415 research outputs found
Ecohydraulics exemplifies the emerging “paradigm of the interdisciplines”
The basic premise underlying ecohydraulics is deceptively simple: create a new discipline focused on the effects of water movement in aquatic ecosystems by melding principles of aquatic ecology (including aspects of fluvial geomorphology) and engineering hydraulics. However, advancing ecohydraulics as a synthetic, organized field of study is challenging because hydraulic engineers and ecologists (1) study processes that differ substantially in spatial and/or temporal scale; (2) have very different approaches to modelling; (3) utilize different sets of mathematical formulations, concepts, and assumptions; and (4) address problems with vastly different patterns of complexity and uncertainty. The differences between engineering and ecology must be reconciled within a set of concepts and practices applicable to ecohydraulics. This reconciliation is essential if ecohydraulics is to achieve the scientific esteem of its parent disciplines. First, we review how the competing paradigms of determinism and empiricism structure engineering and ecology, respectively. We then derive two guiding principles that facilitate the integration of ecology and hydraulics, the single reference framework and the multiple reference framework guiding principles. Third, we provide illustrative examples of these principles using a simple hydraulic fish habitat analysis based on physical habitat simulation (PHABSIM) system of the instream flow incremental methodology (IFIM) and a detailed fish movement model using Eulerian–Lagrangian–Agent methods (ELAMs). Based on these examples, we develop insights and conclusions to guide further advances in ecohydraulics and, perhaps even serve as a template to aid development of other interdisciplinary fields
Gene fusions in vascular tumors and their underlying molecular mechanisms
Introduction: The group of vascular tumors contains many different entities, and is considered difficult by pathologists, as they often have overlapping histological characteristics. Chromosomal translocations have been identified in similar to 20% of mesenchymal tumors and are considered the drivers of tumor formation. Many translocations have been discovered over the past decade through next-generation sequencing. This technological advancement has also revealed several recurrent gene fusions in vascular tumors.Areas covered: This review will discuss the various vascular tumors for which recurrent gene fusions have been identified. The gene fusions and the presumed molecular mechanisms underlying tumorigenesis are shown, and potential implications for targeted therapies discussed. The identification of these gene fusions in vascular tumors has improved diagnostic accuracy, especially since several of these fusions can be easily detected using surrogate immunohistochemical markers.Expert opinion: The identification of gene fusions in a subset of vascular tumors over the past decade has improved diagnostic accuracy, and has provided the pathologists with novel diagnostic tools to accurately diagnose these often difficult tumors. Moreover, the increased understanding of the underlying molecular mechanisms can guide the development of targeted therapeutic strategies.Molecular tumour pathology - and tumour geneticsMTG
A large geometric distortion in the first photointermediate of rhodopsin, determined by double-quantum solid-state NMR
Double-quantum magic-angle-spinning NMR experiments were performed on 11,12-C-13(2)-retinylidene-rhodopsin under illumination at low temperature, in order to characterize torsional angle changes at the C11-C12 photoisomerization site. The sample was illuminated in the NMR rotor at low temperature (similar to 120 K) in order to trap the primary photointermediate, bathorhodopsin. The NMR data are consistent with a strong torsional twist of the HCCH moiety at the isomerization site. Although the HCCH torsional twist was determined to be at least 40A degrees, it was not possible to quantify it more closely. The presence of a strong twist is in agreement with previous Raman observations. The energetic implications of this geometric distortion are discussed
A murine mesenchymal stem cell model for initiating events in osteosarcomagenesis points to CDK4/CDK6 inhibition as a therapeutic target
Osteosarcoma is a high-grade bone-forming neoplasm, with a complex genome. Tumours frequently show chromothripsis, many deletions, translocations and copy number alterations. Alterations in the p53 or Rb pathway are the most common genetic alterations identified in osteosarcoma. Using spontaneously transformed murine mesenchymal stem cells (MSCs) which formed sarcoma after subcutaneous injection into mice, it was previously demonstrated that p53 is most often involved in the transformation towards sarcomas with complex genomics, including osteosarcoma. In the current study, not only loss of p53 but also loss of p16(Ink4a) is shown to be a driver of osteosarcomagenesis: murine MSCs with deficient p15(Ink4b), p16(Ink4a), or p19(Arf) transform earlier compared to wild-type murine MSCs. Furthermore, in a panel of nine spontaneously transformed murine MSCs, alterations in p15(Ink4b), p16(Ink4a), or p19(Arf) were observed in eight out of nine cases. Alterations