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Neural assemblies in hippocampus encode positions. During rest, the hippocam- pus replays sequences of neural activity seen during awake behavior. This replay is linked to memory consolidation and mental exploration of the environment. Re- current networks can be used to model the replay of sequential activity. Multiple sequences can be stored in the synaptic connections. To achieve a high mem- ory capacity, recurrent networks require a pattern separation mechanism. Such a mechanism is global remapping, observed in place cell populations. A place cell fires at a particular position of an environment and is silent elsewhere. Multiple place cells usually cover an environment with their firing fields. Small changes in the environment or context of a behavioral task can cause global remapping, i.e. profound changes in place cell firing fields. Global remapping causes some cells to cease firing, other silent cells to gain a place field, and other place cells to move their firing field and change their peak firing rate. The effect is strong enough to make global remapping a viable pattern separation mechanism. We model two mechanisms that improve the memory capacity of recurrent net- works. The effect of inhibition on replay in a recurrent network is modeled using binary neurons and binary synapses. A mean field approximation is used to de- termine the optimal parameters for the inhibitory neuron population. Numerical simulations of the full model were carried out to verify the predictions of the mean field model. A second model analyzes a hypothesized global remapping mecha- nism, in which grid cell firing is used as feed forward input to place cells. Grid cells have multiple firing fields in the same environment, arranged in a hexagonal grid. Grid cells can be used in a model as feed forward inputs to place cells to produce place fields. In these grid-to-place cell models, shifts in the grid cell firing patterns cause remapping in the place cell population. We analyze the capacity of such a system to create sets of separated patterns, i.e. how many different spatial codes can be generated. The limiting factor are the synapses connecting grid cells to place cells. To assess their capacity, we produce different place codes in place and grid cell populations, by shuffling place field positions and shifting grid fields of grid cells. Then we use Hebbian learning to increase the synaptic weights be- tween grid and place cells for each set of grid and place code. The capacity limit is reached when synaptic interference makes it impossible to produce a place code with sufficient spatial acuity from grid cell firing. Additionally, it is desired to also maintain the place fields compact, or sparse if seen from a coding standpoint. Of course, as more environments are stored, the sparseness is lost. Interestingly, place cells lose the sparseness of their firing fields much earlier than their spatial acuity. For the sequence replay model we are able to increase capacity in a simulated recurrent network by including an inhibitory population. We show that even in this more complicated case, capacity is improved. We observe oscillations in the average activity of both excitatory and inhibitory neuron populations. The oscillations get stronger at the capacity limit. In addition, at the capacity limit, rather than observing a sudden failure of replay, we find sequences are replayed transiently for a couple of time steps before failing. Analyzing the remapping model, we find that, as we store more spatial codes in the synapses, first the sparseness of place fields is lost. Only later do we observe a decay in spatial acuity of the code. We found two ways to maintain sparse place fields while achieving a high capacity: inhibition between place cells, and partitioning the place cell population so that learning affects only a small fraction of them in each environment. We present scaling predictions that suggest that hundreds of thousands of spatial codes can be produced by this pattern separation mechanism. The effect inhibition has on the replay model is two-fold. Capacity is increased, and the graceful transition from full replay to failure allows for higher capacities when using short sequences. Additional mechanisms not explored in this model could be at work to concatenate these short sequences, or could perform more complex operations on them. The interplay of excitatory and inhibitory populations gives rise to oscillations, which are strongest at the capacity limit. The oscillation draws a picture of how a memory mechanism can cause hippocampal oscillations as observed in experiments. In the remapping model we showed that sparseness of place cell firing is constraining the capacity of this pattern separation mechanism. Grid codes outperform place