1,273 research outputs found
Disruption of the developmental programme of Trypanosoma brucei by genetic ablation of TbZFP1, a differentiation-enriched CCCH protein
No full textThe regulation of differentiation is particularly important in microbial eukaryotes that inhabit multiple environments. The parasite Trypanosoma brucei is an extreme example of this, requiring exquisite gene regulation during transmission from mammals to the tsetse fly vector. Unusually, trypanosomes rely almost exclusively on post-transcriptional mechanisms for regulated gene expression. Hence, RNA binding proteins are potentially of great significance in controlling stage-regulated processes. We have previously identified TbZFP1 as a trypanosome molecule transiently enriched during differentiation to tsetse midgut procyclic forms. This small protein (101 amino acids) contains the unusual CCCH zinc finger, an RNA binding motif. Here, we show that genetic ablation of TbZFP1 compromises repositioning of the mitochondrial genome, a specific event in the strictly regulated differentiation programme. Despite this, other events that occur both before and after this remain intact. Significantly, this phenotype correlates with the TbZFP1 expression profile during differentiation. This is the first genetic disruption of a developmental regulator in T. brucei. It demonstrates that programmed events in parasite development can be uncoupled at the molecular level. It also further supports the importance of CCCH proteins in key aspects of trypanosome cell function
Ikke-lineær elementanalyse av fiberforsterkede betongbjelker, ved bruk av stykkevis lineært tøyningsdiagram i strekk
No full textSAMMENDRAG:
Hensikten med denne oppgaven er å undersøke om oppførselen til fiberbetong kan etterliknes på en god måte med et stykkevis lineært diagram i strekk, når alle andre materialegenskaper er i henhold til allerede eksisterende anbefalinger for ikke-lineære elementanalyser. Anbefalingene som oppgaven bygger på, er anbefalingene fra Hendriks and Roosen (2020). Oppgaven tar for seg bjelker fra studiet Xingwei Xue (2019) og analyserer de med løsningsstrategien presentert i denne masteroppgaven. For å kunne se hvordan stykkevis lineært diagram i strekk oppfører seg. Dette sammenliknes for noen bjelker, med en eksponentielle kurve som Hendriks and Roosen (2020) anbefaler for ordinær betong.
Oppgaven viser at stykkevis lineært diagram i strekk etterlikner oppførselen til de fleste bjelkene på en god måte, og treffer godt med den maksimale kraften. Den viser også at den eksponentielle modellen treffer bedre for de laveste fiberinnholdene for bjelken hvor begge modeller er testet. Det konkluderes med at den stykkevis lineære modellen ikke klarer å etterlikne oppsprekkingen av bjelken på korrekt måte. Samtidig viser variasjonen i antall punkter for strekkdiagrammet at å legge til eller fjerne to punkter, ikke endrer oppførselen til bjelkene det er brukt på i nevneverdig grad. Dette fordi bjelkene ikke når store nok tøyninger i strekk til å havne utenfor det første lineære området til kurven frem til strekkfastheten. Momenttrykkbrudd sammen med lokalt brudd i betongen under opplegget til trykkdiagonalen, er de fremtredende bruddformen for alle bjelkene
Ikke-lineær elementanalyse av fiberforsterkede betongbjelker, ved bruk av stykkevis lineært tøyningsdiagram i strekk
No full textSAMMENDRAG:
Hensikten med denne oppgaven er å undersøke om oppførselen til fiberbetong kan etterliknes på en god måte med et stykkevis lineært diagram i strekk, når alle andre materialegenskaper er i henhold til allerede eksisterende anbefalinger for ikke-lineære elementanalyser. Anbefalingene som oppgaven bygger på, er anbefalingene fra Hendriks and Roosen (2020). Oppgaven tar for seg bjelker fra studiet Xingwei Xue (2019) og analyserer de med løsningsstrategien presentert i denne masteroppgaven. For å kunne se hvordan stykkevis lineært diagram i strekk oppfører seg. Dette sammenliknes for noen bjelker, med en eksponentielle kurve som Hendriks and Roosen (2020) anbefaler for ordinær betong.
