16 research outputs found
Proto-oncogene Ets-1 is pathologically expressed in low-grade astrocytomas and glioblastomas in a tissue and location specific pattern and correlates with patient survival
No full textProto-oncogene Ets-1 is pathologically expressed in low-grade astrocytomas and glioblastomas in a tissue and location specific pattern and correlates with patient survival
No full textX-ray laser diffraction for structure determination of the rhodopsin-arrestin complex
No full textabstract: Serial femtosecond X-ray crystallography (SFX) using an X-ray free electron laser (XFEL) is a recent advancement in structural biology for solving crystal structures of challenging membrane proteins, including G-protein coupled receptors (GPCRs), which often only produce microcrystals. An XFEL delivers highly intense X-ray pulses of femtosecond duration short enough to enable the collection of single diffraction images before significant radiation damage to crystals sets in. Here we report the deposition of the XFEL data and provide further details on crystallization, XFEL data collection and analysis, structure determination, and the validation of the structural model. The rhodopsin-arrestin crystal structure solved with SFX represents the first near-atomic resolution structure of a GPCR-arrestin complex, provides structural insights into understanding of arrestin-mediated GPCR signaling, and demonstrates the great potential of this SFX-XFEL technology for accelerating crystal structure determination of challenging proteins and protein complexes.The final version of this article, as published in Scientific Data, can be viewed online at: https://www.nature.com/articles/sdata20162
Simulation of modelling of turbulent trailing edge flow
No full textComputations of turbulent trailing-edge flow have been carried out at a Reynolds number of 1000 (based on the free-stream quantities and the trailing-edge thickness) using an unsteady 3D Reynolds-Averaged Navier–Stokes (URANS) code, in which two-equation (k–?) turbulence models with various low-Re near wall treatments were implemented. Results from a direct numerical simulation (DNS) of the same flow are available for comparison and assessment of the turbulence models used in the URANS code. Two-dimensional URANS calculations are carried out with turbulence mean properties from the DNS used at the inlet; the inflow boundary-layer thickness is 6.42 times the trailing-edge thickness, close to typical turbine blade flow applications. Many of the key flow features observed in DNS are also predicted by the modelling; the flow oscillates in a similar way to that found in bluff-body flow with a von Kármán vortex street produced downstream. The recirculation bubble predicted by unsteady RANS has a similar shape to DNS, but with a length only half that of the DNS.It is found that the unsteadiness plays an important role in the near wake, comparable to the modelled turbulence, but that far downstream the modelled turbulence dominates. A spectral analysis applied to the force coefficient in the wall normal direction shows that a Strouhal number based on the trailing-edge thickness is 0.23, approximately twice that observed in DNS. To assess the modelling approximations, an a priori analysis has been applied using DNS data for the key individual terms in the turbulence model equations. A possible refinement to account for pressure transport is discussed
Mucosa-like differentiation of head and neck cancer cells is inducible and drives the epigenetic loss of cell malignancy
No full textOppel F, Gendreizig S, Martinez-Ruiz L, et al. Mucosa-like differentiation of head and neck cancer cells is inducible and drives the epigenetic loss of cell malignancy. Cell Death & Disease. 2024;15(10): 724.Head and neck squamous cell carcinoma (HNSCC) is a highly malignant disease with high death rates that have remained substantially unaltered for decades. Therefore, new treatment approaches are urgently needed. Human papillomavirus-negative tumors harbor areas of terminally differentiated tissue that are characterized by cornification. Dissecting this intrinsic ability of HNSCC cells to irreversibly differentiate into non-malignant cells may have tumor-targeting potential. We modeled the cornification of HNSCC cells in a primary spheroid model and analyzed the mechanisms underlying differentiation by ATAC-seq and RNA-seq. Results were verified by immunofluorescence using human HNSCC tissue of distinct anatomical locations. HNSCC cell differentiation was accompanied by cell adhesion, proliferation stop, diminished tumor-initiating potential in immunodeficient mice, and activation of a wound-healing-associated signaling program. Small promoter accessibility increased despite overall chromatin closure. Differentiating cells upregulated KRT17 and cornification markers. Although KRT17 represents a basal stem cell marker in normal mucosa, we confirm KRT17 to represent an early differentiation marker in HNSCC tissue. Cornification was frequently found surrounding necrotic areas in human tumors, indicating an involvement of pro-inflammatory stimuli. Indeed, inflammatory mediators activated the differentiation program in primary HNSCC cells. In HNSCC tissue, distinct cell differentiation states were found to create a common tissue architecture in normal mucosa and HNSCCs. Our data demonstrate a loss of cell malignancy upon faithful HNSCC cell differentiation, indicating that targeted differentiation approaches may be therapeutically valuable. Moreover, we describe KRT17 to be a candidate biomarker for HNSCC cell differentiation and early tumor detection. © 2024. The Author(s)
Artists and Radicalism in Germany, 1890-1933: Reform, Politics and the Paradoxes of the Avant-Garde