codes regarding spatial acuity, as shown in Mathis et al. (2012). Our model shows that the grid-to-place transformation is not harnessing the full spatial information from the grid code in order to maintain sparse place fields. This suggests that the two codes are independent, and communication between the areas might be mostly for synchronization. High spatial acuity seems to be a specialization of the grid code, while the place code is more suitable for memory tasks. In a detailed model of hippocampal replay we show that feedback inhibition can increase the number of sequences that can be replayed. The effect of inhibition on capacity is determined using a meanfield model, and the results are verified with numerical simulations of the full network. Transient replay is found at the capacity limit, accompanied by oscillations that resemble sharp wave ripples in hippocampus. In a second model Hippocampal replay of neuronal activity is linked to memory consolidation and mental exploration. Furthermore, replay is a potential neural correlate of episodic memory. To model hippocampal sequence replay, recurrent neural networks are used. Memory capacity of such networks is of great interest to determine their biological feasibility. And additionally, any mechanism that improves capacity has explanatory power. We investigate two such mechanisms. The first mechanism to improve capacity is global, unspecific feedback inhibition for the recurrent network. In a simplified meanfield model we show that capacity is indeed improved. The second mechanism that increases memory capacity is pattern separation. In the spatial context of hippocampal place cell firing, global remapping is one way to achieve pattern separation. Changes in the environment or context of a task cause global remapping. During global remapping, place cell firing changes in unpredictable ways: cells shift their place fields, or fully cease firing, and formerly silent cells acquire place fields. Global remapping can be triggered by subtle changes in grid cells that give feed-forward inputs to hippocampal place cells. We investigate the capacity of the underlying synaptic connections, defined as the number of different environments that can be represented at a given spatial acuity. We find two essential conditions to achieve a high capacity and sparse place fields: inhibition between place cells, and partitioning the place cell population so that learning affects only a small fraction of them in each environments. We also find that sparsity of place fields is the constraining factor of the model rather than spatial acuity. Since the hippocampal place code is sparse, we conclude that the hippocampus does not fully harness the spatial information available in the grid code. The two codes of space might thus serve different purposes.

Submitted by THIAGO DE SOUZA CANDIDO null (thiago.s.candido@gmail.com) on 2016-09-30T14:48:19Z No. of bitstreams: 1 Tese Thiago de Souza Candido.pdf: 8667516 bytes, checksum: a5ceff1a03a2f39c134a0633e677f4df (MD5) / Approved for entry into archive by Ana Paula Grisoto (grisotoana@reitoria.unesp.br) on 2016-10-04T14:33:04Z (GMT) No. of bitstreams: 1 candido_ts_dr_araiq.pdf: 8667516 bytes, checksum: a5ceff1a03a2f39c134a0633e677f4df (MD5) / Made available in DSpace on 2016-10-04T14:33:04Z (GMT). No. of bitstreams: 1 candido_ts_dr_araiq.pdf: 8667516 bytes, checksum: a5ceff1a03a2f39c134a0633e677f4df (MD5) Previous issue date: 2016-09-15 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / O fungo Neurospora crassa tem sido amplamente usado como um organismo modelo para os aspectos fundamentais da biologia dos eucariotos. Neste trabalho, foi investigado o papel funcional de uma ciclina de N. crassa (PCL-1), codificada pela ORF NCU08772 e ortóloga a Pcl10 de Saccharomyces cerevisiae. Na levedura, a proteína Pcl10, em conjunto com a proteína quinase dependente de ciclina Pho85, fosforila a enzima glicogênio sintase, a enzima regulatória da síntese de glicogênio. A fosforilação resulta na inativação da enzima e, portanto, em diminuição do acúmulo de glicogênio. A linhagem pcl-1 de N. crassa apresentou um atraso na germinação dos conídios e um retardo na progressão do ciclo celular quando comparado com a linhagem selvagem, sugerindo que esta ciclina pode regular o desenvolvimento e a divisão celular. Além disto, a linhagem nocauteada acumulou níveis mais elevados de glicogênio que a linhagem selvagem indicando o papel na regulação do metabolismo deste carboidrato. A fosforilação da enzima glicogênio sintase de N. crassa (GSN) foi analisada na linhagem nocaute através de análises de atividade enzimática, e os resultados mostraram que a GSN apresentou baixo índice de fosforilação, portanto alta atividade durante o crescimento, um resultado que pode explicar o alto acúmulo de glicogênio observado. Este resultado