92 research outputs found
Physiological and Pathological Ageing of Astrocytes in the Human Brain
No full textAgeing is the greatest risk factor for dementia, although physiological ageing by itself does not lead to cognitive decline. In addition to ageing, APOE ε4 is genetically the strongest risk factor for Alzheimer’s disease and is highly expressed in astrocytes. There are indications that human astrocytes change with age and upon expression of APOE4. As these glial cells maintain water and ion homeostasis in the brain and regulate neuronal transmission, it is likely that age- and APOE4-related changes in astrocytes have a major impact on brain functioning and play a role in age-related diseases. In this review, we will discuss the molecular and morphological changes of human astrocytes in ageing and the contribution of APOE4. We conclude this review with a discussion on technical issues, innovations, and future perspectives on how to gain more knowledge on astrocytes in the human ageing brain
Aß Pathology and Neuron-Glia Interactions: A Synaptocentric View
No full textAlzheimer's disease (AD) causes the majority of dementia cases worldwide. Early pathological hallmarks include the accumulation of amyloid-ß (Aß) and activation of both astrocytes and microglia. Neurons form the building blocks of the central nervous system, and astrocytes and microglia provide essential input for its healthy functioning. Their function integrates at the level of the synapse, which is therefore sometimes referred to as the "quad-partite synapse". Increasing evidence puts AD forward as a disease of the synapse, where pre- and postsynaptic processes, as well as astrocyte and microglia functioning progressively deteriorate. Here, we aim to review the current knowledge on how Aß accumulation functionally affects the individual components of the quad-partite synapse. We highlight a selection of processes that are essential to the healthy functioning of the neuronal synapse, including presynaptic neurotransmitter release and postsynaptic receptor functioning. We further discuss how Aß affects the astrocyte's capacity to recycle neurotransmitters, release gliotransmitters, and maintain ion homeostasis. We additionally review literature on how Aß changes the immunoprotective function of microglia during AD progression and conclude by summarizing our main findings and highlighting the challenges in current studies, as well as the need for further research
Thurstone's Pairwise Comparison Model to explore preferences of humans for different food items
No full textThe method of pairwise comparisons is a method that is commonly used in psychology to model human preferences for a set of objects. In a pairwise comparison experiment, the preferences of a sample are obtained by comparing the objects in pairs. Each individual in the sample judges every possible pair of objects and expresses which of the two object he prefers. Thurstone's PairwiseComparison Model can then be used on the gathered data in order to obtain rankings of the objects based on the preferences of the sample. This thesis investigates several properties of Thurstone's Pairwise Comparison Model and how it can be used to model human food preferences. In recent years, people have become more aware of the importance of eating healthy food. It may, however, be questioned whether healthy food is generally preferred by the population. This can be examined by means of Thurstone's Pairwise Comparison Model. In order to examine how the model performs, a data study has been carried out using two sets of food products. One set consisted of general foodproducts, while the other set was comprised of snack products. Both sets of objects consisted of both healthy and unhealthy food products. The influence of an introduction text, emphasizing the importance of healthy food, on the preferences of the individuals has been examined as well. For this, each set of food products was judged by two groups, each group receiving a different introduction text before starting the pairwise comparison experiment. The results of the data study yielded that Thurstone's Pairwise Comparison Model is more suitable for modelling preferences of humans for general food products. Furthermore, the introduction text turned out to be not of influence on the preferences of participants.Applied Mathematic
Graduation project The Wharf
No full textThe Wharf Living & working combined in housing Industrial dwelling project in Amsterdam North area, Distelweg, BuiksloterhamAt Home In The CityDwellingArchitectur
The Effective Notch Stress Approach for a Tubular Joint
No full textOffshore wind energy production is increasing rapidly and optimising the design of support structures has the potential to significantly reduce steel and costs. Jacket structures are commonly selected for deeper waters, and the design of these structures is primarily influenced by the fatigue performance of the tubular joints. The fatigue resistance of these joints can typically be evaluated using different stress assessment methods, each associated with a corresponding S-N curve. While the Hot Spot Stress (HSS) approach is commonly used for design purposes, the Effective Notch Stress (ENS) approach offers higher accuracy by taking into account the stress concentration originating from the weld profile. Consequently, the ENS approach has the potential to provide less conservative fatigue life estimations, leading to the reduction of steel and costs. However, the application to and research of the ENS approach for tubular joints is limited. Therefore, the objective of this thesis is to investigate the application of the ENS approach on a tubular joint. The research was divided into three parts, including an investigation on the required FE mesh, a study on sub-modeling of the ENS approach and a comparative analysis on the fatigue life predictions between the HSS and ENS approaches.The FE mesh required for the ENS approach was evaluated on a cruciform joint according to the DNV-RP-C203 validation methodology and the Stress Concentration Factors (SCFs) values obtained for different mesh configurations were compared. Two mesh variants were developed, and different element sizes in the notch were evaluated. The results show that with a maximum element size in the notch equal to 0.39 mm, according to DNV, unacceptable SCF errors are obtained of -4% and 4%. Furthermore, with a maximum notch element size of 0.25 mm, according to IIW, SCF errors of -0.3% and -2.2% were obtained, indicating that accurate results can be obtained but are not guaranteed. Additionally, the accuracy of the mesh was found to be primarily influenced by the number of nodes surrounding the notch, rather than the size of the