--- _id: '17068' abstract: - lang: eng text: In plants, the antagonism between growth and defense is hardwired by hormonal signaling. The perception of pathogen-associated molecular patterns (PAMPs) from invading microorganisms inhibits auxin signaling and plant growth. Conversely, pathogens manipulate auxin signaling to promote disease, but how this hormone inhibits immunity is not fully understood. Ustilago maydis is a maize pathogen that induces auxin signaling in its host. We characterized a U. maydis effector protein, Naked1 (Nkd1), that is translocated into the host nucleus. Through its native ethylene-responsive element binding factor-associated amphiphilic repression (EAR) motif, Nkd1 binds to the transcriptional co-repressors TOPLESS/TOPLESS-related (TPL/TPRs) and prevents the recruitment of a transcriptional repressor involved in hormonal signaling, leading to the de-repression of auxin and jasmonate signaling and thereby promoting susceptibility to (hemi)biotrophic pathogens. A moderate upregulation of auxin signaling inhibits the PAMP-triggered reactive oxygen species (ROS) burst, an early defense response. Thus, our findings establish a clear mechanism for auxin-induced pathogen susceptibility. Engineered Nkd1 variants with increased expression or increased EAR-mediated TPL/TPR binding trigger typical salicylic-acid-mediated defense reactions, leading to pathogen resistance. This implies that moderate binding of Nkd1 to TPL is a result of a balancing evolutionary selection process to enable TPL manipulation while avoiding host recognition. acknowledgement: "The research leading to these results received funding from the European Research Council under the European Union Seventh Framework Programme ERC-2013-STG grant agreement \r\n335691; the Austrian Science Fund (FWF) P27818-B22,I 3033-B22; the Austrian Academy of Sciences (OEAW); and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy - EXC 2070-390732324.\r\nWe would like to thank the GMI/IMBA/IMP core facilities for excellent technical support, especially the BioOptics and Molecular Biology Services. We thank the Plant Sciences and Next Generation Sequencing Facilities at the Vienna BioCenter Core Facilities GmbH (VBCF). We are grateful to the Jirí Friml and Jürgen Kleine-Vehn laboratories for providing useful A. thaliana lines. We thank Mathias Madalinski for peptide synthesis and Dr. J. Matthew Watson for proofreading and valuable feedback on the manuscript. The authors declare no competing interests." article_number: '100269' article_processing_charge: Yes article_type: original author: - first_name: Fernando full_name: Navarrete, Fernando last_name: Navarrete - first_name: Michelle C full_name: Gallei, Michelle C id: 35A03822-F248-11E8-B48F-1D18A9856A87 last_name: Gallei orcid: 0000-0003-1286-7368 - first_name: Aleksandra E. full_name: Kornienko, Aleksandra E. last_name: Kornienko - first_name: Indira full_name: Saado, Indira last_name: Saado - first_name: Mamoona full_name: Khan, Mamoona last_name: Khan - first_name: Khong-Sam full_name: Chia, Khong-Sam last_name: Chia - first_name: Martin A. full_name: Darino, Martin A. last_name: Darino - first_name: Janos full_name: Bindics, Janos last_name: Bindics - first_name: Armin full_name: Djamei, Armin last_name: Djamei citation: ama: Navarrete F, Gallei MC, Kornienko AE, et al. TOPLESS promotes plant immunity by repressing auxin signaling and is targeted by the fungal effector Naked1. Plant Communications. 2022;3(2). doi:10.1016/j.xplc.2021.100269 apa: Navarrete, F., Gallei, M. C., Kornienko, A. E., Saado, I., Khan, M., Chia, K.-S., … Djamei, A. (2022). TOPLESS promotes plant immunity by repressing auxin signaling and is targeted by the fungal effector Naked1. Plant Communications. Elsevier. https://doi.org/10.1016/j.xplc.2021.100269 chicago: Navarrete, Fernando, Michelle C Gallei, Aleksandra E. Kornienko, Indira Saado, Mamoona Khan, Khong-Sam Chia, Martin A. Darino, Janos Bindics, and Armin Djamei. “TOPLESS Promotes Plant Immunity by Repressing Auxin Signaling and Is Targeted by the Fungal Effector Naked1.” Plant Communications. Elsevier, 2022. https://doi.org/10.1016/j.xplc.2021.100269. ieee: F. Navarrete et al., “TOPLESS promotes plant immunity by repressing auxin signaling and is targeted by the fungal effector Naked1,” Plant Communications, vol. 3, no. 2. Elsevier, 2022. ista: Navarrete F, Gallei MC, Kornienko AE, Saado I, Khan M, Chia K-S, Darino MA, Bindics J, Djamei A. 2022. TOPLESS promotes plant immunity by repressing auxin signaling and is targeted by the fungal effector Naked1. Plant Communications. 3(2), 100269. mla: Navarrete, Fernando, et al. “TOPLESS Promotes Plant Immunity by Repressing Auxin Signaling and Is Targeted by the Fungal Effector Naked1.” Plant Communications, vol. 3, no. 2, 100269, Elsevier, 2022, doi:10.1016/j.xplc.2021.100269. short: F. Navarrete, M.C. Gallei, A.E. Kornienko, I. Saado, M. Khan, K.-S. Chia, M.A. Darino, J. Bindics, A. Djamei, Plant Communications 3 (2022). date_created: 2024-05-29T06:10:22Z date_published: 2022-03-14T00:00:00Z date_updated: 2024-08-05T10:27:03Z day: '14' ddc: - '580' department: - _id: JiFr doi: 10.1016/j.xplc.2021.100269 external_id: pmid: - '35529945' file: - access_level: open_access checksum: 1eeb6ee65419e4aa34627fea6857f343 content_type: application/pdf creator: dernst date_created: 2024-08-05T10:26:29Z date_updated: 2024-08-05T10:26:29Z file_id: '17393' file_name: 2022_PlantComm_Navarrete.pdf file_size: 3216686 relation: main_file success: 1 file_date_updated: 2024-08-05T10:26:29Z has_accepted_license: '1' intvolume: ' 3' issue: '2' language: - iso: eng month: '03' oa: 1 oa_version: Published Version pmid: 1 publication: Plant Communications publication_identifier: issn: - 2590-3462 publication_status: published publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: TOPLESS promotes plant immunity by repressing auxin signaling and is targeted by the fungal effector Naked1 tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 3 year: '2022' ... --- OA_place: repository OA_type: green _id: '17069' abstract: - lang: eng text: Fertilization of an egg by multiple sperm (polyspermy) leads to lethal genome imbalance and chromosome segregation defects. In Arabidopsis thaliana, the block to polyspermy is facilitated by a mechanism that prevents polytubey (the arrival of multiple pollen tubes to one ovule). We show here that FERONIA, ANJEA, and HERCULES RECEPTOR KINASE 1 receptor-like kinases located at the septum interact with pollen tube–specific RALF6, 7, 16, 36, and 37 peptide ligands to establish this polytubey block. The same combination of RALF (rapid alkalinization factor) peptides and receptor complexes controls pollen tube reception and rupture inside the targeted ovule. Pollen tube rupture releases the polytubey block at the septum, which allows the emergence of secondary pollen tubes upon fertilization failure. Thus, orchestrated steps in the fertilization process in Arabidopsis are coordinated by the same signaling components to guarantee and optimize reproductive success. acknowledgement: "We thank D. Ye for providing fer-4 and myb97 myb101 myb120 mutant seeds; L. Smith for sharing anj, herk1, anj herk1, and fer anj herk1 mutant seeds; J. F. Harper for providing aca9 mutant seeds; and C. Li and Q. Duan for sharing fer+/− mutant seeds.\r\nL.-J.Q. was funded by the National Natural Science Foundation of China (grant nos. 31991202, 31830004, 31620103903, and 31621001), S.Z. was supported by the Young Elite Scientists Sponsorship Program by the China Association of Science and Technology (2019QNRC001), Z.G. was supported by a NSFC Young Scientists Fund (31900161), A.Y.C. was funded by the US Natural Science Foundation (IOS-1645854, MCB-1715764, and MCB-0955910), J.D. was funded by the National Institute of Health (R01GM109080), and T.D. was supported by the German Research Foundation DFG (SFB924)." article_processing_charge: No article_type: original author: - first_name: Sheng full_name: Zhong, Sheng last_name: Zhong - first_name: Ling full_name: Li, Ling last_name: Li - first_name: Zhijuan full_name: Wang, Zhijuan last_name: Wang - first_name: Zengxiang full_name: Ge, Zengxiang id: f43371a3-09ff-11eb-8013-bd0c6a2f6de8 last_name: Ge orcid: 0000-0001-9381-3577 - first_name: Qiyun full_name: Li, Qiyun last_name: Li - first_name: Andrea full_name: Bleckmann, Andrea last_name: Bleckmann - first_name: Jizong full_name: Wang, Jizong last_name: Wang - first_name: Zihan full_name: Song, Zihan last_name: Song - first_name: Yihao full_name: Shi, Yihao last_name: Shi - first_name: Tianxu full_name: Liu, Tianxu last_name: Liu - first_name: Luhan full_name: Li, Luhan last_name: Li - first_name: Huabin full_name: Zhou, Huabin last_name: Zhou - first_name: Yanyan full_name: Wang, Yanyan last_name: Wang - first_name: Li full_name: Zhang, Li last_name: Zhang - first_name: Hen-Ming full_name: Wu, Hen-Ming last_name: Wu - first_name: Luhua full_name: Lai, Luhua last_name: Lai - first_name: Hongya full_name: Gu, Hongya last_name: Gu - first_name: Juan full_name: Dong, Juan last_name: Dong - first_name: Alice Y. full_name: Cheung, Alice Y. last_name: Cheung - first_name: Thomas full_name: Dresselhaus, Thomas last_name: Dresselhaus - first_name: Li-Jia full_name: Qu, Li-Jia last_name: Qu citation: ama: Zhong S, Li L, Wang Z, et al. RALF peptide signaling controls the polytubey block in Arabidopsis. Science. 2022;375(6578):290-296. doi:10.1126/science.abl4683 apa: Zhong, S., Li, L., Wang, Z., Ge, Z., Li, Q., Bleckmann, A., … Qu, L.-J. (2022). RALF peptide signaling controls the polytubey block in Arabidopsis. Science. American Association for the Advancement of Science. https://doi.org/10.1126/science.abl4683 chicago: Zhong, Sheng, Ling Li, Zhijuan Wang, Zengxiang Ge, Qiyun Li, Andrea Bleckmann, Jizong Wang, et al. “RALF Peptide Signaling Controls the Polytubey Block in Arabidopsis.” Science. American Association for the Advancement of Science, 2022. https://doi.org/10.1126/science.abl4683. ieee: S. Zhong et al., “RALF peptide signaling controls the polytubey block in Arabidopsis,” Science, vol. 375, no. 6578. American Association for the Advancement of Science, pp. 290–296, 2022. ista: Zhong S, Li L, Wang Z, Ge Z, Li Q, Bleckmann A, Wang J, Song Z, Shi Y, Liu T, Li L, Zhou H, Wang Y, Zhang L, Wu H-M, Lai L, Gu H, Dong J, Cheung AY, Dresselhaus T, Qu L-J. 2022. RALF peptide signaling controls the polytubey block in Arabidopsis. Science. 