Oppgaven viser at stykkevis lineært diagram i strekk etterlikner oppførselen til de fleste bjelkene på en god måte, og treffer godt med den maksimale kraften. Den viser også at den eksponentielle modellen treffer bedre for de laveste fiberinnholdene for bjelken hvor begge modeller er testet. Det konkluderes med at den stykkevis lineære modellen ikke klarer å etterlikne oppsprekkingen av bjelken på korrekt måte. Samtidig viser variasjonen i antall punkter for strekkdiagrammet at å legge til eller fjerne to punkter, ikke endrer oppførselen til bjelkene det er brukt på i nevneverdig grad. Dette fordi bjelkene ikke når store nok tøyninger i strekk til å havne utenfor det første lineære området til kurven frem til strekkfastheten. Momenttrykkbrudd sammen med lokalt brudd i betongen under opplegget til trykkdiagonalen, er de fremtredende bruddformen for alle bjelkene.The purpose of this thesis is to investigate whether the behavior of fibrous concrete can be mimicked in a good way with a piecewise linear diagram when all other material properties are in accordance with preexisting nonlinear element analysis recommendations. The recommendations on which the assignment is based are the recommendations from Hendriks and Roosen (2020). The thesis deals with beams from the study Xingwei Xue (2019), and analyzes them with the solution strategy presented in this master thesis. To see how the piecewise linear diagram in a row behaves in tension. This is for some of the beams compared with the recommended exponential curve that Hendriks and Roosen (2020) recommends for ordinary concrete.
The thesis shows that a piecewise linear diagram in tension mimics the behavior of most beams in a good way, and coincides well with the maximum force observed. It also shows that the exponential model performs better for the lowest fiber content of the beam where both models have been tested. It is concluded that the piecewise linear model fails to mimic the cracking of the beam correctly. At the same time, the variation in the number of points for the bar graph shows that adding or removing two points does not significantly change the behavior of the beams it is used on. This is because the beams do not reach large enough stretches in tension to fall outside the first linear range of the curve until the tensile strength
Correction to: Assessing the quality of cardiac rehabilitation programs by measuring adherence to the Australian quality indicators
No full textFollowing publication of the original article [1], the authors identified two errors in the author names. Firstly, the two co-authors’ names J Hendriks and C Gallagher were mistakenly merged into one name ‘Hendriks Gallagher JC’. Secondly, the given name and family name were erroneously transposed. The author group has been updated above and the original article [1] has been corrected
The Impact of Phytosterols on the Healthy and Diseased Brain
No full textThe central nervous system (CNS) is the most cholesterol-rich organ in mammals. Cholesterol homeostasis is essential for proper brain functioning and dysregulation of cholesterol metabolism can lead to neurological problems. Multiple sclerosis (MS) and Alzheimer's disease (AD) are examples of neurological diseases that are characterized by a disturbed cholesterol metabolism. Phytosterols (PS) are plant-derived components that structurally and functionally resemble cholesterol. PS are known for their cholesterol-lowering properties. Due to their ability to reach the brain, researchers have started to investigate the physiological role of PS in the CNS. In this review, the metabolism and function of PS in the diseased and healthy CNS are discussed.This work was supported by grants of the Research Foundation Flanders (FWO; 12J9116N, 12JG119N, and G099618N to Tess Dierckx, Jeroen F.J. Bogie and Jerome J.A. Hendriks).Hendriks, JJA (reprint author), Hasselt Univ, Biomed Res Inst, Diepenbeek, Hassett, Belgium.
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Non-Intrusive Reduced Basis Code for Geothermal, Geodynamic, and Hydrology Benchmarks
No full text<p>This code demonstrate the construction of surrogate models for the three designated studies in the field of geothermal energy, geodynamic, and hydrology using the non-instrusive reduced basis method and neural networks presented in the paper “Perspectives of Physics-Based Machine Learning for Geoscientific Applications Governed by Partial Differential Equations“ by Denise Degen, Daniel Caviedes Voullième, Susanne Buiter, Harrie-Jan Hendriks Franssen, Harry Vereecken, Ana González-Nicolás, and Florian Wellmann. The non-intrusive reduced basis method is a physics-based machine learning technique originating from the field of projection based model order reduction methods.</p>
Durability-based design: the European perspective
No full textIn Europe, design for the durability of new reinforced concrete structures is currently based on a prescriptive approach. The design, execution (construction) and planned maintenance of a concrete structure have to lead to the intended level of safety and serviceability throughout its entire service life. This requires numeric models based on a sound scientific background of mechanistic understanding as the basis for design and management tools and for the further development of standards and regulations. Designers must understand the basic deterioration mechanisms and the potential types and rates of damage development. For example, different types of corrosion cause very different damage developments, some of which reduce structural safety. We propose that the next generation of service life models should either explicitly include the propagation period or implicitly include it by selecting an accepted probability of depassivation that reflects the type of corrosion and its structural implications.</p
CNS delivery of anti-CD52 antibodies modestly reduces disease severity in an animal model for multiple sclerosis
No full textBackground and aims: Alemtuzumab is a humanized monoclonal antibody that depletes CD52-bearing B and T lymphocytes. Clinical trials defined that systemic administration of alemtuzumab reduces disease severity in the relapsing-remitting phase of multiple sclerosis (MS). However, its efficacy in progressive MS patients is limited, which may reflect the inability of alemtuzumab to cross the reconstituted BBB in these patients. Objective: to study whether central nervous system (CNS) delivery of anti-CD52 antibodies reduces disease severity and the neuroinflammatory burden in the experimental autoimmune encephalomyelitis (EAE) model. Methods: Anti-CD52 antibodies were administered intrathecally during the acute and chronic phases of EAE. Flow cytometry and immunohistochemistry were utilized to define immunological and pathological parameters. Results: We show that subcutaneously administrated anti-CD52 antibodies completely abolish EAE disease severity. CNS delivery of anti-CD52 antibodies during both the acute and chronic phases of EAE moderately reduces disease severity and the neuroinflammatory burden. Our findings further suggest that CNS delivery of anti-CD52 antibodies impacts both the peripheral and CNS immune cell compartments in the EAE model but not in healthy mice. Conclusion: Collectively, our findings highlight the therapeutic potential of CNS delivery of alemtuzumab for the treatment of progressive as well as early MS.The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was funded by Sanofi Genzyme, and grants of the Belgian Charcot Foundation, Research Foundation Flanders (FWO), and European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).Hendriks, JJA (corresponding author), Hasselt Univ, Biomed Res Inst, Dept Immunol & Infect, Agoralaan Bldg C, B-3590 Diepenbeek, Belgium.
