The primary aim of this thesis is to develop image processing algorithms to quantitatively determine the link between traumatic brain injury (TBI) severity and chronic traumatic encephalopathy (CTE) neuropathology, specifically looking into the role of blood-brain barrier disruption following TBI. In order to causally investigate the relationship between the tau protein neurodegenerative disease CTE and TBI, mouse models of blast neurotrauma (BNT) and impact neurotrauma (INT) are investigated. First, a high-speed video tracking algorithm is developed based on K-means clustering, active contours and Kalman filtering to comparatively study the head kinematics in blast and impact experiments. Then, to compare BNT and INT neuropathology, methods for quantitative analysis of macroscopic optical images and fluorescent images are described. The secondary aim of this thesis focuses on developing methods for a novel application of metallomic imaging mass spectrometry (MIMS) to biological tissue. Unlike traditional modalities used to assess neuropathology, that suffer from limited sensitivity and analytical capacity, MIMS uses a mass spectrometer -- an analytical instrument for measuring elements and isotopes with high dynamic range, sensitivity and specificity -- as the imaging sensor to generate spatial maps with spectral (vector-valued) data per pixel. Given the vector nature of MIMS data, a unique end-to-end processing pipeline is designed to support data acquisition, visualization and interpretation. A novel multi-modal and multi-channel image registration (MMMCIR) method using multi-variate mutual information as a similarity metric is developed in order to establish correspondence between two images of arbitrary modality. The MMMCIR method is then used to automatically segment MIMS images of the mouse brain and systematically evaluate the levels of relevant elements and isotopes after experimental closed-head impact injury on the impact side (ipsilateral) and opposing side (contralateral) of the brain. This method quantifiably confirms observed differences in gadolinium levels for a cohort of images. Finally, MIMS images of human lacrimal sac biopsy samples are used for preliminary clinicopathological assessments, supporting the utility of the unique insights MIMS provides by correlating areas of inflammation to areas of elevated toxic metals. The image processing methods developed in this work demonstrate the significant capabilities of MIMS and its role in enhancing our understanding of the underlying pathological mechanisms of TBI and other medical conditions. / 2019-07-09T00:00:00Z

Engenharia de ecossistemas refere-se à habilidade de certos organismos de modificar ativamente o ambiente que os cerca. No contexto ecológico, engenheiros de ecossistemas são espécies-chave que modificam ou criam habitats por meios mecânicos ou usando suas próprias estruturas corporais. Ao criarem novos nichos, castores, recifes de corais e sociedades humanas primitivas garantem tanto a própria existência, quanto a de outros organismos no mesmo ecossistema. Devido a seu caráter de longa duração, algumas destas modificações podem persistir até mais do que a duração de uma população de engenheiros, implicando em consequências evolutivas. O estudo teórico de tal fenômeno ecológico é relativamente recente se comparado com a descrição de interações tipo predador-presa ou de competição. Apenas em 1996 Gurney & Lawton introduziram um modelo descrevendo a dinâmica populacional de engenheiros de ecossistemas, mas a partir de lá poucas modificações apareceram. Aqui nós complementamos tal modelo ao permitir que engenheiros se movam difusivamente através dos sítios de um mapa acoplado, uma formulação discreta no espaço e no tempo. A análise de estabilidade local revela a existência dos regimes estável, cíclico e caótico, com uma cascata de bifurcações levando a órbitas caóticas. Obtemos que apenas para altas taxas de crescimento, onde ocorre comportamento caótico, a dispersão influencia na dinâmica das metapopulações. Neste regime, o caos é suprimido e a extinção pode ser evitada. / Ecosystem engineering refers to the ability of certain organisms to actively modify their surrounding environment. In an ecological context, ecosystem engineers are keystone species that modify or create habitats via mechanical means or by using their own physical structures. By creating new niches, beavers, coral reefs and primitive human societies would guarantee both their and other species survival in a shared ecosystem. Due to its long-lasting character, some of this changes might outlive the engineers populations, leading to evolutionary consequences. The theoretical study of such ecological phenomena is relatively recent when compared to the description of predator-prey or competition interactions. Only in 1996 Gurney & Lawton introduced a model to describe the population dynamics of ecosystem engineers, yet since then few modifications appeared. Here we build on this model by allowing the engineers to move diffusively through the patches of a coupled map lattice, a framework discrete both in time and space. The local stability analysis reveals the existence of stable, cyclic and chaotic regimes, with period-doubling bifurcations leading to chaotic orbits. We find that only for large intrinsic growth rates, where chaotic behavior occurs, dispersal influences the metapopulation dynamics. In this regime, chaos is suppressed and extinction can be avoided.

