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- Physik (4114) (remove)
Kreysing, Jan Philipp ; Heidari, Maziar ; Zila, Vojtech ; Cruz León, Sergio ; Obarska-Kosinska, Agnieszka ; Laketa, Vibor ; Welsch, Sonja ; Köfinger, Jürgen ; Turoňová, Beata ; Hummer, Gerhard ; Kräusslich, Hans-Georg ; Beck, Martin
Upon infection, human immunodeficiency virus (HIV-1) releases its cone-shaped capsid into the cytoplasm of infected T-cells and macrophages. As its largest known cargo, the capsid enters the nuclear pore complex (NPC), driven by interactions with numerous FG-repeat nucleoporins (FG-Nups). Whether NPCs structurally adapt to capsid passage and whether capsids are modified during passage remains unknown, however. Here, we combined super-resolution and correlative microscopy with cryo electron tomography and molecular simulations to study nuclear entry of HIV-1 capsids in primary human macrophages. We found that cytosolically bound cyclophilin A is stripped off capsids entering the NPC, and the capsid hexagonal lattice remains largely intact inside and beyond the central channel. Strikingly, the NPC scaffold rings frequently crack during capsid passage, consistent with computer simulations indicating the need for NPC widening. The unique cone shape of the HIV-1 capsid facilitates its entry into NPCs and helps to crack their rings.
Biological as well as advanced artificial intelligences (AIs) need to decide which goals to pursue. We review nature's solution to the time allocation problem, which is based on a continuously readjusted categorical weighting mechanism we experience introspectively as emotions. One observes phylogenetically that the available number of emotional states increases hand in hand with the cognitive capabilities of animals and that raising levels of intelligence entail ever larger sets of behavioral options. Our ability to experience a multitude of potentially conflicting feelings is in this view not a leftover of a more primitive heritage, but a generic mechanism for attributing values to behavioral options that can not be specified at birth. In this view, emotions are essential for understanding the mind. For concreteness, we propose and discuss a framework which mimics emotions on a functional level. Based on time allocation via emotional stationarity (TAES), emotions are implemented as abstract criteria, such as satisfaction, challenge and boredom, which serve to evaluate activities that have been carried out. The resulting timeline of experienced emotions is compared with the “character” of the agent, which is defined in terms of a preferred distribution of emotional states. The long-term goal of the agent, to align experience with character, is achieved by optimizing the frequency for selecting individual tasks. Upon optimization, the statistics of emotion experience becomes stationary.
Wastl, Jürgen ; Duin, Evert C. ; Iuzzolino, Lucia ; Dörner, Wolfgang ; Link, Thomas ; Hoffmann, Silke ; Sticht, Heinrich ; Dau, Holger ; Lingelbach, Klaus ; Maier, Uwe-G.
We analyzed a eukaryotically encoded rubredoxin from the cryptomonad Guillardia theta and identified additional domains at the N- and C-termini in comparison to known prokaryotic paralogous molecules. The cryptophytic N-terminal extension was shown to be a transit peptide for intracellular targeting of the protein to the plastid, whereas a C-terminal domain represents a membrane anchor. Rubredoxin was identified in all tested phototrophic eukaryotes. Presumably facilitated by its C-terminal extension, nucleomorph-encoded rubredoxin (nmRub) is associated with the thylakoid membrane. Association with photosystem II (PSII) was demonstrated by co-localization of nmRub and PSII membrane particles and PSII core complexes and confirmed by comparative electron paramagnetic resonance measurements. The midpoint potential of nmRub was determined as +125 mV, which is the highest redox potential of all known rubredoxins. Therefore, nmRub provides a striking example of the ability of the protein environment to tune the redox potentials of metal sites, allowing for evolutionary adaption in specific electron transport systems, as for example that coupled to the PSII pathway.