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A Conceptual Integrated Parametric Design Tool for Excavation Sites
No full textBuilding Information Modelling (BIM) technologies are changing the conventional structural design process. BIM level-1 and level-2 are providing guidelines and frameworks for standardization with the standard Industry Foundation Classes (IFC) and collaborative design respectively. However, the predicted full potential of BIM, BIM level-3, which is a smart design system, is still in its infancy stage. Many studies focus on single technologies that BIM envelopes and do not grasp the benefit of incorporating all technologies into one model. Additionally, the industry is lagging in the adaptation of BIM technologies, since, as of today, only one company in the world is BIM level-2 certified. Witteveen+Bos recognises the potential of smart systems and is developing many innovative software solutions. In this thesis, as the objective stated, a conceptual partly BIM level-3 excavation site design tool has been developed. The developed tool, integrates parametric design with Plaxis, GIS and RockWorks. The developed tool helps stakeholders to visually explore many design solutions in a short amount of time, based on the costs, MKI, structural- and environmental requirements and the characteristics of the surroundings. The name SET (Smart Engineering Tool) was given to this tool.Three essential boundary conditions are distinguished for the design of an excavation pit. Soil Layers, groundwater levels and the surrounding buildings. These boundary conditions impose loads and requirements on the excavation pit. The way the groundwater can be kept out determines mostly the costs. For this reason, SET works-out designs with a natural impermeable clay layer, an artificial underwater concrete floor or an artificial impermeable gel layer. Additionally, designs with different retaining walls and grout anchors or struts are worked-out. The design of an excavation pit must meet structural and environmental requirements. A vertical, horizontal and moment equilibrium must hold in the excavation pit. In urban areas, the most important concern is avoiding inadmissible damage or hindrance to adjacent structures, because the surrounding buildings are owned by third parties and deformations, causing damage to these buildings, happen quick. For this reason, the design of the excavation pit must meet the settlement requirements of the surrounding buildings. For each design, “Economisch Meest Voordelige Inschrijving” (EMVI) (Economically Most Attractive Tender) scores are used to quantify each design on durability, the impact on the surroundings, hindrance and risk. EMVI in combination with the cost estimates is used to find the design with the best cost to quality ratio. Rijkswaterstaat has determined a “Milieu Kosten Indicator” (MKI) (Environmental Cost Indicator) value for each building material. In this thesis, this value is used to quantify the environmental impact of a designAn analysis was made on the capabilities that a design tool should have. A literature study was performed on the BIM technologies. From this analysis six BIM technologies are included in the development of the tool. These are: parametric design, algorithmic design, collaborative design, central repository, interoperability and standardization. Additionally, for the development of the design tool, different programming languages and development platforms were considered. A combination of Python and JavaScript together with the Web-based Graphics Library (WebGL) was found to be most suitable. A Python back-end processes the data and runs a design algorithm, while the web-based front-end facilitates collocative design and 3D visualisations. The sever, created with the Python module Django, is used for the communication between Python and JavaScript. The JavaScript module Three.js is used to utilize the WebGL capabilities. The development of the design tool, called SET (Smart Engineering Tool), is based on the method of rapid prototyping. This includes prototyping, test and review, refine and iterate. The prototyping process is split into four stages: (1) Interoperability and Standardization, (2) Design algorithm, (3) Collaboration, Interaction and 3D Visuals and (4) Integration. In each of these stages, an essential part of SET was developed. SET is interoperable with Plaxis 2D, a geotechnical finite element program and uses the input of GIS and RockWorks. SET’s internal design algorithm determines what excavation site designs should be calculated by Plaxis. This is based on user settings, and the boundary conditions, surrounding and environmental requirements. The boundary conditions are extracted from GIS files and from RockWorks models. The surrounding buildings are extracted from GIS, and RockWorks supplies the soil stratification. The design tool interprets these boundary conditions and standardizes the data. All data is transferred to a parallel computer, where finite element calculations are performed in Plaxis. Plaxis calculates the vertical, horizontal and moment equilibria and the deformations of the soil. SET analyses