165 research outputs found
Gene-environment interactions in Inflammatory Bowel Disease:Emphasis on smoking and autophagy
No full textInflammatoire darmziekten (IBD), bestaande uit de ziekte van Crohn (ZvC) en colitis ulcerosa (CU) worden gekenmerkt door chronische ontsteking van het darmslijmvlies. Er ligt een genetische gevoeligheid ter grondslag aan het ontstaan van IBD, maar het zijn juist omgevingsfactoren die deze gevoeligheid voor en het beloop van de ziekte kunnen beïnvloeden. Een belangrijke omgevingsfactor die aantoonbaar van invloed is op IBD is roken. Roken verergert de mate van ontstekingen bij de ZvC, maar opvallend genoeg blijken patiënten met CU juist een gunstig effect te hebben op de ontstekingen bij deze ziekte. Als we darmepitheel cellen en T-lymfocyten bloot te stellen aan sigarettenrook, zien we dat het inflammatie-geïnduceerde apoptose remt wat de ZvC verergerd, maar in CU juist gunstig is. Heat shock eiwitten lijken hierin een belangrijke rol te spelen en dan met name HSPA6. We laten zien dat sigarettenrook het HSPA6 expressie verhoogt (op zowel RNA als eiwit niveau) en het anti-apoptotisch eiwit, Bcl-Xl stabiliseert. Deze bevindingen samen met de significante associatie in het HSPA6 gen met CU suggereren dat HSPA6 bijdraagt aan het anti-apoptotisch effect van sigarettenrook in CU. Welke componenten in sigarettenrook precies verantwoordelijk zijn voor dit effect, en hoe deze aangrijpen, is nog onduidelijk. De T300A variant van het ATG16L1 gen is één van de bekendste en sterkste ZvC-geassocieerde risicovarianten en een mogelijke interactie met sigarettenrook is nog niet eerder aangetoond. ATG16L1 is essentieel is voor (niet-selectieve) autofagie, een proces dat een rol speelt in de overleving van de cel, maar het is ook belangrijk voor de afbraak van bacteriën. We laten zien dat de opname van E. coli en pathogene E. coli (AIEC) in monocyten met de T300A mutatie, significant is verhoogt. Sigarettenrook onderdrukt deze verhoogde opname van E. coli, maar niet van AIEC. Verder laten we zien dat monocyten met de T300A mutatie die zijn gestimuleerd met inflammatoire triggers of sigarettenrook minder goed in staat zijn AIEC af te breken, resulterend in een verstoorde balans van de darmflora en verergering van de ZvC.Crohn’s disease (CD) and ulcerative colitis (UC) are autoimmune chronic inflammatory disorders of the intestine that are collectively known as inflammatory bowel diseases (IBDs). It finds its origin in an exaggerated inflammatory response to gut luminal contents, caused by an inaccurate response to environmental factors due to the specific genetic makeup of the individual. A typical environmental factor from the Western life style is cigarette smoking, which is beneficial for UC, but detrimental for CD. In this thesis, we aimed to identify smoke-induced mechanisms that could explain the dichotomy in UC and CD. We found that cigarette smoking protects intestinal epithelial cells and T-cells against inflammation-induced apoptosis. This generalized effect of cigarette smoke may lead to mucosal healing in UC, but at the same time further impair proper T-cell termination in CD. To extend our search for genes/proteins responsible for the smoke-induced anti-apoptotic signaling, we found that smoke dose-dependently enhanced the expression of heat shock protein HSPA6 and that HSPA6 physically interacts with and stabilizes the anti-apoptotic protein, Bcl-XL. Further, we found that HSPA6 resides in an UC susceptibility locus. These results reveal a potential mechanism in the smoke-dependent effect on UC. It remains to be determined which smoke-contained component(s) are responsible for the induction of HSPA6 and contribute to the anti-apoptotic effect of cigarette smoking and potential protection against colitis.The T300A variant in ATG16L1 is one of the most well known CD-associated variants and a potential interaction with cigarette smoking was not yet identified. ATG16L1 is essential for non-selective autophagy, a process important for cell survival, but it also plays a crucial role in confering resistance to infection by elimination intracellular pathogens, thereby defining mucosal tolerance. Here, we show that uptake of E. coli and of the pathogenic variant (AIEC) was increased in monocytes carrying the T300A variant and cigarette smoke only impaired the uptake of AIEC. Further, monocytes carrying the T300A variant showed impaired killing of AIEC, especially in combination with inflammatory triggers or cigarette smoke, resulting in modulation of intestinal flora, thereby further aggravating CD pathology
Gene-environment interactions in Inflammatory Bowel Disease: Emphasis on smoking and autophagy