The core of this work is represented by the investigation of the chiral phase transition, using Monte Carlo simulations and unimproved staggered fermions, both in the weak and strong coupling regimes of Quantum Chromodynamics. Based on recent results from Monte Carlo simulations, both using unimproved staggered fermions and Wilson fermions, the chiral phase transition in the continuum and chiral limit shows compatibility with a second-order phase transition for Nf (number of flavours) in range [2:7], at zero baryon chemical potential. This achievement relies on the analytic continuation of Nf to non-integer values on the lattice, which allows to make use of extrapolation techniques to the chiral limit, where simulations are not possible. Furthermore, these results provide a resolution to the ambiguous scenario for Nf = 2 in the chiral limt. The first part of this thesis is devoted to the investigation of the chiral phase transition when a non-zero imaginary baryon chemical potential is involved, whose value corresponds to the 81% of the Roberge-Weiss one. Using the same extrapolation techniques aforementioned, the order of the chiral phase transition in the continuum and chiral limit shows compatibility with a second-order phase transition for Nf in range [2:6], highlighting a lack of dependence of the order of the chiral phase transition on the imaginary baryon chemical potential value. The second part of this thesis is about the study of the extension of the first-order chiral region in the strong coupling regime, at zero baryon chemical potential. Using Monte Carlo techniques, this can be done by investigating the Z2 boundary on a coarse lattice, whose temporal extent reads Nt = 2, and simulations are realised for Nf = 4, 8. The results in the weak coupling regime show, for $Nt = 8, 6, 4 and fixed Nf value, an inflating first-order chiral region. As in the strong coupling limit a second-order chiral phase transition is expected, the first-order chiral region has to shrink as the strong coupling regime is approached, resulting in a non-monotonic behaviour of the Z2 boundary. For Nf = 8, a critical mass on the Z2 boundary has been obtained, confirming the expected non-monotonic behaviour. For Nf = 4 the results do not provide a unique conclusion: Either a Z2 boundary at extremely low bare quark mass or a second-order chiral phase transition in the O(2) universality class in the chiral limit can take place. In addition to the two main topics, the performances of the second-order minimum norm integrator (2MN) and the fourth-order minimum norm integrator (4MN) have been compared, after implementing the 4MN one in the CL2QCD code used to realise our simulations. The 2MN integrator had already been implemented in the code since the first version was released. The two integrators belong to the class of symplectic integrators and represent an essential component of the RHMC algorithm, involved in our investigation. This step is extremely important, in order to guarantee the best quality when collecting data from simulations, and the results of the comparison suggested to favor the 2MN integrator, for both the topics.
A powerful technique to distinguish the enantiomers of a chiral molecule is the Coulomb Explosion Imaging (CEI). This technique allows us to determine the handedness of a single molecule. In CEI, the molecule becomes charged by losing many electrons in a very short period of time by interacting with the light. The repulsion forces between the positive charged particles of the molecule leads the molecule to break into parts-fragments. By measuring the three vector momentum of (at least) four fragments, the handedness observable can be determined. In this thesis, CEI is induced by absorption of a single high energy photon, which creates an inner-shell hole (K shell) of the molecule. The subsequent cascade of Auger decays lead to fragmentation. We decided to work with the formic acid molecule in this thesis. Two different experiments were conducted. The first experiment focused on exciting electrons to different energy states, while the second experiment focused on extracting directly a photoelectron to the continuum and measure the angular distribution of the photoelectron in the molecular frame. The primary goal was to search for chiral signal in a pure achiral planar molecule under the previous electron processes. The results of these findings were further implemented to two more molecules.
In the framework of the LHC Injectors Upgrade Project (LIU), the CERN Proton Synchrotron Booster (PSB) went through major upgrades resulting in new effects to study, challenges to overcome and new parameter regimes to explore. To assess the achievable beam brightness limit of the machine, a series of experimental and computational studies in the transverse planes were performed. In particular, the new injection scheme induces optics perturbations that are strongly enhanced near the half-integer resonance. In this thesis, methods for dynamically measuring and correcting these perturbations and their impact on the beam performance will be presented. Additionally, the quality of the transverse beam distributions and strategies for improvement will be addressed. Finally, the space charge effects when dynamically crossing the half-integer resonance will be characterized. The results of these studies and their broader significance beyond the PSB will be discussed.
