The Experts below are selected from a list of 121413 Experts worldwide ranked by ideXlab platform
Vesterinen Tuomas - One of the best experts on this subject based on the ideXlab platform.
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Identifying the Explanatory Domain of the Looping Effect: Congruent and Incongruent Feedback Mechanisms of Interactive Kinds
'Walter de Gruyter GmbH', 2021Co-Authors: Vesterinen TuomasAbstract:Ian Hacking uses the looping effect to describe how classificatory practices in the human sciences interact with the classified people. While arguably this interaction renders the affected human kinds unstable and hence different from natural kinds, realists argue that also some prototypical natural kinds are interactive and human kinds in general are stable enough to support explanations and predictions. I defend a more fine-grained realist interpretation of interactive human kinds by arguing for an explanatory Domain Account of the looping effect. First, I argue that knowledge of the feedback mechanisms that mediate the looping effect can supplement, and help to identify, the applicability Domain over which a kind and its property variations are stably explainable. Second, by applying this Account to cross-cultural case studies of psychiatric disorders, I distinguish between congruent feedback mechanisms that explain matches between classifications and kinds, and incongruent feedback mechanisms that explain mismatches. For example, congruent mechanisms maintain Western auditory experiences in schizophrenia, whereas exporting diagnostic labels inflicts incongruence by influencing local experiences. Knowledge of the mechanisms can strengthen explanatory Domains, and thereby facilitate classificatory adjustments and possible interventions on psychiatric disorders
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Identifying the Explanatory Domain of the Looping Effect: Congruent and Incongruent Feedback Mechanisms of Interactive Kinds
2021Co-Authors: Vesterinen TuomasAbstract:Winner of the 2020 Essay Competition of the International Social Ontology Society. Ian Hacking uses the looping effect to describe how classificatory practices in the human sciences interact with the classified people. While arguably this interaction renders the affected human kinds unstable and hence different from natural kinds, realists argue that also some prototypical natural kinds are interactive and human kinds in general are stable enough to support explanations and predictions. I defend a more fine-grained realist interpretation of interactive human kinds by arguing for an explanatory Domain Account of the looping effect. First, I argue that knowledge of the feedback mechanisms that mediate the looping effect can supplement, and help to identify, the applicability Domain over which a kind and its property variations are stably explainable. Second, by applying this Account to cross-cultural case studies of psychiatric disorders, I distinguish between congruent feedback mechanisms that explain matches between classifications and kinds, and incongruent feedback mecha- nisms that explain mismatches. For example, congruent mechanisms maintain Western auditory experiences in schizophrenia, whereas exporting diagnostic labels inflicts incongruence by influencing local experiences. Knowledge of the mechanisms can strengthen explanatory Domains, and thereby facilitate classificatory adjustments and possible interventions on psychiatric disorders
Hanspeter Rottensteiner - One of the best experts on this subject based on the ideXlab platform.
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linker regions and flexibility around the metalloprotease Domain Account for conformational activation of adamts 13
Journal of Thrombosis and Haemostasis, 2015Co-Authors: Louis Deforche, Elien Roose, Aline Vandenbulcke, Nele Vandeputte, Hendrik B Feys, Timothy A Springer, Joshua Muia, J E Sadler, K Soejima, Hanspeter RottensteinerAbstract:Summary Background Recently, conformational activation of ADAMTS-13 was identified. This mechanism showed the evolution from a condensed conformation, in which the proximal MDTCS and distal T2-CUB2 Domains are in close contact with each other, to an activated, open structure due to binding with von Willebrand factor (VWF). Objectives Identification of cryptic epitope/exosite exposure after conformational activation and of sites of flexibility in ADAMTS-13. Methods The activating effect of 25 anti-T2-CUB2 antibodies was studied in the FRETS-VWF73 and the vortex assay. Cryptic epitope/exosite exposure was determined with ELISA and VWF binding assay. The molecular basis for flexibility was hypothesized through rapid automatic detection and alignment of repeats (RADAR) analysis, tested with ELISA using deletion variants and visualized using electron microscopy. Results Eleven activating anti-ADAMTS-13 antibodies, directed against the T5-CUB2 Domains, were identified in the FRETS-VWF73 assay. RADAR analysis identified three linker regions in the distal Domains. Interestingly, identification of an antibody recognizing a cryptic epitope in the metalloprotease Domain confirmed the contribution of these linker regions to conformational activation of the enzyme. The proof of flexibility around both the T2 and metalloprotease Domains, as shown by by electron microscopy, further supported this contribution. In addition, cryptic epitope exposure was identified in the distal Domains, because activating anti-T2-CUB2 antibodies increased the binding to folded VWF up to ~3-fold. Conclusion Conformational activation of ADAMTS-13 leads to cryptic epitope/exosite exposure in both proximal and distal Domains, subsequently inducing increased activity. Furthermore, three linker regions in the distal Domains are responsible for flexibility and enable the interaction between the proximal and the T8-CUB2 Domains.
Louis Deforche - One of the best experts on this subject based on the ideXlab platform.
