Embryonic stem (ES) cells provide a potentially unlimited cell source for cellular therapies; however, reliable methods must be developed to provide clinically-relevant numbers of homogeneous therapeutic cell populations. Dynamic cultures may encourage ES cell differentiation and amenable to large-scale cell production. Our goal was to optimize dynamic culture parameters (bioreactor type, speed, cell seeding density, conditioned medium, and hypoxia) to maximize the generation of hematopoietic stem and progenitor cells (HSPCs) from ES cells and also to investigate the ability of dynamic culture-derived HSPCs to generate terminally differentiated hematopoietic cells. Our results indicate that varying cell seeding density and speed in two different bioreactors significantly affects embryoid body formation and ES cell differentiation efficiency into progenitor cells. In general, increased cell seeding density generated higher percentages of HSPCs in both bioreactors. In addition, rotary (Synthecon) bioreactors produced more sca-1⁺ progenitors, and spinner flasks generated more c-kit⁺ progenitors, demonstrating their unique differentiation profiles. cDNA microarray analysis of genes involved in pluripotency, germ layer formation, and hematopoietic differentiation showed that unique gene expression profiles were observed in the two bioreactors with the expression of specific hematopoietic genes more up regulated in the Synthecon cultures compared to spinner flasks. Combining bioreactor cultures with directed differentiation strategies via conditioned medium and hypoxic culture may further encourage hematopoietic differentiation. Dynamically cultured ES cell-derived hematopoietic stem and progenitor cells were further differentiated into a phenotype typical of dendritic cells which had the ability to process antigen. Additionally, microarray analysis of isolated ES cell-derived HSPCs demonstrated differences in the gene expression from native HSCs isolated from the fetal liver or bone marrow of mice. Insight gained from this work should be continued by comparing the differentiation efficiency of HSPCs derived in dynamic and traditional static culture methods into functional, terminally differentiated hematopoietic cells to generate clinically-relevant numbers of transplantable, therapeutic cells. / text

Denna rapport beskriver ett arbete genomfört av åtta studenter i kursen TDDD96 Kandidatprojekt i programvaruutveckling vid Linköpings universitet under vårterminen 2020. Arbetet efterfrågades av företaget Ericsson AB. Syftet var att göra den existerande processen att begära och bevilja tillträden till lokaler enklare. Den åstadkomna produkten blev en webbapplikation som hanterar den ovannämnda processen med hjälp av en interagerbar och visuell karta. Användarvänligheten stod i fokus enligt kundens önskemål. Rapporten innehåller en gemensam beskrivning av utvecklingsprocessen, presentera resultatet och diskutera resultatet av. Rapporten innehåller också individuella bidrag från gruppmedlemmarna inom områden som är relevanta till projektarbetet.

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Yes / Human memory is content addressable—i.e., contents of the memory can be accessed using partial information about the bound features of a stored item. In this study, we used a cross-feature cuing technique to examine how the human visual system encodes, binds, and retains information about multiple stimulus features within a set of moving objects. We sought to characterize the roles of three different features (position, color, and direction of motion, the latter two of which are processed preferentially within the ventral and dorsal visual streams, respectively) in the construction and maintenance of object representations. We investigated the extent to which these features are bound together across the following processing stages: during stimulus encoding, sensory (iconic) memory, and visual shortterm memory. Whereas all features examined here can serve as cues for addressing content, their effectiveness shows asymmetries and varies according to cue–report pairings and the stage of information processing and storage. Position-based indexing theories predict that position should be more effective as a cue compared to other features. While we found a privileged role for position as a cue at the stimulus-encoding stage, position was not the privileged cue at the sensory and visual short-term memory stages. Instead, the pattern that emerged from our findings is one that mirrors the parallel processing streams in the visual system. This stream-specific binding and cuing effectiveness manifests itself in all three stages of information processing examined here. Finally, we find that the Leaky Flask model proposed in our previous study is applicable to all three features.