elements in the notch.The accuracy of sub-modeling for the ENS approach on a tubular T-joint was evaluated by varying global modeling choices and sub-model sizes. The accuracy was measured by comparing sub-modeling stress results against those from a global T-joint FE model with the ENS approach applied. The results show that a global model composed of 3D elements with a weld profile that corresponds to the sub-model is recommended. Simplifying the global model by excluding the weld profile or using 2D elements has been found to provide inconsistent and inaccurate results. Moreover, a sub-model of the weld area with a size as small as 1.67 degrees of the brace radial angle has been found to provide consistent results. Thereby, sub-modeling reduces the required mesh size by a factor of 15, compared to the global modeling approach. Additionally, a rather surprising maximum principal stress error of approximately -6% was observed as a result of sub-modeling for all varied load types and sub-model sizes.A comparative study between the HSS and the ENS approach was conducted for the computed fatigues of a tubular T-joint. Various FE models were composed for the T-joint subjected to different load cases, and equivalent SCFs were computed by introducing a correction factor based on the S-N curves of both approaches. The results show that the ENS approach provides a lower computed fatigue life over the HSS approach when applied to a tubular joint. This discrepancy is attributed to the FAT225 S-N curve, used for the ENS approach, which is not tailored for tubular joints but for welded straight plates. For the HSS approach, the choice of element type (2D vs 3D) and the inclusion of a weld profile have a significant effect on the stress distribution and the resulting fatigue life prediction. It was found that a model consisting of 3D elements with the inclusion of a weld profile yields the longest computed fatigue life for a tubular joint.To conclude, the application of the ENS approach was investigated for a tubular joint, by evaluating the mesh sensitivity, examining the accuracy of sub-modeling and comparing the computed fatigue lives with those from the HSS approach. Further research is recommended to improve the computational efficiency of the ENS mesh and to achieve a deeper understanding of the -6% error found by sub-modeling. Additionally, the development of an S-N curve tailored for tubular joints is suggested to improve the accuracy of the ENS approach for this type of joint.Civil Engineering | Structural Engineerin
Detecting clonality in contralateral breast cancers
No full textWhen a second tumor arises in the contralateral breast in a patient with a previous or synchronous breast cancer, it is of clinical importance to determine if this tumor is a new unrelated tumor or a metastasis, i.e. clone, of the primary tumor. A new, unrelated tumor may be treated similarly as the first one since treatment was successful, while a distant metastasis demands a change of therapy and has a more adverse prognosis. In clinic, a second tumor is generally regarded as a new primary. If there is clinical suspicion that the second tumor may be a metastasis, clinico-pathological characteristics of the two tumors are used assess the clonality status. Clinico-pathological characteristics, however, are not reliable predictors to determine if a second tumor is a metastasis. Recent studies have investigated tumor clonality using techniques from molecular genetics. These models appear to perform well, but have several drawbacks.In this thesis a more advanced classification model is being developed that can detect tumor clonality based on SNP array data. For this, two segmentation algorithms, ASCAT and OncoSNP, and two comparison methods, Log LR and adapted SI, have been incorporated. For each tumor, the segmentation algorithms construct a copy number profile based on the SNP array data. Given the copy number profiles, the comparison methods compute a p-value which reflects the probability that a pair is of clonal origin. Both comparison methods are permutation methods which test the null hypothesis of independence against the alternative hypothesis assuming clonality. The proposed model consists of a decision tree which assigns each pair to one of six categories depending on the significance of the four resulting p-values.The model has been tested on 23 fresh frozen pairs by means of expert judgment. The results were promising: the four pairs which were unanimously labeled as clonal by the experts were also regarded as such by the model. No independent pairs were assigned as clonal by the model. Moreover, the decision tree showed to have a higher sensitivity than the clinical assessments as the latter only managed to detect two out of four clonal pairs. A discordance between the clinico-pathological judgments and decision tree results was found for three out of 18 pairs for which both assessments were available.The model appears to be suitable in practice, but is not yet applicable as a stand-alone model. There were two ambiguous pairs which were labeled as independent by the model but for which the experts had varying opinions about the clonality status. Until the ambiguous pairs can be reliably categorized, it is advised to take into account both the model results and clinical assessments when determining tumor clonality. Finally, the performance of the model remains to be tested on FFPE pairs.Applied Mathematic
Instrumentatie meetring RandstadRailtunnel: TNO-rapport 2008-D-R1094/B
No full textDe Engineering van deze instrumentatie is gebaseerd op de informatie als omschreven in de volgende documenten: * Basisprojectplan F540 'RandstadRail', kenmerk: PLATFORM GPB_BPP_04_1441, versie 04 d.d. 17 oktober 2005 *Onderzoeksplan RR (versie 2, 30 juni 2006).doc Onderzoeksplan: Beheerst zakkingen – RR: De aanleg van RandstadRail in Rotterdam biedt, samen met de aanleg van de Noord-Zuidlijn te Amsterdam, uitgelezen mogelijkheden de ervaring die in de verschillende praktijkprojecten de afgelopen jaren is opgedaan in een stedelijke omgeving te valideren. Vanuit het Gemeenschappelijk Praktijkonderzoek Boortunnels (GPB) wordt voorgesteld om bij het praktijkonderzoek RandstadRail (RR) aandacht te besteden aan de volgende thema’s / onderwerpen: \u95 Onderzoek naar de constructieve, geotechnische en boortechnologische aspecten van de aanleg van een geboorde tunnel welke zich gedeeltelijk in Holocene kleilagen bevindt; \u95 Onderzoek naar de constructieve, geotechnische en boortechnologische aspecten van de aanleg van een geboorde tunnel welke zich in door middel van verschillende grondverbeteringstechnieken verbeterde grondlagen bevindt
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