119 research outputs found

    In de achtertuin van het Carons Hofke: archeologisch onderzoek te Merksplas, Carons Hofke

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    Dit rapport werd ingediend bij het agentschap samen met een aantal afzonderlijke digitale bijlagen. Een aantal van deze bijlagen zijn niet inbegrepen in dit pdf document en zijn niet online beschikbaar. Sommige bijlagen (grondplannen, fotos, spoorbeschrijvingen, enz.) kunnen van belang zijn voor een betere lezing en interpretatie van dit rapport. Indien u deze bijlagen wenst te raadplegen kan u daarvoor contact opnemen met: [email protected]

    Vlakdekkend archeologisch onderzoek op de Arsenaalsite te Mechelen

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    Dit rapport werd ingediend bij het agentschap samen met een aantal afzonderlijke digitale bijlagen. Een aantal van deze bijlagen zijn niet inbegrepen in dit pdf document en zijn niet online beschikbaar. Sommige bijlagen (grondplannen, fotos, spoorbeschrijvingen, enz.) kunnen van belang zijn voor een betere lezing en interpretatie van dit rapport. Indien u deze bijlagen wenst te raadplegen kan u daarvoor contact opnemen met: [email protected]

    Archeologisch onderzoek van Wereldoorlog I-erfgoed langs de Briekestraat te Ieper (prov. West-Vlaanderen)

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    Dit rapport werd ingediend bij het agentschap samen met een aantal afzonderlijke digitale bijlagen. Een aantal van deze bijlagen zijn niet inbegrepen in dit pdf document en zijn niet online beschikbaar. Sommige bijlagen (grondplannen, fotos, spoorbeschrijvingen, enz.) kunnen van belang zijn voor een betere lezing en interpretatie van dit rapport. Indien u deze bijlagen wenst te raadplegen kan u daarvoor contact opnemen met: [email protected]

    Fighting Putin and the Kremlin’s grip in neo-authoritarian Russia: the experience of liberal journalists

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    Slavtcheva-Petkova, V. (2017). Fighting Putin and the Kremlin’s grip in neo-authoritarian Russia: the experience of liberal journalists. Journalism. Copyright Β© [2017]. Reprinted by permission of SAGE Publications.Russia is one of the most dangerous countries for journalists and the conflict with Ukraine and Russia’s involvement in Syria present even further challenges for the future of Russian journalism. In addition to the financial pressures, physical attacks, abductions and harassment, liberal journalists now face an increasing threat to the democratising role they see themselves as playing. President Vladimir Putin’s soaring popularity and the elaborate range of tactics used to suppress press freedom are forcing liberal media to rethink their mission(s) and identity(ies). This paper presents empirical evidence on the range of tactics used by Russian authorities as well as the coping strategies adopted by journalists. The study shows that some Russian media and journalists demonstrate a great degree of resilience in their efforts to expose wrongdoings and hold the powerful to account. The article questions the applicability of Western-centric normative media system theories because it shows that the breadth, depth, and mechanisms of control in modern-day Russia are very different from the ones used during Soviet times, and yet, Russian media and society do not appear to be on a linear journey from authoritarianism to democracy. The article presents the findings of a semi-ethnographic study of some of Russia’s most influential liberal news outlets – Novaya Gazeta, Radio Echo of Moscow and Radio Free Europe/Liberty. The study was conducted in May 2014 in the midst of the conflict with Ukraine. It involved observations of editorial meetings, documentary analysis and interviews with editors, deputy editors and journalists

    Derivation of High Purity Neuronal Progenitors from Human Embryonic Stem Cells

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    The availability of human neuronal progenitors (hNPs) in high purity would greatly facilitate neuronal drug discovery and developmental studies, as well as cell replacement strategies for neurodegenerative diseases and conditions, such as spinal cord injury, stroke, Parkinson's disease, Alzheimer's disease, and Huntington's disease. Here we describe for the first time a method for producing hNPs in large quantity and high purity from human embryonic stem cells (hESCs) in feeder-free conditions, without the use of exogenous noggin, sonic hedgehog or analogs, rendering the process clinically compliant. The resulting population displays characteristic neuronal-specific markers. When allowed to spontaneously differentiate into neuronal subtypes in vitro, cholinergic, serotonergic, dopaminergic and/or noradrenergic, and medium spiny striatal neurons were observed. When transplanted into the injured spinal cord the hNPs survived, integrated into host tissue, and matured into a variety of neuronal subtypes. Our method of deriving neuronal progenitors from hESCs renders the process amenable to therapeutic and commercial use

    Genomic profiling of plasmablastic lymphoma using array comparative genomic hybridization (aCGH): revealing significant overlapping genomic lesions with diffuse large B-cell lymphoma