No full textInflammatoire darmziekten (IBD), bestaande uit de ziekte van Crohn (ZvC) en colitis ulcerosa (CU) worden gekenmerkt door chronische ontsteking van het darmslijmvlies. Er ligt een genetische gevoeligheid ter grondslag aan het ontstaan van IBD, maar het zijn juist omgevingsfactoren die deze gevoeligheid voor en het beloop van de ziekte kunnen beïnvloeden. Een belangrijke omgevingsfactor die aantoonbaar van invloed is op IBD is roken. Roken verergert de mate van ontstekingen bij de ZvC, maar opvallend genoeg blijken patiënten met CU juist een gunstig effect te hebben op de ontstekingen bij deze ziekte. Als we darmepitheel cellen en T-lymfocyten bloot te stellen aan sigarettenrook, zien we dat het inflammatie-geïnduceerde apoptose remt wat de ZvC verergerd, maar in CU juist gunstig is. Heat shock eiwitten lijken hierin een belangrijke rol te spelen en dan met name HSPA6. We laten zien dat sigarettenrook het HSPA6 expressie verhoogt (op zowel RNA als eiwit niveau) en het anti-apoptotisch eiwit, Bcl-Xl stabiliseert. Deze bevindingen samen met de significante associatie in het HSPA6 gen met CU suggereren dat HSPA6 bijdraagt aan het anti-apoptotisch effect van sigarettenrook in CU. Welke componenten in sigarettenrook precies verantwoordelijk zijn voor dit effect, en hoe deze aangrijpen, is nog onduidelijk. De T300A variant van het ATG16L1 gen is één van de bekendste en sterkste ZvC-geassocieerde risicovarianten en een mogelijke interactie met sigarettenrook is nog niet eerder aangetoond. ATG16L1 is essentieel is voor (niet-selectieve) autofagie, een proces dat een rol speelt in de overleving van de cel, maar het is ook belangrijk voor de afbraak van bacteriën. We laten zien dat de opname van E. coli en pathogene E. coli (AIEC) in monocyten met de T300A mutatie, significant is verhoogt. Sigarettenrook onderdrukt deze verhoogde opname van E. coli, maar niet van AIEC. Verder laten we zien dat monocyten met de T300A mutatie die zijn gestimuleerd met inflammatoire triggers of sigarettenrook minder goed in staat zijn AIEC af te breken, resulterend in een verstoorde balans van de darmflora en verergering van de ZvC
Towards Self-Reliant Development: Inhabitant Housing Capacity Gap of Rural Inhabitants on Mt. Elgon
No full textRural communities in developing countries show a socially inclusive, resilient, and self-reliant model for their housing, despite the lack of individual capacities. However, due to scarce opportunities, many people move to the cities, often returning to challenging living conditions. As a result, both urban and rural inhabitants struggle to reach the desired living standards and well-being. This article explores general capacities of rural inhabitants in Kenya and identifies what shortages prevent inhabitant well-being within their housing. Outcomes of the interviews performed on two hundred families (four communities) evaluate whether the different communities still build housing by themselves, if they would like to continue this ‘self-reliant model’, or would prefer professionals ro realize their housing. The conclusion indicates that inhabitants would prefer to build housing by themselves and exposes why these communities change to ‘external’, housing solutions. Housing alternatives which lie within their capacities, play a crucial role in sustaining the communities’ self-reliance in relation to their housing.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Situated Architectur
The Total Cost of Living in Relation to Energy Efficiency Upgrades in the Dutch, Multi-Residential Building Stock
No full textDecarbonizing the housing stock is one of the largest challenges in the built environment today, and is getting attention not only from policymakers, but also from social housing corporations, financial and tenants’ organisations. In line with the international Paris-Climate-Change-Conference 2015, Dutch cities and housing associations have embraced this challenge with the ambitions to become carbon neutral in 2050. To reach such ambitious goals, both the rate and depth of renovation need to increase significantly. In the Netherlands, the Energy Agreement for Sustainable Growth, indicates that 300.000 dwellings have to be renovated annually, in accordance with the Energy Performance of Buildings Directive adopted by the European Union, to improve the Dutch building stock towards energy neutrality. Several technical solutions to eliminate the energy demand in dwelling have been developed and tested. Nevertheless, the intake rate of deep retrofitting is low. Currently, most improvements in residential buildings consist of basic maintenance and shallow renovation, but broader or deeper energy renovation measures are required. Despite more recent developments, there are still significant barriers related to financing, lack of information, and user acceptance. Complex