1,714 research outputs found
Improving NK cell-based immunotherapy of cancer by exploration of migration and inhibitory receptor-ligand interactions
No full textThe possibility to utilize the immune system as a mean to target malignantly transformed cells has emerged as a novel treatment modality during the last decades and is a field that is under rapid development. Natural Killer (NK) cells are immune cells with an intrinsic ability to recognize and lyse tumor-transformed cells. Their role in immune surveillance of cancer is well established and clinical studies have also highlighted their treatment potential. However, the efficacy has so far been suboptimal and means to further improve NK cell-based immunotherapy against cancer is under intensive investigation. This thesis mainly focuses on how to enhance NK cell treatment efficacy against acute myeloid leukemia (AML), a disease with poor prognosis that is in urgent need for novel and more efficacious treatment options.The potential to better home NK cells to the tumor environment is a highly appealing, but so far relatively unexplored approach to improve treatment efficacy for adoptive NK cell transfer. In Papers I and II, we have utilized a clinically approved mRNA transfection technique to explore how ex vivo expanded NK cells can be engineered to express the gain-of-function bone marrow (BM) homing receptor variant CXCR4R334X. We have shown that CXCR4R334X-expressing NK cells display an increased in vitro migration potential towards the ligand SDF-1 without compromising functionality in any other aspect. We have further highlighted the importance of the CXCR4-SDF-1 axis for in vivo BM homing using both CXCR4R334X mRNA transfected cells and CXCR4 knocked-out cells generated using the CRISPR/Cas9 technology. Finally, we showed that CXCR4R334X-expressing NK cells can be utilized to improve leukemia clearance in vivo, and furthermore have the potential to mediate a survival benefit in this context.Education is a complicated process in which NK cells are dynamically tuned by surrounding HLA class I molecules facilitating a strong effector response against target cells lacking such molecules. Members of the killer cell immunoglobulin-like receptor (KIR) family and the natural killer group 2 member A (NKG2A) receptor have previously been shown to mediate education. In paper III, we have shown for the first time that the LIR-1 receptor can mediate education in ex vivo expanded NK cells. We have identified an educated LIR-1-expressing NK cell subset that display an elevated degranulation capacity towards HLA class I deficient or low tumor targets and further showed that this subset also has a phenotype which resembles that of educated cells. In addition, we have displayed that the subset can be detuned after blockade with specific LIR-1 monoclonal antibodies in line with the rheostat model. Finally, we revealed that this subset has a potent ADCC capacity that even can overcome inhibitory signals from cognate HLA class I ligands. We have postulated that these traits make this subset highly attractive for NK cell-based immunotherapy and could be utilized in various cancer settings, including AML.Isocitrate dehydrogenase (IDH) 1 and 2 are frequently mutated in AML. IDH inhibitors (IDHi) have emerged as novel therapeutic agents. However, only a portion of the patients respond to treatment and the relapse rate is high. In paper IV, we have employed the TF- 1 AML cell line overexpressing the hotspot mutation IDH2R140Q as a model system to study the epigenetical and transcriptional landscape before and after treatment with an IDHi. We have shown that TF-1 IDH2R140Q cells display a hypermethylated DNA profile leading to differential gene expression, which can be further linked to a dysregulated transcriptional network involving myeloid-related transcription factors. We further displayed that this, at least in part, can be reversed upon treatment with the IDHi. Moreover, we showed that both TF-1 IDH2R140Q cells and primary AML cells carrying IDH mutations have hypermethylated HLA class I genes leading to HLA class I downregulation. This was associated with an increased sensitivity to NK cell-mediated responses against the IDH2R140Q mutated TF-1 cells compared to wild-type (WT) TF-1 cells. Lastly, we showed that HLA class I genes in IDH mutated primary AML cells of patients that did not respond to treatment