18 research outputs found
Annexin A1 and annexin A5 in cardiovascular disease
No full textThis study involves two members of the annexin family of proteins and their relationship to cardiovascular disease. The main findings are the inhibiting effect of annexin A5 on clearing away dead cells and, therefore, the enhancing effect on ‘arteriosclerosis’. Annexin A1 has an anti-inflammatory effect and was successful in the treatment of ‘arteriosclerosis’ as well as the reduction of damage following myocardial infarction. These findings may lead to the development of new drugs
Quantization effects in PDMM: A first study for synchronous distributed averaging
No full textNowadays, large-scale networks of computing units, often characterized by the absence of central control, have become more commonplace in many applications. To facilitate data processing in these large-scale networks distributed signal processing is required. The iterative behaviour of distributed processing algorithms combined with the limited energy, computational power, and bandwidth, limitations imposed by such networks, place tight constraints on the transmission capacities of the individual nodes. For this reason quantization in distributed algorithms has become an interesting and popular topic. Already considerable research has been performed into quantization effects for various distributed algorithms, such as alternating-direction method of multipliers (ADMM). However, for the primal-dual method of multipliers (PDMM), a recently proposed promising distributed algorithm, no research into the effects of quantization exists. In this thesis the effects of subtractively dithered uniform quantization in PDMM are investigated for the synchronous distributed averaging problem. This specific averaging problem, which is often considered as the canonical distributed problem, was selected to start the research from a natural point. As such, the theory developed in this thesis can form a foundation for further research into quantization effects in PDMM in general. The quantization effects are discussed by considering the convergence rate of the algorithm. This is done by deriving expressions for the mean squared error (MSE) that include quantization noise. Also the required bitrate for quantized PDMM is considered. It was concluded that for practical applications quantization in PDMM can be applied with a near-fixed-rate quantizer, such that significant bitrate reduction can be achieved, without compromising the rate of convergence.Electrical Engineering, Mathematics and Computer ScienceMicroelectronicsCircuits and System
Design and feasibility study for the application of an inflatable rubber structure in a navigation lock
No full textIntroduction In navigation locks levelling is executed under free flow. The net flow from the upper section into the lower section of the waterway is considered as a water loss. An innovative water saving concept is an IRS Lock. IRS stands for inflatable rubber structure. The concept consists of an air filled IRS applied in a lock chamber. In this way part of the water loss is substituted by an ‘air loss’. It was not clear whether or not the IRS Lock concept is a feasible water saving solution. IRSs are formed by a rubber sheet connected to a foundation. The sheet is so flexible that it is considered to have no bending stiffness. The shape of the IRS results from the loads acting on the sheet. During the use of an IRS, four phases are distinguished; the inflation, the inflated, the deflation and the deflated phase. In each phase, the internal pressure is different and thus a different shape results. In case of the IRS Lock, the IRS is completely submerged and the hydrostatic load is the main load. Also loads occur by flows from lock operations and vessel movements. The different phases of use, shapes and the new application area make the design of the IRS Lock a complex process. Design A first design of the IRS Lock has been developed. The Eastern Lock, located in the Terneuzen Lock complex, was used as an environment for the design. In the design the sheet of the IRS is connected to the lock chamber walls. In navigation locks a minimum keel clearance is required between the vessel and the lock chamber bottom. The IRS is located above the bottom of the lock chamber. The water level in the lock chamber, and therefore also the available depth and keel clearance, varies by the tide. The first design of the IRS is optimized in such a way that the design results in a large water saving while maintaining the minimum required keel clearance. The designed IRS has a crest height of 2,5 meter and still allows the draught of the design vessel. In total three IRSs are applied in the length of the Eastern Lock. Additionally, several elements of the IRS Lock have been elaborated. Among others the strength of the rubber sheet has been verified. Functional performance The functional performance of the first design of the IRS Lock has been assessed. Per Lock cycle the designed IRSs will save 9056 m3 of water. Because of the tidal fluctuations in the water levels, and the limitations in available depth and keel clearance, the IRS can only be used for 6 of the 18 lock cycles per tidal period. The total amount of water that is saved per tidal period is on average 25% of the total water loss. As part of a RAMS-analysis, a Failure Mode Effect Analysis has been performed. Measures have been taken to keep the risk of failure at an acceptable level. From the functional performance it follows that the designed IRS Lock is technically feasible. An alternative for the IRS Lock is a pumping station that pumps the lost water back into the upper section of the waterway. It has been found that in all possible situations the IRS Lock will use more energy per unit of saved volume than a pumping station. Also the Life Cycle Costs are higher. This makes the IRS Lock economically less attractive.Hydraulic EngineeringCivil Engineering and Geoscience