375(6578), 290–296. mla: Zhong, Sheng, et al. “RALF Peptide Signaling Controls the Polytubey Block in Arabidopsis.” Science, vol. 375, no. 6578, American Association for the Advancement of Science, 2022, pp. 290–96, doi:10.1126/science.abl4683. short: S. Zhong, L. Li, Z. Wang, Z. Ge, Q. Li, A. Bleckmann, J. Wang, Z. Song, Y. Shi, T. Liu, L. Li, H. Zhou, Y. Wang, L. Zhang, H.-M. Wu, L. Lai, H. Gu, J. Dong, A.Y. Cheung, T. Dresselhaus, L.-J. Qu, Science 375 (2022) 290–296. date_created: 2024-05-29T06:11:10Z date_published: 2022-01-20T00:00:00Z date_updated: 2025-04-24T11:39:46Z day: '20' department: - _id: JiFr doi: 10.1126/science.abl4683 external_id: pmid: - '35050671' intvolume: ' 375' issue: '6578' language: - iso: eng main_file_link: - open_access: '1' url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9040003 month: '01' oa: 1 oa_version: Submitted Version page: 290-296 pmid: 1 publication: Science publication_identifier: eissn: - 1095-9203 issn: - 0036-8075 publication_status: published publisher: American Association for the Advancement of Science quality_controlled: '1' scopus_import: '1' status: public title: RALF peptide signaling controls the polytubey block in Arabidopsis type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 375 year: '2022' ... --- _id: '17070' abstract: - lang: eng text: We investigate the formation of magnetic Bose polaron, an impurity atom dressed by spin-wave excitations, in a one-dimensional spinor Bose gas. Within an effective potential model, the impurity is strongly confined by the host excitations which can even overcome the impurity-medium repulsion leading to a self-localized quasi-particle state. The phase diagram of the attractive and self-bound repulsive magnetic polaron, repulsive non-magnetic (Fröhlich-type) polaron and impurity-medium phase-separation regimes is explored with respect to the Rabi-coupling between the spin components, spin–spin interactions and impurity-medium coupling. The residue of such magnetic polarons decreases substantially in both strong attractive and repulsive branches with strong impurity-spin interactions, illustrating significant dressing of the impurity. The impurity can be used to probe and maneuver the spin polarization of the magnetic medium while suppressing ferromagnetic spin–spin correlations. It is shown that mean-field theory fails as the spinor gas approaches immiscibility since the generated spin-wave excitations are prominent. Our findings illustrate that impurities can be utilized to generate controllable spin–spin correlations and magnetic polaron states which can be realized with current cold atom setups. article_number: '083030' article_processing_charge: Yes article_type: original arxiv: 1 author: - first_name: S I full_name: Mistakidis, S I last_name: Mistakidis - first_name: Georgios full_name: Koutentakis, Georgios id: d7b23d3a-9e21-11ec-b482-f76739596b95 last_name: Koutentakis - first_name: F full_name: Grusdt, F last_name: Grusdt - first_name: P full_name: Schmelcher, P last_name: Schmelcher - first_name: H R full_name: Sadeghpour, H R last_name: Sadeghpour citation: ama: 'Mistakidis SI, Koutentakis G, Grusdt F, Schmelcher P, Sadeghpour HR. Inducing spin-order with an impurity: phase diagram of the magnetic Bose polaron. New Journal of Physics. 2022;24(8). doi:10.1088/1367-2630/ac836c' apa: 'Mistakidis, S. I., Koutentakis, G., Grusdt, F., Schmelcher, P., & Sadeghpour, H. R. (2022). Inducing spin-order with an impurity: phase diagram of the magnetic Bose polaron. New Journal of Physics. IOP Publishing. https://doi.org/10.1088/1367-2630/ac836c' chicago: 'Mistakidis, S I, Georgios Koutentakis, F Grusdt, P Schmelcher, and H R Sadeghpour. “Inducing Spin-Order with an Impurity: Phase Diagram of the Magnetic Bose Polaron.” New Journal of Physics. IOP Publishing, 2022. https://doi.org/10.1088/1367-2630/ac836c.' ieee: 'S. I. Mistakidis, G. Koutentakis, F. Grusdt, P. Schmelcher, and H. R. Sadeghpour, “Inducing spin-order with an impurity: phase diagram of the magnetic Bose polaron,” New Journal of Physics, vol. 24, no. 8. IOP Publishing, 2022.' ista: 'Mistakidis SI, Koutentakis G, Grusdt F, Schmelcher P, Sadeghpour HR. 2022. Inducing spin-order with an impurity: phase diagram of the magnetic Bose polaron. New Journal of Physics. 24(8), 083030.' mla: 'Mistakidis, S. I., et al. “Inducing Spin-Order with an Impurity: Phase Diagram of the Magnetic Bose Polaron.” New Journal of Physics, vol. 24, no. 8, 083030, IOP Publishing, 2022, doi:10.1088/1367-2630/ac836c.' short: S.I. Mistakidis, G. Koutentakis, F. Grusdt, P. Schmelcher, H.R. Sadeghpour, New Journal of Physics 24 (2022). date_created: 2024-05-29T06:11:35Z date_published: 2022-09-08T00:00:00Z date_updated: 2024-07-31T12:14:55Z day: '08' ddc: - '530' department: - _id: MiLe doi: 10.1088/1367-2630/ac836c external_id: arxiv: - '2204.10960' file: - access_level: open_access checksum: 85776a9d3abe163b33b322c8e346752a content_type: application/pdf creator: dernst date_created: 2024-07-31T12:13:16Z date_updated: 2024-07-31T12:13:16Z file_id: '17358' file_name: 2022_NewJournPhysics_Mistakidis.pdf file_size: 4201283 relation: main_file success: 1 file_date_updated: 2024-07-31T12:13:16Z has_accepted_license: '1' intvolume: ' 24' issue: '8' language: - iso: eng month: '09' oa: 1 oa_version: Published Version publication: New Journal of Physics publication_identifier: issn: - 1367-2630 publication_status: published publisher: IOP Publishing quality_controlled: '1' scopus_import: '1' status: public title: 'Inducing spin-order with an impurity: phase diagram of the magnetic Bose polaron' tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 24 year: '2022' ... --- _id: '17071' abstract: - lang: eng text: "The eukaryotic nucleus pro­tects the genome and is enclosed by the two membranes of the nuclear envelope. Nuclear pore complexes (NPCs) perforate the nuclear envelope to facilitate nucleocytoplasmic transport. With a molecular weight of ∼120 MDa, the human NPC is one of the larg­est protein complexes. Its ~1000 proteins are taken in multiple copies from a set of about 30 distinct nucleoporins (NUPs). They can be roughly categorized into two classes. Scaf­fold NUPs contain folded domains and form a cylindrical scaffold architecture around a central channel. Intrinsically disordered NUPs line the scaffold and extend into the central channel, where they interact with cargo complexes. The NPC architecture is highly dynamic. It responds to changes in nuclear envelope tension with conforma­tional breathing that manifests in dilation and constriction movements. Elucidating the scaffold architecture, ultimately at atomic resolution, will be important for gaining a more precise understanding of NPC function and dynamics but imposes a substantial chal­lenge for structural biologists.\r\nConsiderable progress has been made toward this goal by a joint effort in the field. A synergistic combination of complementary approaches has turned out to be critical. In situ structural biology techniques were used to reveal the overall layout of the NPC scaffold that defines the spatial reference for molecular modeling. High-resolution structures of many NUPs were determined in vitro. Proteomic analysis and extensive biochemical work unraveled the interaction network of NUPs. Integra­tive modeling has been used to combine the different types of data, resulting in a rough outline of the NPC scaffold. Previous struc­tural models of the human NPC, however, were patchy and limited in accuracy owing to several challenges: (i) Many of the high-resolution structures of individual NUPs have been solved from distantly related species and, consequently, do not comprehensively cover their human counterparts. (ii) The scaf­fold is interconnected by a set of intrinsically disordered linker NUPs that are not straight­forwardly accessible to common structural biology techniques. (iii) The NPC scaffold intimately embraces the fused inner and outer nuclear membranes in a distinctive topol­ogy and cannot be studied in isolation. (iv) The conformational dynamics of scaffold NUPs limits the resolution achievable in structure determination.\r\nIn this study, we used artificial intelligence (AI)–based prediction to generate an exten­sive repertoire of structural models of human NUPs and their subcomplexes. The resulting models cover various domains and interfaces that so far remained structurally uncharac­terized. Benchmarking against previous and unpublished x-ray and cryo–electron micros­copy structures revealed unprecedented accu­racy. We obtained well-resolved cryo–electron tomographic maps of both the constricted and dilated conformational states of the hu­man NPC. Using integrative modeling, we fit­ted the structural models of individual NUPs into the cryo–electron microscopy maps. We explicitly included several linker NUPs and traced their trajectory through the NPC scaf­fold. We elucidated in great detail how mem­brane-associated and transmembrane NUPs are distributed across the fusion topology of both nuclear membranes. The resulting architectural model increases the structural coverage of the human NPC scaffold by about twofold. We extensively validated our model against both earlier and new experimental data. The completeness of our model has enabled microsecond-long coarse-grained molecular dynamics simulations of the NPC scaffold within an explicit membrane en­vironment and solvent. These simulations reveal that the NPC scaffold prevents the constriction of the otherwise stable double-membrane fusion pore to small diameters in the absence of membrane tension\r\nOur 70-MDa atomically re­solved model covers >90% of the human NPC scaffold. It captures conforma­tional changes that occur during dilation and constriction. It also reveals the precise anchoring sites for intrinsically disordered NUPs, the identification of which is a prerequisite for a complete and dy­namic model of the NPC. Our study exempli­fies how AI-based structure prediction may accelerate the elucidation of subcellular ar­chitecture at atomic resolution." acknowledgement: "We acknowledge support from the Electron Microscopy Core Facility (EMCF) and IT services of European Molecular Biology Laboratory (EMBL) Heidelberg. We thank S. Welsch at the Central Electron Microscopy Facility of the Max Planck Institute of Biophysics for technical expertise. We thank T. Hoffman and R. Alves for help with the AlphaFold installation.