Identification and characterization of acute myeloid leukemia stem cells

Ossenkoppele, G.J. [Promotor]Schuurhuis, G.J. [Copromotor]Zweegman, S. [Copromotor

Designing supplementary space in multi-family housing

La démographie et les modes de vie ont considérablement évolué au cours des dernières décades. De tels changements sont destinés à influencer la conception de l’habitation et ils incluent notamment une série de besoins émergents: s’en suivent des besoins additionnels en espace pour répondre à l’arrivée de ces activités additionnelles au niveau du logement. La planification en vue de répondre à ces besoins émergeants constitue le principal thème de la présente thèse. Dans le cas de la maison unifamiliale détachée, le sous-sol est disponible pour offrir des espaces appropriés à ces besoins émergents. Par contre, une telle ressource n’est normalement pas présente dans le cas d’un édifice multifamilial. La thèse propose un espace additionnel spécifique en vue de répondre à ces besoins émergents : l’espace supplétif. Même si un tel espace n’est pas envisagé dans les publications du domaine, des précédents existent quant à sa présence en planification multifamiliale. Le but de la présente étude est d’offrir des lignes directrices quant à la conception et l’intégration d’un tel espace supplétif. Elle va s’appuyer sur l’approche systémique en raison de la logique de déduire la solution à partir d’une analyse de l’objectif. L’application de l’approche systémique implique donc que tous les critères correspondant à la nature spécifique de l’espace supplétif seront extrapolés à partir de l’objectif. Dans le cas la présente étude, ce sont les critères du bureau à domicile qui seront d’abord précisés car il s’agit de l’activité émergente la plus exigeante. Les critères seront traités comme vecteurs d’un modèle générique indicatif de la manière d’organiser l’espace supplétif. Ce modèle visera le bureau à domicile en vue d’offrir les solutions pertinentes et il se concentrera principalement sur les critères d’intimité visuelle et spatiale. La contribution du modèle sera de suggérer des lignes directrices en vue d’incorporer l’espace supplétif à l’intérieur des édifices résidentiels de type multifamilial, ce que la planification conventionnelle n’offre pas. C’est le concept d’adaptabilité qui est à la base de toute stratégie visant à permettre le changement en architecture et en habitation, d’autant plus lorsqu’il s’agit d’un espace supplétif. À cet effet, l’espace supplétif va recourir à l’approche Open Building afin d’appliquer le concept d’adaptabilité, en raison de ses avantages majeurs tant au niveau conceptuel que constructif. Différentes applications de l’approche Open Building, telles que le projet NEXT21 et le protocole KSI (Kikou support and Infill), offrent des exemples susceptibles de constituer d’efficaces lignes directrices pour la conception d’un espace supplétif. La faisabilité du modèle d’espace supplétif proposé est vérifiable et démontrable dans le monde réel. Les systèmes constructifs industrialisés sont en mesure de permettre le changement sans démolition car leurs joints mécaniques « à sec » rencontrent généralement les normes DfD (Design for Disassembly), non seulement en ce qui concerne l’espace supplétif mais pour l’ensemble du logement.Demographics and lifestyles have changed considerably in the past few decades. These changes are bound to influence the design of housing and they notably include a series of emerging needs: additional spatial needs due to additional activities brought to the traditional housing premises. Planning for those emerging needs is the main theme of this thesis. In a typical single-family detached house, the basement is available to accommodate the spatial requirements for these emerging needs. However, such a provision does not typically exist in multi-family housing. This thesis proposes a specific additional space to accommodate these emerging needs: the supplementary space. Although such a space has not been explored in the literature, there are precedents for its application in multi-family floor planning. The objective of this study is to provide guidelines for the design and the integration of this supplementary space. It relies on the systems approach as the design-decision methodology due to its logic of deducting the solution from the analysis of the objective. Applying the systems approach means that all the criteria corresponding to the specific purpose of the supplementary space will be extrapolated from the objective. However, once the supplementary space is being used to deal with emerging needs, it will then introduce its own relevant criteria. This study will start with the criteria for designing a home office because this is the most demanding emerging needs activity. The criteria are organized as vectors of a generic model indicating how the supplementary space can be formulated. The model will target the workplace at home and subsequently offer solutions to them. This study focuses on the planning provisions dealing mainly with visual and spatial privacy. The overall outcome of the model is to suggest guidelines to incorporate the supplementary space within multi-family residential buildings, a feature not offered in traditional planning. The concept of adaptability is the key design strategy to accommodate change in architecture and housing, even more in the case of a supplementary space. Therefore, the supplementary space model will apply the concept of adaptability through the Open Building (OB) approach; elaborating more on the practical design and construction features. Different OB applications, such as the NEXT21 project and the KSI (Kikou Support and Infill) protocol in Japan, are examples that can be used as efficient guidelines to design a supplementary space. The feasibility of the supplementary space model can be validated and served in the real world. Industrialized building systems are capable of accommodating change without demolition as their dry mechanical joints are generally at meeting the DfD (design for disassembly) standards, not only for the supplementary space but also for the whole dwelling unit