with IDHi remained hypermethylated, indicating that this patient group may benefit from treatment based on adoptive NK cell infusions.Overall, this thesis provides evidence that NK cell migration can be modulated to redirect NK cells to bone marrow compartments for improved leukemia clearance. Furthermore, it includes a paper where the inhibitory receptor LIR-1 for the first time is shown to mediate education of ex vivo expanded NK cells, and identifies a unique subset of highly educated NK cells with a robust ADCC capacity that have the potential to be utilized against various cancer types including AML. Finally, the thesis includes a manuscript which shows that mutations in IDH can confer an increased NK cell sensitivity, and that IDH mutated AML patients resistant to treatment with IDHi constitute a subgroup of AML that may specifically benefit from NK cell-based immunotherapy. In conclusion, the thesis provides novel insights on how NK cells can be utilized to improve treatment for AML and potentially also other types of BM residing malignancies.List of scientific papersI. Emily Levy, Robert Reger, Filip Segerberg†, Mélanie Lambert†, Caroline Leijonhufvud†, Yvonne Baumer, Mattias Carlsten‡, Richard W. Childs‡. Enhanced Bone Marrow Homing of Natural Killer Cells Following mRNA Transfection With Gain-of-Function Variant CXCR4R334X. Frontiers in Immunology. 2019;10:1262. https://doi.org/10.3389/fimmu.2019.01262 II. Filip Segerberg†, Mélanie Lambert†, Laura Sanz-Ortega, Agneta Andersson, Richard W. Childs, Mattias Carlsten. Improved leukemia clearance following adoptive transfer of natural killer cells engineered with the bone marrow homing receptor CXCR4-R334X. [Manuscript]III. Caroline Leijonhufvud, Robert Reger†, Filip Segerberg†, Jakob Theorell, Heinrich Schlums, Yenan T. Bryceson, Richard W. Childs, Mattias Carlsten. LIR-1 educates expanded human NK cells and defines a unique antitumor NK cell subset with potent antibody-dependent cellular cytotoxicity. Clinical & Translational Immunology. 2021;10(10):e1346. https://doi.org/10.1002/cti2.1346 IV. Anna Palau, Filip Segerberg†, Michael Lidschreiber†, Katja Lidschreiber, Aonghus J. Naughton, Maria Needhamsen, Lisa Anna Ljung, Maja Jagodic, Patrick Cramer, Sören Lehmann‡, Mattias Carlsten‡, Andreas Lennartsson‡. Perturbed epigenetic transcriptional regulation in AML with IDH mutations causes increased susceptibility to NK cells. [Manuscript]</p
Filip Spannbrucker
No full textFilip Spannbrucker Filip Spannbrucker, česká barokní architektura, hrabě František Josef Schlik, Jean Baptiste Mathey, Jičínsko The main aim of this thesis is to present the life and work of Filip Spannbrucker (approximately 1672?1729), Prague architect and builder, in the context of contemporary artistic and social course of events. In the first part of this work there will be outlined Spannbrucker's life and professional career based on elaborate archival research. Special attention will be devoted to proprietors and a patronage of building projects wherein Spannbrucker participated or whereof was an author. In the connection, his work will be brought in contiguity of contemporaneous cultural, socioeconomical and aesthetical notions and relations. In the second part of this thesis there will be pointed out a characteristic and spring of inspiration of Spannbrucker's architecture by means of an accurate formal analysis. Final part will be a catalog of Filip Spannbrucker's works. Filip Spannbrucker, Czech baroque architecture, count František Josef Schlik, Jean Baptiste Mathey, region of Jičí
Location-Based Discovery and Network Handover Management for Heterogeneous IEEE 802.11ah IoT Applications
No full textThis research was funded by the Flemish IDEAL-IoT project (FWO SBO, grant nr. S004017N). The author Serena Santi is funded by the Flemish FWO SB grant (nr. 1S82120N). The author Filip Lemic was supported by the EU MSCA grant (nr. 893760). The computational resources were provided by the VSC (Flemish Supercomputer Center), funded by FWO and the Flemish Government -department EWI
Modular System for Distributed User Data Management