\r\nFunding: M.B. acknowledges funding by EMBL, the Max Planck Society, and the European Research Council (ComplexAssembly 724349). J.K. acknowledges funding from the Federal Ministry of Education and Research of Germany (FKZ 031L0100). The work by M.S. and G.H. on computer simulations was supported by the Max Planck Society. M.S. was supported by the EMBL Interdisciplinary Postdoc Programme under Marie Curie COFUND actions. M.S. and G.H. were supported by the Landes-Offensive zur Entwicklung Wissenschaftlich-ökonomischer Exzellenz (LOEWE) DynaMem program of the State of Hessen." article_number: abm9506 article_processing_charge: No article_type: original author: - first_name: Shyamal full_name: Mosalaganti, Shyamal last_name: Mosalaganti - first_name: Agnieszka full_name: Obarska-Kosinska, Agnieszka last_name: Obarska-Kosinska - first_name: Marc full_name: Siggel, Marc last_name: Siggel - first_name: Reiya full_name: Taniguchi, Reiya last_name: Taniguchi - first_name: Beata full_name: Turoňová, Beata last_name: Turoňová - first_name: Christian E. full_name: Zimmerli, Christian E. last_name: Zimmerli - first_name: Katarzyna full_name: Buczak, Katarzyna last_name: Buczak - first_name: Florian full_name: Schmidt, Florian id: A2EF226A-AF19-11E9-924C-0525E6697425 last_name: Schmidt - first_name: Erica full_name: Margiotta, Erica last_name: Margiotta - first_name: Marie-Therese full_name: Mackmull, Marie-Therese last_name: Mackmull - first_name: Wim J. H. full_name: Hagen, Wim J. H. last_name: Hagen - first_name: Gerhard full_name: Hummer, Gerhard last_name: Hummer - first_name: Jan full_name: Kosinski, Jan last_name: Kosinski - first_name: Martin full_name: Beck, Martin last_name: Beck citation: ama: Mosalaganti S, Obarska-Kosinska A, Siggel M, et al. AI-based structure prediction empowers integrative structural analysis of human nuclear pores. Science. 2022;376(6598). doi:10.1126/science.abm9506 apa: Mosalaganti, S., Obarska-Kosinska, A., Siggel, M., Taniguchi, R., Turoňová, B., Zimmerli, C. E., … Beck, M. (2022). AI-based structure prediction empowers integrative structural analysis of human nuclear pores. Science. American Association for the Advancement of Science. https://doi.org/10.1126/science.abm9506 chicago: Mosalaganti, Shyamal, Agnieszka Obarska-Kosinska, Marc Siggel, Reiya Taniguchi, Beata Turoňová, Christian E. Zimmerli, Katarzyna Buczak, et al. “AI-Based Structure Prediction Empowers Integrative Structural Analysis of Human Nuclear Pores.” Science. American Association for the Advancement of Science, 2022. https://doi.org/10.1126/science.abm9506. ieee: S. Mosalaganti et al., “AI-based structure prediction empowers integrative structural analysis of human nuclear pores,” Science, vol. 376, no. 6598. American Association for the Advancement of Science, 2022. ista: Mosalaganti S, Obarska-Kosinska A, Siggel M, Taniguchi R, Turoňová B, Zimmerli CE, Buczak K, Schmidt F, Margiotta E, Mackmull M-T, Hagen WJH, Hummer G, Kosinski J, Beck M. 2022. AI-based structure prediction empowers integrative structural analysis of human nuclear pores. Science. 376(6598), abm9506. mla: Mosalaganti, Shyamal, et al. “AI-Based Structure Prediction Empowers Integrative Structural Analysis of Human Nuclear Pores.” Science, vol. 376, no. 6598, abm9506, American Association for the Advancement of Science, 2022, doi:10.1126/science.abm9506. short: S. Mosalaganti, A. Obarska-Kosinska, M. Siggel, R. Taniguchi, B. Turoňová, C.E. Zimmerli, K. Buczak, F. Schmidt, E. Margiotta, M.-T. Mackmull, W.J.H. Hagen, G. Hummer, J. Kosinski, M. Beck, Science 376 (2022). date_created: 2024-05-29T06:12:02Z date_published: 2022-06-10T00:00:00Z date_updated: 2024-07-31T12:10:32Z day: '10' department: - _id: MaJö doi: 10.1126/science.abm9506 external_id: pmid: - '35679397' intvolume: ' 376' issue: '6598' language: - iso: eng month: '06' oa_version: None pmid: 1 publication: Science publication_identifier: eissn: - 1095-9203 issn: - 0036-8075 publication_status: published publisher: American Association for the Advancement of Science quality_controlled: '1' scopus_import: '1' status: public title: AI-based structure prediction empowers integrative structural analysis of human nuclear pores type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 376 year: '2022' ... --- _id: '17072' abstract: - lang: eng text: The collapse of polypeptides is thought important to protein folding, aggregation, intrinsic disorder, and phase separation. However, whether polypeptide collapse is modulated in cells to control protein states is unclear. Here, using integrated protein manipulation and imaging, we show that the chaperonin GroEL-ES can accelerate the folding of proteins by strengthening their collapse. GroEL induces contractile forces in substrate chains, which draws them into the cavity and triggers a general compaction and discrete folding transitions, even for slow-folding proteins. This collapse enhancement is strongest in the nucleotide-bound states of GroEL and is aided by GroES binding to the cavity rim and by the amphiphilic C-terminal tails at the cavity bottom. Collapse modulation is distinct from other proposed GroEL-ES folding acceleration mechanisms, including steric confinement and misfold unfolding. Given the prevalence of collapse throughout the proteome, we conjecture that collapse modulation is more generally relevant within the protein quality control machinery. acknowledgement: We thank A. L. Horwich, K. Chakraborty, and B. Schuler for providing plasmids, and R. van Leeuwen, M. Mayer, J. van Zon, W. Noorduin, and P. R. ten Wolde for comments and critical reading of the manuscript. Work in the group of S.J.T. was supported by the Netherlands Organization for Scientific Research (NWO). Work in the group of H.S.R. was supported by a grant from the NIH (R01GM114405). article_number: eabl6293 article_processing_charge: Yes article_type: original author: - first_name: Mohsin M. full_name: Naqvi, Mohsin M. last_name: Naqvi - first_name: Mario full_name: Avellaneda Sarrió, Mario id: DC4BA84C-56E6-11EA-AD5D-348C3DDC885E last_name: Avellaneda Sarrió orcid: 0000-0001-6406-524X - first_name: Andrew full_name: Roth, Andrew last_name: Roth - first_name: Eline J. full_name: Koers, Eline J. last_name: Koers - first_name: Antoine full_name: Roland, Antoine last_name: Roland - first_name: Vanda full_name: Sunderlikova, Vanda last_name: Sunderlikova - first_name: Günter full_name: Kramer, Günter last_name: Kramer - first_name: Hays S. full_name: Rye, Hays S. last_name: Rye - first_name: Sander J. full_name: Tans, Sander J. last_name: Tans citation: ama: Naqvi MM, Avellaneda Sarrió M, Roth A, et al. Protein chain collapse modulation and folding stimulation by GroEL-ES. Science Advances. 2022;8(9). doi:10.1126/sciadv.abl6293 apa: Naqvi, M. M., Avellaneda Sarrió, M., Roth, A., Koers, E. J., Roland, A., Sunderlikova, V., … Tans, S. J. (2022). Protein chain collapse modulation and folding stimulation by GroEL-ES. Science Advances. American Association for the Advancement of Science. https://doi.org/10.1126/sciadv.abl6293 chicago: Naqvi, Mohsin M., Mario Avellaneda Sarrió, Andrew Roth, Eline J. Koers, Antoine Roland, Vanda Sunderlikova, Günter Kramer, Hays S. Rye, and Sander J. Tans. “Protein Chain Collapse Modulation and Folding Stimulation by GroEL-ES.” Science Advances. American Association for the Advancement of Science, 2022. https://doi.org/10.1126/sciadv.abl6293. ieee: M. M. Naqvi et al., “Protein chain collapse modulation and folding stimulation by GroEL-ES,” Science Advances, vol. 8, no. 9. American Association for the Advancement of Science, 2022. ista: Naqvi MM, Avellaneda Sarrió M, Roth A, Koers EJ, Roland A, Sunderlikova V, Kramer G, Rye HS, Tans SJ. 2022. Protein chain collapse modulation and folding stimulation by GroEL-ES. Science Advances. 8(9), eabl6293. mla: Naqvi, Mohsin M., et al. “Protein Chain Collapse Modulation and Folding Stimulation by GroEL-ES.” Science Advances, vol. 8, no. 9, eabl6293, American Association for the Advancement of Science, 2022, doi:10.1126/sciadv.abl6293. short: M.M. Naqvi, M. Avellaneda Sarrió, A. Roth, E.J. Koers, A. Roland, V. Sunderlikova, G. Kramer, H.S. Rye, S.J. Tans, Science Advances 8 (2022). date_created: 2024-05-29T06:12:19Z date_published: 2022-03-01T00:00:00Z date_updated: 2024-08-05T08:30:29Z day: '01' ddc: - '570' department: - _id: MiSi doi: 10.1126/sciadv.abl6293 external_id: pmid: - '35245117' file: - access_level: open_access checksum: 9511579306cce7e04107d3d6389ed614 content_type: application/pdf creator: dernst date_created: 2024-07-31T12:01:51Z date_updated: 2024-07-31T12:01:51Z file_id: '17357' file_name: 2022_ScienceAdv_Naqvi.pdf file_size: 2404150 relation: main_file success: 1 file_date_updated: 2024-07-31T12:01:51Z has_accepted_license: '1' intvolume: ' 8' issue: '9' language: - iso: eng month: '03' oa: 1 oa_version: Published Version pmid: 1 publication: Science Advances publication_identifier: issn: - 2375-2548 publication_status: published publisher: American Association for the Advancement of Science quality_controlled: '1' scopus_import: '1' status: public title: Protein chain collapse modulation and folding stimulation by GroEL-ES tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 8 year: '2022' ... --- _id: '17075' abstract: - lang: eng text: Disorders associated with the malfunction of amino acid transporters mainly affect the function of the intestine, kidney, brain, and liver. Mutations of brain amino acid transporters, for example, alter neuronal excitability (e.g., episodic ataxia due to SLC1A3 (EAAT1) defect and hyperekplexia due to SLC6A5 (GLYT2) deficiency) or brain development (SLC1A1 (EAAT3), SLC3A2/SLC7A5 (CD98hc/LAT1), and SLC1A4 (ASCT1) deficiencies). Mutations of renal and intestinal amino acid transporters SLC3A1/SLC7A9 (rBAT/b0,+AT) and SLC1A1 (EAAT3) cause renal problems (cystinuria and dicarboxylic aminoaciduria, respectively) and malabsorption that can affect whole-body homoeostasis (Hartnup disorder SLC6A19 (B0AT1), lysinuric protein intolerance SLC3A2/SLC7A7 (CD98hc/y+LAT1), and hyperdibasic aminoaciduria type 1). Mutations in the neuronal system A amino acid transporter SLC38A8 (SNAT8) cause eye developmental and visual defects. Inborn errors associated with mitochondrial SLC25 family members such as SLC25A12 (neuronal- and muscle-specific mitochondrial aspartate/glutamate transporter 1; AGC1) (global cerebral