Modelos de Relações Quantitativas entre Estrutura Química e Atividade Biológica (QSAR), previamente gerados no grupo para uma série de brometos de N-benzil-N,N-dimetil-2-(4-X-benzamido)etan-1-amônio substituídos (compostos estruturalmente análogos à procaína), mostraram uma contribuição positiva da lipofilicidade (expressa pelo parâmetro lipofílico, logPapp) para a atividade de bloqueio da transmissão neuromuscular observada para estes. Como os compostos desta série são sais de amônio quaternários, sendo alguns altamente hidrofílicos, as determinações dos seus valores de logPapp pelo método shake-flask acarretam dificuldades experimentais, levando a altas incertezas. Para contornar estas dificuldades, em outro trabalho iniciado no grupo, sugeriu-se, como estratégia metodológica, avaliar a aplicação do conceito do par iônico, usando, para tanto, um contraíon grande e hidrofóbico. Assim, observou-se, para um único composto desta série, o aumento da sua lipofilicidade, por possível formação de par iônico, tornando-o menos hidrofílico. Nesta dissertação, visando ampliar os estudos envolvendo a aplicação desta estratégia metodológica e seus efeitos sobre a lipofilicidade, outros compostos foram selecionados para que uma faixa mais ampla de valores de LogPapp pudesse ser avaliada. Para tanto, os valores de logPapp de cinco compostos desta série foram determinados pelo método shake-flask, usando o sistema n-octanol/água, avaliando-se, ainda, os efeitos da força iônica na partição. Para estes, a faixa de valores de LogPapp determinados variou de -1,73 a 0,99. Para avaliar a aplicação do conceito do par iônico como estratégia, os valores de LogPapp destes compostos foram determinados na presença de diferentes concentrações do contraíon hidrofóbico n-octil sulfato de sódio (OcS). Verificou-se aumento da lipofilicidade com aumento das concentrações de OcS. Obteve-se, também, os correspondentes valores de LogPapp extrapolados para concentração zero de OcS (LogPapp0), que concordaram, dentro do erro experimental, com os valores determinados diretamente na ausência de OcS. Estes resultados indicam que o conceito do par iônico pode ser aplicado como estratégia metodológica, para melhorar as condições experimentais e diminuir as incertezas nas determinações de valores de LogPapp para esta série de brometos de amônio quaternários hidrofílicos. Finalmente, foram realizados experimentos complementares para verificar a formação de par iônico: (i) determinações dos valores de logP da benzamida (composto sem carga permanente) na presença de OcS; (ii) análise por RMN de um dos compostos desta série, na presença de OcS. Ambos indicaram que, somente para os brometos de amônio quaternários estudados, o aumento da lipofilicidade observado ocorre por possível formação de par iônico. E, ainda, foi avaliada a aplicação do conceito do par iônico e seus efeitos sobre a lipofilicidade do QX-222 e do brometo de neostigmina (compostos altamente hidrofílicos), revelando limitações na sua aplicação como estratégia metodológica. / Quantitative Structure-Activity Relationships (QSAR) models previously generated in our group for a set of N-benzyl-N,N-dimethyl-2-(4-X-benzamido)ethan-1-ammonium bromides (procaine structural analogs) showed a positive contribution of the lipophilic term (expressed by the partition coefficient, logPapp) to their neuromuscular blockage activity. However, since some of them are hydrophilic quaternary ammonium bromides, their logPapp measurements were usually associated with experimental shortcomings, leading to low accuracy logPapp values. In order to make these experiments more feasible, the application of the ion-pair concept was evaluated as a methodological strategy in another previous work, initially to one compound of this set. For this purpose, logPapp measurements have been done in the presence of a large and hydrophobic counter ion, leading to an increase of its lipophilicity, due to possible ion-pair formation. In the present work, in order to further investigate this strategy and its effects on the lipophilicity, we include more compounds, allowing the assessment of a wider range of logPapp values. Thus, logPapp values of five compounds were obtained by the shake-flask method, using n-octanol/water, with and without ionic strength adjustment. For them, logPapp range values were determined from -1.73 to 0.99. To evaluate the application of the ion-pair concept as strategy, logPapp values of these compounds were determined in the presence of eleven sodium octyl sulfate (OcS) concentrations. It was observed that the lipophilicity of these compounds, increased with the addition of OcS. Moreover, we obtained the corresponding logPapp values extrapolated to zero OcS concentration (logPapp0), which agreed, within the experimental error, with the corresponding values determined in absence of OcS. These results suggest that the ion-pair concept can be applied as a strategy to improve the experimental conditions, increasing the accuracy of logPapp measurements for this set of hydrophilic quaternary ammonium bromides. Finally, supplementary experiments were done to verify the ion-pair formation: (i) measurement of logP values of benzamide (not a permanent ion) in presence of OcS; (ii) NMR spectroscopy analysis of one compound of this set, also in presence of OcS. Both indicated that only for the studied quaternary ammonium bromides the lipophilicity increase is due to possible ion-pair formation. Additionally, the application of the ion-pair concept and its effects on the lipophilicity was evaluated for QX-222 and for neostigmine bromide (highly hydrophilic compounds), which revealed limitations in its application as a methodological strateg