No full textThis thesis seeks to lay the foundations for a socio-historical analysis of German radicalism and the avant-garde. Following first the development of the German applied arts movement from 1890, and then the debates over the role of painting from within and beyond the avant-garde in the interwar period, it addresses the ways the reform of artistic and technical-vocational education was intertwined with the questions of the ‘art proletariat’ and the nature of intellectual labour in capitalist economy. It argues that the history of what was widely conceived as the ‘avant-garde’ in the interwar period was still responding to the same set of concerns addressed in the context of the applied arts movement. The concept of functional, ‘useful’ artistic labour as opposed to the ‘useless’ fine arts, a concept connecting the prewar reform movement with the interwar avant-garde, is translated here into a new model of professional politics serving the radical or vanguard artist. ‘Radicalism’ is discussed here neither in terms of political positions per se nor with regard to artistic innovation, but instead as a distinct historical phenomenon of professional politics. The question is not what makes an artwork or an idea radical, but how artistic radicalism itself was shaped. The secession of the applied artist from the traditional art institutions is seen as a decisive moment in this process. Precisely this outsider position – beyond fine arts and traditional crafts – determined the increasingly exclusionary policies of the avant-garde movement. Thus this thesis ultimately proposes a new interpretation of the conflict between the advocates and enemies of modern art as a whole. It was the artists’ own professional politics which shaped this conflict and determined affiliations with specific political parties, and not the opposite. The relation of artistic developments to larger political issues must, I argue, be read through the specific professional politics emerging out of the polarity between the vanguard artist-reformer and the so-called ‘art proletariat’
J.UCS Special Issue:I-Know 03 - Hot Spots in Knowledge Management
No full textThe increasing complexity of both the environment in which companies operate and of their internal workings combined with an increasingly high pressure for innovation make knowledge and its efficient management central to business success today. The management of knowledge is more than directly managing knowledge as a resource. It is more concerned with providing knowledge-friendly environments in which knowledge can flourish and develop. The development of such environments can be addressed from many different perspectives, which makes knowledge management a very interdisciplinary field of research. It concerns human resources management, organizational development and information technology management to mention just the three most important fields. This special issue on hot spots in knowledge management offers the reader a broad overview of the leading edge developments, technologies and applications in knowledge management. The issue serves two distinct purposes: (1) It may help shaping the reader s thinking in the way required for a successful implementation of knowledge management in an organization, (2) it may serve as a stimulus for the reader s research in knowledge management. The following 13 papers fall in four categories: Knowledge Management in Business Knowledge Mining Knowledge Representation Convergence of Knowledge Management with other Domains The first category - knowledge management in business - addresses knowledge management from a more business-oriented perspective. In more detail, the papers of this group address the following topics: Peter Schuett from IBM Stuttgart (Germany) presents in his paper The post-Nonaka Knowledge Management a new generation of knowledge management that can be divided in three categories (1) processes, (2) organization and culture, and (3) information technology. The objective of the paper is to provide solutions for increasing the productivity of knowledge workers through knowledge management. He argues that in order to increase productivity we need to understand the work environment of knowledge workers. To provide guidance, P. Schuett identifies 11 factors which help understanding and improving a knowledge worker s environment. This factors fall in the following three groups work processes, organisation and culture, and information technology. Klaus North and Tina Hornung from the University of Applied Sciences in Wiesbaden (Germany) entitled their paper The Benefits of Knowledge Management - Results from the German award _Knowledge Manager 2002_. Based on the evaluation of almost 40 companies the authors present which added-value and benefit knowledge management can generate. The benefits are grouped in the following five perspectives: learn and growth, business processes, customer satisfaction, financial results, and employee satisfaction. The results of the study revealed that knowledge management can generate the highest benefit in business processes (e.g. acceleration and higher transparency), customer satisfaction (e.g. better response times), and employee satisfaction (e.g. improved team work and increased motivation). The paper Managing Operation Knowledge for the Metal Industry written by Sheng-Tun Li and Huang-Chih Hseih from the National Kaohsiung First University of Science Technology (Taiwan) presents a three-stage life cycle for the ontology design. The application of the resulting ontology in a metal industry company proves the effectiveness and efficiency of their approach. In their paper Filters in the Strategy Formulation Process Leena Ilmola and Anna Kotsalo-Mustonen from Helsinki University of Technology (Finland) present a new software tool supporting strategy formulation processes. Based on three different types of filters that hinder effective knowledge flows in companies a software tool is