hypomyelination), SLC25A13 (aspartate/glutamate transporter 2) (citrin deficiency), SLC25A15 (ornithine-citrulline carrier 2) (homocitrullinuria, hyperornithinemia, and hyperammonemia syndrome), and SLC25A22 (mitochondrial glutamate/H+ symporter 1, GC1) (neonatal myoclonic epilepsy) will be dealt within Chap. 43 (defects of mitochondrial carriers). acknowledgement: The authors thank Dr. Christian Lueck (Canberra Hospital) for clarification of differential diagnosis in cases of episodic ataxia. The authors thank Dr. Rafael Artuch (Hospital San Joan de Deu, Barcelona) for reference values of plasma amino acid concentration. The authors also thank Lisa Kraus (Institute of Science and Technology-Austria) and Dr. Susanna Bodoy (IRB-Barcelona) that helped in preparing tables and bibliography. article_processing_charge: No author: - first_name: Manuel full_name: Palacín, Manuel last_name: Palacín - first_name: Stefan full_name: Bröer, Stefan last_name: Bröer - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 citation: ama: 'Palacín M, Bröer S, Novarino G. Amino Acid Transport Defects. In: Blau N, Vici CD, Ferreira CR, Vianey-Saban C, van Karnebeek CDM, eds. Physician’s Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases. 2nd ed. Cham: Springer Nature; 2022:291-312. doi:10.1007/978-3-030-67727-5_18' apa: 'Palacín, M., Bröer, S., & Novarino, G. (2022). Amino Acid Transport Defects. In N. Blau, C. D. Vici, C. R. Ferreira, C. Vianey-Saban, & C. D. M. van Karnebeek (Eds.), Physician’s Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases (2nd ed., pp. 291–312). Cham: Springer Nature. https://doi.org/10.1007/978-3-030-67727-5_18' chicago: 'Palacín, Manuel, Stefan Bröer, and Gaia Novarino. “Amino Acid Transport Defects.” In Physician’s Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases, edited by Nenad Blau, Carlo Dionisi Vici, Carlos R. Ferreira, Christine Vianey-Saban, and Clara D.M. van Karnebeek, 2nd ed., 291–312. Cham: Springer Nature, 2022. https://doi.org/10.1007/978-3-030-67727-5_18.' ieee: 'M. Palacín, S. Bröer, and G. Novarino, “Amino Acid Transport Defects,” in Physician’s Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases, 2nd ed., N. Blau, C. D. Vici, C. R. Ferreira, C. Vianey-Saban, and C. D. M. van Karnebeek, Eds. Cham: Springer Nature, 2022, pp. 291–312.' ista: 'Palacín M, Bröer S, Novarino G. 2022.Amino Acid Transport Defects. In: Physician’s Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases. , 291–312.' mla: Palacín, Manuel, et al. “Amino Acid Transport Defects.” Physician’s Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases, edited by Nenad Blau et al., 2nd ed., Springer Nature, 2022, pp. 291–312, doi:10.1007/978-3-030-67727-5_18. short: M. Palacín, S. Bröer, G. Novarino, in:, N. Blau, C.D. Vici, C.R. Ferreira, C. Vianey-Saban, C.D.M. van Karnebeek (Eds.), Physician’s Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases, 2nd ed., Springer Nature, Cham, 2022, pp. 291–312. date_created: 2024-05-29T06:13:04Z date_published: 2022-02-22T00:00:00Z date_updated: 2024-07-31T11:45:50Z day: '22' department: - _id: GaNo doi: 10.1007/978-3-030-67727-5_18 edition: '2' editor: - first_name: Nenad full_name: Blau, Nenad last_name: Blau - first_name: Carlo Dionisi full_name: Vici, Carlo Dionisi last_name: Vici - first_name: 'Carlos R. ' full_name: 'Ferreira, Carlos R. ' last_name: Ferreira - first_name: Christine full_name: Vianey-Saban, Christine last_name: Vianey-Saban - first_name: Clara D.M. full_name: van Karnebeek, Clara D.M. last_name: van Karnebeek language: - iso: eng month: '02' oa_version: None page: 291-312 place: Cham publication: Physician's Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases publication_identifier: eisbn: - '9783030677275' isbn: - '9783030677268' publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Amino Acid Transport Defects type: book_chapter user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2022' ... --- _id: '17076' abstract: - lang: eng text: "Introduction: The levels of many blood proteins are associated with Alzheimer's disease (AD) or its pathological hallmarks. Elucidating the molecular factors that control circulating levels of these proteins may help to identify proteins associated with disease risk mechanisms.\r\n\r\nMethods: Genome-wide and epigenome-wide studies (nindividuals ≤1064) were performed on plasma levels of 282 AD-associated proteins, identified by a structured literature review. Bayesian penalized regression estimated contributions of genetic and epigenetic variation toward inter-individual differences in plasma protein levels. Mendelian randomization (MR) and co-localization tested associations between proteins and disease-related phenotypes.\r\n\r\nResults: Sixty-four independent genetic and 26 epigenetic loci were associated with 45 proteins. Novel findings included an association between plasma triggering receptor expressed on myeloid cells 2 (TREM2) levels and a polymorphism and cytosine-phosphate-guanine (CpG) site within the MS4A4A locus. Higher plasma tubulin-specific chaperone A (TBCA) and TREM2 levels were significantly associated with lower AD risk.\r\n\r\nDiscussion: Our data inform the regulation of biomarker levels and their relationships with AD." acknowledgement: This research was funded in whole, or in part, by Wellcome [108890/Z/15/Z, 104036/Z/14/Z]. For the purpose of open access, the author has applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission. The authors are grateful to the families who took part in this study, the general practitioners, and the Scottish School of Primary Care for their help in recruiting them and the wider Generation Scotland team. Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006]. Genotyping and DNA methylation profiling of the Generation Scotland samples was carried out by the Genetics Core Laboratory at the Wellcome Trust Clinical Research Facility, Edinburgh, Scotland, and was funded by the Medical Research Council (MRC) UK and the Wellcome Trust (Wellcome Trust Strategic Award “STratifying Resilience and Depression Longitudinally” ([STRADL] Reference [104036/Z/14/Z]). Andrew M. McIntosh is supported by Wellcome [104036/Z/14/Z, 216767/Z/19/Z, 220857/Z/20/Z], United Kingdom Research and Innovation (UKRI) MRC [MC_PC_17209, MR/S035818/1] and the European Union H2020 [SEP-210574971]. Ian J. Deary received support from Age UK, Wellcome, and the Medical Research Council. David J. Porteous is supported by Wellcome as prinicpal investigator (PI), and MRC and National Institute for Health Research (NIHR) grants as co-PI, made to the University of Edinburgh. Robert F. Hillary and Danni A. Gadd are supported by funding from the Wellcome 4-year PhD in Translational Neuroscience—training the next generation of basic neuroscientists to embrace clinical research [108890/Z/15/Z]. Daniel L. McCartney and Riccardo E. Marioni are supported by Alzheimer's Research UK major project grant ARUK-PG2017B-10. Riccardo E. Marioni is supported by Alzheimer's Society major project grant AS-PG-19b-010. Proteomic analyses in STRADL were supported by Dementias Platform UK (DPUK). DPUK funded this work through core grant support from the Medical Research Council [MR/L023784/2]. Kathryn L. Evans was supported by a grant from Alzheimer's Research UK, paid to the University of Edinburgh. Alejo J. Nevado-Holgado was funded by a Horizon 2020 Virtual Brain Cloud project (H2020-SC1-DTH-2018-1), in addition to funding from the MRC, UK Rosetrees, and King Abdullah University of Science and Technology, Saudi Arabia. Caroline Hayward is supported by an MRC University Unit Programme Grant MC_UU_00007/10 (QTL in Health and Disease). Liu Shi is funded by DPUK through MRC [MR/L023784/2] and the UK Medical Research Council Award to the University of Oxford [MC_PC_17215]. Liu Shi received support from the NIHR Biomedical Research Centre at Oxford Health NHS Foundation Trust. Matthew R. Robinson is funded by a Swiss National Science Foundation Eccellenza Grant [PCEGP3-181181]. article_number: e12280 article_processing_charge: Yes article_type: original author: - first_name: Robert F. full_name: Hillary, Robert F. last_name: Hillary - first_name: Danni A. full_name: Gadd, Danni A. last_name: Gadd - first_name: Daniel L. full_name: McCartney, Daniel L. last_name: McCartney - first_name: Liu full_name: Shi, Liu last_name: Shi - first_name: Archie full_name: Campbell, Archie last_name: Campbell - first_name: Rosie M. full_name: Walker, Rosie M. last_name: Walker - first_name: Craig W. full_name: Ritchie, Craig W. last_name: Ritchie - first_name: Ian J. full_name: Deary, Ian J. last_name: Deary - first_name: Kathryn L. full_name: Evans, Kathryn L. last_name: Evans - first_name: Alejo J. full_name: Nevado‐Holgado, Alejo J. last_name: Nevado‐Holgado - first_name: Caroline full_name: Hayward, Caroline last_name: Hayward - first_name: David J. full_name: Porteous, David J. last_name: Porteous - first_name: Andrew M. full_name: McIntosh, Andrew M. last_name: McIntosh - first_name: Simon full_name: Lovestone, Simon last_name: Lovestone - first_name: Matthew Richard full_name: Robinson, Matthew Richard id: E5D42276-F5DA-11E9-8E24-6303E6697425 last_name: Robinson orcid: 0000-0001-8982-8813 - first_name: Riccardo E. full_name: Marioni, Riccardo E. last_name: Marioni citation: ama: 'Hillary RF, Gadd DA, McCartney DL, et al. Genome‐ and epigenome‐wide studies of plasma protein biomarkers for Alzheimer’s disease implicate TBCA and TREM2 in disease risk. Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring. 2022;14(1). doi:10.1002/dad2.12280' apa: 'Hillary, R. F., Gadd, D. A., McCartney, D. L., Shi, L., Campbell, A., Walker, R. M., … Marioni, R. E. (2022). Genome‐ and epigenome‐wide studies of plasma protein biomarkers for Alzheimer’s disease implicate TBCA and TREM2 in disease risk. Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring. Wiley. https://doi.org/10.1002/dad2.12280' chicago: 'Hillary, Robert F., Danni A. Gadd, Daniel L. McCartney, Liu Shi, Archie Campbell, Rosie M. Walker, Craig W. Ritchie, et al. “Genome‐ and Epigenome‐wide Studies of Plasma Protein Biomarkers for Alzheimer’s Disease Implicate TBCA and TREM2 in Disease Risk.” Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring. Wiley, 2022. https://doi.org/10.1002/dad2.12280.' ieee: 'R. F. Hillary et al., “Genome‐ and epigenome‐wide studies of plasma protein biomarkers for Alzheimer’s disease implicate TBCA and TREM2 in disease risk,” Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring, vol. 14, no. 1. Wiley, 2022.' ista: 'Hillary RF, Gadd DA, McCartney DL, Shi L, Campbell A, Walker RM, Ritchie CW, Deary IJ, Evans KL, Nevado‐Holgado AJ, Hayward C, Porteous DJ, McIntosh AM, Lovestone S, Robinson MR, Marioni RE. 2022. Genome‐ and epigenome‐wide studies of plasma protein biomarkers for Alzheimer’s disease implicate TBCA and TREM2 in disease risk. Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring. 14(1), e12280.' mla: 'Hillary, Robert F., et al. “Genome‐ and Epigenome‐wide Studies of Plasma Protein Biomarkers for Alzheimer’s Disease Implicate TBCA and TREM2 in Disease Risk.” Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring, vol. 14, no. 1, e12280, Wiley, 2022, doi:10.1002/dad2.12280.' short: 'R.F. Hillary, D.A. Gadd, D.L. McCartney, L. Shi, A. Campbell, R.M. Walker, C.W. Ritchie, I.J. Deary, K.L. Evans, A.J. Nevado‐Holgado, C. Hayward, D.J. Porteous, A.M. McIntosh, S. Lovestone, M.R. Robinson, R.E. Marioni, Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring 14 (2022).' date_created: 2024-05-29T06:13:25Z date_published: 2022-04-20T00:00:00Z date_updated: 2024-07-31T11:33:50Z day: '20' ddc: - '570' department: - _id: MaRo doi: 10.1002/dad2.12280 external_id: pmid: - '35475137' file: - access_level: open_access checksum: 49c8597b588ef1c63897703a32b7967b content_type: application/pdf creator: dernst date_created: 2024-07-31T11:27:29Z date_updated: 2024-07-31T11:27:29Z file_id: '17356' file_name: 2023_AlzheimersDementia_Hillary.pdf file_size: 975181 relation: main_file success: 1 file_date_updated: 2024-07-31T11:27:29Z has_accepted_license: '1' intvolume: ' 14' issue: '1' language: - iso: eng month: '04' oa: 1 oa_version: Published Version pmid: 1 publication: 'Alzheimer''s & Dementia: Diagnosis, Assessment & Disease Monitoring' publication_identifier: eissn: - 2352-8729 publication_status: published publisher: Wiley quality_controlled: '1' scopus_import: '1' status: public title: Genome‐ and epigenome‐wide studies of plasma protein biomarkers for Alzheimer's disease implicate TBCA and TREM2 in disease risk tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 14 year: '2022' ... --- _id: '17077' abstract: - lang: eng text: "Resolving a conjecture of Füredi from 1988, we prove that with high probability, the random graph \U0001D53E(\U0001D45B, 1/2) admits a friendly bisection of its vertex set, i.e., a\r\npartition of its vertex set into two parts whose sizes differ by at most one in which\r\n\U0001D45B − \U0001D45C(\U0001D45B) vertices have more neighbours in their own part as across. Our proof is constructive, and in the process, we develop a new method to study stochastic processes\r\ndriven by degree information in random graphs; this involves combining enumeration\r\ntechniques with an abstract second moment argument." acknowledgement: "We thank the referees for extensive comments which helped improve the paper substantially.\r\nThe first author was supported in part by NSF grants DMS-1954395 and DMS-1953799. The second author was supported by NSF grant DMS-1953990. The third author was supported by NSF grant DMS180052. The fourth and fifth authors were both supported by NSF Graduate Research Fellowship Program DGE-1745302." article_processing_charge: No article_type: original arxiv: 1 author: - first_name: Asaf full_name: Ferber, Asaf last_name: Ferber - first_name: Matthew Alan full_name: Kwan, Matthew Alan id: 5fca0887-a1db-11eb-95d1-ca9d5e0453b3 last_name: Kwan orcid: 0000-0002-4003-7567 - first_name: Bhargav full_name: Narayanan, Bhargav last_name: Narayanan - first_name: Ashwin full_name: Sah, Ashwin last_name: Sah - first_name: Mehtaab full_name: Sawhney, Mehtaab last_name: Sawhney citation: ama: Ferber A, Kwan MA, Narayanan B, Sah A, Sawhney M. Friendly bisections of random graphs. Communications of the American Mathematical Society. 2022;2(10):380-416. doi:10.1090/cams/13 apa: Ferber, A., Kwan, M. A., Narayanan, B., Sah, A., & Sawhney, M. (2022). Friendly bisections of random graphs. Communications of the American Mathematical Society. American Mathematical Society. https://doi.org/10.1090/cams/13 chicago: Ferber, Asaf, Matthew Alan Kwan, Bhargav Narayanan, Ashwin Sah, and Mehtaab Sawhney. “Friendly Bisections of Random Graphs.” Communications of the American Mathematical Society. American Mathematical Society, 2022. https://doi.org/10.1090/cams/13. ieee: A. Ferber, M. A. Kwan, B. Narayanan, A. Sah, and M. Sawhney, “Friendly bisections of random graphs,” Communications of the American Mathematical Society, vol. 2, no. 10. American Mathematical Society, pp. 380–416, 2022. ista: Ferber A, Kwan MA, Narayanan B, Sah A, Sawhney M. 2022. Friendly bisections of random graphs. Communications of the American Mathematical Society. 2(10), 380–416. mla: Ferber, Asaf, et al. “Friendly Bisections of Random Graphs.” Communications of the American Mathematical Society, vol. 2, no. 10, American Mathematical Society, 2022, pp. 380–416, doi:10.1090/cams/13. short: A. Ferber, M.A. Kwan, B. Narayanan, A. Sah, M. Sawhney, Communications of the American Mathematical Society 2 (2022) 380–416. corr_author: '1' date_created: 2024-05-29T06:13:37Z date_published: 2022-12-20T00:00:00Z date_updated: 2024-07-15T08:06:05Z day: '20' ddc: - '500' department: - _id: MaKw doi: 10.1090/cams/13 external_id: arxiv: - '2105.13337' file: - access_level: open_access checksum: 719861e76f5bce3d0362d8171daa26fc content_type: application/pdf creator: cchlebak date_created: 2024-07-12T12:55:02Z date_updated: 2024-07-12T12:55:02Z file_id: '17230' file_name: 2022_CommAMS_Ferber.pdf file_size: 335965 relation: main_file success: 1 file_date_updated: 2024-07-12T12:55:02Z has_accepted_license: '1' intvolume: ' 2' issue: '10' language: - iso: eng license: https://creativecommons.org/licenses/by/3.0/ month: '12' oa: 1 oa_version: Published Version page: 380-416 publication: Communications of the American Mathematical Society publication_identifier: issn: - 2692-3688 publication_status: published publisher: American Mathematical Society quality_controlled: '1' status: public title: Friendly bisections of random graphs tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/3.0/legalcode name: Creative Commons Attribution 3.0 Unported (CC BY 3.0) short: CC BY (3.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 2 year: '2022' ... --- _id: '17084' abstract: - lang: eng text: 'Given a graph where every vertex has exactly one labeled token, how can we most quickly execute a given permutation on the tokens? In (sequential) token swapping, the goal is to use the shortest possible sequence of swaps, each of which exchanges the tokens at the two endpoints of an edge of the graph. In parallel token swapping, the goal is to use the fewest rounds, each of which consists of one or more swaps on the edges of a matching. We prove that both of these problems remain NP-hard when the graph is restricted to be a tree. These token swapping problems have been studied by disparate groups of researchers in discrete mathematics, theoretical computer science, robot motion planning, game theory, and engineering. Previous work establishes NP-completeness on general graphs (for both problems), constant-factor approximation algorithms, and some poly-time exact algorithms for simple graph classes such as cliques, stars, paths, and cycles. Sequential and parallel token swapping on trees were first studied over thirty years ago (as "sorting with a transposition tree") and over twenty-five years ago (as "routing permutations via matchings"), yet their complexities were previously unknown. We also show limitations on approximation of sequential token swapping on trees: we identify a broad class of algorithms that encompass all three known polynomial-time algorithms that achieve the best known approximation factor (which is 2) and show that no such algorithm can achieve an approximation factor less than 2.' acknowledgement: "g Anna Lubiw: Supported by the Natural Sciences and Engineering Research Council of\r\nCanada (NSERC). Jayson Lynch: Supported by the Natural Sciences and Engineering Research Council of Canada (NSERC). Zuzana Masárová: Supported by Wittgenstein Prize, Austrian Science Fund (FWF), grant no. Z 342-N31. Virginia Vassilevska Williams: Supported by an NSF CAREER Award, NSF Grants CCF-1528078, CCF-1514339 and CCF-1909429, a BSF Grant BSF:2012338, a Google Research Fellowship and a Sloan Research Fellowship.\r\nNicole Wein: Supported by a grant to DIMACS from the Simons Foundation (820931). This work was done while the author was at MIT.\r\nThis research was initiated at the 34th Bellairs Winter Workshop on Computational Geometry, co-organized by Erik Demaine and Godfried Toussaint, held on March 22–29,\r\n2019 in Holetown, Barbados. We thank the other participants of that workshop for providing a\r\nstimulating research environment." alternative_title: - LIPIcs article_number: '3' article_processing_charge: Yes arxiv: 1 author: - first_name: Oswin full_name: Aichholzer, Oswin last_name: Aichholzer - first_name: Erik D. full_name: Demaine, Erik D. last_name: Demaine - first_name: Matias full_name: Korman, Matias last_name: Korman - first_name: Anna full_name: Lubiw, Anna last_name: Lubiw - first_name: Jayson full_name: Lynch, Jayson last_name: Lynch - first_name: Zuzana full_name: Masárová, Zuzana id: 45CFE238-F248-11E8-B48F-1D18A9856A87 last_name: Masárová orcid: 0000-0002-6660-1322 - first_name: Mikhail full_name: Rudoy, Mikhail last_name: Rudoy - first_name: Virginia full_name: Vassilevska Williams, Virginia last_name: Vassilevska Williams - first_name: Nicole full_name: Wein, Nicole last_name: Wein citation: ama: 'Aichholzer O, Demaine ED, Korman M, et al. Hardness of token swapping on trees. In: 30th Annual European Symposium on Algorithms. Vol 244. Schloss Dagstuhl - Leibniz-Zentrum für Informatik; 2022. doi:10.4230/LIPIcs.ESA.2022.3' apa: 'Aichholzer, O., Demaine, E. D., Korman, M., Lubiw, A., Lynch, J., Masárová, Z., … Wein, N. (2022). Hardness of token swapping on trees. In 30th Annual European Symposium on Algorithms (Vol. 244). Berlin/Potsdam, Germany: Schloss Dagstuhl - Leibniz-Zentrum für Informatik. https://doi.org/10.4230/LIPIcs.ESA.2022.3' chicago: Aichholzer, Oswin, Erik D. Demaine, Matias Korman, Anna Lubiw, Jayson Lynch, Zuzana Masárová, Mikhail Rudoy, Virginia Vassilevska Williams, and Nicole Wein. “Hardness of Token Swapping on Trees.” In 30th Annual European Symposium on Algorithms, Vol. 244. Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2022. https://doi.org/10.4230/LIPIcs.ESA.2022.3. ieee: O. Aichholzer et al., “Hardness of token swapping on trees,” in 30th Annual European Symposium on Algorithms, Berlin/Potsdam, Germany, 2022, vol. 244. ista: 'Aichholzer O, Demaine ED, Korman M, Lubiw A, Lynch J, Masárová Z, Rudoy M, Vassilevska Williams V, Wein N. 2022. Hardness of token swapping on trees. 30th Annual European Symposium on Algorithms. ESA: European Symposium on Algorithms, LIPIcs, vol. 244, 3.' mla: Aichholzer, Oswin, et al. “Hardness of Token Swapping on Trees.” 30th Annual European Symposium on Algorithms, vol. 244, 3, Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2022, doi:10.4230/LIPIcs.ESA.2022.3. short: O. Aichholzer, E.D. Demaine, M. Korman, A. Lubiw, J. Lynch, Z. Masárová, M. Rudoy, V. Vassilevska Williams, N. Wein, in:, 30th Annual European Symposium on Algorithms, Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2022. conference: end_date: 2022-09-09 location: Berlin/Potsdam, Germany name: 'ESA: European Symposium on Algorithms' start_date: 2022-09-05 corr_author: '1' date_created: 2024-05-29T06:27:16Z date_published: 2022-09-01T00:00:00Z date_updated: 2025-04-15T07:16:56Z day: '01' ddc: - '510' department: - _id: HeEd - _id: UlWa doi: 10.4230/LIPIcs.ESA.2022.3 external_id: arxiv: - '2103.06707' file: - access_level: open_access checksum: a1fbd3e7baad510fbcb998cf4a7d9f7f content_type: application/pdf creator: dernst date_created: 2024-08-12T08:51:44Z date_updated: 2024-08-12T08:51:44Z file_id: '17420' file_name: 2022_LIPIcS_Aichholzer.pdf file_size: 1406071 relation: main_file success: 1 file_date_updated: 2024-08-12T08:51:44Z has_accepted_license: '1' intvolume: ' 244' language: - iso: eng month: '09' oa: 1 oa_version: Published Version project: - _id: 268116B8-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z00342 name: Mathematics, Computer Science publication: 30th Annual European Symposium on Algorithms publication_status: published publisher: Schloss Dagstuhl - Leibniz-Zentrum für Informatik quality_controlled: '1' scopus_import: '1' status: public title: Hardness of token swapping on trees tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: conference user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 244 year: '2022' ... --- _id: '17085' abstract: - lang: eng text: Mosses are a cosmopolitan group of land plants, sister to vascular plants, with a high potential for molecular and cell biological research. The species Physcomitrium patens has helped gaining better understanding of the biological processes of the plant cell, and it has become a central system to understand water-to-land plant transition through 2D-to-3D growth transition, regulation of asymmetric cell division, shoot apical cell establishment and maintenance, phyllotaxis and regeneration. P. patens was the first fully sequenced moss in 2008, with the latest annotated release in 2018. It has been shown that many gene functions and networks are conserved in mosses when compared to angiosperms. Importantly, this model organism has a simplified and accessible body structure that facilitates close tracking in time and space with the support of live cell imaging set-ups and multiple reporter lines. This has become possible thanks to its fully established molecular toolkit, with highly efficient PEG-assisted, CRISPR/Cas9 and RNAi transformation and silencing protocols, among others. Here we provide examples on how mosses exhibit advantages over vascular plants to study several processes and their future potential to answer some other outstanding questions in plant cell biology. acknowledgement: 'The authors would like to thank Dr. Jeroen de Keijzer and Dr. Tijs Ketelaar for their thoughtful and detailed review of the manuscript. Also, the funding agencies Technology, Knowledge and Innovation, division Horticulture and Propagating Material (TKI T&U) and the Dutch Research Council (NWO) (reference number: TKILWV20.390) for funding JFC and the ERC grant to Prof. J. Friml (reference number: PR1023ERC02) for funding HT. The authors would like to sincerely apologise for the literature not cited that may be relevant for this chapter and is not present due to space constraints.' article_processing_charge: No author: - first_name: Jordi full_name: Floriach-Clark, Jordi last_name: Floriach-Clark - first_name: Han full_name: Tang, Han id: 19BDF720-25A0-11EA-AC6E-928F3DDC885E last_name: Tang orcid: 0000-0001-6152-6637 - first_name: Viola full_name: Willemsen, Viola last_name: Willemsen citation: ama: 'Floriach-Clark J, Tang H, Willemsen V. Mosses: Accessible Systems for Plant Development Studies. In: Abdurakhmonov IY, ed. Model Organisms in Plant Genetics. IntechOpen; 2022. doi:10.5772/intechopen.100535' apa: 'Floriach-Clark, J., Tang, H., & Willemsen, V. (2022). Mosses: Accessible Systems for Plant Development Studies. In I. Y. Abdurakhmonov (Ed.), Model Organisms in Plant Genetics. IntechOpen. https://doi.org/10.5772/intechopen.100535' chicago: 'Floriach-Clark, Jordi, Han Tang, and Viola Willemsen. “Mosses: Accessible Systems for Plant Development Studies.” In Model Organisms in Plant Genetics, edited by Ibrokhim Y. Abdurakhmonov. IntechOpen, 2022. https://doi.org/10.5772/intechopen.100535.' ieee: 'J. Floriach-Clark, H. Tang, and V. Willemsen, “Mosses: Accessible Systems for Plant Development Studies,” in Model Organisms in Plant Genetics, I. Y. Abdurakhmonov, Ed. IntechOpen, 2022.' ista: 'Floriach-Clark J, Tang H, Willemsen V. 2022.Mosses: Accessible Systems for Plant Development Studies. In: Model Organisms in Plant Genetics. .' mla: 'Floriach-Clark, Jordi, et al. “Mosses: Accessible Systems for Plant Development Studies.” Model Organisms in Plant Genetics, edited by Ibrokhim Y. Abdurakhmonov, IntechOpen, 2022, doi:10.5772/intechopen.100535.' short: J. Floriach-Clark, H. Tang, V. Willemsen, in:, I.Y. Abdurakhmonov (Ed.), Model Organisms in Plant Genetics, IntechOpen, 2022. date_created: 2024-05-29T06:35:13Z date_published: 2022-06-23T00:00:00Z date_updated: 2025-05-14T11:20:40Z day: '23' department: - _id: JiFr doi: 10.5772/intechopen.100535 ec_funded: 1 editor: - first_name: Ibrokhim Y. full_name: Abdurakhmonov, Ibrokhim Y. last_name: Abdurakhmonov language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.5772/intechopen.100535 month: '06' oa: 1 oa_version: Published Version project: - _id: 261099A6-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '742985' name: Tracing Evolution of Auxin Transport and Polarity in Plants publication: Model Organisms in Plant Genetics publication_identifier: isbn: - '9781839697500' publication_status: published publisher: IntechOpen quality_controlled: '1' status: public title: 'Mosses: Accessible Systems for Plant Development Studies' type: book_chapter user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2022' ... --- _id: '17086' abstract: - lang: eng text: 'We consider a high-dimensional mean estimation problem over a binary hidden Markov model, which illuminates the interplay between memory in data, sample size, dimension, and signal strength in statistical inference. In this model, an estimator observes n samples of a d-dimensional parameter vector θ∗∈Rd, multiplied by a random sign Si (1≤i≤n), and corrupted by isotropic standard Gaussian noise. The sequence of signs {Si}i∈[n]∈{−1,1}n is drawn from a stationary homogeneous Markov chain with flip probability δ∈[0,1/2]. As δ varies, this model smoothly interpolates two well-studied models: the Gaussian Location Model for which δ=0 and the Gaussian Mixture Model for which δ=1/2. Assuming that the estimator knows δ, we establish a nearly minimax optimal (up to logarithmic factors) estimation error rate, as a function of ∥θ∗∥,δ,d,n. We then provide an upper bound to the case of estimating δ, assuming a (possibly inaccurate) knowledge of θ∗. The bound is proved to be tight when θ∗ is an accurately known constant. These results are then combined to an algorithm which estimates θ∗ with δ unknown a priori, and theoretical guarantees on its error are stated.' acknowledgement: "Part of this work was done when YZ was a postdoc at Technion where he received funding from\r\nthe European Union’s Horizon 2020 research and innovation programme under grant agreement No 682203-ERC-[Inf-Speed-Tradeoff]. The work of of NW was supported in part by the Israel Science Foundation (ISF) under Grant 1782/22. NW is grateful to Guy Bresler for introducing him to this problem, for the initial ideas that led to this research, and for many helpful discussions on the topic." alternative_title: - NeurIPS article_processing_charge: No arxiv: 1 author: - first_name: Yihan full_name: Zhang, Yihan id: 2ce5da42-b2ea-11eb-bba5-9f264e9d002c last_name: Zhang orcid: 0000-0002-6465-6258 - first_name: Nir full_name: Weinberger, Nir last_name: Weinberger citation: ama: 'Zhang Y, Weinberger N. Mean estimation in high-dimensional binary Markov Gaussian mixture models. In: 36th Conference on Neural Information Processing Systems. Vol 35. ML Research Press; 2022.' apa: 'Zhang, Y., & Weinberger, N. (2022). Mean estimation in high-dimensional binary Markov Gaussian mixture models. In 36th Conference on Neural Information Processing Systems (Vol. 35). New Orleans, LA, United States: ML Research Press.' chicago: Zhang, Yihan, and Nir Weinberger. “Mean Estimation in High-Dimensional Binary Markov Gaussian Mixture Models.” In 36th Conference on Neural Information Processing Systems, Vol. 35. ML Research Press, 2022. ieee: Y. Zhang and N. Weinberger, “Mean estimation in high-dimensional binary Markov Gaussian mixture models,” in 36th Conference on Neural Information Processing Systems, New Orleans, LA, United States, 2022, vol. 35. ista: 'Zhang Y, Weinberger N. 2022. Mean estimation in high-dimensional binary Markov Gaussian mixture models. 36th Conference on Neural Information Processing Systems. NeurIPS: Neural Information Processing Systems, NeurIPS, vol. 35.' mla: Zhang, Yihan, and Nir Weinberger. “Mean Estimation in High-Dimensional Binary Markov Gaussian Mixture Models.” 