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Radboud University, 03 oktober 2023, Promotor : Vermeulen, M., Contains fulltext : 297317.pdf (Publisher’s version ) (Closed access), The intestinal epithelium – the cell wall that separates the intestinal tract from the rest of the body – is constantly renewed by intestinal stem cells that divide continuously. This process is under strict control to ensure that cell division and cell death are balanced, and that cells develop into the right type. Colon cancer occurs when this balance is disturbed. This is usually caused by DNA mutations in intestinal stem cells, causing them to escape normal control mechanisms and divide uncontrollably. Mutations can arise as a result of natural cell division, but they can also be exacerbated by external factors, such as inflammation and certain dietary patterns. The development of colon cancer is mainly driven by specific mutations in so-called driver genes, which strongly influence the behaviour of cells and genes. To better understand colon tissue and cancer development, researchers use colonic organoids: cell structures that closely resemble healthy colon tissue and colon tumours. These can be grown in the lab, which makes it possible to manipulate specific components and measure their effects at molecular level. This PhD thesis describes various molecular processes involved in the development of healthy colon cells and colon cancer, as well as the methods that can be used to investigate these processes. We focus in particular on colon tumours with SMAD4 mutations, which are associated with aggressive tumours and an increased risk of metastases.

De grondwaterkwaliteit staat onder druk door klimaatverandering en maatschappelijke en technologische ontwikkelingen. In de bodem en ondergrond beschermen drie van nature aanwezige ‘barrières’ het grondwater tegen verontreinigingen. Afsluitende lagen zorgen voor een fysieke barrière; reactieve bestanddelen in de ondergrond vormen door afbraak, omzettingen en binding een geochemische barrière; en afbraak door micro-organismen in de bovengrond fungeert als een biologische barrière. In het project Kennisimpuls grondwaterkwaliteit is de beschermende werking van deze barrières in beeld gebracht en zijn risico’s voor aantasting van de barrières geanalyseerd.

Contains fulltext : 245272.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 237636.pdf (Publisher’s version ) (Open Access), Bladder urothelial cell carcinoma (UCC) incidence is about three times higher in men compared with women. There are several indications for the involvement of hormonal factors in the aetiology of UCC. Here, we provide evidence of androgen signalling in UCC progression. Microarray and qPCR analysis revealed that the androgen receptor (AR) mRNA level is upregulated in a subset of UCC cases. In an AR-positive UCC-derived cell line model, UM-UC-3-AR, androgen treatment increased clonogenic capacity inducing the formation of big stem cell-like holoclones, while AR knockdown or treatment with the AR antagonist enzalutamide abrogated this clonogenic advantage. Additionally, blockage of AR signalling reduced the cell migration potential of androgen-stimulated UM-UC-3-AR cells. These phenotypic changes were accompanied by a rewiring of the transcriptome with almost 300 genes being differentially regulated by androgens, some of which correlated with AR expression in UCC patients in two independent data sets. Our results demonstrate that AR signals in UCC favouring the development of an aggressive phenotype and highlights its potential as a therapeutic target for bladder cancer.

Contains fulltext : 245272.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 237636.pdf (Publisher’s version ) (Open Access), Bladder urothelial cell carcinoma (UCC) incidence is about three times higher in men compared with women. There are several indications for the involvement of hormonal factors in the aetiology of UCC. Here, we provide evidence of androgen signalling in UCC progression. Microarray and qPCR analysis revealed that the androgen receptor (AR) mRNA level is upregulated in a subset of UCC cases. In an AR-positive UCC-derived cell line model, UM-UC-3-AR, androgen treatment increased clonogenic capacity inducing the formation of big stem cell-like holoclones, while AR knockdown or treatment with the AR antagonist enzalutamide abrogated this clonogenic advantage. Additionally, blockage of AR signalling reduced the cell migration potential of androgen-stimulated UM-UC-3-AR cells. These phenotypic changes were accompanied by a rewiring of the transcriptome with almost 300 genes being differentially regulated by androgens, some of which correlated with AR expression in UCC patients in two independent data sets. Our results demonstrate that AR signals in UCC favouring the development of an aggressive phenotype and highlights its potential as a therapeutic target for bladder cancer.

Contains fulltext : 237636.pdf (Publisher’s version ) (Open Access), Bladder urothelial cell carcinoma (UCC) incidence is about three times higher in men compared with women. There are several indications for the involvement of hormonal factors in the aetiology of UCC. Here, we provide evidence of androgen signalling in UCC progression. Microarray and qPCR analysis revealed that the androgen receptor (AR) mRNA level is upregulated in a subset of UCC cases. In an AR-positive UCC-derived cell line model, UM-UC-3-AR, androgen treatment increased clonogenic capacity inducing the formation of big stem cell-like holoclones, while AR knockdown or treatment with the AR antagonist enzalutamide abrogated this clonogenic advantage. Additionally, blockage of AR signalling reduced the cell migration potential of androgen-stimulated UM-UC-3-AR cells. These phenotypic changes were accompanied by a rewiring of the transcriptome with almost 300 genes being differentially regulated by androgens, some of which correlated with AR expression in UCC patients in two independent data sets. Our results demonstrate that AR signals in UCC favouring the development of an aggressive phenotype and highlights its potential as a therapeutic target for bladder cancer.