the successful Plaxis results and performs a unity check on bending moments in the retaining walls together with an analysis on the settlements requirements of the surrounding buildings. SET is tested and reviewed, by a geotechnical expert and an engineer, with two test cases. The results of these tests cases were analysed and validated. The functionalities and the user-friendliness of the tool have been scrutinized. Based on these tests, SET was reviewed, and refinements and iterations of the design tool emerged. During the development of SET, Witteveen+Bos was working on a tender. The tendered project is a design of a bus lane next to the existing train tracks and is called “Hoogwaardig Openbaar Vervoer in het Gooi” (high quality public transport), in short “HOV in ‘t Gooi”. The currently level intersection of the bus lane with the ‘Oosterengweg’ was used to test SET with two test cases. A tunnel for the Oosterengweg underneath the train track and bus lane, was the first case and a tunnel for the train tracks and bus lane underneath the Oosterengweg, was the second case. The first case, was a similar solution as the final tender design of Witteveen+Bos. The second case however, was an “out of the box” design and which was initially deemed unfeasible by Witteveen+Bos. The testcases took around one hour to prepare in SET. For both test cases, the corresponding Plaxis calculations took around a day of computation time to finish. As a result, SET found many feasible designs for both test cases, in two days. The design of the train and bus tunnel, that was deemed unfeasible, was found to be feasible and almost a third of the cost compared to the Oosterengweg tunnel. However, it must be noted that the costs to redirect the train tracks and the maximum obstruction time of the train was not included in these designs. It can be concluded that SET is partly BIM level-3. The foundations of the SET lie in BIM level-1 and -2. The design tool supports 2D and 3D visuals and parametric design is used in an object-oriented manner for the design of the excavation pit. The tool does not use the all-enveloping BIM standard IFC. However, the design tool does use standardization. Based on requirements from the surroundings and the environment, SET helps to explore a large number of designs in a short period of time and visualizes different designs in 3D and in an interactive graph. The data is managed from a server, which acts as a central repository. Stakeholders can access this server from a web browser and are able to analyse their preferred designs within the extended design space. SET shows 6 major benefits. (1) During the conceptual design phase, the feasibility of designs in a large design space can be analysed without being labour intensive and within a short amount of time. (2) The decisions concerning the final design can be postponed to the very end. Thus, designs that would conventionally be deemed unfeasible in the conceptual stage can emerge as feasible in later stages. (3) The possibility of a collaborative platform stimulates shared and parallel decision making. Each stakeholder can incorporate various requirements, limitations and responsibilities into the model, which utilizes the knowledge and expertise of each stakeholder. (4) The design tool can be used from the very beginning in meetings and discussions with clients to convey information in real time, by the means of 3D visuals. Clients can be granted remote access to SET and evaluate design solutions from the comfort of their office, without sharing valuable scripts and sensitive or private data. (5) Calculations can be processed automatically on a parallel server without the supervision of an engineer. (6) SET integrates multiple design tools like GIS, RockWorks and Plaxis. Overall, SET reduces the required labour to create a design and increases the productivity of an engineer. This reduces the costs of the design process and allows engineers to create “out of the box designs”. Civil Engineering | Hydraulic StructuresCivil Engineering | Hydraulic Engineerin
Environmental impacts during the operational phase of residential buildings
No full textTo date, the focus in the field of sustainable building has been on new building design. However, existing residential buildings inflict great environmental burden through three causes: continuous energy consumption, regular building maintenance and replacements. This publication analyses and compares these three causes of environmental burden and shows that material resources needed for replacements generally have a limited potential to reduce environmental impact. Reducing energy consumption for climate control and electrical appliances is much more effective. According to the author, sustainable measures should be tested for shifts in the kind of environmental impact caused due to the use of alternative types of energy resources and altered material quantities. The sustainability of the electricity supply is essential to decrease the total environmental impact of the residential building stock.Sustainable and Healthy HousingOTB Research Institut
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