technical characteristics are not always taken into account by tenants; the focus is usually on the ease of use, comfort and living expenses.To this end, the present study sets of to investigate the relationship between energy efficiency upgrade measures and cost of living. Focusing on the post-war, multi-family social housing in the Netherlands, a framework of refurbishment measures that affect the energy efficiency were identified, and their performance was simulated. The variations refer to the façade design, thermal envelope upgrade, winter-garden addition and reviewable energy. The energy efficiency indicator is the energy cost reduction, as well as the carbon footprint of the energy use. Furthermore, the rental price adjustment was estimated, taking into account the refurbishment investment and the operation cost of the renovated dwellings. All tested combination of variables resulted in significant energy savings, up to 70%, while energy generation was proven to be cost-effective, as it has a considerable positive effect on the energy use and the energy cost, without increasing the rental price.The results aim at supporting the decision-making discussion between the stakeholders, primarily housing associations and tenants. The relation between the energy consumption and rental price for the different options identifies the effect of design variation and demonstrated the attractive solutions that the tenants are more likely to accept, taking into account the overall cost of living and sustainability benefits.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Building Product InnovationHousing Institutions & GovernanceHousing ManagementDesign & Construction ManagementArchitectural Engineerin
«Труд в крови». О языке женского субъекта и животного субъекта в поэтическом сборнике Matecznik [Матечник] Малгожаты Лебды
No full textAnouk Herman’s aim in this article is to introduce the ecofeminist theory of the animal subject and its absent referent in the poetry book Matecznik by Polish author Małgorzata Lebda. Ecofeminism provides tools for elaborate analysis of the conceptual connections between women (as well as persons of nonbinary identities) and animals and may be used as a theoretical background for ecocritical research on literature. Ecofeminist philosophers Carol J. Adams and Marti Kheel have developed theories regarding relationships of human and non-human phenomena. They examine the issues of sexuality and carnality in the context of the killing and hunting of animals, themes which constitute important motifs in Lebda’s poetry.Celem niniejszej pracy jest przybliżenie ekofeministycznej teorii zwierzęcego podmiotu i jego nieobecnego przedmiotu odniesienia w tomiku Matecznik Małgorzaty Lebdy. Ekofeminizm dostarcza narzędzi do rozbudowanej analizy konceptualnych związków pomiędzy kobietami (a także osobami niebinarnymi) i zwierzętami, może być również stanowić teoretyczne zaplecze ekokrytycznego badania literatury. Ekofeministyczne myślicielki, Carol J. Adams i Marti Kheel, rozwinęły teorie dotyczące relacji ludzkich i nieludzkich fenomenów, zbadały także zagadnienia seksualności i cielesności w kontekście zabijania i polowania na zwierzęta. Wszystkie te problemy są ważnymi motywami w twórczości Małgorzaty Lebdy.Цель этой статьи – представить экофеминистскую теорию животного субъекта и его отсутствующего референтного объекта в книге Matecznik [Матечник] Малгожаты Лебды. Экофеминизм предоставляет инструменты для обширного анализа концептуальных отношений между женщинами (и небинарными людьми) и животными, а также может служить теоретической основой для экокритического исследования литературы. Мыслители-экофеминистки Кэрол Дж. Адамс и Марти Хил разработали теории о взаимосвязи между человеческими и нечеловеческими феменами и исследовали вопросы сексуальности и телесности в контексте убийства и охоты на животных. Все эти проблемы являются важными мотивами творчества Малгожаты Лебды
Arginine 357 of SecY is needed for SecA-dependent initiation of preprotein translocation
No full textThe Escherichia coli SecYEG complex forms a transmembrane channel for both protein export and membrane protein insertion. Secretory proteins and large periplasmic domains of membrane proteins require for translocation in addition the SecA ATPase. The conserved arginine 357 of SecY is essential for a yet unidentified step in the SecA catalytic cycle. To further dissect its role, we have analysed the requirement for R357 in membrane protein insertion. Although R357 substitutions abolish post-translational translocation, they allow the translocation of periplasmic domains targeted co-translationally by an N-terminal transmembrane segment. We propose that R357 is essential for the initiation of SecA-dependent translocation only.