No full textTitle: Modular System for Distributed User Data Management Author: Filip Pavliš, Author's email: [email protected] Department: Department of Distributed and Dependable Systems Supervisor: Mgr. Pavel Ježek, Department of Distributed and Dependable Systems Abstract: The main objective of this project was to create a multiplatform modular system for distributed data management. The system supports both local and remote accessible data storage. Therefore a part of the solution is also a server for remote data access. System also provides parallel usage of a local and remote storage which guarantees that the storage is accessible also when connection to server is lost. In this case, system is capable to synchronize changes between the server and a client. A client can use multiple instances of his storage and our system is able to synchronize them through central server. The system provides abstraction over data model to separate plugin developers from its specific behavior. As practical preview of system usability was created an extension application called TuaLoca. The application will contain implementation of preview plugins and basic user interaction. Keywords: Distributed Data Management, Modular system, Synchronization on the SQL Queries Level, Distributed Solution for Interface LIN
Heritage book from Mircea Filip collection
No full textMircea Filip collection were integrated in the Scientific Library in 2016. It contains patrimony of great importance. The author invites readers to an exciting journey into the world of books, gathered in a life of Man, to discover together their charm and wisdom, the spirit of the characters created in different time spaces. True biblical values have today become the books on which the dedication or Ex-Libris of the author is preserved
Ignác Filip Semmelweis - his life and contribution to obstetrics
No full textAuthor: Anežka Pikmanová Institution: Charles University, Faculty od Medicine in Hradec Králové, Department of Non-medical Studies Title: Ignác Filip Semmelweis - his life and contribution to obstetrics Supervisor: doc. PhDr. Jana Kutnohorská, CSc. Number of pages: 73 Number of attachements: 1 Year od defense: 2025 Keywords: Ignác Filip Semmelweis, obstetrics in the 18th and 19th centuries, puerperal fever, mothers, midwives, obstetricians, obstetric education, obstetric clinics, prevention, treatment, hygiene measures, death The bachelor thesis is about the life of Ignác Filip Semmelweis and his contribution to obstetrics. The thesis consists of a theoretical and an empirical part. The theoretical part focuses on obstetrics in the 18th and 19th centuries, the life of Ignác Filip Semmelweis - his childhood, studies, work at the Klein clinic in Wien, Semmelweis' discovery, publishing activities, his work at the Saint Roch Hospital in Pest and the end of his life. The empirical part deals with the analysis of a survey that focused on the awareness of the professional public (students of general nursing, certified general nurse, midwifery, pediatric nurse) about Ignác Fillip Semmelweis and his professional activity. The survey was participated by students of Faculty of Medicine in Hradec Králové and..
Filip Buonaccorsi Kallimach „De legitimo amore”
No full textThe article is an analysis of three works by Filip Kallimach (Filippo Buonaccorsi) regarding marriage (elegy XXII, Epithalamium Fanniae ac Musaei, carmen Ad se ipsum). In the collections of Roman elegies from the Augustian era, there are no wedding pieces. The source of Callimachus’ idea is found by the author of the article in Epithalamium in Stellam et Violentillam by P. Papinius Statius and, indirectly, through the epithalamium of Statius – in the unpreserved elegies of L. Arruntius Stella, a poet of Domitian times.The article is an analysis of three works by Filip Kallimach (Filippo Buonaccorsi) regarding marriage (elegy XXII, Epithalamium Fanniae ac Musaei, carmen Ad se ipsum). In the collections of Roman elegies from the Augustian era, there are no wedding pieces. The source of Callimachus’ idea is found by the author of the article in Epithalamium in Stellam et Violentillam by P. Papinius Statius and, indirectly, through the epithalamium of Statius – in the unpreserved elegies of L. Arruntius Stella, a poet of Domitian times
Ignác Filip Semmelweis - his life and contribution to obstetrics