As Redes Neurais Pulsadas são objeto de intensa pesquisa na atualidade. Neste trabalho é avaliado o potencial de aplicação deste paradigma neural, na tarefa de reconhecimento automático do locutor. Após uma revisão dos tópicos considerados importantes para o entendimento do reconhecimento automático do locutor e das redes neurais artificiais, é realizada a implementação e testes do modelo de neurônio com resposta por impulsos. A partir deste modelo é proposta uma nova arquitetura de rede com neurônios pulsados para a implementação de um sistema de reconhecimento automático do locutor. Para a realização dos testes foi utilizada a base de dados Speaker Recognition v1.0, do CSLU – Center for Spoken Language Understanding do Oregon Graduate Institute - E.U.A., contendo frases gravadas a partir de linhas telefônicas digitais. Para a etapa de classificação foi utilizada uma rede neural do tipo perceptron multicamada e os testes foram realizados no modo dependente e independente do texto. A viabilidade das Redes Neurais Pulsadas para o reconhecimento automático do locutor foi constatada, demonstrando que este paradigma neural é promissor para tratar as informações temporais do sinal de voz. / Pulsed Neural Networks have received a lot of attention from researchers. This work aims to verify the capability of this neural paradigm when applied to a speaker recognition task. After a description of the automatic speaker recognition and artificial neural networks fundamentals, a spike response model of neurons is tested. A novel neural network architecture based on this neuron model is proposed and used in a speaker recognition system. Text dependent and independent tests were performed using the Speaker Recognition v1.0 database from CSLU – Center for Spoken Language Understanding of Oregon Graduate Institute - U.S.A. A multilayer perceptron is used as a classifier. The Pulsed Neural Networks demonstrated its capability to deal with temporal information and the use of this neural paradigm in a speaker recognition task is promising.

Thesis advisor: Jan R. Engelbrecht / Thesis advisor: Renato E. Mirollo / Many phenomena in nature that involve ordering in time can be understood as collective behavior of coupled oscillators. One paradigm for studying a population of self-sustained oscillators is the Kuramoto model, where each oscillator is described by a phase variable, and interacts with other oscillators through trigonometric functions of phase differences. This dissertation studies $N$ identical Kuramoto oscillators in a general form \[ \dot{\theta}_{j}=A+B\cos\theta_{j}+C\sin\theta_{j}\qquad j=1,\dots,N, \] where coefficients $A$, $B$, and $C$ are symmetric functions of all oscillators $(\theta_{1},\dots,\theta_{N})$. Dynamics of this model live in group orbits of M\"obius transformations, which are low-dimensional manifolds in the full state space. When the system is a phase model (invariant under a global phase shift), trajectories in a group orbit can be identified as flows in the unit disk with an intrinsic hyperbolic metric. A simple criterion for such system to be a gradient flow is found, which leads to new classes of models that can be described by potential or Hamiltonian functions while exhibiting a large number of constants of motions. A generalization to extended phase models with non-identical couplings gives rise to richer structures of fixed points and bifurcations. When the coupling weights sum to zero, the system is simultaneously gradient and Hamiltonian. The flows mimic field lines of a two-dimensional electrostatic system consisting of equal amounts of positive and negative charges. Bifurcations on a partially synchronized subspace are discussed as well. / Thesis (PhD) — Boston College, 2017. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Physics.