foi confirmado por análise de 2D-PAGE seguida por western blot, utilizando anticorpos anti-GSN. GSN apresentou na linhagem mutante isoformas menos fosforiladas que a enzima presente na linhagem selvagem. As proteínas recombinantes PHO85, PCL-1 foram utilizadas em ensaios de fosforilação in vitro da enzima GSN e os resultados mostraram que a enzima GSN foi fosforilada pelo complexo PHO85/PCL-1 no sítio putativo Ser636. O papel da ciclina na resposta ao cálcio foi investigado, e os resultados mostraram que a linhagem pcl-1 mostrou uma resistência ao estresse provocado por altas concentrações de cálcio quando comparada com a linhagem selvagem. Análises de expressão gênica por RT-qPCR foram realizadas e a linhagem pcl-1 mostrou estar envolvida na regulação de genes do metabolismo do cálcio. Os resultados indicam que a proteína PCL1 de N. crassa pode ser uma ciclina multifuncional e pode estar envolvida na regulação de vários processos celulares essenciais dependendo do ambiente. / The fungus Neurospora crassa has been widely used a model organism for the fundamental aspects of eukaryotes biology. This work investigated the functional role of a N. crassa cyclin (PCL-1), encoded by the ORF NCU08772, and orthologous to the Saccharomyces cerevisiae Pcl10 cyclin. In yeast, Pcl10 protein, together with the Pho85 cyclin-dependent protein kinase, phosphorylates the glycogen synthase enzyme, the regulatory enzyme in glycogen synthesis. Phosphorylation results in enzyme inactivation and therefore in decreased glycogen accumulation. The N. crassa pcl-1 strain showed a delay in conidia germination and in the progression of the cell cycle compared to the wild-type strain, suggesting that the cyclin may regulate development and cell division. Furthermore, the mutant strain accumulated higher glycogen levels than wild-type strain indicating its role in the regulation of the carbohydrate metabolism. The phosphorylation rate of the N. crassa glycogen synthase (GSN) was analyzed in the mutant strain by enzymatic activity assays, and the results showed that GSN was less phosphorylated during growth; therefore, high activity, and this result may explain the high glycogen accumulation observed in the mutant strain. This result was confirmed by 2D-PAGE gels followed by western blot using anti-GSN antibodies. The GSN isoforms presented in the mutant strain were less phosphorylated than the enzyme present in the wild-type strain. The recombinant proteins PHO85 and PCL-1 were used in in vitro phosphorylation assays of GSN enzyme, and the results showed that the enzyme was phosphorylated by the PHO85/PCL-1 complex at the putative site Ser636. The role of the cyclin in the response to calcium was investigated, and the results showed that the pcl-1 strain is more resistant than the wild-type strain to the stress caused by high calcium concentration. Gene expression analysis by RTqPCR was performed to analyze genes involved in calcium metabolism, and the pcl-1 strain showed to regulate the expression of some calcium metabolism genes. The results indicate that the N. crassa PCL1 cyclin may be multifunctional and may be involved in the regulation of several cellular processes depending on the environment. / FAPESP: 2012/08652-4

This project is aimed at making comparison between current existing Internet- of-Things (IoT) platforms, SensibleThings (ST) and Global Sensors Networks (GSN). Project can be served as a further work of platforms’ investigation. Comparing and learning from each other aim to contribute to the improvement of future platforms development. Detailed comparison is mainly with the respect of platform feature, communication and data present-frequency performance under stress, and platform node scalability performance on one limited device. Study is conducted through developing applications on each platform, and making measuring performance under the same condition in household network environment. So far, all these respects have had results and been concluded. Qualitatively comparing, GSN performs better in the facets of node’s swift development and deployment, data management, node subscription and connection retry mechanism. Whereas, ST is superior in respects of network package encryption, platform reliability, session initializing latency, and degree of developing freedom. In quantitative comparison, nodes on GSN has better data push pressure resistence while ST nodes works with lower session latency. In terms of data present-frequency, ST node can reach higher updating frequency than GSN node. In the aspect of node sclability on one limited device, ST nodes take the advantage in averagely lower latency than GSN node when nodes number is less than 15 on limited device. But due to sharing mechanism of GSN, on one limited device, it's nodes shows more scalable if platform nodes have similar job.