In deze Deltafact wordt ingegaan op ‘vergrijzing’ van grondwater, de voortschrijdende beïnvloeding van de chemische kwaliteit van grondwater. De betekenis van vergrijzing wordt beschreven en er wordt ingegaan op de oorzaken. Hierbij worden onder andere de typen bronnen beschreven die bijdragen aan vergrijzing. Tenslotte worden handelingsperspectieven gegeven om vergrijzing te mitigeren.

Het adagium voor het beheer van stortplaatsen ‘isoleren, beheersen, controleren (IBC)’ krijgt concurrentie. Althans, een tien jaar durend experiment moet bewijzen dat innovatief en duurzaam stortbeheer zonder milieuhygiënische risico’s mogelijk is. Dit is onderdeel van de Green Deal duurzaam stortbeheer, waar het Ministerie van IenM en de stortbranche zich naar verwachting begin volgend jaar aan committeren.

Het adagium voor het beheer van stortplaatsen ‘isoleren, beheersen, controleren (IBC)’ krijgt concurrentie. Althans, een tien jaar durend experiment moet bewijzen dat innovatief en duurzaam stortbeheer zonder milieuhygiënische risico’s mogelijk is. Dit is onderdeel van de Green Deal duurzaam stortbeheer, waar het Ministerie van IenM en de stortbranche zich naar verwachting begin volgend jaar aan committeren.

Dit rapport beschrijft de opzet, evaluatie en resultaten van een modellering van uitloging van metalen en metalloïden uit bodems naar het grondwater. Deze studie had de volgende doelen: 1. het bepalen van representatieve concentraties van metalen en metalloïden in het ondiepe (eerste meter) grondwater; 2. het bepalen van representatieve waarden voor bodemparameters, die de uitloging van metalen en metalloïden bepalen, zoals reactiviteit van opgelost organische koolstof, gehalten aan oxiden en reactiviteit van metalen en metalloïden; 3. het verbeteren van het bestaande modelinstrumentarium voor het modelleren van de uitloging van metalen en metalloïden uit de bodem, inclusief de onzekerheid van deze modellen.

We focus on the space E

We focus on the space E

Let k,n ∈ N with k< n and let G

In deze verkennende studie is de uitloging van een aantal anorganische stoffen vanuit de bodem naar het grondwater onderzocht door gebruik te maken van een geochemisch rekenmodel. Het betreft de stoffen antimoon, arseen, barium, cadmium, chroom, kobalt, koper, kwik, lood, molybdeen, nikkel, tin, vanadium en zink. In dit onderzoek is de uitloging berekend uit de drie belangrijkste bodemtypen zand, klei en veen

Let k,n ∈ N with k< n and let G

We prove that every separable and metrizable space admits a metrizable compactification with a remainder that is both path connected and locally path connected. This result answers a question of P. Simon. © 2008 American Mathematical Society.

Dijkstra, Goodsell, and Wright have shown that if a nonconvex compactum in ℝ

We prove that every separable and metrizable space admits a metrizable compactification with a remainder that is both path connected and locally path connected. This result answers a question of P. Simon. © 2008 American Mathematical Society.

Dijkstra, Goodsell, and Wright have shown that if a nonconvex compactum in ℝ

We find universal functions for the class of lower semi-continuous (LSC) functions with at most n-dimensional domain. In an earlier paper we proved that a space is almost n-dimensional if and only if it is homeomorphic to the graph of an LSC function with an at most n-dimensional domain. We conclude that the class of almost n-dimensional spaces contains universal elements (that are topologically complete). These universal spaces can be thought of as higher-dimensional analogues of complete Erdös space. © 2007 American Mathematical Society Reverts to public domain 28 years from publication.