Literary Representations of Non-heteronormative and Trans People in Polish Young Adult (YA) Literature: the example of Natalia Osińska’s trilogy and Anouk Herman’s novel <i>Nigdy nie będziesz szło samo</i>
No full textThe author focuses on literary representations of LGBT+ youth in Polish novels classified as Young Adult Literature (YAL). They use a three-part framework created by Michael Cart and Christine A. Jenkins to analyse books viewed as emblematic for Polish queer YAL: Natalia Osińska’s trilogy (Fanfik 2016, Slash 2017, Fluff 2019) and Anouk Herman’s novel Nigdy nie będziesz szło samo [You’ll Never Walk Alone, 2023]. When describing literary representations of coming out and queer youth subcultures, the author draws attention to the multidimensionality of the identities of the characters in this type of literary work. They are presented not only in the context of their gender identity and sexual orientation, but also through the prism of their economic situation and place of birth. The queerness of the characters is not limited to issues of gender and sexuality, but also involves challenging the norm of neurotypicality. According to the author, the novels analysed represent an interesting cultural representation of the Polish community of young people who identify as gay, lesbian, transgender and non-binary, as well as their allies (parents, friends)
Unilateral changes of the multifidus in persons with lumbar disc herniation: a systematic review and meta-analysis
No full textBACKGROUND: Lumbar disc herniation (LDH) is one of the most often diagnosed degenerative pathologies within the lumbar spine. Paraspinal muscle involvement could be a possible mediator in the pathophysiology of disc herniation and influences the course of pain and disability after both surgical or nonsurgical treatment. To potentially improve treatment, it may be important to assess multifidus muscle morphology in patients diagnosed with a LDH. OBJECTIVE: A systematic literature review and meta-analysis regarding the multifidus morphology in patients diagnosed with a LDH was conducted to assess the differences in multifidus muscle morphology between persons with LDH and healthy controls, and between the involved and the uninvolved side within subjects experiencing unilateral LDH. METHODS: A systematic search was conducted of articles published up to and including November 2019 using the Pubmed, Web of Science, EMBASE, and MEDLINE Ovid search engines. The articles obtained from this search were screened based on title and abstract using the predetermined eligibility criteria. Included full text articles were assessed for their methodologic quality using the modified Downs and Black checklist. Heterogeneous data regarding multifidus muscle morphology was included in the descriptive analysis; data that was homogenous was included in the meta-analysis. RESULTS: We identified 3,176 articles. Based on the screening for inclusion/exclusion criteria, 18 articles were included. Studies were either cross sectional or case-control studies assessing side-toside differences or comparing patients diagnosed with a LDH to a healthy control group. Nine studies investigated whole muscle atrophy, six looked at muscle fat infiltration, seven studies assessed microscopic muscle properties including muscle fiber size, distribution, and muscle fibrosis. From the 18 articles, 10 were included in the meta-analysis. In the meta-analysis, a comparison was made between side-to-side differences for muscle fiber size, distribution, and whole muscle size. Descriptive analysis showed increased fat infiltration and atrophy (muscle and individual fiber) of the multifidus muscle when comparing side-to-side differences or comparing cases to controls. Meta-analysis showed a significant decrease in type I and II muscle fiber size (p=.002, .01, respectively) combined with a significant increase in the number of type I muscle fibers (p=.008) at the side of LDH. Regarding whole muscle size, no significant differences were found. CONCLUSIONS: This study shows the presence of ipsilateral multifidus muscle changes in persons with unilateral LDH. (C) 2020 Elsevier Inc. All rights reserved.This research did not receive any specific grant from funding agencies in the public, commercial, or not-forprofit sectors. None of the authors state to have professional
and financial affiliations that may be perceived to have biased the presentation.Stevens, S (corresponding author), Hasselt Univ, Fac Rehabil Sci, Rehabil Res Ctr, Agoralaan Bldg A, B-3590 Diepenbeek, Belgium.
[email protected]
Guiding the specification of sociotechnical Machine Learning systems: Addressing vulnerabilities and challenges in Machine Learning practice
No full textThere is a need for a more comprehensive sociotechnical systems view on ML. Such a view looks at the development and use of an ML system in practice as being a sociotechnical ML system: "a system consisting of technical artefacts, human agents and institutions, in which a machine-based subsystem influences its real or virtual environment by automating, supporting or augmenting decision-making". This research takes on this view to design a sociotechnical guide for ML practice, centring the specication of sociotechnical ML systems. Taking on the guidelines contributes to a safe and effective development and use of ML systems.Complex Systems Engineering and Management (CoSEM
To Bid or not to Bid: that is the Question: Relating Contractor Bid Decisions to Tender Design Related Attributes
No full textThe construction industry has always been an important driver of the economy. An important part of the projects in this industry is commissioned by public entities. However, recently a trend can be observed in which the procurement process fails more often than before. Due to the current times of economic expansion in the Netherlands contractors are more selective in project selection. Failed procurement processes are however undesirable since the transaction costs and time invested in such a process can mount up. Many scholars have investigated the bid decision of contractors (Bagies & Fortune, 2006; Shokri-Ghasabeh & Chileshe, 2016). Yet, in order to contribute to solving the issue mentioned above not all considerations of contractors are relevant. Therefore, this research specifically focused on those considerations, or decision attributes, that a client can influence during the tender design phase. Resulting in the following research question: “What tender design related attributes are key decision drivers in the contractor’s bid decision and how do these key decision drivers influence the bid decision in economic times of expansion for publicly procured non-residential construction projects in the Netherlands?”Civil Engineering | Construction Management and Engineerin
- …