Modelos de Relações Quantitativas entre Estrutura Química e Atividade Biológica (QSAR), previamente gerados no grupo para uma série de brometos de N-benzil-N,N-dimetil-2-(4-X-benzamido)etan-1-amônio substituídos (compostos estruturalmente análogos à procaína), mostraram uma contribuição positiva da lipofilicidade (expressa pelo parâmetro lipofílico, logPapp) para a atividade de bloqueio da transmissão neuromuscular observada para estes. Como os compostos desta série são sais de amônio quaternários, sendo alguns altamente hidrofílicos, as determinações dos seus valores de logPapp pelo método shake-flask acarretam dificuldades experimentais, levando a altas incertezas. Para contornar estas dificuldades, em outro trabalho iniciado no grupo, sugeriu-se, como estratégia metodológica, avaliar a aplicação do conceito do par iônico, usando, para tanto, um contraíon grande e hidrofóbico. Assim, observou-se, para um único composto desta série, o aumento da sua lipofilicidade, por possível formação de par iônico, tornando-o menos hidrofílico. Nesta dissertação, visando ampliar os estudos envolvendo a aplicação desta estratégia metodológica e seus efeitos sobre a lipofilicidade, outros compostos foram selecionados para que uma faixa mais ampla de valores de LogPapp pudesse ser avaliada. Para tanto, os valores de logPapp de cinco compostos desta série foram determinados pelo método shake-flask, usando o sistema n-octanol/água, avaliando-se, ainda, os efeitos da força iônica na partição. Para estes, a faixa de valores de LogPapp determinados variou de -1,73 a 0,99. Para avaliar a aplicação do conceito do par iônico como estratégia, os valores de LogPapp destes compostos foram determinados na presença de diferentes concentrações do contraíon hidrofóbico n-octil sulfato de sódio (OcS). Verificou-se aumento da lipofilicidade com aumento das concentrações de OcS. Obteve-se, também, os correspondentes valores de LogPapp extrapolados para concentração zero de OcS (LogPapp0), que concordaram, dentro do erro experimental, com os valores determinados diretamente na ausência de OcS. Estes resultados indicam que o conceito do par iônico pode ser aplicado como estratégia metodológica, para melhorar as condições experimentais e diminuir as incertezas nas determinações de valores de LogPapp para esta série de brometos de amônio quaternários hidrofílicos. Finalmente, foram realizados experimentos complementares para verificar a formação de par iônico: (i) determinações dos valores de logP da benzamida (composto sem carga permanente) na presença de OcS; (ii) análise por RMN de um dos compostos desta série, na presença de OcS. Ambos indicaram que, somente para os brometos de amônio quaternários estudados, o aumento da lipofilicidade observado ocorre por possível formação de par iônico. E, ainda, foi avaliada a aplicação do conceito do par iônico e seus efeitos sobre a lipofilicidade do QX-222 e do brometo de neostigmina (compostos altamente hidrofílicos), revelando limitações na sua aplicação como estratégia metodológica. / Quantitative Structure-Activity Relationships (QSAR) models previously generated in our group for a set of N-benzyl-N,N-dimethyl-2-(4-X-benzamido)ethan-1-ammonium bromides (procaine structural analogs) showed a positive contribution of the lipophilic term (expressed by the partition coefficient, logPapp) to their neuromuscular blockage activity. However, since some of them are hydrophilic quaternary ammonium bromides, their logPapp measurements were usually associated with experimental shortcomings, leading to low accuracy logPapp values. In order to make these experiments more feasible, the application of the ion-pair concept was evaluated as a methodological strategy in another previous work, initially to one compound of this set. For this purpose, logPapp measurements have been done in the presence of a large and hydrophobic counter ion, leading to an increase of its lipophilicity, due to possible ion-pair formation. In the present work, in order to further investigate this strategy and its effects on the lipophilicity, we include more compounds, allowing the assessment of a wider range of logPapp values. Thus, logPapp values of five compounds were obtained by the shake-flask method, using n-octanol/water, with and without ionic strength adjustment. For them, logPapp range values were determined from -1.73 to 0.99. To evaluate the application of the ion-pair concept as strategy, logPapp values of these compounds were determined in the presence of eleven sodium octyl sulfate (OcS) concentrations. It was observed that the lipophilicity of these compounds, increased with the addition of OcS. Moreover, we obtained the corresponding logPapp values extrapolated to zero OcS concentration (logPapp0), which agreed, within the experimental error, with the corresponding values determined in absence of OcS. These results suggest that the ion-pair concept can be applied as a strategy to improve the experimental conditions, increasing the accuracy of logPapp measurements for this set of hydrophilic quaternary ammonium bromides. Finally, supplementary experiments were done to verify the ion-pair formation: (i) measurement of logP values of benzamide (not a permanent ion) in presence of OcS; (ii) NMR spectroscopy analysis of one compound of this set, also in presence of OcS. Both indicated that only for the studied quaternary ammonium bromides the lipophilicity increase is due to possible ion-pair formation. Additionally, the application of the ion-pair concept and its effects on the lipophilicity was evaluated for QX-222 and for neostigmine bromide (highly hydrophilic compounds), which revealed limitations in its application as a methodological strateg