Usando as facilidades do sistema de tempo de vôo do Acelerador Pelletron 8UD da USP, foram medidas seções de choque diferenciais absolutas para os grupos \'n IND. 0\', \'n IND. 1\', \'n IND. 2\', \'n IND. 3\', (\'n IND. 4\'+\'n IND. 5\'), \'n IND. 6\' e \'n IND. 7\' na reação \'ANTPOT. 11 B\' (p, \'n IND. 0\') \'ANTPOT. 11 C\' e para os grupos de nêutrons \'n IND. 0\' e \'n IND. 1\' na reação \'ANTPOT. 10 B\' (p, \'n IND. 0\') \'ANTPOT. 10 C\' nas energias de próton incidente de 14.0, 14.3 e 14.6 MeV no intervalo angular de 20 a 160 graus. Foram também medidas funções de excitação em \'teta IND. lab\' = 30 graus de \'E IND. p\' = 13.7 e 14.7 MeV em intervalos de 100 keV. A análise teórica foi conduzida no sentido de se determinar as contribuições relativas dos processos de mecanismo direto e de núcleo composto. Para este fim, foi assumido um modelo de dois canais acoplados, e os modelos DWBA para o processo direto e de Hauser-Feshbach para o núcleo composto foram usados de maneira a simularem os cálculos exatos de canais acoplados via escolha do termo de absorção W no potencial óptico. Os resultados indicam que aproximadamente a metade da seção de choque é devida ao mecanismo de núcleo composto. A análise teórica visou ainda obter o fator de \"enhancement elástico para o canal \'ANTPOT. 11 B\' (p, \'n IND. 0\') \'ANTPOT. 11 C\' em \'E IND. p\' = 14.3 MeV. Este fator foi demonstrado a aparecer em reações de troca de carga que seguem via núcleo composto por Harney, Weidenmüller e Richter e predito a atingir o valor de 2 quando há conservação de isospin. Os nossos resultados mostram um fator de enhancement maior do que 1, indicando que a mistura de isospin é fraca nessa reação. / Using the time-of-flight facilities of the são Paulo 8UD Pelletron Accelerator, absolute differential cross sections for the \'n IND. 0\', \'n IND. 1\', \'n IND. 2\', \'n IND. 3\', (\'n IND. 4\'+\'n IND. 5\'), \'n IND. 6\' and \'n IND. 7\' groups for the reaction \'ANTPOT. 11 B\' (p, \'n IND. 0\') \'ANTPOT. 11 C\' and the \'n IND. 0\' and \'n IND. 1\' neutron groups for the reaction \'ANTPOT. 10 B\' (p, \'n IND. 0\') \'ANTPOT. 10 C\' have been measured at incident proton energies of 14.0, 14.3 and 14.6 MeV in the angular interval of 20 to 160 degrees. Excitation functions at \'teta IND. lab\' = 20 deg from \'E IND. p\' = 13.7 to 14.7 MeV in intervals of 100 keV were also measured. The theoretical analysis was conducted to determine the relative contributions of the direct and compound nucleus processes in the differential cross sections. To this end, a two coupled channel model for the reactions was assumed. The DWBA model for the direct and the Hauser-Feshbach for the compound nucleus processes were used in such a way as to simulate the exact coupled channels calculation through an appropriate choice of the absorption term W in the optical potential. The results indicate that about half of the cross section is due to the compound nucleus mechanism. The theoretical analysis aimed at obtaining the elastic enhancement factor for the channel \'ANTPOT. 11 B\' (p, \'n IND. 0\') \'ANTPOT. 11 C\' at \'E IND. p\' = 14.3 MeV. This factor has been demonstrated to appear in compound nucleus charge exchange reactions by Harney, Weidenmüller and Richter and predicted to attain the value 2 when isospin is conserved. Our results show an enhancement factor larger than 1 indicating that isospin mixing is weak in this reaction.

Sincronismo é um comportamento dinâmico que pode ser detectado na atividade dos neurônios que formam estruturas corticais, e essa atividade parece ser fundamental para a realização de processos relacionados a aprendizado, compreensão e reconhecimento. Estruturas corticais podem ser modeladas por redes de mapas acoplados. Nessas redes, a existência de solução síncrona é determinada pela equação que governa a atividade de cada mapa, pela topologia de acoplamento entre os mapas e pelos valores dos parâmetros. O enfoque deste trabalho é empregar redes de mapas acoplados voltados à detecção de simetria, e segmentação de imagens, via sincronismo. / Synchronism is a dynamical behavior that can be found in the neural activity of cortical structures, and this behavior seems to be fundamental in learning, understanding and recognition processes. Cortical structures can be modeled by using coupled map lattices. In such lattices, the existence of synchronous solution is determined by the equation that rules the activity of each map, by the coupling topology among the maps, and by the parameter values. The goal of this work is to employ coupled map lattices in symmetry detection and image segmentation, via synchronism.