Waste materials often contain increased levels of potentially toxic trace elements compared to natural materials such as soils. In many countries, the recycling of waste materials in the environment, such as in construction works, is regulated by environmental criteria that aim to ensure long-term environmental protection. These criteria are increasingly based on the potential "leaching" of contaminants, i.e. the release of contaminants from the solid phase to the water phase with which the material may be in contact (e.g., percolating rainwater). The extent to which contaminants are susceptible for leaching processes depends on many chemical and physical factors, such as the specific chemical form of the contaminant ("chemical speciation") and transport processes such as convection and diffusion. To better understand the environmental risks associated with the application of waste materials in the environment, it is important to gain a fundamental understanding of the underlying speciation and transport processes that control the leaching of contaminants, as well as the fate of these contaminants in soil and groundwater.The complexity of speciation in combination with transport processes (referred to as "reactive transport") make that the identification of the major controlling processes responsible for observed leaching phenomena is generally not straightforward. However, hypotheses with respect to possible involved processes can often be translated in (computer) models that simulate these processes. The verification of predictions made by such models against experimental data may lead to either confirmation or rejection of the underlying hypotheses. The latter may result in modification and/or expansion of the model, until the system is sufficiently understood and adequate model predictions are obtained. Used in this way, models form valuable instruments in the scientific process of gaining knowledge, and contribute to the identification of the dominant processes

We find universal functions for the class of lower semi-continuous (LSC) functions with at most n-dimensional domain. In an earlier paper we proved that a space is almost n-dimensional if and only if it is homeomorphic to the graph of an LSC function with an at most n-dimensional domain. We conclude that the class of almost n-dimensional spaces contains universal elements (that are topologically complete). These universal spaces can be thought of as higher-dimensional analogues of complete Erdös space. © 2007 American Mathematical Society Reverts to public domain 28 years from publication.

Soil and surface water along roads are exposed to pollution from motorways. The main pollutants are polycyclic aromatic hydrocarbons (PAH), mineral oil, heavy metals and salt. These pollutants originate from vehicles (fuel, wires, leakage), wear and degradation of road surfaces and road furniture (i.e. crash barriers) and the application of de-icing salts. Runoff, vehicle spray and dry deposition disperse these contaminants into the soft shoulder (verges) of the roads and surface water to a measurable distance of about 50 up to more then 150 m from the road. Despite many monitoring programs, little is known about the risks of this diffuse pollution for soil and water quality and the geochemical and physical factors which determine these risks. Also little is known about the effects of possible measures. Therefore, extensive research has been carried out at two local motorways. Specific measurements on runoff, vehicle spray and effects of measures have been carried out for one year (13 months). This resulted in several new insights. The pollutants appear to adsorb effectively to natural soils. In vulnerable areas groundwater can be protected by adjusting the policy to removing the contaminated upper topsoil of the verges. Discharges of runoff into local surface water are not recommended.

We present a weakly closed, one-dimensional, line-free subgroup of the separable Banach space c that is not homeomorphic to complete Erdos space. The existence of this example disproves a conjecture of Dobrowolski, Grabowski, and Kawamura. © 2006 American Mathematical Society.

We present a weakly closed, one-dimensional, line-free subgroup of the separable Banach space c that is not homeomorphic to complete Erdos space. The existence of this example disproves a conjecture of Dobrowolski, Grabowski, and Kawamura. © 2006 American Mathematical Society.

It is shown that the homeomorphism groups of the (generalized) Sierpiński carpet and the universal Menger continua are not zero-dimensional. These results were corollaries to a 1966 theorem of Brechner. New proofs were needed because we also show that Brechner's proof is inadequate. The method by which we obtain our results, the construction of closed imbeddings of complete Erdo″s space in the homeomorphism groups, is of independent interest. ©2005 American Mathematical Society.

In 1940 Paul Erds introduced the 'rational Hilbert space', which consists of all vectors in the real Hilbert space' ℓ

In 1940 Paul Erds introduced the 'rational Hilbert space', which consists of all vectors in the real Hilbert space' ℓ

It is shown that the homeomorphism groups of the (generalized) Sierpiński carpet and the universal Menger continua are not zero-dimensional. These results were corollaries to a 1966 theorem of Brechner. New proofs were needed because we also show that Brechner's proof is inadequate. The method by which we obtain our results, the construction of closed imbeddings of complete Erdo″s space in the homeomorphism groups, is of independent interest. ©2005 American Mathematical Society.

It is proved that the oountably infinite power of complete Erdos space C

Let M be either a topological manifold, a Hilbert cube manifold, or a Menger manifold and let D be an arbitrary countable dense subset of M. Consider the topological group H(M, D) which consists of all autohomeomorphisms of M that map D onto itself equipped with the compact-open topology. We present a complete solution to the topological classification problem for H(M, D) as follows. If M is a one-dimensional topological manifold, then H(M, D) is homeomorphic to ℚ

It is proved that the oountably infinite power of complete Erdos space C

Let M be either a topological manifold, a Hilbert cube manifold, or a Menger manifold and let D be an arbitrary countable dense subset of M. Consider the topological group H(M, D) which consists of all autohomeomorphisms of M that map D onto itself equipped with the compact-open topology. We present a complete solution to the topological classification problem for H(M, D) as follows. If M is a one-dimensional topological manifold, then H(M, D) is homeomorphic to ℚ

Een geochemische analyse van de bodem, om inzicht te krijgen in de gewenste bodemkwaliteit voor stedelijke infiltratiegebieden

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