Negotiated Religious Meaning: Qing and Nationalist Approaches to Religious Superscription

This paper largely serves as a case study comparing the wildly divergent attempts, both in terms of execution and success, of the Qing dynasty and Nationalist regime in using religious symbols to appeal to the Chinese populace. While both attempted to win national support and popularity, religious superscription also reflected attempts to verify the legitimacy of the current government. Differences in the execution of religious superscription reflect the two varying approaches of the Qing and the Nationalists: an emphasis on utilizing tradition to promote imperial authority versus a total disregard of tradition in hopes of rapid change at a national level

Moleculen, mechanismen, maatwerk

Oratie uitgesproken door Prof.dr. J.V.M.G. Bovée bij de aanvaarding van het ambt van hoogleraar Pathologie, in het bijzonder de Pathologie van Bot- en Wekedelentumoren aan de Universiteit Leiden op vrijdag 7 maart 2014LUMC / Geneeskund

Clonal Evolution through Loss of Chromosomes and Subsequent Polyploidization in Chondrosarcoma

Near-haploid chromosome numbers have been found in less than 1% of cytogenetically reported tumors, but seem to be more common in certain neoplasms including the malignant cartilage-producing tumor chondrosarcoma. By a literature survey of published karyotypes from chondrosarcomas we could confirm that loss of chromosomes resulting in hyperhaploid-hypodiploid cells is common and that these cells may polyploidize. Sixteen chondrosarcomas were investigated by single nucleotide polymorphism (SNP) array and the majority displayed SNP patterns indicative of a hyperhaploid-hypodiploid origin, with or without subsequent polyploidization. Except for chromosomes 5, 7, 19, 20 and 21, autosomal loss of heterozygosity was commonly found, resulting from chromosome loss and subsequent duplication of monosomic chromosomes giving rise to uniparental disomy. Additional gains, losses and rearrangements of genetic material, and even repeated rounds of polyploidization, may affect chondrosarcoma cells resulting in highly complex karyotypes. Loss of chromosomes and subsequent polyploidization was not restricted to a particular chondrosarcoma subtype and, although commonly found in chondrosarcoma, binucleated cells did not seem to be involved in these events

Malignant Transformation of Giant Cell Tumor of Bone and the Association with Denosumab Treatment:A Radiology and Pathology Perspective

Objective. Malignancy in giant cell tumor of bone (mGCTB) is categorized as primary (concomitantly with conventional GCTB) or secondary (after radiotherapy or other treatment). Denosumab therapy has been suggested to play a role in the etiology of secondary mGCTB. In this case series from a tertiary referral sarcoma center, we aimed to find distinctive features for malignant transformation in GCTB on different imaging modalities. Furthermore, we assessed the duration of denosumab treatment and lag time to the development of malignancy. Methods. From a histopathology database search, 6 patients were pathologically confirmed as having initial conventional GCTB and subsequently with secondary mGCTB. Results. At the time of mGCTB diagnosis, 2 cases were treated with denosumab only, 2 with denosumab and surgery, 1 with multiple curettages and radiotherapy, and 1 with surgery only. In the 4 denosumab treated patients, the mean lag time to malignant transformation was 7 months (range 2-11 months). Imaging findings suspicious of malignant transformation related to denosumab therapy are the absence of fibro-osseous matrix formation and absent neocortex formation on CT, and stable or even increased size of the soft tissue component. Conclusion. In 4 patients treated with denosumab, secondary mGCTB occurred within the first year after initiation of treatment. Radiotherapy-associated mGCTB has a longer lag time than denosumab-associated mGCTB. Close clinical and imaging follow-up during the first months of denosumab therapy is key, as mGCTB tends to have rapid aggressive behavior, similar to other high-grade sarcomas. Nonresponders should be (re) evaluated for their primary diagnosis of conventional GCTB

Membrane permeation of arginine-rich cell-penetrating peptides independent of transmembrane potential as a function of lipid composition and membrane fluidity