IHMCIF: an extension of the PDBx/mmCIF data standard for integrative structure determination methods
(2024)
Vallat, Brinda ; Webb, Benjamin M. ; Westbrook, John D. ; Goddard, Thomas D. ; Hanke, Christian Alexander ; Graziadei, Andrea ; Peisach, Ezra ; Zalevsky, Arthur ; Sagendorf, Jared ; Tangmunarunkit, Hongsuda ; Voinea, Serban ; Sekharan, Monica ; Yu, Jian ; Bonvin, Alexander M. J. J. ; DiMaio, Frank ; Hummer, Gerhard ; Meiler, Jens ; Tajkhorshid, Emad ; Ferrin, Thomas E. ; Lawson, Catherine L. ; Leitner, Alexander ; Rappsilber, Juri ; Seidel, Claus ; Jeffries, Cy M. ; Burley, Stephen K. ; Hoch, Jeffrey C. ; Kurisu, Genji ; Morris, Kyle ; Patwardhan, Ardan ; Velankar, Sameer ; Schwede, Torsten ; Trewhella, Jill ; Kesselman, Carl ; Berman, Helen M. ; Sali, Andrej
IHMCIF (github.com/ihmwg/IHMCIF) is a data information framework that supports archiving and disseminating macromolecular structures determined by integrative or hybrid modeling (IHM), and making them Findable, Accessible, Interoperable, and Reusable (FAIR). IHMCIF is an extension of the Protein Data Bank Exchange/macromolecular Crystallographic Information Framework (PDBx/mmCIF) that serves as the framework for the Protein Data Bank (PDB) to archive experimentally determined atomic structures of biological macromolecules and their complexes with one another and small molecule ligands (e.g., enzyme cofactors and drugs). IHMCIF serves as the foundational data standard for the PDB-Dev prototype system, developed for archiving and disseminating integrative structures. It utilizes a flexible data representation to describe integrative structures that span multiple spatiotemporal scales and structural states with definitions for restraints from a variety of experimental methods contributing to integrative structural biology. The IHMCIF extension was created with the benefit of considerable community input and recommendations gathered by the Worldwide Protein Data Bank (wwPDB) Task Force for Integrative or Hybrid Methods (wwpdb.org/task/hybrid). Herein, we describe the development of IHMCIF to support evolving methodologies and ongoing advancements in integrative structural biology. Ultimately, IHMCIF will facilitate the unification of PDB-Dev data and tools with the PDB archive so that integrative structures can be archived and disseminated through PDB.
The spike protein of SARS-CoV-2 is a highly flexible membrane receptor that triggers the translocation of the virus into cells by attaching to the human receptors. Like other type I membrane receptors, this protein has several extracellular domains connected by flexible hinges. The presence of these hinges results in high flexibility, which consequently results in challenges in defining the conformation of the protein. Here, We developed a new method to define the conformational space based on a few variables inspired by the robotic field’s methods to determine a robotic arm’s forward kinematics. Using newly performed atomistic molecular dynamics (MD) simulations and publicly available data, we found that the Denavit-Hartenberg (DH) parameters can reliably show the changes in the local conformation. Furthermore, the rotational and translational components of the homogenous transformation matrix constructed based on the DH parameters can identify the changes in the global conformation of the spike and also differentiate between the conformation with a similar position of the spike head, which other types of parameters, such as spherical coordinates, fail to distinguish between such conformations. Finally, the new method will be beneficial for looking at the conformational heterogeneity in all other type I membrane receptors.
Highlights
• Sampling the large conformational space of disordered proteins requires extensive molecular dynamics (MD) simulations.
• Fragment assembly complements MD simulations to produce extensive ensembles of disordered proteins with atomic detail.
• Hierarchical chain growth (HCG) ensembles capture key experimental descriptors “out of the box”.
• HCG has revealed local structural characteristics associated with protein dysfunction in neurodegeneration.
Abstract
Disordered proteins and nucleic acids play key roles in cellular function and disease. Here, we review recent advances in the computational exploration of the conformational dynamics of flexible biomolecules. While atomistic molecular dynamics (MD) simulation has seen a lot of improvement in recent years, large-scale computing resources and careful validation are required to simulate full-length disordered biopolymers in solution. As a computationally efficient alternative, hierarchical chain growth (HCG) combines pre-sampled chain fragments in a statistically reproducible manner into ensembles of full-length atomically detailed biomolecular structures. Experimental data can be integrated during and after chain assembly. Applications to the neurodegeneration-linked proteins α-synuclein, tau, and TDP-43, including as condensate, illustrate the use of HCG. We conclude by highlighting the emerging connections to AI-based structural modeling including AlphaFold2.