in the Rb/p16 pathway could indicate that osteosarcoma cells are vulnerable to CDK4/CDK6 inhibitor treatment. Indeed, using two-dimensional (n = 7) and three-dimensional (n = 3) cultures of human osteosarcoma cell lines, it was shown that osteosarcoma cells with defective p16(INK4A) are sensitive to the CDK4/CDK6 inhibitor palbociclib after 72-hour treatment. A tissue microarray analysis of 109 primary tumour biopsies revealed a subset of patients (20-23%) with intact Rb, but defective p16 or overexpression of CDK4 and/or CDK6. These patients might benefit from CDK4/CDK6 inhibition, therefore our results are promising and might be translated to the clinic.Osteosarcoma is a tumour with a highly complex genome, which hampers the identification of driver genes. Using a model of murine mesenchymal stem cells (MSCs) with deficient p15(Ink4b), p16(Ink4a), or p19(Arf) that transform earlier compared to wild-type MSCs, the authors demonstrated that loss of p16(Ink4a) is a driver of osteosarcomagenesis. This can be exploited with a CDK4/CDK6 inhibitor, as osteosarcoma cells showed sensitivity to palbociclib which might be used as a novel therapeutic option.Molecular tumour pathology - and tumour geneticsMTG
This advert makes me cry: Disclosure of emotional response to advertisement on Facebook
As social media is transforming how consumers interact with brands and how brand-related content is consumed, this paper aims to investigate if and how Facebook users express their emotions towards advertisements of brand share on the site. Seven hundred and three comments about the Lloyds 250th Anniversary advertisement on Facebook were analysed as positive, negative or neutral attitude towards the advert. Facebook users found the advertisement emotionally appealing and voluntarily report their emotion of love, pride and in some cases anger. The presence of an iconic image like the black horse and the cover music was found to be emotionally appealing. The background music as well aroused positive emotions and engaging. This study introduces the possibility of analysing Facebook comments on brand content to understand consumers’ emotional responses and attitudes to the brand. Managers can explore these opportunities to identify what consumers find interesting in advertisements and how best to develop their creative strategies. It also offers the opportunity to allocate resources better to engage consumers with creative advertisement. Unlike interviews or surveys, this is a pioneering study on measuring emotional responses to advertisement through users’ self-report on social media
FOS rearrangement and expression in cementoblastoma
Cementoblastomas are rare odontogenic tumors developing in close proximity to the roots of teeth. Due to their striking morphologic resemblance to osteoblastomas of the peripheral skeleton, we set out to determine whether cementoblastomas harbor the same FOS rearrangements with overexpression of c-FOS as has recently been described for osteoblastomas. In total, 16 cementoblastomas were analyzed for FOS expression by immunohistochemistry and for FOS rearrangements by fluorescence in situ hybridization (FISH). We observed strong and diffuse staining of c-FOS in 71% of cementoblastomas and identified a FOS rearrangement in all cases (n=3) applicable for FISH. In the remaining cases, FISH failed due to decalcification. Cementoblastomas harbor similar FOS rearrangements and show overexpression of c-FOS like osteoblastomas, suggesting that both entities might represent parts of the spectrum of the same disease.Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas
Expanding the spectrum of EWSR1-NFATC2-rearranged benign tumors a common genomic abnormality in vascular malformation/hemangioma and simple bone cyst
A simple bone cyst (SBC) is a cystic bone lesion predominantly affecting young males. The cyst is lined by a fibrous membrane and filled with serosanguinous fluid. EWSR1/FUS-NFATC2 rearrangements were recently identified in SBC. We here report exactly the same rearrangement in 3 lesions diagnosed as vascular malformations of 2 elderly patients. In total, through Archer FusionPlex, fluorescence in situ hybridization and/or reverse transcriptase-polymerase chain reaction the EWSR1-NFATC2 rearrangement was identified in 6 of 9 SBC, 3 of 12 benign vascular tumors, and none of 5 aneurysmal bone cyst lacking USP6 fusion. Using fluorescence in situ hybridization, it was apparent that amplification of the fusion, as seen in EWSR1-NFATC2 round cell sarcomas, was absent, and that in the vascular tumors the fusion was present both in the lining cells as well as in the surrounding spindle cells. Of note, not all of the spaces in the vascular malformations were lined by endothelial cells. Aggrecan was positive in all cases but was not specific. NKX2-2 and NKX3-1 staining were negative in all cases. Thus, even though the overlap between the 2 entities is limited to the presence of few thick-walled cysts lacking endothelial lining in the benign vascular malformations, the spectrum of benign tumors containing NFATC2 fusions should be expanded and contains not only SBC in the young, but also vascular malformation/hemangioma in elderly patients.Molecular tumour pathology - and tumour geneticsMTG
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