| 1. |
- Gattinger, Pia, et al.
(författare)
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Neutralization of SARS-CoV-2 requires antibodies against conformational receptor-binding domain epitopes
- 2022
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 77:1, s. 230-242
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Tidskriftsartikel (refereegranskat)abstract
- Background: The determinants of successful humoral immune response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are of critical importance for the design of effective vaccines and the evaluation of the degree of protective immunity conferred by exposure to the virus. As novel variants emerge, understanding their likelihood of suppression by population antibody repertoires has become increasingly important.Methods: In this study, we analyzed the SARS-CoV-2 polyclonal antibody response in a large population of clinically well-characterized patients after mild and severe COVID-19 using a panel of microarrayed structurally folded and unfolded SARS-CoV-2 proteins, as well as sequential peptides, spanning the surface spike protein (S) and the receptor-binding domain (RBD) of the virus.Results: S- and RBD-specific antibody responses were dominated by immunoglobulin G (IgG), mainly IgG1, and directed against structurally folded S and RBD and three distinct peptide epitopes in S2. The virus neutralization activity of patients´ sera was highly correlated with IgG antibodies specific for conformational but not sequential RBD epitopes and their ability to prevent RBD binding to its human receptor angiotensin-converting enzyme 2 (ACE2). Twenty percent of patients selectively lacked RBD-specific IgG. Only immunization with folded, but not with unfolded RBD, induced antibodies against conformational epitopes with high virus-neutralizing activity. Conformational RBD epitopes required for protection do not seem to be altered in the currently emerging virus variants.Conclusion: These results are fundamental for estimating the protective activity of antibody responses after natural infection or vaccination and for the design of vaccines, which can induce high levels of SARS-CoV-2–neutralizing antibodies conferring sterilizing immunity.
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| 2. |
- Mittler, Eva, et al.
(författare)
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Human antibody recognizing a quaternary epitope in the Puumala virus glycoprotein provides broad protection against orthohantaviruses
- 2022
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science. - 1946-6234 .- 1946-6242. ; 14:636
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Tidskriftsartikel (refereegranskat)abstract
- The rodent-borne hantavirus Puumala virus (PUUV) and related agents cause hemorrhagic fever with renal syndrome (HFRS) in humans. Other hantaviruses, including Andes virus (ANDV) and Sin Nombre virus, cause a distinct zoonotic disease, hantavirus cardiopulmonary syndrome (HCPS). Although these infections are severe and have substantial case fatality rates, no FDA-approved hantavirus countermeasures are available. Recent work suggests that monoclonal antibodies may have therapeutic utility. We describe here the isolation of human neutralizing antibodies (nAbs) against tetrameric Gn/Gc glycoprotein spikes from PUUV-experienced donors. We define a dominant class of nAbs recognizing the "capping loop" of Gn that masks the hydrophobic fusion loops in Gc. A subset of nAbs in this class, including ADI-42898, bound Gn/Gc complexes but not Gn alone, strongly suggesting that they recognize a quaternary epitope encompassing both Gn and Gc. ADI-42898 blocked the cell entry of seven HCPS- and HFRS-associated hantaviruses, and single doses of this nAb could protect Syrian hamsters and bank voles challenged with the highly virulent HCPS-causing ANDV and HFRS-causing PUUV, respectively. ADI-42898 is a promising candidate for clinical development as a countermeasure for both HCPS and HFRS, and its mode of Gn/Gc recognition informs the development of broadly protective hantavirus vaccines.
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| 3. |
- Mittler, Eva, et al.
(författare)
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Structural and mechanistic basis of neutralization by a pan-hantavirus protective antibody
- 2023
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 15:700
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Tidskriftsartikel (refereegranskat)abstract
- Emerging rodent-borne hantaviruses cause severe diseases in humans with no approved vaccines or therapeutics. We recently isolated a monoclonal broadly neutralizing antibody (nAb) from a Puumala virus-experienced human donor. Here, we report its structure bound to its target, the Gn/Gc glycoprotein heterodimer comprising the viral fusion complex. The structure explains the broad activity of the nAb: It recognizes conserved Gc fusion loop sequences and the main chain of variable Gn sequences, thereby straddling the Gn/Gc heterodimer and locking it in its prefusion conformation. We show that the nAb's accelerated dissociation from the divergent Andes virus Gn/Gc at endosomal acidic pH limits its potency against this highly lethal virus and correct this liability by engineering an optimized variant that sets a benchmark as a candidate pan-hantavirus therapeutic.
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| 4. |
- Möhring, Michael, et al.