Nesta tese de doutoramento foram propostos dois modelos teóricos (ZPM e GFA) para a obtenção da seção de choque de fusão e um (ZPM) para o cálculo do potencial de polarização para o canal elástico e correspondente seção de choque de espalhamento. Foi usado em todos os cálculos deste trabalho, tanto no tratamento da fusão quanto no do espalhamento elástico, o Potencial de São Paulo (SP), que possui como uma das principais características a total ausência de parâmetros ajustáveis. Conseqüentemente, todos os cálculos apresentados no contexto de diferentes modelos constituem previsões teóricas ao invés de simples ajustes de dados. Em uma análise comparativa acerca dos cálculos para a fusão, os modelos GFA e ZPM se mostraram equivalentes e compatíveis com cálculos de canais acoplados usuais, com a vantagem de incorporarem acoplamentos à toda banda vibracional e de permitirem a obtenção de cálculos acurados de seções de choque de fusão em energias extremamente abaixo da barreira. Aplicamos o modelo de ZPM ao cálculo da função de excitação de fusão para 112 sistemas de íons pesados, envolvendo tanto núcleos par-par como núcleos ímpar-par e ímpar-ímpar (incluindo alguns núcleos fracamente ligados), e confrontamos os resultados obtidos com dados experimentais existentes na literatura. Enquanto o modelo de penetração de barreira não-deformado prevê discordâncias de até onze ordens de magnitude, as previsões do modelo de ZPM mostraram-se de acordo com os dados dentro de duas ordens de grandeza. Ao confrontarmos os resultados do modelo de ZPM para as seções de choque de espalhamento elástico com dados experimentais para alguns sistemas em energias em torno da barreira coulombiana, pudemos constatar uma boa concordância. Desta forma, demonstramos que é possível tratar os canais de espalhamento elástico e de fusão de maneira consistente dentro do mesmo contexto. / In this Ph.D. thesis two theoretical models (ZPM and GFA) were proposed in order to obtain fusion cross sections and one (ZPM) to calculate the polarization potential for the elastic channel and the corresponding scattering cross section. The São Paulo (SP) potential, which has as one of its main characteristics the complete absence of adjustable parameters, was used as bare interaction in the calculations of the present work. Therefore, all results, presented in the context of different models, correspond to theoretical predictions instead of simply data fit. After a comparative analysis of fusion calculations, the GFA and ZPM models demonstrated to be equivalents and compatible with the usual coupled channel calculations, with the advantage of incorporating inelastic couplings to the complete vibrational band and of providing accurate fusion cross sections at extreme low energies relative to the Coulomb barrier. We applied the ZPM model to the calculation of the fusion excitation function for 112 heavy-ion systems, involving not only even-even nuclei but also odd-even and odd-odd ones (including some weakly-bound nuclei), and we compared the theoretical results with experimental data existing in literature. While the usual non-deformed barrier penetration model provides enhancements up to eleven orders of magnitude, the ZPM model predictions are in good agreement with the data within only two orders of magnitude. When confronting the ZPM model results with experimental data of elastic scattering cross sections for some systems, at energies around the Coulomb barrier, we found out good agreement between them. Therefore, we demonstrated that it is possible to treat the elastic scattering and fusion channels in a consistent manner, within the same context.

A teoria das redes complexas tem se consolidado por seu forte caráter interdisciplinar, relativa simplicidade conceitual e ampla aplicabilidade na modelagem de sistemas reais. Embora tendo evoluído rapidamente, uma série de problemas ainda não foram estudados usando as redes complexas. Em especial, sistemas envolvendo acoplamento e interação entre diferentes redes complexas têm sido pouco investigados. Na presente monografia, apresentamos duas contribuições fundamentais no estudo desses sistemas. A primeira consiste num modelo que descreve a interação entre um padrão de massa evoluindo numa rede regular com uma rede complexa que se organiza para impedir a evolução desse padrão. Os vértices da rede complexa se ativam e se movem sobre a rede regular conforme são requisitados por seus vizinhos, que se ativam pela rede regular. Essa última ativação ocorre quando a concentração de massa ultrapassa um limiar na respectiva posição do vértice e consiste em liberar uma difusão oposta de massa neutralizadora contra a massa original. A dinâmica mostrou-se completamente relacionada à estrutura da rede de