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    <p>Abstract</p> <p>Background</p> <p>Plasmablastic lymphoma (PL) is a subtype of diffuse large B-cell lymphoma (DLBCL). Studies have suggested that tumors with PL morphology represent a group of neoplasms with clinopathologic characteristics corresponding to different entities including extramedullary plasmablastic tumors associated with plasma cell myeloma (PCM). The goal of the current study was to evaluate the genetic similarities and differences among PL, DLBCL (AIDS-related and non AIDS-related) and PCM using array-based comparative genomic hybridization.</p> <p>Results</p> <p>Examination of genomic data in PL revealed that the most frequent segmental gain (> 40%) include: 1p36.11-1p36.33, 1p34.1-1p36.13, 1q21.1-1q23.1, 7q11.2-7q11.23, 11q12-11q13.2 and 22q12.2-22q13.3. This correlated with segmental gains occurring in high frequency in DLBCL (AIDS-related and non AIDS-related) cases. There were some segmental gains and some segmental loss that occurred in PL but not in the other types of lymphoma suggesting that these foci may contain genes responsible for the differentiation of this lymphoma. Additionally, some segmental gains and some segmental loss occurred only in PL and AIDS associated DLBCL suggesting that these foci may be associated with HIV infection. Furthermore, some segmental gains and some segmental loss occurred only in PL and PCM suggesting that these lesions may be related to plasmacytic differentiation.</p> <p>Conclusion</p> <p>To the best of our knowledge, the current study represents the first genomic exploration of PL. The genomic aberration pattern of PL appears to be more similar to that of DLBCL (AIDS-related or non AIDS-related) than to PCM. Our findings suggest that PL may remain best classified as a subtype of DLBCL at least at the genome level.</p

    Small-Molecule Synthetic Compound Norcantharidin Reverses Multi-Drug Resistance by Regulating Sonic Hedgehog Signaling in Human Breast Cancer Cells

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    Multi-drug resistance (MDR), an unfavorable factor compromising treatment efficacy of anticancer drugs, involves upregulated ATP binding cassette (ABC) transporters and activated Sonic hedgehog (Shh) signaling. By preparing human breast cancer MCF-7 cells resistant to doxorubicin (DOX), we examined the effect and mechanism of norcantharidin (NCTD), a small-molecule synthetic compound, on reversing multidrug resistance. The DOX-prepared MCF-7R cells also possessed resistance to vinorelbine, characteristic of MDR. At suboptimal concentration, NCTD significantly inhibited the viability of DOX-sensitive (MCF-7S) and DOX-resistant (MCF-7R) cells and reversed the resistance to DOX and vinorelbine. NCTD increased the intracellular accumulation of DOX in MCF-7R cells and suppressed the upregulated the mdr-1 mRNA, P-gp and BCRP protein expression, but not the MRP-1. The role of P-gp was strengthened by partial reversal of the DOX and vinorelbine resistance by cyclosporine A. NCTD treatment suppressed the upregulation of Shh expression and nuclear translocation of Gli-1, a hallmark of Shh signaling activation in the resistant clone. Furthermore, the Shh ligand upregulated the expression of P-gp and attenuated the growth inhibitory effect of NCTD. The knockdown of mdr-1 mRNA had not altered the expression of Shh and Smoothened in both MCF-7S and MCF-7R cells. This indicates that the role of Shh signaling in MDR might be upstream to mdr-1/P-gp, and similar effect was shown in breast cancer MDA-MB-231 and BT-474 cells. This study demonstrated that NCTD may overcome multidrug resistance through inhibiting Shh signaling and expression of its downstream mdr-1/P-gp expression in human breast cancer cells

    Dynamic Chromatin Localization of Sirt6 Shapes Stress- and Aging-Related Transcriptional Networks

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    The sirtuin Sirt6 is a NAD-dependent histone deacetylase that is implicated in gene regulation and lifespan control. Sirt6 can interact with the stress-responsive transcription factor NF-ΞΊB and regulate some NF-ΞΊB target genes, but the full scope of Sirt6 target genes as well as dynamics of Sirt6 occupancy on chromatin are not known. Here we map Sirt6 occupancy on mouse promoters genome-wide and show that Sirt6 occupancy is highly dynamic in response to TNF-Ξ±. More than half of Sirt6 target genes are only revealed upon stress-signaling. The majority of genes bound by NF-ΞΊB subunit RelA recruit Sirt6, and dynamic Sirt6 relocalization is largely driven in a RelA-dependent manner. Integrative analysis with global gene expression patterns in wild-type, Sirt6βˆ’/βˆ’, and double Sirt6βˆ’/βˆ’ RelAβˆ’/βˆ’ cells reveals the epistatic relationships between Sirt6 and RelA in shaping diverse temporal patterns of gene expression. Genes under the direct joint control of Sirt6 and RelA include several with prominent roles in cell senescence and organismal aging. These data suggest dynamic chromatin relocalization of Sirt6 as a key output of NF-ΞΊB signaling in stress response and aging

    Identification of Spt5 Target Genes in Zebrafish Development Reveals Its Dual Activity In Vivo

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    Spt5 is a conserved essential protein that represses or stimulates transcription elongation in vitro. Immunolocalization studies on Drosophila polytene chromosomes suggest that Spt5 is associated with many loci throughout the genome. However, little is known about the prevalence and identity of Spt5 target genes in vivo during development. Here, we identify direct target genes of Spt5 using fogsk8 zebrafish mutant, which disrupts the foggy/spt5 gene. We identified that fogsk8 and their wildtype siblings differentially express less than 5% of genes examined. These genes participate in diverse biological processes from stress response to cell fate specification. Up-regulated genes exhibit shorter overall gene length compared to all genes examined. Through chromatin immunoprecipitation in zebrafish embryos, we identified a subset of developmentally critical genes that are bound by both Spt5 and RNA polymerase II. The protein occupancy patterns on these genes are characteristic of both repressive and stimulatory elongation regulation. Together our findings establish Spt5 as a dual regulator of transcription elongation in vivo and identify a small but diverse set of target genes critically dependent on Spt5 during development
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