Adaptive Neuro-Fuzzy Inference System (ANFIS) Integrated with Genetic Algorithm to Optimize Piezoelectric Cantilever-Oscillator-Spring Energy Harvester: Verification with Closed-Form Solution

Piezoelectric vibration-based energy harvesters (PVEHs) are designed to convert mechanical energy into electric energy. Researchers deal with issues like inefficient amount of energy and frequency bandwidth. Optimizing and widening the PVEH can address the issues. As a modification to the dynamic magnification concept of conventional PVEH, a novel integrated oscillatory multisystem of cantilever-oscillator-spring is proposed. In this project maximizing the widened effective frequency bandwidth with respect to the oscillator mass and spring constant is the main goal. The closed-form voltage function obtained numerically-analytically is expensive in terms of computational time and cannot be used in the genetic optimization. In this regard, soft computing techniques is adopted. Utilizing adaptive-neuro-fuzzy-inference-system (ANFIS), a regressor model is designed to estimate voltage function evaluations in the genetic optimization, such fuzzy system is tuned with decent type and number of membership functions according to the root-mean-square-error criteria. Fuzzy inference system (FIS) is implemented using 64 and 49 fuzzy rules derived from Gaussian membership functions (MFs) and passed to the genetic algorithm initiating with 100 iterations and 30 populations. Using roulette wheel, tournament, and random selection methods, optimal values of the mass and stiffness ratios are found to yield the most widened frequency bandwidth. Findings reveal integration of the proposed oscillator-spring subsystem drastically reinforces utmost generated voltage. Furthermore, tuning parameters result the maximum widened frequency bandwidth which improves the harvester performance up to 3 times the conventional values

The appearance of place identity in the urban landscape by using the natural factors (a case study of Yasouj)

This study has examined the effects of natural factors (urban landscape) on the place identity. In order to perform this, the place identity has been measured and also its relationship with the components of natural factors, absolute elements, living elements and natural elements have been measured. The study is descriptive and the statistical population has been Yasouj which is a city in Iran. To analyze the data the SPSS software has been used. The results have been investigated in two levels of descriptive and inferential statistics. In the inferential statistics, Pearson correlation coefficient has been used to evaluate the research hypotheses. In this study, the variable of place identity is in high level and the natural factors are also in high level which these results indicate a positive relationship between place identity and natural factors. The results indicate that natural factors have significant role on Yasouj landscape and also increase the place identity. It can be inferred that the development of natural factors and reaching it to the qualified level will develop the place identity

Fast and accurate prediction of positive and negative urine cultures by flow cytometry

Background: Urinary tract infection (UTI) is a widespread infectious disease in humans. Urine culture, a huge workload in the microbiology laboratory, is still the standard diagnostic test for UTI, but most of the cultures are negative. A reliable screening method could reduce unnecessary cultures and quicken reporting of negative results. Methods: We evaluated the usefulness of a flow cytometry (FC) screening method in the prediction of positive urine culture to reduce the number of urine cultures. The urine specimens sent to the laboratory for culture were tested with the flow cytometer Accuri C6. FC bacterial counts were compared to standard urine culture results to assess the best cut-off values. Results: Two hundred nine urine samples were included, of which 79 (37.8 %) were culture positive. On comparing the culture and the FC data in the ROC curve, the FC bacterial counts of >= 10(6) bacteria/mL provided a reliable screening for bacteriuria with a sensitivity and specificity of 99 and 58 %, respectively. All negative FC results (<106 bacteria/mL) showed a negative predictive value of 99 % with a negative likelihood ratio of 0.02. The FC bacterial counts of >= 10(8)/mL showed a positive predictive value of 99 % with a positive likelihood ratio of 60.9. Conclusions: Counting bacteria in human urine samples by the FC is a fast, accurate and cost-effective screening method for bacteriuria. Our results showed that FC is able to rule out UTI, which can lead to a substantial reduction (36 %) of urine cultures. It also demonstrated that this method predicts positive cultures accurately