A trusted execution environment (TEE) is an isolated environment used for trusted execution. TEE solutions are usually proprietary and specific for a certain hardware specification, thereby limiting developers that use those TEEs. A potential solution to this issue is the use of open-source alternatives such as the TEE framework Keystone and the Reduced Instruction Set Computer V (RISC-V) hardware. These alternatives are rather young and are not as well established as the variants developed by ARM and Intel. To this end, the assurance in Keystone and RISC-V are analysed by studying a remote attestation assurance use case using the goal structuring notation (GSN) method. The aim is to investigate how GSN can be utilised to build assurance cases for TEEs on RISC-V. This thesis presents a process of how GSNs can be created to argue assurance for a TEE solution. Furthermore, Keystone operates under a specific threat model with made assumptions that may have a large impact depending on the use case. Therefore, Keystone is analysed to understand whether the framework mitigates existing vulnerabilities in TEEs. It is concluded that GSN is a viable method for arguing assurance in TEEs, providing great freedom in the creation of the GSN model. The freedom is also its weakness since the argument composition has a high impact on the argument. Furthermore, we conclude that Keystone mitigates multiple known vulnerabilities primarily through made assumptions in its threat model. These cases need to be considered by developers utilising Keystone to determine whether or not the assumptions are valid for their use case.

Assurance Cases have been effectively used for improving the safety of real-time safety systems. However, until now, Assurance Case techniques have not been applied to building confidence in the correctness of Scientific Computing (SC) software. Our approach is to employ Assurance Case techniques to the case of a specific medical image analysis software, 3dfim+, and then generalize the results/template for other medical and SC software. Using the Goal Structuring Notation (GSN), we develop an Assurance Case to support the top goal that "Program 3dfim+ delivers correct outputs when used for its intended use/purpose in its intended environment." This claim is supported by several sub-claims, including the claims that high-quality requirements exist and that the implementation complies with the requirements. The full argument decomposes each sub-claim further until at the bottom level evidence is provided. The evidence provided includes the requirements documentation, test cases and expert review. To simplify the Assurance Case diagram, a new generic module, parameterized over quality, was developed to argue that each quality has been achieved. Evaluation of the full Assurance Case shows that this approach is feasible for building confidence in SC software, even in the practical situation where confidence is sought, but redesign and reimplementation are not possible. The exercise uncovered issues with the original documentation for 3dfim+, including missing assumptions, and ambiguity with the chosen sign convention. Furthermore, although no errors in output were found, the Assurance Case highlights that confidence in the original 3dfim+ software could be improved through additional checks for input validity. / Thesis / Master of Science (MSc)

ISO 26262 is an international standard valid for the automotive domain. It regulates all the activities to perform for developing safety critical systems in such domain. To be compliant with ISO 26262, all the required activities have to be performed and all the required work products have to be provided. Furthermore, in addition to develop a system in a safe way, following the safety standard guidelines, the achieved safety has also to be demonstrated. This is done through a safety case, a structured argument showing that a system is acceptably safe. ISO 26262 focuses on single systems and does not contain guidelines for product lines. Product line engineering is a valid approach to systematize reuse, aimed at reducing the effort needed to develop similar systems. But, it loses its strength when dealing with safety critical systems, since it is not aligned with safety standards. Hence, when developing a safety critical product line in the automotive domain, the work products required by ISO 26262 have to be provided every time from scratch, including the safety case, for each single system of the product line. This thesis work focuses on providing an approach for building and modeling a safety case for safety critical product lines in the automotive domain. Furthermore, the considered product line engineering approach is aligned with ISO 26262, through the inclusion of safety activities in the product line development process. Giving in this way, the concrete possibility to overtake to the current limitations, reducing the effort needed to develop and certificate each single system of a safety critical product line. To illustrate the validity of the proposed approach a safety critical product line developed by Scania is used as case study.