No full textAuthor: Anežka Pikmanová Institution: Charles University, Faculty od Medicine in Hradec Králové, Department of Non-medical Studies Title: Ignác Filip Semmelweis - his life and contribution to obstetrics Supervisor: doc. PhDr. Jana Kutnohorská, CSc. Number of pages: 73 Number of attachements: 1 Year od defense: 2025 Keywords: Ignác Filip Semmelweis, obstetrics in the 18th and 19th centuries, puerperal fever, mothers, midwives, obstetricians, obstetric education, obstetric clinics, prevention, treatment, hygiene measures, death The bachelor thesis is about the life of Ignác Filip Semmelweis and his contribution to obstetrics. The thesis consists of a theoretical and an empirical part. The theoretical part focuses on obstetrics in the 18th and 19th centuries, the life of Ignác Filip Semmelweis - his childhood, studies, work at the Klein clinic in Wien, Semmelweis' discovery, publishing activities, his work at the Saint Roch Hospital in Pest and the end of his life. The empirical part deals with the analysis of a survey that focused on the awareness of the professional public (students of general nursing, certified general nurse, midwifery, pediatric nurse) about Ignác Fillip Semmelweis and his professional activity. The survey was participated by students of Faculty of Medicine in Hradec Králové and...Autor: Anežka Pikmanová Instituce: Karlova univerzita, Lékařská fakulta v Hradci Králové, Ústav nelékařských studií Název práce: Ignác Filip Semmelweis - jeho život a přínos pro porodnictví Vedoucí práce: doc. PhDr. Jana Kutnohorská, CSc. Počet stran: 73 Počet příloh: 1 Rok obhajoby: 2025 Klíčová slova: Ignác Filip Semmelweis, porodnictví 18. a 19. století, horečka omladnic, rodičky, porodní báby, porodníci, porodnické vzdělání, porodnické kliniky, prevence, léčba, hygienická opatření, úmrtí Bakalářská práce pojednává o Ignáci Filipu Semmelweisovi, jeho životě a přínosu pro porodnictví. Práce je rozdělena na teoretickou a empirickou část. Teoretická část se věnuje porodnictví 18. a 19. století, osobě Ignáce Filipa Semmelweise - jeho mládí, studiu, působení na Kleinově klinice ve Vídni, Semmelweisově objevu, publikaci, činnosti v nemocnici sv. Rocha v Pešti a na univerzitní porodnické klinice v Pešti a závěru Semmelweisova života. Empirická část se zabývá analýzou dotazníkového šetření, které bylo zaměřeno na informovanost odborné veřejnosti (studentů oborů všeobecné ošetřovatelství, diplomovaná všeobecná sestra, porodní asistence a dětská sestra) o osobě Ignáce Filipa Semmelweise a jeho odborné činnosti. Výzkumného šetření se zúčastnili studenti Lékařské fakulty Univerzity Karlovy v Hradci Králové...Department of Non - Medical StudiesÚstav nelékařských studiíLékařská fakulta v Hradci KrálovéFaculty of Medicine in Hradec Králov
Political branding of Filip Turek in the campaign for the 2024 European Parliament elections
No full textThis thesis focuses on the political branding of Filip Turek in the campaign period before the 2024 European Parliament elections from the perspective of Catherine Needham's criteria for a successful political brand. In the theoretical part, the author presents the fundamentals of political branding and the concept of criteria for a successful political brand. The objective of the thesis is to determine whether Catherine Needham's criteria can be applied to Filip Turek's brand in the examined period, and how, if at all, the brand deviated from them. This objective is achieved by using qualitative research methods. Filip Turek's posts on social media sites Instagram and X, and several debates or interviews in which he participated, are subjected to thematic analysis. This data is accompanied by the findings that emerged from the research interviews conducted with respondents from different fields. The respondents include, for example, an expert on marketing practice, a political journalist and a person with an insight into Filip Turek's campaign. Based on the conducted analysis, it is decided that Catherine Needham's criteria for a successful political brand can be applied to the brand in the examined period. The brand deviated from these criteria in not fulfilling the 'value-based' criterion and in..
Nymphalis vaualbum
No full textNymphalis vaualbum ([Denis & Schiffermüller], 1775) —A solitary specimen was observed by Bretherton (1973) near Crno Lake on Mt. Durmitor. Interestingly, the author observed a specimen in the same area more than 30 years later, on July 3rd 2000.Published as part of Franeta, Filip, 2018, Checklist of the butterflies (Lepidoptera: Papilionoidea) of Montenegro, pp. 128-148 in Zootaxa 4392 (1) on page 140, DOI: 10.11646/zootaxa.4392.1.6, http://zenodo.org/record/119549
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