Unprecedented C-selective interstrand cross-linking through in situ oxidation of Furan-Modified Oligodeoxynucleotides

Chemical reagents that form interstrand cross-links have been used for a long time in cancer therapy. They covalently link two strands of DNA, thereby blocking transcription. Cross-link repair enzymes, however, can restore the transcription processes, causing resistance to certain anti-cancer drugs. The mechanism of these cross-link repair processes has not yet been fully revealed. One of the obstacles in this study is the lack of sufficient amounts of well-defined, stable, cross-linked duplexes to study the pathways of cross-link repair enzymes. Our group has developed a cross-link strategy where a furan moiety is incorporated into oligodeoxynucleotides (ODNs). These furan-modified nucleic acids can form interstrand cross-links upon selective furan oxidation with N-bromosuccinimide. We here report on the incorporation of the furan moiety at the 2'-position of a uridine through an amido or ureido linker. The resulting modified ODNs display an unprecedented selectivity for cross-linking toward a cytidine opposite the modified residue, forming one specific cross-linked duplex, which could be isolated in good yield. Furthermore, the structure of the formed cross-linked duplexes could be unambiguously characterized

Bistable Gestalts reduce activity in the whole of V1, not just the retinotopically predicted parts

Activity in the primary visual cortex reduces when certain stimuli can be perceptually organized as a unified Gestalt. This reduction could offer important insights into the nature of feedback computations within the human visual system; however, the properties of this response reduction have not yet been investigated in detail. Here we replicate this reduced V1 response, but find that the modulation in V1 (and V2) to the perceived organization of the input is not specific to the retinotopic location at which the sensory input from that stimulus is represented. Instead, we find a response modulation that is equally evident across the primary visual cortex. Thus in contradiction to some models of hierarchical predictive coding, the perception of an organized Gestalt causes a broad feedback effect that does not act specifically on the part of the retinotopic map representing the sensory input

Krüppel-like factors in cancer progression: three fingers on the steering wheel

Kruppel-like factors (KLFs) comprise a highly conserved family of zinc finger transcription factors, that are involved in a plethora of cellular processes, ranging from proliferation and apoptosis to differentiation, migration and pluripotency. During the last few years, evidence on their role and deregulation in different human cancers has been emerging. This review will discuss current knowledge on Kruppel-like transcription in the epithelial-mesenchymal transition (EMT), invasion and metastasis, with a focus on epithelial cancer biology and the extensive interface with pluripotency. Furthermore, as KLFs are able to mediate different outcomes, important influences of the cellular and microenvironmental context will be highlighted. Finally, we attempt to integrate diverse findings on KLF functions in EMT and stem cell biology to fit in the current model of cellular plasticity as a tool for successful metastatic dissemination

Direct Methods in High Resolution Electron Microscopy

New approaches are proposed to retrieve the wavefunction at the object and from this, to retrieve the projected structure of the object. The wavefunction is retrieved by capturing images at a series of closely spaced focus values and to process the whole 3D data. The structure of the object is retrieved using a formalism based on electron channelling

Accelerated hermeticity testing of biocompatible moisture barriers used for the encapsulation of implantable medical devices

Barrier layers for the long-term encapsulation of implantable medical devices play a crucial role in the devices’ performance and reliability. Typically, to understand the stability and predict the lifetime of barriers (therefore, the implantable devices), the device is subjected to accelerated testing at higher temperatures compared to its service parameters. Nevertheless, at high temperatures, reaction and degradation mechanisms might be different, resulting in false accelerated test results. In this study, the maximum valid temperatures for the accelerated testing of two barrier layers were investigated: atomic layer deposited (ALD) Al2O3 and stacked ALD HfO2/Al2O3/HfO2, hereinafter referred to as ALD-3. The in-house developed standard barrier performance test is based on continuous electrical resistance monitoring and microscopic inspection of Cu patterns covered with the barrier and immersed in phosphate buffered saline (PBS) at temperatures up to 95 °C. The results demonstrate the valid temperature window to perform temperature acceleration tests. In addition, the optimized ALD layer in combination with polyimide (polyimide/ALD-3/polyimide) works as effective barrier at 60 °C for 1215 days, suggesting the potential applicability to the encapsulation of long-term implants

Introduction of a pseudo-6th order ISDN splitter with bandstop topology

A newly developed ‘integrated services digital network’ (ISDN) splitter with bandstop (BS) topology is presented and compared to an actual ISDN splitter with a traditional lowpass (LP) topology. The LP-to-BS topology change reduced the amount of filter stages: a LP ISDN splitter requires an 8th order elliptic-like filter in order to be compliant to the standard ‘TS 101 952-1-4 V1.1.1’ [1] of the European Telecommunications Standards Institute (ETSI), whereas the BS ISDN splitter only needs a pseudo-6th order elliptic-like filter. The design of the new BS ISDN filter is discussed in the light of the enforced ETSI specifications. Furthermore, both the ISDN splitters are compared in the field of their specific stopband performance and their physical implementation. The area reduction that comes together with the introduction of the new ISDN splitter with BS topology is more than 25%

'Meten' en 'weten' voor een gefundeerd kinderrechtenbeleid: een kritische reflectie over de zin en onzin van kinderrechtenindicatoren

De titel van dit rapport is geïnspireerd op Pleysier & Pauwels (2011), die in hun bijdrage getiteld “Als ‘meten’ niet noodzakelijk ‘weten’ is, hoe kunnen we dan beter ‘meten’ om meer te ‘weten’?” gekende beperkingen van bestaande (criminologische)onderzoeksmethoden uiteenzetten en praktische adviezen aanreiken om hier op een zo positief mogelijke manier mee om te gaan. Het opzet van deze tekst is gelijkaardig. Vaak geformuleerde kritieken op het gebruik van kinderrechtenindicatoren worden onder de loep genomen en aan de Vlaamse context getoetst. Daarnaast wordt onderzocht of nationaal dan wel internationaal inspiratie kan worden gevonden tot het ontwikkelen van constructieve strategieën om in de mate van het mogelijke aan deze kritieken tegemoet te komen.nrpages: 57status: publishe

Evaluatie van de kind- en jongereneffectrapportage (JoKER)

In opdracht van de Vlaamse Overheid, heeft het Kenniscentrum Kinderrechten vzw (KeKi) een evaluatie ondernomen van de kind- en jongereneffectrapportage (JoKER). Deze heeft geleid tot een SWOT-analyse, gestructureerd aan de hand van volgende thema’s: ‘toepassingsgebied’, ‘kwaliteit’, ‘proces’, ‘ondersteuning en controle’, ‘effectiviteit’ en ‘impact’