introduced that helps overcome these filters. Matteo Bonifacio and Alessandra Molani from University of Trento (Italy) are the authors of the paper The Richness of Diversity in Knowledge Creation: an Interdisciplinary Overview. They propose theoretical, practical and technological arguments supporting a distributed approach to knowledge management. Knowledge diversity in theory, practice, and technology is considered an important source of value for the approach of the authors. The last paper in this category has the title SCBS Social Capital Benchmarking System Profiting from Social Capital when Building Network Organisations. Jos_ Mar_a Viedma from Polytechnic University of Catalonia (Spain) argues that the competitive advantage of a company does not only rely on a company s internal intellectual capital but also on the external intellectual capital of other companies, organisations and institutions. The author presents a social capital benchmarking system which serves as a new management method and a new management tool which identifies, audits and benchmarks the resources and capabilities existing in cluster organisations. Knowledge mining including retrieval, classification and discovery constitutes another main stream in knowledge management. The papers of this second category address the following topics: The paper Unified Access to Heterogeneous Audiovisual Archives is written by Y. Avrithis, G. Stamou, and M. Wallace from National Technical University of Athens (Greece), F. Marques, P. Salembier, X Giro from Technical University of Catalonia (Spain) and W. Haas, H. Vallant, M. Zufferey from Joanneum Research (Austria). The authors present an integrated information system that offers enhanced search and retrieval capabilities to users of heterogeneous digital audio-visual archives. The idea is to extract semantic information from audio/video and text data taking into account context information of a user. Pruning-based Identification of Domain Ontologies is the title of a paper co-authored by Raphael Volz, Rudi Studer, and Alexander Maedche from FZI Research Center for Information Technologies (Germany) and Boris Lauser from FAO of the UN (Italy). This paper introduces a new pruning-based approach of extracting a domain ontology from large-scale thesauri. In this context pruning presents a completely automatic bootstrapping approach for ontology development. The aim of pruning is to automatically extract from an existing vocabulary a subset of the conceptualization which is relevant to the target domain. In a later stage, the automatically identified initial domain ontology can easily be refined by experts. Christian Biemann, Uwe Quasthoff, Karsten Boehm from University of Leipzig (Germany) and Christian Wolff from Chemnitz University of Technology (Germany) are the authors of the paper Automatic Discovery and Aggregation of Compound Names for the Use in Knowledge Representations. They argue that the treatment of multiword terms as single semantic entities is an inherent problem of automatic acquisition of information structures (e.g. Topic Maps). As a solution to this problem the authors present a method for learning multiword terms from large text corpora. The following two papers belong to an evergreen category in knowledge management, namely knowledge representation. Kai Mertins, Peter Heisig, and Kay Alwert from Fraunhofer IPK (Germany) are the authors of the paper Process Oriented Knowledge Structuring. The paper presents three different types of knowledge structures and their visualization (e.g., Topic Maps, Knowledge Navigator) which support the structuring and maintenance of complex knowledge bases. Towards the Semantic Grid: Putting Knowledge to Work in Design Optimisation is a paper authored by Fang Tao, Liming Chen, Nigel Shadbolt, Graeme Pound and Simon Cox from the University of Southampton (UK). They present a knowledge-based approach which uses existing sources to acquire knowledge needed for engineering design search and optimization. In order to reuse this knowledge and to provide guidance at knowledge intensive points, a knowledge advisor is proposed. This advisor gives a context-aware critique to guide users through effective operations of building domain workflows. The last paper category - convergence of knowledge management with other domains - reflects signals indicating that research of other domains converges with research in knowledge management. Such converging fields include problem solving, eLearning, linguistics etc. The paper Knowledge Management for Computational Problem Solving written by D.T. Lee, G.C. Lee and Y.W. Huang from Academia Sinica (Taiwan) argues that algorithmic research is an established knowledge engineering process allowing researchers to identify significant problems, to better understand existing approaches and to obtain new, effective and efficient solutions. To support researchers in this process a problem-centred collaborative knowledge management architecture associated with computational problem solving is presented. Lilia Efimova and Janine Swaak from the Telematica Instituut (The Netherlands) discuss in their paper entitled Converging Knowledge Management, Training and e-Learning: Scenarios to Make it Work the added value of using knowledge management methods to support human resource learning management efforts and vice versa of using human resource training instruments to support knowledge management. Examples for existing practices of joint work include linking communities of practice and formal learning programmes or fostering the cooperation between a Chief Knowledge Officer and Human Resource teams. I hope that the broad variety of 13 contributions provides the reader with a comprehensive overview of the most intriguing hot spots in knowledge management in 2003. Graz, July 2003 Klaus Tochtermann Know-Center, Gra