Acharya, Shreyasi ; Adamová, Dagmar ; Agarwal, Apar ; Aglieri Rinella, Gianluca ; Aglietta, Luca ; Agnello, Michelangelo ; Agrawal, Neelima ; Ahammed, Zubayer ; Ahmad, Shakeel ; Ahn, Sang Un ; Ahuja, Ishaan ; Akindinov, Alexander ; Akishina, Valentina ; Al-Turany, Mohammad ; Aleksandrov, Dmitry ; Alessandro, Bruno ; Alfanda, Haidar Mas’ud ; Alfaro Molina, Jose Ruben ; Ali, Bushra ; Alici, Andrea ; Alizadehvandchali, Negin ; Alkin, Anton ; Alme, Johan ; Alocco, Giacomo ; Alt, Torsten ; Altamura, Anna Rita ; Altsybeev, Igor ; Alvarado Garcia, Jesús Ricardo ; Anaam, Mustafa Naji ; Andrei, Cristian ; Andreou, Nicodemos ; Andronic, Anton ; Andronov, Evgeny ; Anguelov, Venelin ; Antinori, Federico ; Antonioli, Pietro ; Apadula, Nicole ; Aphecetche, Laurent Bernard ; Appelshäuser, Harald ; Arata, Carolina ; Arcelli, Silvia ; Aresti, Mauro ; Arnaldi, Roberta ; Arneiro, Jhoao Gabriel Martins Campos Almeida ; Arsene, Ionut Cristian ; Arslandok, Mesut ; Augustinus, Andre ; Averbeck, Ralf Peter ; Azmi, Mohd Danish ; Baba, Hitoshi ; Badalà, Angela ; Bae, Joonsuk ; Baek, Yong Wook ; Bai, Xiaozhi ; Bailhache, Raphaëlle ; Bailung, Yoshini ; Bala, Renu ; Balbino, Alessandro ; Baldisseri, Alberto ; Balis, Bartosz ; Banerjee, Debjani ; Banoo, Zarina ; Barbasova, Veronika ; Barile, Francesco ; Barioglio, Luca ; Barlou, Maria ; Barman, Banajit ; Barnaföldi, Gergely Gábor ; Barnby, Lee Stuart ; Barreau, Emilie Martine ; Ramillien Barret, Valerie ; Barreto De Oliveira Campos, Leonardo ; Bartels, Clara ; Barth, Klaus ; Bartsch, Esther ; Bastid, Nicole ; Basu, Sumit ; Batigne, Guillaume ; Battistini, Daniel ; Batyunya, Boris ; Bauri, Dibakar ; Bazo Alba, José Luis ; Bearden, Ian Gardner ; Beattie, Caitlin ; Becht, Pascal ; Behera, Debadatta ; Belikov, Iouri ; Bell Hechavarria, Ailec de la Caridad ; Bellini, Francesca ; Bellwied, Rene ; Belokurova, Svetlana ; Espinoza Beltran, Lucina Gabriela ; Vasquez Beltran, Yael Antonio ; Bencédi, Gyula ; Bensaoula, Adel ; Beolè, Stefania ; Berdnikov, Yaroslav ; Berdnikova, Anastasia ; Bergmann, Luisa ; Besoiu, Mihaela Gabriela ; Betev, Latchezar ; Bhaduri, Partha Pratim ; Bhasin, Anju ; Bhat, Mohammad Asif ; Bhattacharjee, Buddhadeb ; Bianchi, Livio ; Bianchi, Nicola ; Bielčík, Jaroslav ; Bielčíková, Jana ; Bigot, Alexandre Patrick ; Bilandzic, Ante ; Biro, Gabor ; Biswas, Saikat ; Bize, Nicolas Luc ; Blair, Justin Thomas ; Blau, Dmitry S. ; Blidaru, Mihail-Bogdan ; Bluhme, Nora ; Blume, Christoph ; Boca, Gianluigi ; Bock, Friederike ; Bodova, Tea ; Bok, Jeongsu ; Boldizsar, Laszlo ; Bombara, Marek ; Bond, Peter Matthew ; Bonomi, Germano ; Borel, Herve ; Borissov, Alexander ; Borquez Carcamo, Andres Gerardo ; Bossi, Hannah ; Botta, Elena ; El Mard Bouziani, Youssef ; Bratrud, Lars ; Braun-Munzinger, Peter ; Bregant, Marco ; Broz, Michal ; Bruno, Giuseppe Eugenio ; Buckland, Matthew Daniel ; Budnikov, Dmitry ; Büsching, Henner ; Bufalino, Stefania ; Bühler, Paul ; Burmasov, Nazar ; Buthelezi, Edith Zinhle ; Bylinkin, Alexander ; Bysiak, Sebastian Adam ; Cabanillas Noris, Juan Carlos ; Torres Cabrera, Maria Fernanda ; Cai, Mengke ; Caines, Helen Louise ; Caliva, Alberto ; Calvo Villar, Ernesto ; Mejia Camacho, Juan Manuel ; Camerini, Paolo ; Canedo, Fabio de Moraes Canedo ; Weyhmiller, Sierra Lisa ; Carabas, Mihai ; Amatriain Carballo, Aitor ; Carnesecchi, Francesca ; Caron, Robin Albert Andre ; Abranches De Carvalho, Leopoldo ; Castillo Castellanos, Javier Ernesto ; Castoldi, Matteo ; Catalano, Fabio ; Cattaruzzi, Samuele ; Ceballos Sanchez, Cesar ; Cerri, Rebecca ; Chakaberia, Irakli ; Chakraborty, Pritam ; Chandra, Sinjini ; Chapeland, Sylvain ; Chartier, Marielle ; Chattopadhay, Souvik ; Chattopadhyay, Subhasis ; Chattopadhyay, Sukalyan ; Cheng, Tiantian ; Cheshkov, Cvetan Valeriev ; Chibante Barroso, Vasco Miguel ; Chinellato, David Dobrigkeit ; Chizzali, Emma Sophia ; Cho, Jaeyoon ; Cho, Soyeon ; Chochula, Peter ; Chochulska, Zuzanna Anna ; Choudhury, Dhrubajyoti ; Christakoglou, Panagiotis ; Christensen, Christian Holm ; Christiansen, Peter L. ; Chujo, Tatsuya ; Ciacco, Mario ; Cicalò, Corrado ; Ciupek, Michael Rudolf ; Clai, Giulia ; Colamaria, Fabio Filippo ; Colburn, Jonathan Samuel ; Colella, Domenico ; Colocci, Manuel ; Concas, Matteo ; Conesa Balbastre, Gustavo ; Conesa Del Valle, Zaida ; Contin, Giacomo ; Contreras Nuno, Jesus Guillermo ; Coquet, Maurice ; Cortese, Pietro ; Cosentino, Mauro Rogerio ; Costa, Filippo ; Costanza, Susanna ; Cot, Corentin ; Crkovská, Jana ; Crochet, Philippe ; Cruz Torres, Reynier ; Cui, Pengyao ; Dainese, Andrea ; Dange, Gautam ; Danisch, Meike Charlotte ; Danu, Andrea ; Das, Prottay ; Das, Prottoy ; Das, Supriya ; Dash, Archita Rani ; Dash, Sadhana ; De Caro, Annalisa ; De Cataldo, Giacinto ; Cuveland, Jan de ; De Falco, Alessandro ; De Gruttola, Daniele ; De Marco, Nora ; De Martin, Chiara ; De Pasquale, Salvatore ; Deb, Rohaan ; Del Grande, Raffaele ; Dello Stritto, Luigi ; Deng, Wenjing ; Devereaux, Kyle Christian ; Dhankher, Preeti ; Di Bari, Domenico ; Di Mauro, Antonio ; Diab, Batoul ; Arteche Diaz, Raul ; Dietel, Thomas ; Ding, Yanchun ; Ditzel, Janik ; Divià, Roberto ; Dixit, Dhruv Utpalkumar ; Djuvsland, Øystein ; Dmitrieva, Uliana ; Dobrin, Alexandru Florin ; Donigus, Benjamin ; Dubinski, Jan Michal ; Dubla, Andrea ; Dudi, Sandeep ; Dupieux, Pascal ; Dzalaiova, Natalia ; Eder, Tabea Maria ; Ehlers, Raymond James, III ; Eisenhut, Florian ; Ejima, Ren ; Elia, Domenico ; Erazmus, Barbara Ewa ; Ercolessi, Francesca ; Espagnon, Bruno ; Eulisse, Giulio ; Evans, David ; Evdokimov, Sergey ; Fabbietti, Laura ; Faggin, Mattia ; Faivre, Julien ; Fan, Feng ; Fan, Wenqing ; Fantoni, Alessandra ; Fasel, Markus ; Feliciello, Alessandro ; Feofilov, Grigori A. ; Fernández Téllez, Arturo ; Ferrandi De Oliveira, Lucas ; Bertran Ferrer, Marta ; Ferrero, Andrea ; Ferrero, Chiara ; Ferretti, Alessandro ; Feuillard, Victor Jose Gaston ; Filova, Vendulka ; Finogeev, Dmitry ; Fionda, Fiorella Maria Celeste ; Flatland, Erlend ; Flor, Fernando Antonio ; Flores, Amanda Nicole ; Foertsch, Siegfried Valentin ; Fokin, Ilya ; Fokin, Sergey ; Follo, Umberto ; Fragiacomo, Enrico ; Frajna, Eszter ; Fuchs, Ulrich ; Funicello, Nicola ; Furget, Christophe ; Furs, Artur ; Fusayasu, Takahiro ; Gaardhoeje, Jens Joergen ; Gagliardi, Martino ; Gago Medina, Alberto Martín ; Gahlaut, Tanu ; Duarte Galvan, Carlos ; Gangadharan, Dhevan Raja ; Ganoti, Paraskevi ; Garabatos Cuadrado, Jose Maria ; Martinez Garcia, Josue ; García Chávez, Tonatiuh ; Garcia-Solis, Edmundo Javier ; Gargiulo, Corrado ; Gasik, Piotr ; Gaur, Hari Mohan ; Gautam, Amrit ; Ducati, Maria Beatriz de Leone Gay ; Germain, Marie ; Ghimouz, Abderrahmane ; Ghosh, Chandrasekhar ; Giacalone, Marco ; Gioachin, Giulia ; Giubellino, Paolo ; Giubilato, Piero ; Glaenzer, Aude Marie Camille ; Glässel, Peter ; Glimos, Ewa ; Goh, Daniel Jia Qin ; Gonzalez Sebastian, Victor Luis ; Gordeev, Pavel ; Gorgon, Marek Boguslaw ; Goswami, Kangkan ; Gotovac, Sven ; Grabski, Varlen ; Graczykowski, Łukasz Kamil ; Grecka, Ekaterina ; Grelli, Alessandro ; Grigoraș, Costin ; Grigoryev, Vladislav ; Grigoryan, Smbat ; Grosa, Fabrizio ; Große-Oetringhaus, Jan Fiete ; Grosso, Raffaele ; Grund, David ; Grünwald, Nadine Alice ; Garcia Guardiano, Gabriel ; Guernane, Rachid ; Guilbaud, Maxime Rene Joseph ; Gulbrandsen, Kristjan Herlache ; Gündem, Tuba ; Gunji, Taku ; Guo, Wenda ; Gupta, Anik ; Gupta, Ramni ; Gupta, Rashi ; Gwizdziel, Katarzyna ; Gyulai, Laszlo ; Hadjidakis, Cynthia Marie ; Haider, Fakhar Ul ; Haidlova, Sara ; Haldar, Mintu ; Hamagaki, Hideki ; Hamdi, Abdennacer ; Han, Younghoon ; Hanley, Brian Gerald ; Hannigan, Ryan ; Hansen, Joachim ; Haque, Md Rihan ; Harris, John William ; Harton, Austin Vincent ; Hartung, Michael Volker ; Hassan, Hadi ; Hatzifotiadou, Despina ; Hauer, Philip ; Havener, Laura Brittany ; Hellbär, Ernst ; Helstrup, Håvard ; Hemmer, Marvin ; Herman, Tomáš ; Hernandez, Sabrina Gabrielle ; Herrera Corral, Gerardo Antonio ; Herrmann, Florian ; Herrmann, Sarah Nina Edwige ; Hetland, Kristin Fanebust ; Heybeck, Benedict ; Hillemanns, Hartmut ; Hippolyte, Boris ; Hoffmann, Felix Willi ; Hofman, Bas ; Hong, Geunhee ; Horst, Maximilian ; Horzyk, Adrian ; Hou, Yongzhen ; Hristov, Peter ; Huhn, Patrick ; Huhta, Laura Maria ; Humanic, Thomas J. ; Hutson, Alek ; Hutter, Dirk ; Hwang, Minyoung Chris ; Ilkaev, Radiy ; Inaba, Motoi ; Innocenti, Gian Michele ; Ippolitov, Mikhail ; Isakov, Artem ; Isidori, Tommaso ; Islam, Md Samsul ; Iurchenko, Semen ; Ivanov, Marian ; Ivanov, Marian ; Ivanov, Vladimir ; Iversen, Kaare Endrup ; Jablonski, Miroslaw ; Jacak, Barbara ; Jacazio, Nicolò ; Jacobs, Peter Martin ; Jadlovska, Slavka ; Jadlovsky, Jan ; Jaelani, Syaefudin ; Jahnke, Cristiane ; Jakubowska, Monika Joanna ; Janik, Malgorzata Anna ; Janson, Thomas ; Ji, Su-jeong ; Jia, Shihai ; Paz Jimenez, Alom Antonio ; Jonas, Florian ; Jones, Daniel Matthew ; Jowett, John M. ; Jung, Jerome ; Jung, Michael ; Junique, Antoine Jean-Simon ; Jusko, Anton ; Kaewjai, Jetnipit ; Kalinak, Peter ; Kalweit, Alexander Philipp ; Karasu Uysal, Ayben ; Karatović, David ; Karavichev, Oleg V. ; Karavicheva, Tatiana L. ; Karpechev, Evgeny ; Karwowska, Maja Jadwiga ; Kebschull, Udo ; Keidel, Ralf ; Keil, Markus ; Ketzer, Bernhard ; Khade, Swapnesh Santosh ; Khan, Ahsan Mehmood ; Khan, Shaista ; Khanzadeev, Alexei ; Kharlov, Yury ; Khatun, Anisa ; Khuntia, Arvind ; Khuranova, Zhanna ; Kileng, Bjarte ; Kim, Beomkyu ; Kim, Chong ; Kim, Dong Jo ; Kim, Eun Joo ; Kim, Jaehyun ; Kim, Jiyoung ; Kim, Junlee ; Kim, Minjung ; Kim, Se Yong ; Kim, Taejun ; Kimura, Kento ; Kirkova, Aleksandrina ; Kirsch, Stefan ; Kisel, Ivan ; Kiselev, Sergej N. ; Kisiel, Adam Ryszard ; Kitowski, Jacek Pawel ; Klay, Jennifer Lynn ; Klein, Jochen ; Klein, Spencer Robert ; Klein-Bösing, Christian ; Kleiner, Matthias ; Klemenz, Thomas ; Kluge, Alexander ; Kobdaj, Chinorat ; Kohara, Ryotaro ; Kollegger, Thorsten ; Kondratyev, Andrey ; Kondratyeva, Natalia ; König, Joshua Leon ; Königstorfer, Stephan Alexander ; Konopka, Piotr Jan ; Kornakov, Georgy ; Korwieser, Maximilian ; Koryciak, Sebastian Dominik ; Koster, Cornelia ; Kotliarov, Artem ; Kovacic, Nino ; Kovalenko, Vladimir ; Kowalski, Marek ; Kozhuharov, Venelin Valeriev ; Králik, Ivan ; Kravčáková, Adela ; Krcal, Lubos ; Krivda, Marian ; Krizek, Filip ; Krizkova Gajdosova, Katarina ; Krug, Cristiano ; Krüger, Mario ; Krupová, Diana Maria ; Kryshen, Evgeny ; Kucera, Vit ; Kuhn, Christian Claude ; Kuijer, Paulus Gerardus ; Kumaoka, Takuya ; Kumar, Deekshit ; Kumar, Lokesh ; Kumar, Navneet ; Kumar, Shyam ; Kundu, Sourav ; Kurashvili, Podist ; Kurepin, Alexander ; Kurepin, Alexey B. ; Kuryakin, Alexey ; Kushpil, Svetlana ; Kuskov, Vladislav ; Kutyla, Monika ; Kweon, Min Jung ; Kwon, Youngil ; La Pointe, Sarah Louise ; La Rocca, Paola ; Lakrathok, Anantachai ; Lamanna, Massimo ; Landou, Aimeric Robin ; Langoy, Rune ; Larionov, Pavel ; Laudi, Elisa ; Lautner, Lukas ; Narcio Laveaga, Rafael Angel ; Lavicka, Roman ; Lea, Ramona ; Lee, Hyungjun ; Legrand, Iosif-charles ; Legras, Gauthier ; Lehrbach, Johannes ; Lelek, Tomasz Marcin ; Lemmon, Roy Crawford ; Leon Monzon, Ildefonso ; Lesch, Marcel Markus ; Lesser, Ezra Douglas ; Lévai, Peter ; Li, Mingze ; Li, Xiaomei ; Liang-gilman, Beatrice Eva ; Lien, Jørgen André ; Lietava, Roman ; Likmeta, Iris ; Lim, Bong-Hwi ; Lim, Sanghoon ; Lindenstruth, Volker ; Lindner, Amelia ; Lippmann, Christian ; Liu, Donghai ; Liu, Jian ; Setoue Liveraro, Gianni Shigeru ; Mckibben Lofnes, Ingrid ; Loizides, Constantinos ; Lokos, Sandor ; Lomker, Johanna ; Lopez, Xavier Bernard ; López Torres, Ernesto ; Lu, Pengzhong ; Lugo, Fabiola Viridiana ; Luhder, Jens Robert ; Lunardon, Marcello ; Luparello, Grazia ; Ma, Yu-Gang ; Mager, Magnus ; Maire, Antonin ; Majerz, Emilia Maria ; Makariev, Martin Vasilev ; Malaev, Mikhail ; Malfattore, Giovanni ; Malik, Nasir Mehdi ; Malik, Qasim Waheed ; Malik, Salman Khurshid ; Malinina, Liudmila ; Mallick, Dukhishyam ; Mallick, Neelkamal ; Mandaglio, Giuseppe ; Mandal, Sushobhan Kumar ; Manea, Alexandru ; Manko, Vladislav ; Manso, Franck ; Manzari, Vito ; Mao, Yaxian ; Marcjan, Robert Waclaw ; 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Measurements of the pT-dependent flow vector fluctuations in Pb-Pb collisions at sNN−−−√=5.02 TeV using azimuthal correlations with the ALICE experiment at the LHC are presented. A four-particle correlation approach [1] is used to quantify the effects of flow angle and magnitude fluctuations separately. This paper extends previous studies to additional centrality intervals and provides measurements of the pT-dependent flow vector fluctuations at sNN−−−√=5.02 TeV with two-particle correlations. Significant pT-dependent fluctuations of the V⃗ 2 flow vector in Pb-Pb collisions are found across different centrality ranges, with the largest fluctuations of up to ∼15% being present in the 5% most central collisions. In parallel, no evidence of significant pT-dependent fluctuations of V⃗ 3 or V⃗ 4 is found. Additionally, evidence of flow angle and magnitude fluctuations is observed with more than 5σ significance in central collisions. These observations in Pb-Pb collisions indicate where the classical picture of hydrodynamic modeling with a common symmetry plane breaks down. This has implications for hard probes at high pT, which might be biased by pT-dependent flow angle fluctuations of at least 23% in central collisions. Given the presented results, existing theoretical models should be re-examined to improve our understanding of initial conditions, quark--gluon plasma (QGP) properties, and the dynamic evolution of the created system.