Cell-penetrating peptides (CPPs) are prominent delivery vehicles to confer cellular entry of (bio-) macromolecules. Internalization efficiency and uptake mechanism depend, next to the type of CPP and cargo, also on cell type. Direct penetration of the plasma membrane is the preferred route of entry as this circumvents endolysosomal sequestration. However, the molecular parameters underlying this import mechanism are still poorly defined. Here, we make use of the frequently used HeLa and HEK cell lines to address the role of lipid composition and membrane potential. In HeLa cells, at low concentrations, the CPP nona-arginine (R9) enters cells by endocytosis. Direct membrane penetration occurs only at high peptide concentrations through a mechanism involving activation of sphingomyelinase which converts sphingomyelin into ceramide. In HEK cells, by comparison, R9 enters the cytoplasm through direct membrane permeation already at low concentrations. This direct permeation is strongly reduced at room temperature and upon cholesterol depletion, indicating a complex dependence on membrane fluidity and microdomain organisation. Lipidomic analyses show that in comparison to HeLa cells HEK cells have an endogenously low sphingomyelin content. Interestingly, direct permeation in HEK cells and also in HeLa cells treated with exogenous sphingomyelinase is independent of membrane potential. Membrane potential is only required for induction of sphingomyelinase-dependent uptake which is then associated with a strong hyperpolarization of membrane potential as shown by whole-cell patch clamp recordings. Next to providing new insights into the interplay of membrane composition and direct permeation, these results also refute the long-standing paradigm that transmembrane potential is a driving force for CPP uptake

Reaching across continents : engaging students through virtual collaborations

Business schools have the responsibility of preparing students for work in multicultural organizations and global markets. This paper examines a situated learning experience for undergraduates through a virtual collaboration between a UK university and a Brazilian university. This facilitated remote communication using social media and smart devices, allowing students from both institutions to enhance their cross-cultural management competencies. A qualitative approach was used for the research, drawing on the reflections of the tutors from both institutions, and feedback received from students in the UK and Brazil. This paper provides empirical observations regarding the use of this innovative pedagogic approach, generating discussion of the implications for teaching, thus contributing to the literature on international collaborations in cross-cultural management education

Breakpoint characterization of large deletions in EXT1 or EXT2 in 10 Multiple Osteochondromas families

<p>Abstract</p> <p>Background</p> <p>Osteochondromas (cartilage-capped bone tumors) are by far the most commonly treated of all primary benign bone tumors (50%). In 15% of cases, these tumors occur in the context of a hereditary syndrome called multiple osteochondromas (MO), an autosomal dominant skeletal disorder characterized by the formation of multiple cartilage-capped bone tumors at children's metaphyses. MO is caused by various mutations in <it>EXT1 </it>or <it>EXT2</it>, whereby large genomic deletions (single-or multi-exonic) are responsible for up to 8% of MO-cases.</p> <p>Methods</p> <p>Here we report on the first molecular characterization of ten large <it>EXT1</it>- and <it>EXT2</it>-deletions in MO-patients. Deletions were initially indentified using MLPA or FISH analysis and were subsequently characterized using an MO-specific tiling path array, allele-specific PCR-amplification and sequencing analysis.</p> <p>Results</p> <p>Within the set of ten large deletions, the deleted regions ranged from 2.7 to 260 kb. One <it>EXT2 </it>exon 8 deletion was found to be recurrent. All breakpoints were located outside the coding exons of <it>EXT1 </it>and <it>EXT2</it>. Non-allelic homologous recombination (NAHR) mediated by <it>Alu</it>-sequences, microhomology mediated replication dependent recombination (MMRDR) and non-homologous end-joining (NHEJ) were hypothesized as the causal mechanisms in different deletions.</p> <p>Conclusions</p> <p>Molecular characterization of <it>EXT1</it>- and <it>EXT2</it>-deletion breakpoints in MO-patients indicates that NAHR between <it>Alu-</it>sequences as well as NHEJ are causal and that the majority of these deletions are nonrecurring. These observations emphasize once more the huge genetic variability which is characteristic for MO. To our knowledge, this is the first study characterizing large genomic deletions in <it>EXT1 </it>and <it>EXT2</it>.</p

Histological response to radiotherapy is an early event in myxoid liposarcoma

Compared to other sarcomas, myxoid liposarcoma (MLS) is exceptionally sensitive to radiation therapy, but the underlying mechanism remains unknown. The objective was to assess the tissue-based changes in MLS during and after neoadjuvant radiotherapy in 26 patients of the DOREMY trial. Morphological assessment was performed on biopsies pre-treatment, after 8 fractions, 16 factions, and after surgical resection and included percentage of viable tumor cells, hyalinization, necrosis, and fatty maturation. Furthermore, immunohistochemistry was performed for apoptosis (cleaved caspase-3), anti-apoptosis (Bcl-2), activity of mTOR signaling (phospho-S6), hypoxia (CAIX), proliferation (Ki67), inflammation (CD45 and CD68), and microvessel density (CD34 Chalkley count). A pronounced reduction in vital tumor cells was observed early with a drop to 32.5% (median) tumor cells (IQR 10–93.8%) after 8 fractions. This decreased further to 10% (IQR 5–30%) after 16 fractions and 7.5% (IQR 5–15%) in the surgical specimen. All but one patient had an excellent response with MTG6Molecular tumour pathology - and tumour genetic