Verbetering van verstaanbaarheid in teleconferenties door het gebruik van beamformen
No full textDe verstaanbaarheid van de aanwezigen bij teleconferenties is minder dan bij gesprekken waarbij beide partijen zich in \'e\'en ruimte bevinden, aangezien stoorsignalen net zo goed worden opgenomen en verder de ruimtelijke informatie van de spraak verloren gaat. Een systeem werd ontworpen dat real-time bepaalt uit welke richting iemand spreekt, geluid uit overige richtingen onderdrukt en het geluid daarna afspeelt alsof het uit de richting kwam waarvandaan gesproken werd om zo het probleem te verhelpen. Acht microfoons nemen het geluid op, waarna dit geluid in het frequentiedomein wordt verwerkt. Eerst wordt er in vijf richtingen gebeamformd, waarna van elk van deze vijf richtingen de energie wordt bepaald. De richting met de hoogste energie wordt dan gekozen uit als de gewenste. Convolutie met een `head-related transfer function' geeft dan geluid dat lijkt alsof het uit de bepaalde richting komt. Dan wordt door middel van de Overlap-Add-methode het signaal teruggetransformeerd naar het tijdsdomein, waarna het wordt afgespeeld via een koptelefoon. De ontworpen beamformer werkt het beste boven frequenties van 2000 Hz. De richtingbepaling werkt voldoende nauwkeurig en snel. Verder kunnen luisteraars herkennen uit welke richting oorspronkelijk gesproken werd. Aanbevolen wordt in een vervolg een frequentieonafhankelijk beamformalgoritme te gebruiken, een richtingbepaling op basis van kruiscorrelatie toe te passen en een manier te ontwerpen die het geluid ruimtelijk weergeeft door luidsprekers.Multimedia Signal ProcessingElectrical Engineering, Mathematics and Computer Scienc
Influence and Applicability of the Eurocode: For locks that are part of the Flood Defense System
No full textSince the entrance of the Eurocode a lot of commotion emerged for the hydraulic engineer. The implementation of the Eurocode entailed a problem for the hydraulic structures that are part of the flood defense system. According the law, the locks that are part of the flood defense system should meet the requirements based on the most critical standard. Previously, for hydraulic structures the critical standard was Leidraad Kunstwerken (based on the Waterwet). This standard was more conservative than the NEN (based on the Woningwet). Since the NEN is replaced with the Eurocode, a higher safety class is added that is more conservative than the LK. So, hydraulic structures are forced by the law to be designed based on the Eurocode, while the Eurocode is actually addressed to buildings and bridges. So, the question arises: would it be correct to apply the Eurocode for designing locks that are part of the flood defense system. This research contributes to clarify the previous mentioned issue. It starts by exploring the issue in more detail, which eventually exposes the conflict between the Eurocode and LK. This conflict is restricted to the partial factor for water level difference, which comes down to the applicability of the reliability index (which indicates the degree of safety). Both the Eurocode as the LK prescribes a different reliability index. This difference in conception is researched in two ways. First, the influences on the structural design and the costs are analyzed. By means of a case study, two designs are made for the different standards (LK/NEN and Eurocode). This exposes the elements which are strongly affected. From there, it is searched to possible optimizations in the design in order to reduce the costs. The second perspective which is analyzed is the influence on the dike ring. By using the Eurocode for the structural design of the lock, the failure probability of the dike-ring will decrease. This change is analyzed and translated to a decrease in risk. Subsequently, the decrease is balanced with the required investment to upgrade the structural design. The use of the Eurocode can now be analyzed from an economic point of view. These two studies will finally conclude the influence and the applicability of the Eurocode for locks that are part of the flood defense system.Hydraulic StructuresHydraulic EngineeringCivil Engineering and Geoscience
Engineering solutions to neural stem cell differentiation challenges