Topical haemostatic agents for skin wounds: a systematic review

Background: Various agents and techniques have been introduced to limit intra-operative blood loss from skin lesions. No uniformity regarding the type of haemostasis exists and this is generally based on the surgeon's preference. To study the effectiveness of haemostatic agents, standardized wounds like donor site wounds after split skin grafting (SSG) appear particularly suitable. Thus, we performed a systematic review to assess the effectiveness of haemostatic agents in donor site wounds. Methods. We searched all randomized clinical trials (RCTs) on haemostasis after SSG in Medline, Embase and the Cochrane Library until January 2011. Two reviewers independently assessed trial relevance and quality and performed data analysis. Primary endpoint was effectiveness regarding haemostasis. Secondary endpoints were wound healing, adverse effects, and costs. Results: Nine relevant RCTs with a fair methodological quality were found, comparing epinephrine, thrombin, fibrin sealant, alginate dressings, saline, and mineral oil. Epinephrine achieved haemostasis significantly faster than thrombin (difference up to 2.5 minutes), saline or mineral oil (up to 6.5 minutes). Fibrin sealant also resulted in an up to 1 minute quicker haemostasis than thrombin and up to 3 minutes quicker than placebo, but was not directly challenged against epinephrine. Adverse effects appeared negligible. Due to lack of clinical homogeneity, meta-analysis was impossible. Conclusion: According to best available evidence, epinephrine and fibrin sealant appear superior to achieve haemostasis when substantial topical blood loss is anticipated, particularly in case of (larger) SSGs and burn debridement

The role of microenvironment and immunity in drug response in leukemia

Leukemia is a cancer of the white blood cells, with over 54,000 new cases per year diagnosed worldwide and a 5-year survival rate below 60%. This highlights a need for research into the mechanisms behind its etiology and causes of therapy failure. The bone marrow microenvironment, in which adult stem cells are maintained in healthy individuals, has been implicated as a source of chemoresistance and disease relapse. Here the various ways that the microenvironment can contribute to the resistance and persistence of leukemia are discussed. The targeting of the microenvironment by leukemia cells to create an environment more suitable for cancer progression is described. The role of soluble factors, drug transporters, microvesicles, as well as the importance of direct cell–cell contact, in addition to the effects of inflammation and immune surveillance in microenvironment-mediated drug resistance are discussed. An overview of the clinical potential of translating research findings to patients is also provided. Understanding of and further research into the role of the bone marrow microenvironment in leukemia progression and relapse are crucial towards developing more effective treatments and reduction in patient morbidity

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Correlation of biophysical properties and cytotoxic potential of recombinant glutamate receptors

Data from both in vivo and in vitro studies indicate that prolonged exposure of neurons to glutamate results in over-activation of N-methyl-D-aspartate (NMDA)-type receptors, allowing an increase in [Ca²⁺]i and resulting in cell death. However, details of the molecular mechanisms, particularly the role of the NMDA receptor's structure, function, and subunit composition that underlie these events have been difficult to study in neuronal systems. We have co-expressed recombinant NMDA receptors with the marker protein (ß-galactosidase in human embryonic kidney cells and determined the amount of viable transfected cells by immunostaining with NR1 specific antibodies and / or assaying for ß-gal expression. Incubation of NR1 / NR2A/ ß-gal transfected HEK-293 cells in bicarbonate-buffered physiological salt solution for 6 hours resulted in loss of transfected cells when NMDA was included. This effect was dose-dependent with an EC₅₀ between 150-300 | μM NMDA. When these experiments were repeated with cells expressing Ca⁺²-impermeable mutant NR1 (N598R) / NR2A receptors, cell death was diminished by -75%. On the other hand, in experiments with wild-type NR1/NR2Atransfected cells, substitution of N-methyl-glucamine for Na⁺ in the salt solution decreased cell death by 50%, suggesting that cytotoxicity was mediated in part by Na⁺ flux through NMDA receptors. Using this system, it was shown that the rapid desensitization of non-NMDA receptors is protective against agonist-induced cell death. In addition, the effect of zinc on NMDA toxicity was examined. In NR1 / NR2A-transfected cells, zinc reduced the cyotoxicity of NMDA with an IC₅₀ of -500 nM. Furthermore, it was shown that zinc inhibits the peak glutamate-evoked current responses and accelerates desensitization in whole-cell patch clamp recordings from NR1 / NR2A and NR1 / NR2B transfected cells. However, NR1 / NR2A was ~20-fold more sensitive to zinc inhibition than NR1 / NR2B, with IC₅₀S of~500 nM and -10 μM, respectively. Finally, the effect of serum albumin on NMDA toxicity was analyzed. It was shown that serum albumin does not potentiate NMDA toxicity in transfected HEK-293 cells. However, the inhibitory effect of zinc on NMDA toxicity was reduced in the presence of serum albumin. Hence, increased concentrations of serum albumin in the brain observed during pathological conditions, could disrupt the regulatory function of Zn²⁺ on NMDA receptors.Medicine, Faculty ofGraduat