(författare)
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Predictive maintenance information systems : The underlying conditions and technological aspects
- 2020
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Ingår i: International Journal of Enterprise Information Systems. - : IGI Global. - 1548-1115 .- 1548-1123. ; 16:2, s. 22-37
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Tidskriftsartikel (refereegranskat)abstract
- Predictive maintenance has the potential to improve the reliability of production and service provisioning. However, there is little knowledge about the proper implementation of predictive maintenance in research and practice. Therefore, we conducted a multi-case study and investigated underlying conditions and technological aspects for implementing a predictive maintenance system and where it leads to. We found that predictive maintenance initiatives are triggered by severe impacts of failures on revenue and profit. Furthermore, successful predictive maintenance initiatives require that pre-conditions are fulfilled: Data must be available and accessible. Very important is also the support by the management. We identified four factors important for the implementation of predictive maintenance. The integration of data is highly facilitated by Cloud-based mechanisms. The detection of events is enabled by advanced analytics. The execution of predictive maintenance operations is supported by data-driven process automation and visualization.
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| 5. |
- Volkert, Dorothee, et al.
(författare)
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ESPEN guideline on nutrition and hydration in dementia : Update 2024
- 2024
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Ingår i: Clinical Nutrition. - : Churchill Livingstone. - 0261-5614 .- 1532-1983. ; 43:6, s. 1599-1626
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS : Dementia is accompanied by a variety of changes that result in an increased risk of malnutrition and low-intake dehydration. This guideline update aims to give evidence-based recommendations for nutritional care of persons with dementia in order to prevent and treat these syndromes. METHODS : The previous guideline version was reviewed and expanded in accordance with the standard operating procedure for ESPEN guidelines. Based on a systematic search in three databases, strength of evidence of appropriate literature was graded by use of the SIGN system. The original recommendations were reviewed and reformulated, and new recommendations were added, which all then underwent a consensus process. RESULTS : 40 recommendations for nutritional care of older persons with dementia were developed and agreed, seven at institutional level and 33 at individual level. As a prerequisite for good nutritional care, organizations caring for persons with dementia are recommended to employ sufficient qualified staff and offer attractive food and drinks with choice in a functional and appealing environment. Nutritional care should be based on a written care concept with standardized operating procedures. At the individual level, routine screening for malnutrition and dehydration, nutritional assessment and close monitoring are unquestionable. Oral nutrition may be supported by eliminating potential causes of malnutrition and dehydration, and adequate social and nursing support (including assistance, utensils, training and oral care). Oral nutritional supplements are recommended to improve nutritional status but not to correct cognitive impairment or prevent cognitive decline. Routine use of dementia-specific ONS, ketogenic diet, omega-3 fatty acid supplementation and appetite stimulating agents is not recommended. Enteral and parenteral nutrition and hydration are temporary options in patients with mild or moderate dementia, but not in severe dementia or in the terminal phase of life. In all stages of the disease, supporting food and drink intake and maintaining or improving nutrition and hydration status requires an individualized, comprehensive approach. Due to a lack of appropriate studies, most recommendations are good practice points. CONCLUSION : Nutritional care should be an integral part of dementia management. Numerous interventions are available that should be implemented in daily practice. Future high-quality studies are needed to clarify the evidence.
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| 6. |
- Zimmermann, Alfred, et al.
(författare)
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Conceptualizing Artificial Intelligence-Based Service Ecosystems
- 2021
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Ingår i: Advances in the Human Side of Service Engineering - Proceedings of the AHFE 2021 Virtual Conference on The Human Side of Service Engineering, July 25-29, 2021, USA. - Cham : Springer. - 9783030808396 - 9783030808402 ; , s. 377-384
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Konferensbidrag (refereegranskat)abstract
- Platforms and their surrounding ecosystems are becoming increasingly important components of many companies' strategies. Artificial Intelligence, in particular, has created new opportunities to create and develop ecosystems around the platform. However, there is not yet a methodology to systematically develop these new opportunities for enterprise development strategy. Therefore, this paper aims to lay a foundation for the conceptualization of Artificial Intelligence-based service ecosystems exploiting a Service-Dominant Logic. The basis for conceptualization is the study of value creation and particularly effective network effects. This research investigates the fundamental idea of extending specific digital concepts considering the influence of Artificial Intelligence on the design of intelligent services, along with their architecture of digital platforms and ecosystems, to enable a smooth evolutionary path and adaptability for human-centric collaborative systems and services. The paper explores an extended digital enterprise conceptual model through a combined, iterative, and permanent task of co-creating value between humans and intelligent systems as part of a new idea of cognitively adapted intelligent services.
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