No full textBackground Damage dealt to the central nervous system (CNS) caused by trauma or disease can have detrimental effects on human quality of life because the CNS has limited regenerative capabilities. Efforts to replace lost neural cells require improved knowledge and methods for differentiation of neural stem cells (NSCs).Objective In this thesis, I aim to chart our current scientific knowledge and progression of neural differentiation and explore practically the feasibility of continuous ultrasound (US) stimulation on neural progenitor cells (NPCs) differentiating into neurons in vitro.Methods I performed a literature study examining previous studies that investigated electrical stimulation, nanoparticles, or ultrasound to improve in vitro or in vivo differentiation of neural stem cells. Using finite element method (FEM) frequency analyses with COMSOL Multiphysics, I investigated the use of a 24-wells plate with piezoelectric lead zirconate titanate [Pb(ZrxTi1–x)O3] (PZT) US transducers. Additionally, I validated in vitro previous findings on the feasibility of differentiation of NSCs to NPCs.Results With the knowledge gained from literature and findings from the experiments, I created a mold for the fabrication of a custom variant of a 24-wells plate made with polydimethylsiloxane (PDMS) to which 2.03 mm thick PZT can be mounted.Conclusion Future research efforts should focus on further developing this technique, specifically into electrical schemes to optimize US transmission to NPCs.Biomedical Engineerin
Latrophilin’s social protein network
No full textLatrophilins (LPHNs) are adhesion GPCRs that are originally discovered as spider’s toxin receptors, but are now known to be involved in brain development and linked to several neuronal and non-neuronal disorders. Latrophilins act in conjunction with other cell adhesion molecules and may play a leading role in its network organization. Here, we focus on the main protein partners of latrophilins, namely teneurins, FLRTs and contactins and summarize their respective temporal and spatial expression patterns, links to neurodevelopmental disorders as well as their structural characteristics. We discuss how more recent insights into the separate cell biological functions of these proteins shed light on the central role of latrophilins in this network. We postulate that latrophilins control the refinement of synaptic properties of specific subtypes of neurons, requiring discrete combinations of proteins.</p
Two-photon polymerized scaffolds for neuronal differentiation of mouse embryonic stem cells
No full textThe central nervous system has a very limited capacity to regenerate damaged tissue. Therefore, regeneration strategies focus on transplantation of neural stem cells or differentiated neural cells. In order to make such a treatment effective, it is important to understand the mechanisms that enable cell differentiation. It is well known that besides biochemical cues, also mechanical and geometric properties of the cell environment, such as topography, curvature and stiffness, can influence the process, which has been studied mostly in 2D. In order to conduct relevant cell studies in vitro, it is therefore important to mimic the 3D structure of the in-vivo cell environment. Many different approaches have been adopted to create scaffolds for neuronal cells, such as freeze-drying, electrospinning and stereolitography. The main drawbacks of these methods are the limited resolution and the constraints in terms of achievable geometries. Two-photon polymerization overcomes these problems by using a laser to polymerize a photosensitive material in extremely confined volumes, achieving a submicrometric resolution. In this study, we fabricated 3D microscaffolds made of an acrylate polymer called IP-Dip by employing two-photon polymerization in order to study the effect of curved versus straight lattice geometries on the differentiation of mouse embryonic stem cells into neural progenitor cells. First, feasibility studies were carried out with HeLa cancer cells and the effect of curvature on these cells was investigated on 2.5D structures. We established a workflow for conducting these experiments from the fabrication up until the analysis. By employing confocal imaging, image stacks were obtained and then analysed to obtain the volumetric cell occupancy of the scaffolds and identify the location of the cells within the scaffolds. We concluded that mESCs could successfully grow and differentiate within the 3D scaffolds without a specific preference for a curved over a straight lattice structure.Mechanical Engineering | Micro-optics and Optomechatronic
Estrogen protects the blood-brain barrier from inflammation-induced disruption and increased lymphocyte trafficking
No full textThis work was supported by ARUK – PPG2013B-2 and FISM-3/15/F14 to ES, Barts and the London Trust to MY, and British Heart Foundation Fellowship FS/12/38/29640 to C
Putting on molecular weight: Enabling cryo-EM structure determination of sub-100-kDa proteins
No full textSignificant advances in the past decade have enabled high-resolution structure determination of a vast variety of proteins by cryogenic electron microscopy single particle analysis. Despite improved sample preparation, next-generation imaging hardware, and advanced single particle analysis algorithms, small proteins remain elusive for reconstruction due to low signal-to-noise and lack of distinctive structural features. Multiple efforts have therefore been directed at the development of size-increase techniques for small proteins. Here we review the latest methods for increasing effective molecular weight of proteins <100 kDa through target protein binding or target protein fusion - specifically by using nanobody-based assemblies, fusion tags, and symmetric scaffolds. Finally, we summarize these state-of-the-art techniques into a decision-tree to facilitate the design of tailored future approaches, and thus for further exploration of ever-smaller proteins that make up the largest part of the human genome.BN/Dimphna Meijer La