The aim of this thesis was to create a web application used for centralized management and configuration of wireless networks on access points running on OpenWrt distribution. The reader is acquainted with common principles of wireless networks including description of existing solutions for their centralized management. After that the thesis introduces the reader to OpenWrt distribution and to a method of its configuration using UCI model. The reader is then introduced to the main technologies used in this thesis. Author further describes architecture, user interface and implementation of the web application. The created web application is platform agnostic and provides easy way to manage and configure access points with OpenWrt distribution.

APIs can have different architectures and standards, one of which is REST. REST stands for representational state transfer and is a commonly used architecture when implementing and creating APIs for the web. Choosing a web framework for a REST API implementation is not as trivial as one might think; there are many metrics to consider, one of which is performance. In this study, we compared the most used back-end web frameworks in 2021, ASP.NET Core, Express.js, and Flask, to see which performs best in throughput, response time, and computer resource usage. Finding the best-performing framework will help future developers choose which framework to use in terms of performance. Selecting a good framework from the beginning is essential to prevent the need to change framework in the future. To benchmark the different APIs, we did an experiment where we used JMeter, an open-source software for testing the performance of websites and APIs. By varying the number of virtual users and throughput, we were able to find the limit of each framework and their respective resource usage during different loads. We have concluded that ASP.NET Core had the best performance when it comes to response time and throughput. Furthermore, ASP.NET Core had the most efficient memory utilization throughout the entire experiment, and during loads higher than 4500 throughputs per second, it was also the most CPU efficient. Below 4500 throughput per second, Express.js was the most CPU-efficient framework but still had more memory usage than ASP.NET Core. According to our metrics, the performance of Flask was far behind Express.js and ASP.NET Core and should therefore not be considered a high-performance framework.

Solubility is the amount of solute in the solvent system at phase equilibrium with certain temperature and pressure. Many of the new chemical entities are lipophilic molecules that require techniques to enhance solubility. Solubility enhancement can be achieved by either physical and/or chemical modification of the drug. Various techniques are available for solubility enhancement of poorly soluble drugs include particle size reduction, salt formation, solid dispersions, use of surfactants, prodrug, crystal modification, etc. In this study, the three model drugs belong to BCS class II and IV having low solubility with a certain range of physicochemical properties were studies in solubility enhancement using fusion method, co-precipitation, nano-milling and spray drying techniques. The two different polymers employed for solubility enhancement are PEG 8000 and PVP 40,000. Solubility was determined by Shake Flask method at the temperature of 37±0.1 °C. The objective is to investigate the enhancement of solubility of the three model drugs namely Glipizide, Carvedilol and Furosemide in 1:1, 1:5 and 1:10 drug-polymer ratios and are characterized by Differential Scanning Calorimetry (DSC). The Solubility of Glipizide was enhanced from 11.18 ± 1.78 µg/ml to 35.73 ± 0.04 µg/ml by 219 % increase with nano-milling technique at 1:5 ratio with PEG 8000 as carrier whereas with PVP 40000 as carrier, 286 % increase in solubility to 43.26 ± 7.87 µg/ml was observed at 1:1 ratio by fusion method. The solubility of Carvedilol was enhanced from 5.04 ± 0.55 µg/ml to 17.51 ± 0.94 µg/ml by 246 % at 1:5 ratio by fusion method with PEG8000 as carrier and 2924 % enhancement in solubility to 152.70 ± 9.09 µg/ml at 1:10 ratio by nano-milling with PVP40000 as the carrier. Furosemide showed an increase in solubility from 55.94 ± 2.48 µg/ml to 164.11 ± 9.18 µg/ml by 193 % at 1:10 ratio by nano-milling technique with PEG8000 as carrier whereas with PVP40000 as carrier, 444 % increase was observed at 1:1 ratio by nano-milling technique with solubility of 304.52 ± 23.11 µg/ml. The data showed that the decrease in percentage crystallinity and enthalpy of fusion of the model drugs upon implementing solubility enhancement techniques with the effect of particle size and the carrier used resulted in the increase of aqueous solubility of the model drugs.