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linker regions and flexibility around the metalloprotease Domain Account for conformational activation of adamts 13
Journal of Thrombosis and Haemostasis, 2015Co-Authors: Louis Deforche, Elien Roose, Aline Vandenbulcke, Nele Vandeputte, Hendrik B Feys, Timothy A Springer, Joshua Muia, J E Sadler, K Soejima, Hanspeter RottensteinerAbstract:Summary Background Recently, conformational activation of ADAMTS-13 was identified. This mechanism showed the evolution from a condensed conformation, in which the proximal MDTCS and distal T2-CUB2 Domains are in close contact with each other, to an activated, open structure due to binding with von Willebrand factor (VWF). Objectives Identification of cryptic epitope/exosite exposure after conformational activation and of sites of flexibility in ADAMTS-13. Methods The activating effect of 25 anti-T2-CUB2 antibodies was studied in the FRETS-VWF73 and the vortex assay. Cryptic epitope/exosite exposure was determined with ELISA and VWF binding assay. The molecular basis for flexibility was hypothesized through rapid automatic detection and alignment of repeats (RADAR) analysis, tested with ELISA using deletion variants and visualized using electron microscopy. Results Eleven activating anti-ADAMTS-13 antibodies, directed against the T5-CUB2 Domains, were identified in the FRETS-VWF73 assay. RADAR analysis identified three linker regions in the distal Domains. Interestingly, identification of an antibody recognizing a cryptic epitope in the metalloprotease Domain confirmed the contribution of these linker regions to conformational activation of the enzyme. The proof of flexibility around both the T2 and metalloprotease Domains, as shown by by electron microscopy, further supported this contribution. In addition, cryptic epitope exposure was identified in the distal Domains, because activating anti-T2-CUB2 antibodies increased the binding to folded VWF up to ~3-fold. Conclusion Conformational activation of ADAMTS-13 leads to cryptic epitope/exosite exposure in both proximal and distal Domains, subsequently inducing increased activity. Furthermore, three linker regions in the distal Domains are responsible for flexibility and enable the interaction between the proximal and the T8-CUB2 Domains.
Aline Vandenbulcke - One of the best experts on this subject based on the ideXlab platform.
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linker regions and flexibility around the metalloprotease Domain Account for conformational activation of adamts 13
Journal of Thrombosis and Haemostasis, 2015Co-Authors: Louis Deforche, Elien Roose, Aline Vandenbulcke, Nele Vandeputte, Hendrik B Feys, Timothy A Springer, Joshua Muia, J E Sadler, K Soejima, Hanspeter RottensteinerAbstract:Summary Background Recently, conformational activation of ADAMTS-13 was identified. This mechanism showed the evolution from a condensed conformation, in which the proximal MDTCS and distal T2-CUB2 Domains are in close contact with each other, to an activated, open structure due to binding with von Willebrand factor (VWF). Objectives Identification of cryptic epitope/exosite exposure after conformational activation and of sites of flexibility in ADAMTS-13. Methods The activating effect of 25 anti-T2-CUB2 antibodies was studied in the FRETS-VWF73 and the vortex assay. Cryptic epitope/exosite exposure was determined with ELISA and VWF binding assay. The molecular basis for flexibility was hypothesized through rapid automatic detection and alignment of repeats (RADAR) analysis, tested with ELISA using deletion variants and visualized using electron microscopy. Results Eleven activating anti-ADAMTS-13 antibodies, directed against the T5-CUB2 Domains, were identified in the FRETS-VWF73 assay. RADAR analysis identified three linker regions in the distal Domains. Interestingly, identification of an antibody recognizing a cryptic epitope in the metalloprotease Domain confirmed the contribution of these linker regions to conformational activation of the enzyme. The proof of flexibility around both the T2 and metalloprotease Domains, as shown by by electron microscopy, further supported this contribution. In addition, cryptic epitope exposure was identified in the distal Domains, because activating anti-T2-CUB2 antibodies increased the binding to folded VWF up to ~3-fold. Conclusion Conformational activation of ADAMTS-13 leads to cryptic epitope/exosite exposure in both proximal and distal Domains, subsequently inducing increased activity. Furthermore, three linker regions in the distal Domains are responsible for flexibility and enable the interaction between the proximal and the T8-CUB2 Domains.
K Soejima - One of the best experts on this subject based on the ideXlab platform.
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linker regions and flexibility around the metalloprotease Domain Account for conformational activation of adamts 13
Journal of Thrombosis and Haemostasis, 2015Co-Authors: Louis Deforche, Elien Roose, Aline Vandenbulcke, Nele Vandeputte, Hendrik B Feys, Timothy A Springer, Joshua Muia, J E Sadler, K Soejima, Hanspeter RottensteinerAbstract:Summary Background Recently, conformational activation of ADAMTS-13 was identified. This mechanism showed the evolution from a condensed conformation, in which the proximal MDTCS and distal T2-CUB2 Domains are in close contact with each other, to an activated, open structure due to binding with von Willebrand factor (VWF). Objectives Identification of cryptic epitope/exosite exposure after conformational activation and of sites of flexibility in ADAMTS-13. Methods The activating effect of 25 anti-T2-CUB2 antibodies was studied in the FRETS-VWF73 and the vortex assay. Cryptic epitope/exosite exposure was determined with ELISA and VWF binding assay. The molecular basis for flexibility was hypothesized through rapid automatic detection and alignment of repeats (RADAR) analysis, tested with ELISA using deletion variants and visualized using electron microscopy. Results Eleven activating anti-ADAMTS-13 antibodies, directed against the T5-CUB2 Domains, were identified in the FRETS-VWF73 assay. RADAR analysis identified three linker regions in the distal Domains. Interestingly, identification of an antibody recognizing a cryptic epitope in the metalloprotease Domain confirmed the contribution of these linker regions to conformational activation of the enzyme. The proof of flexibility around both the T2 and metalloprotease Domains, as shown by by electron microscopy, further supported this contribution. In addition, cryptic epitope exposure was identified in the distal Domains, because activating anti-T2-CUB2 antibodies increased the binding to folded VWF up to ~3-fold. Conclusion Conformational activation of ADAMTS-13 leads to cryptic epitope/exosite exposure in both proximal and distal Domains, subsequently inducing increased activity. Furthermore, three linker regions in the distal Domains are responsible for flexibility and enable the interaction between the proximal and the T8-CUB2 Domains.