controle. A presença de concentradores no modelo de Barabási-Albert tem papel fundamental para acelerar o processo de geração de massa neutralizadora. Por outro lado, a distribuição uniforme de vizinhos da rede de Erdös-Rényi resultou numa melhora de desempenho na presença de várias regiões distintas contendo massa original. A segunda contribuição consiste num modelo de interação entre duas espécies (predador e presa) através de campos sensitivos, que dependem da distância Euclidiana entre dois indivíduos e do seu respectivo tipo. Padrões espaço-temporais emergem nesse sistema e estão diretamente relacionados à intensidade de atração entre os indivíduos da mesma espécie. Para entender a evolução do sistema e quantificar a transferência de informação entre os diferentes aglomerados, duas redes complexas são construídas onde os vértices representam os indivíduos. Na primeira rede, o peso das conexões é dado pela distância Euclidiana entre os indivíduos e na segunda, pelo tempo que eles permaneceram suficientemente próximos. A partir de um mecanismo de fusão entre as duas redes, obtemos uma terceira rede complexa onde os vértices correspondem a grupos espaciais definidos a partir de um processo de limiarização dos pesos da primeira rede. Algumas configurações de parâmetros privilegiam a sobrevivência de presas enquanto outras beneficiam a caça dos predadores. / Complex network theory has become very popular because of its interdisciplinarity, conceptual simplicity and wide applicability to model real systems. Although fast growing, there is a number of problems which have not been addressed by using complex networks. For example, few efforts have been directed to systems involving coupling and interaction between different complex networks. In the following monography, we present two fundamental contributions in the study of such systems. The first consists in a model which describes the interaction dynamics between a mass pattern evolving in a regular network with a complex network, which are expected to control the pattern evolution. As soon as a complex network node is activated by the regular network, it requests help from its topological neighbours and activates them. The activation is triggered when the mass concentration overcomes a threshold in the node position and consists in liberating an opposite diffusion intended to eliminate the original pattern. The dynamics is completely related to the structure of the control network. The existence of hubs in the Barabási-Albert model plays a fundamental role to accelerate the opposite mass generation. Conversely, the uniform distribution of neighbours in the Erdös-Rényi network provided an increase in the efficiency when several focuses of the original pattern were distributed in the regular network. The second contribution consists in a model based on interactions between two species (predator and prey) provided by sensitive fields which depends of the Euclidean distance between two agents and on their respective types. Spatio-temporal patterns emerge in the system which are directly related to the attraction intensity between same species agents. To understand the dynamics evolution and quantify the information transfer through different clusters, we built two complex networks where the nodes represent the agents. In the first network, the edge weight is given by the Euclidean distance between two agents and, in the second network, by the amount of time two agents become close one another. By following a merging process, another network is obtained whose nodes correspond to spatial groups defined by a weight thresholding process in the first network. Some configurations favor the preys survival, while predators efficiency are improved by other ones.

Chan Sze-Man. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (leaves 65-73). / Abstracts in English and Chinese. / Acknowledgment --- p.i / Table of Contents --- p.ii / Abstract --- p.v / Abstract (Chinese Version) --- p.vi / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Molybdenum in the Environment --- p.1 / Chapter 1.1.1 --- General Chemistry of Molybdenum --- p.1 / Chapter 1.1.2 --- Molybdenum in Animals and Plants --- p.1 / Chapter 1.1.3 --- Uses of Molybdenum Compounds --- p.3 / Chapter 1.2 --- Inductively Coupled Plasma Atomic Emission Spectrometry --- p.4 / Chapter 1.2.1 --- Principle of ICP-AES --- p.4 / Chapter 1.2.2 --- Inductively Coupled Plasma Emission Source --- p.5 / Chapter 1.2.3 --- Optical System --- p.6 / Chapter 1.2.4 --- Advantages of ICP-AES --- p.7 / Chapter 1.2.5 --- Disadvantages of ICP-AES --- p.8 / Chapter 1.3 --- Preconcentration Method --- p.9 / Chapter 1.4 --- Polysiloxane --- p.11 / Chapter 1.4.1 --- Introduction of Silica-gel --- p.11 / Chapter 1.4.2 --- Introduction of Sol-gel Processes --- p.13 / Chapter 1.4.3 --- Hybrid Inorganic-organic Sol-gel Materials --- p.14 / Chapter 1.4.4 --- Advantages Using Sol-gel Preparation of Organomodified Silica --- p.16 / Chapter 1.5 --- Chelating Resin --- p.19 / Chapter 1.6 --- Scope of Work --- p.21 / Chapter Chapter 2 --- Experimental --- p.22 / Chapter 2.1 --- Apparatus and Instrument --- p.22 / Chapter 2.2 --- Chemicals --- p.24 / Chapter 2.3 --- Samples --- p.25 / Chapter 2.4 --- Procedures --- p.26 / Chapter 2.4.1 --- Preparation of Diethylenetriaminetetraacetic-acid Functionalized Polysiloxane --- p.26 / Chapter 2.4.1.1 --- Preparation of Silica Precursor --- p.26 / Chapter 2.4.1.2 --- Functionalization with Diethylenetriamine --- p.27 / Chapter 2.4.1.3 --- Carboxymethylation of the amine groups of the Polysiloxane --- p.28 / Chapter 2.4.2 --- Preconcentration and Determination of Molybdenum --- p.29 / Chapter 2.4.2.1 --- Optimum pH for Adsorption --- p.29 / Chapter 2.4.2.2 --- Amount of Polysiloxane Required for Sorption of Trace Amount of Molybdenum --- p.29 / Chapter 2.4.2.3 --- Equilibrium Time --- p.30 / Chapter 2.4.2.4 --- Total Adsorption Capacity --- p.30 / Chapter 2.4.2.5 --- Adsorption Isotherm of Molybdenum --- p.30 / Chapter 2.4.2.6 --- Desorption Studies --- p.31 / Chapter 2.4.2.7 --- Effect of Foreign Ions on Preconcentration --- p.31 / Chapter 2.4.2.8 --- Preparation of the Mini-column --- p.32 / Chapter 2.4.2.9 --- Effect of Flow Rate --- p.33 / Chapter 2.4.2.10 --- Reusability of the Mini-column --- p.33 / Chapter 2.4.2.11 --- Preconcentration Factor and Detection Limit --- p.33 / Chapter 2.4.2.12 --- Determination of Mo(VI) in Seawater by ICP-AES --- p.33 / Chapter Chapter 3 --- Results and Discussion --- p.35 / Chapter 3.1 --- Characterization of Diethylenetriaminetetraacetic-acid Functionalized Polysiloxane --- p.35 / Chapter 3.2 --- pH Dependence of Mo(VI) Ion Uptake --- p.44 / Chapter 3.3 --- Amount of Polysiloxane Required for Adsorption of Trace Amount of Mo(VI) --- p.45 / Chapter 3.4 --- Equilibrium Time --- p.46 / Chapter 3.5 --- Total Adsorption Capacity --- p.47 / Chapter 3.6 --- Adsorption Isotherm of Molybdenum --- p.48 / Chapter 3.7 --- Desorption Studies --- p.54 / Chapter 3.8 --- Effect of Foreign Ions on Preconcentration --- p.55 / Chapter 3.9 --- Effect of Flow Rate on the Recovery of Mo(VI) --- p.57 / Chapter 3.10 --- Reusability of the Column --- p.58 / Chapter 3.11 --- Preconcentration Factor --- p.59 / Chapter 3.12 --- Detection Limit --- p.59 / Chapter 3.13 --- Accuracy --- p.60 / Chapter 3.14 --- Determination of Mo(VI) in Seawater Samples --- p.61 / Chapter 3.15 --- Precision --- p.62 / Chapter Chapter 4 --- Conclusion --- p.63 / Chapter Chapter 5 --- References --- p.65

Multiple sclerosis (MS) is a neurodegenerative disease associated with immune attack of the central nervous system (CNS) leading to neuronal and axonal loss. This affects neurotransmission accumulating residual disability and the development of neurological signs such as spasticity. Numerous studies have reported a beneficial role of cannabinoids in alleviating symptoms associated with neurological damage. The endocannabinoid system has been shown to control experimental spasticity in experimental autoimmune encephalomyelitis (EAE) an animal model of multiple sclerosis (MS). The orphan G-protein coupled receptor 55 (GPR55) has been identified as a functionally -related cannabinoid receptor known to be stimulated by lysophosphatidylinositol. In the current study a novel GPR55 gene knockoutmouse and GPR55-transfected cell line was obtained and characterised andthe function and distribution of GPR55 was analyzed. Due to the lack of GPR55 specific antibodies, we attempted to generate GPR55-specific monoclonal antibodies in GPR55 knockout mice, however none of these reacted only specifically to the native protein. As alternatives to antibodies, GPR55 mRNA levels were quantified using quantitative polymerase chain reaction (qPCR) and in situ hybridization. The GPR55 knockout mice on the C57BL/6 mouse background failed to generate an autoimmune response during EAE in an initial experiment suggesting that GPR55 controls immune function. Disease was variable in the C57BL/6 mice and EAE was induced in the GPR55 knockout mice on the ABH background and animals developed spasticity. VSN16R is a drug that has shown to inhibit experimental spasticity and binds specifically to GPR55, without the typical side effects associated with cannabis. This compound was found to be an allosteric modulator of GPR55. Animals were treated with VSN16R however the anti-spastic effect remained in the GPR55 knockout mice. Hence, the effect of VSN16R is not mediated by GPR55 in EAE and a novel target needs to be identified.