large number of switches and a Programmable Logic Device (PLD) is a natural implementation for state transition description. The simulation and experimental results describe and verify the current control technique for the converter. A novel predictive current control technique is proposed for a three-phase multilevel converter, which controls the capacitors' voltage and load current with minimum current ripple and switching losses. The advantage of this contribution is that the technique can be applied to more voltage levels without significantly changing the control circuit. The three-phase five-level inverter with a pure inductive load has been implemented to track three-phase reference currents using analogue circuits and a programmable logic device.

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The flying capacitor multilevel inverter (FCMLI) is a multiple voltage level inverter topology intended for high-power and high-voltage operations at low distortion. It uses capacitors, called flying capacitors, to clamp the voltage across the power semiconductor devices. A method for controlling the FCMLI is proposed which ensures that the flying capacitor voltages remain nearly constant using the preferential charging and discharging of these capacitors. A static synchronous compensator (STATCOM) and a static synchronous series compensator (SSSC) based on five-level flying capacitor inverters are proposed. Control schemes for both the FACTS controllers are developed and verified in terms of voltage control, power flow control, and power oscillation damping when installed in a single-machine infinite bus (SMIB) system. Simulation studies are performed using PSCAD/EMTDC to validate the efficacy of the control scheme and the FCMLI-based flexible alternating current transmission system (FACTS) controllers.

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The soil C saturation concept suggests a limit to whole soil organic carbon (SOC) accumulation determined by inherent physicochemical characteristics of four soil C pools: unprotected, physically protected, chemically protected, and biochemically protected. Previous attempts to quantify soil C sequestration capacity have focused primarily on silt and clay protection and largely ignored the effects of soil structural protection and biochemical protection. We assessed two contrasting models of SOC accumulation, one with no saturation limit (i.e., linear first-order model) and one with an explicit soil C saturation limit (i.e., C saturation model). We isolated soil fractions corresponding to the C pools (i.e., free particulate organic matter POM], microaggregate-associated C, silt- and clay-associated C, and non-hydrolyzable C) from eight long-term agroecosystern experiments across the United States and Canada. Due to the composite nature of the physically protected C pool, we firactioned it into mineral- vs. POM-associated C. Within each site, the number of fractions fitting the C saturation model was directly related to maximum SOC content, suggesting that a broad range in SOC content is necessary to evaluate fraction C saturation. The two sites with the greatest SOC range showed C saturation behavior in the chemically, biochemically, and some mineral-associated fractions of the physically protected pool. The unprotected pool and the aggregate-protected POM showed linear, nonsaturating behavior. Evidence of C saturation of chemically and biochemically protected SOC pools was observed at sites far from their theoretical C saturation level, while saturation of aggregate-protected fractions occurred in soils closer to their C saturation level.