36th Conference on Neural Information Processing Systems, vol. 35, ML Research Press, 2022. short: Y. Zhang, N. Weinberger, in:, 36th Conference on Neural Information Processing Systems, ML Research Press, 2022. conference: end_date: 2022-12-09 location: New Orleans, LA, United States name: 'NeurIPS: Neural Information Processing Systems' start_date: 2022-11-28 corr_author: '1' date_created: 2024-05-29T06:37:16Z date_published: 2022-12-01T00:00:00Z date_updated: 2024-08-05T09:48:58Z day: '01' ddc: - '000' department: - _id: MaMo external_id: arxiv: - '2206.02455' file: - access_level: open_access checksum: 05f6f9f8fc34e224e0cad045b9489030 content_type: application/pdf creator: dernst date_created: 2024-08-05T09:44:49Z date_updated: 2024-08-05T09:44:49Z file_id: '17392' file_name: 2022_NeurIPS_Zhang.pdf file_size: 476307 relation: main_file success: 1 file_date_updated: 2024-08-05T09:44:49Z has_accepted_license: '1' intvolume: ' 35' language: - iso: eng month: '12' oa: 1 oa_version: Published Version publication: 36th Conference on Neural Information Processing Systems publication_identifier: isbn: - '9781713871088' publication_status: published publisher: ML Research Press quality_controlled: '1' scopus_import: '1' status: public title: Mean estimation in high-dimensional binary Markov Gaussian mixture models type: conference user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 35 year: '2022' ... --- _id: '17088' abstract: - lang: eng text: 'In this paper, we consider the problem of sparsifying BERT models, which are a key building block for natural language processing, in order to reduce their storage and computational cost. We introduce the Optimal BERT Surgeon (oBERT), an efficient and accurate pruning method based on approximate second-order information, which we show to yield state-of-the-art results in both stages of language tasks: pre-training and fine-tuning. Specifically, oBERT extends existing work on second-order pruning by allowing for pruning weight blocks, and is the first such method that is applicable at BERT scale. Second, we investigate compounding compression approaches to obtain highly compressed but accurate models for deployment on edge devices. These models significantly push boundaries of the current state-of-the-art sparse BERT models with respect to all metrics: model size, inference speed and task accuracy. For example, relative to the dense BERT-base, we obtain 10x model size compression with < 1% accuracy drop, 10x CPU-inference speedup with < 2% accuracy drop, and 29x CPU-inference speedup with < 7.5% accuracy drop. Our code, fully integrated with Transformers and SparseML, is available at https://github.com/neuralmagic/sparseml/tree/main/research/optimal_BERT_surgeon_oBERT.' article_processing_charge: Yes arxiv: 1 author: - first_name: Eldar full_name: Kurtic, Eldar id: 47beb3a5-07b5-11eb-9b87-b108ec578218 last_name: Kurtic - first_name: Daniel full_name: Campos, Daniel last_name: Campos - first_name: Tuan full_name: Nguyen, Tuan last_name: Nguyen - first_name: Elias full_name: Frantar, Elias id: 09a8f98d-ec99-11ea-ae11-c063a7b7fe5f last_name: Frantar - first_name: Mark full_name: Kurtz, Mark last_name: Kurtz - first_name: Benjamin full_name: Fineran, Benjamin last_name: Fineran - first_name: Michael full_name: Goin, Michael last_name: Goin - first_name: Dan-Adrian full_name: Alistarh, Dan-Adrian id: 4A899BFC-F248-11E8-B48F-1D18A9856A87 last_name: Alistarh orcid: 0000-0003-3650-940X citation: ama: 'Kurtic E, Campos D, Nguyen T, et al. The optimal BERT surgeon: Scalable and accurate second-order pruning for large language models. In: Proceedings of the 2022 Conference on Empirical Methods in Natural Language Processing. Association for Computational Linguistics; 2022:4163-4181. doi:10.18653/v1/2022.emnlp-main.279' apa: 'Kurtic, E., Campos, D., Nguyen, T., Frantar, E., Kurtz, M., Fineran, B., … Alistarh, D.-A. (2022). The optimal BERT surgeon: Scalable and accurate second-order pruning for large language models. In Proceedings of the 2022 Conference on Empirical Methods in Natural Language Processing (pp. 4163–4181). Abu Dhabi, United Arab Emirates: Association for Computational Linguistics. https://doi.org/10.18653/v1/2022.emnlp-main.279' chicago: 'Kurtic, Eldar, Daniel Campos, Tuan Nguyen, Elias Frantar, Mark Kurtz, Benjamin Fineran, Michael Goin, and Dan-Adrian Alistarh. “The Optimal BERT Surgeon: Scalable and Accurate Second-Order Pruning for Large Language Models.” In Proceedings of the 2022 Conference on Empirical Methods in Natural Language Processing, 4163–81. Association for Computational Linguistics, 2022. https://doi.org/10.18653/v1/2022.emnlp-main.279.' ieee: 'E. Kurtic et al., “The optimal BERT surgeon: Scalable and accurate second-order pruning for large language models,” in Proceedings of the 2022 Conference on Empirical Methods in Natural Language Processing, Abu Dhabi, United Arab Emirates, 2022, pp. 4163–4181.' ista: 'Kurtic E, Campos D, Nguyen T, Frantar E, Kurtz M, Fineran B, Goin M, Alistarh D-A. 2022. The optimal BERT surgeon: Scalable and accurate second-order pruning for large language models. Proceedings of the 2022 Conference on Empirical Methods in Natural Language Processing. EMNLP: Conference on Empirical Methods in Natural Language Processing, 4163–4181.' mla: 'Kurtic, Eldar, et al. “The Optimal BERT Surgeon: Scalable and Accurate Second-Order Pruning for Large Language Models.” Proceedings of the 2022 Conference on Empirical Methods in Natural Language Processing, Association for Computational Linguistics, 2022, pp. 4163–81, doi:10.18653/v1/2022.emnlp-main.279.' short: E. Kurtic, D. Campos, T. Nguyen, E. Frantar, M. Kurtz, B. Fineran, M. Goin, D.-A. Alistarh, in:, Proceedings of the 2022 Conference on Empirical Methods in Natural Language Processing, Association for Computational Linguistics, 2022, pp. 4163–4181. conference: end_date: 2022-12-11 location: Abu Dhabi, United Arab Emirates name: 'EMNLP: Conference on Empirical Methods in Natural Language Processing' start_date: 2022-12-07 corr_author: '1' date_created: 2024-05-29T06:40:55Z date_published: 2022-12-01T00:00:00Z date_updated: 2024-07-31T11:05:32Z day: '01' ddc: - '000' department: - _id: DaAl doi: 10.18653/v1/2022.emnlp-main.279 external_id: arxiv: - '2203.07259' file: - access_level: open_access checksum: c47b9edd8a9f743ac77a593de6d2e84a content_type: application/pdf creator: dernst date_created: 2024-07-31T11:03:34Z date_updated: 2024-07-31T11:03:34Z file_id: '17354' file_name: 2022_EMNLP_Kurtic.pdf file_size: 522563 relation: main_file success: 1 file_date_updated: 2024-07-31T11:03:34Z has_accepted_license: '1' language: - iso: eng month: '12' oa: 1 oa_version: Published Version page: 4163-4181 publication: Proceedings of the 2022 Conference on Empirical Methods in Natural Language Processing publication_status: published publisher: Association for Computational Linguistics quality_controlled: '1' related_material: link: - relation: software url: https://github.com/neuralmagic/sparseml/tree/main/research/optimal_BERT_surgeon_oBERT scopus_import: '1' status: public title: 'The optimal BERT surgeon: Scalable and accurate second-order pruning for large language models' tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: conference user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2022' ... --- _id: '17115' abstract: - lang: eng text: Cascades are RNA-guided multi-subunit CRISPR-Cas surveillances complexes that target foreign nucleic acids for destruction. Here, we present a 2.9-Å resolution cryo-electron (cryo-EM) structure of the D. vulgaris type I-C Cascade bound to a double-stranded (ds)DNA target. Our data shows how the 5’-TTC-3’ protospacer adjacent motif (PAM) sequence is recognized, and provides a unique mechanism through which the displaced, single-stranded non-target strand (NTS) is stabilized via stacking interactions with protein subunits in order to favor R-loop formation and prevent dsDNA re-annealing. Additionally, we provide structural insights into how diverse anti-CRISPR (Acr) proteins utilize distinct strategies to achieve a shared mechanism of type I-C Cascade inhibition by blocking initial DNA binding. These observations provide a structural basis for directional R-loop formation and reveal how divergent Acr proteins have converged upon common molecular mechanisms to efficiently shut down CRISPR immunity. article_processing_charge: No author: - first_name: Roisin E. full_name: O’Brien, Roisin E. last_name: O’Brien - first_name: Jack Peter Kelly full_name: Bravo, Jack Peter Kelly id: 96aecfa5-8931-11ee-af30-aa6a5d6eee0e last_name: Bravo orcid: 0000-0003-0456-0753 - first_name: Delisa full_name: Ramos, Delisa last_name: Ramos - first_name: Grace N. full_name: Hibshman, Grace N. last_name: Hibshman - first_name: Jacquelyn T. full_name: Wright, Jacquelyn T. last_name: Wright - first_name: David W. full_name: Taylor, David W. last_name: Taylor citation: ama: O’Brien RE, Bravo JPK, Ramos D, Hibshman GN, Wright JT, Taylor DW. Modes of inhibition used by phage anti-CRISPRs to evade type I-C Cascade. bioRxiv. 2022. doi:10.1101/2022.06.15.496202 apa: O’Brien, R. E., Bravo, J. P. K., Ramos, D., Hibshman, G. N., Wright, J. T., & Taylor, D. W. (2022). Modes of inhibition used by phage anti-CRISPRs to evade type I-C Cascade. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2022.06.15.496202 chicago: O’Brien, Roisin E., Jack Peter Kelly Bravo, Delisa Ramos, Grace N. Hibshman, Jacquelyn T. Wright, and David W. Taylor. “Modes of Inhibition Used by Phage Anti-CRISPRs to Evade Type I-C Cascade.” BioRxiv. Cold Spring Harbor Laboratory, 2022. https://doi.org/10.1101/2022.06.15.496202. ieee: R. E. O’Brien, J. P. K. Bravo, D. Ramos, G. N. Hibshman, J. T. Wright, and D. W. Taylor, “Modes of inhibition used by phage anti-CRISPRs to evade type I-C Cascade,” bioRxiv. Cold Spring Harbor Laboratory, 2022. ista: O’Brien RE, Bravo JPK, Ramos D, Hibshman GN, Wright JT, Taylor DW. 2022. Modes of inhibition used by phage anti-CRISPRs to evade type I-C Cascade. bioRxiv, 10.1101/2022.06.15.496202. mla: O’Brien, Roisin E., et al. “Modes of Inhibition Used by Phage Anti-CRISPRs to Evade Type I-C Cascade.” BioRxiv, Cold Spring Harbor Laboratory, 2022, doi:10.1101/2022.06.15.496202. short: R.E. O’Brien, J.P.K. Bravo, D. Ramos, G.N. Hibshman, J.T. Wright, D.W. Taylor, BioRxiv (2022). date_created: 2024-06-04T06:43:30Z date_published: 2022-06-15T00:00:00Z date_updated: 2024-06-04T07:03:02Z day: '15' doi: 10.1101/2022.06.15.496202 extern: '1' language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1101/2022.06.15.496202 month: '06' oa: 1 oa_version: Preprint publication: bioRxiv publication_status: published publisher: Cold Spring Harbor Laboratory status: public title: Modes of inhibition used by phage anti-CRISPRs to evade type I-C Cascade type: preprint user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2022' ... --- _id: '17116' abstract: - lang: eng text: CRISPR (Clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) systems are a type of adaptive immune response in bacteria and archaea that utilize crRNA (CRISPR RNA)-guided effector complexes to target complementary RNA or DNA for destruction. The prototypical type III-A and III-B CRISPR-Cas systems utilize multi-subunit effector complexes composed of individual proteins to cleave ssRNA targets at 6-nt intervals, as well as non-specifically degrading ssDNA and activating cyclic oligoadenylate (cOA) synthesis. Recent studies have shown that type III systems can contain subunit fusions yet maintain canonical type III RNA-targeting capabilities. To understand how a multi-subunit fusion effector functions, we determine structures of a variant type III-D effector and biochemically characterize how it cleaves RNA targets. These findings provide insights into how multi-subunit fusion proteins are tethered together and assemble into an active and programmable RNA endonuclease, how the effector utilizes a novel mechanism for target RNA seeding, and the structural basis for the evolution of type III effector complexes. Furthermore, our results provide a blueprint for fusing subunits in class 1 effectors for design of user-defined effector complexes with disparate activities.Important noteWhile this manuscript was in preparation, a manuscript describing the structure of the type III-E effector was published1. We reference these important findings; however, a careful comparison of the structures will follow once the coordinates have been released by the PDB. article_processing_charge: No author: - first_name: Evan A. full_name: Schwartz, Evan A. last_name: Schwartz - first_name: Jack Peter Kelly full_name: Bravo, Jack Peter Kelly id: 96aecfa5-8931-11ee-af30-aa6a5d6eee0e last_name: Bravo orcid: 0000-0003-0456-0753 - first_name: Luis A. full_name: Macias, Luis A. last_name: Macias - first_name: Caitlyn L. full_name: McCafferty, Caitlyn L. last_name: McCafferty - first_name: Tyler L. full_name: Dangerfield, Tyler L. last_name: Dangerfield - first_name: Jada N. full_name: Walker, Jada N. last_name: Walker - first_name: Jennifer S. full_name: Brodbelt, Jennifer S. last_name: Brodbelt - first_name: Peter C. full_name: Fineran, Peter C. last_name: Fineran - first_name: Robert D. full_name: Fagerlund, Robert D. last_name: Fagerlund - first_name: David W. full_name: Taylor, David W. last_name: Taylor citation: ama: Schwartz EA, Bravo JPK, Macias LA, et al. Assembly of multi-subunit fusion proteins into the RNA-targeting type III-D CRISPR-Cas effector complex. bioRxiv. doi:10.1101/2022.06.13.496011 apa: Schwartz, E. A., Bravo, J. P. K., Macias, L. A., McCafferty, C. L., Dangerfield, T. L., Walker, J. N., … Taylor, D. W. (n.d.). Assembly of multi-subunit fusion proteins into the RNA-targeting type III-D CRISPR-Cas effector complex. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2022.06.13.496011 chicago: Schwartz, Evan A., Jack Peter Kelly Bravo, Luis A. Macias, Caitlyn L. McCafferty, Tyler L. Dangerfield, Jada N. Walker, Jennifer S. Brodbelt, Peter C. Fineran, Robert D. Fagerlund, and David W. Taylor. “Assembly of Multi-Subunit Fusion Proteins into the RNA-Targeting Type III-D CRISPR-Cas Effector Complex.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2022.06.13.496011. ieee: E. A. Schwartz et al., “Assembly of multi-subunit fusion proteins into the RNA-targeting type III-D CRISPR-Cas effector complex,” bioRxiv. Cold Spring Harbor Laboratory. ista: Schwartz EA, Bravo JPK, Macias LA, McCafferty CL, Dangerfield TL, Walker JN, Brodbelt JS, Fineran PC, Fagerlund RD, Taylor DW. Assembly of multi-subunit fusion proteins into the RNA-targeting type III-D CRISPR-Cas effector complex. bioRxiv, 10.1101/2022.06.13.496011. mla: Schwartz, Evan A., et al. “Assembly of Multi-Subunit Fusion Proteins into the RNA-Targeting Type III-D CRISPR-Cas Effector Complex.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2022.06.13.496011. short: E.A. Schwartz, J.P.K. Bravo, L.A. Macias, C.L. McCafferty, T.L. Dangerfield, J.N. Walker, J.S. Brodbelt, P.C. Fineran, R.D. Fagerlund, D.W. Taylor, BioRxiv (n.d.). date_created: 2024-06-04T06:44:16Z date_published: 2022-06-14T00:00:00Z date_updated: 2024-06-04T06:58:41Z day: '14' doi: 10.1101/2022.06.13.496011 extern: '1' language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1101/2022.06.13.496011 month: '06' oa: 1 oa_version: Preprint publication: bioRxiv publication_status: submitted publisher: Cold Spring Harbor Laboratory status: public title: Assembly of multi-subunit fusion proteins into the RNA-targeting type III-D CRISPR-Cas effector complex type: preprint user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2022' ... --- _id: '17117' abstract: - lang: eng text: Cas12a2 is a CRISPR-associated nuclease that performs RNA-guided degradation of non-specific single-stranded (ss)RNA, ssDNA and double-stranded (ds)DNA upon recognition of a complementary RNA target, culminating in abortive infection (Dmytrenko 2022). Here, we report structures of Cas12a2 in binary, ternary, and quaternary complexes to reveal a complete activation pathway. Our structures reveal that Cas12a2 is autoinhibited until binding a cognate RNA target, which exposes the RuvC active site within a large, positively charged cleft. Double-stranded DNA substrates are captured through duplex distortion and local melting, stabilized by pairs of ‘aromatic clamp’ residues that are crucial for dsDNA degradation and in vivo immune system function. Our work provides a structural basis for this unprecedented mechanism of abortive infection to achieve population-level immunity, which can be leveraged to create rational mutants that degrade a spectrum of collateral substrates. article_processing_charge: No author: - first_name: Jack Peter Kelly full_name: Bravo, Jack Peter Kelly id: 96aecfa5-8931-11ee-af30-aa6a5d6eee0e last_name: Bravo orcid: 0000-0003-0456-0753 - first_name: Thom full_name: Hallmark, Thom last_name: Hallmark - first_name: Bronson full_name: Naegle, Bronson last_name: Naegle - first_name: Chase L. full_name: Beisel, Chase L. last_name: Beisel - first_name: Ryan N. full_name: Jackson, Ryan N. last_name: Jackson - first_name: David W. full_name: Taylor, David W. last_name: Taylor citation: ama: Bravo JPK, Hallmark T, Naegle B, Beisel CL, Jackson RN, Taylor DW. Large-scale structural rearrangements unleash indiscriminate nuclease activity of CRISPR-Cas12a2. bioRxiv. 2022. doi:10.1101/2022.06.13.495754 apa: Bravo, J. P. K., Hallmark, T., Naegle, B., Beisel, C. L., Jackson, R. N., & Taylor, D. W. (2022). Large-scale structural rearrangements unleash indiscriminate nuclease activity of CRISPR-Cas12a2. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2022.06.13.495754 chicago: Bravo, Jack Peter Kelly, Thom Hallmark, Bronson Naegle, Chase L. Beisel, Ryan N. Jackson, and David W. Taylor. “Large-Scale Structural Rearrangements Unleash Indiscriminate Nuclease Activity of CRISPR-Cas12a2.” BioRxiv. Cold Spring Harbor Laboratory, 2022. https://doi.org/10.1101/2022.06.13.495754. ieee: J. P. K. Bravo, T. Hallmark, B. Naegle, C. L. Beisel, R. N. Jackson, and D. W. Taylor, “Large-scale structural rearrangements unleash indiscriminate nuclease activity of CRISPR-Cas12a2,” bioRxiv. Cold Spring Harbor Laboratory, 2022. ista: Bravo JPK, Hallmark T, Naegle B, Beisel CL, Jackson RN, Taylor DW. 2022. Large-scale structural rearrangements unleash indiscriminate nuclease activity of CRISPR-Cas12a2. bioRxiv, 10.1101/2022.06.13.495754. mla: Bravo, Jack Peter Kelly, et al. “Large-Scale Structural Rearrangements Unleash Indiscriminate Nuclease Activity of CRISPR-Cas12a2.” BioRxiv, Cold Spring Harbor Laboratory, 2022, doi:10.1101/2022.06.13.495754. short: J.P.K. Bravo, T. Hallmark, B. Naegle, C.L. Beisel, R.N. Jackson, D.W. Taylor, BioRxiv (2022). date_created: 2024-06-04T06:44:59Z date_published: 2022-06-13T00:00:00Z date_updated: 2024-06-04T06:55:16Z day: '13' doi: 10.1101/2022.06.13.495754 extern: '1' language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1101/2022.06.13.495754 month: '06' oa: 1 oa_version: Preprint publication: bioRxiv publication_status: published publisher: Cold Spring Harbor Laboratory status: public title: Large-scale structural rearrangements unleash indiscriminate nuclease activity of CRISPR-Cas12a2 type: preprint user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2022' ... --- _id: '17383' abstract: - lang: eng text: "We present a computational inverse design framework for a new class of volumetric deployable structures that have compact rest states and deploy into bending-active 3D target surfaces. Umbrella meshes consist of elastic beams, rigid plates, and hinge joints that can be directly printed or assembled in a zero-energy fabrication state. During deployment, as the elastic beams of varying heights rotate from vertical to horizontal configurations, the entire structure transforms from a compact block into a target curved surface. Umbrella Meshes encode both intrinsic and extrinsic curvature of the target surface and in principle are free from the area expansion ratio bounds of past auxetic material systems.\r\nWe build a reduced physics-based simulation framework to accurately and efficiently model the complex interaction between the elastically deforming components. To determine the mesh topology and optimal shape parameters for approximating a given target surface, we propose an inverse design optimization algorithm initialized with conformal flattening. Our algorithm minimizes the structure's strain energy in its deployed state and optimizes actuation forces so that the final deployed structure is in stable equilibrium close to the desired surface with few or no external constraints. We validate our approach by fabricating a series of physical models at various scales using different manufacturing techniques." article_processing_charge: No article_type: original author: - first_name: Yingying full_name: Ren, Yingying id: 93d68d10-3540-11ef-a265-f748a50dba3d last_name: Ren - first_name: Uday full_name: Kusupati, Uday last_name: Kusupati - first_name: Julian full_name: Panetta, Julian last_name: Panetta - first_name: Florin full_name: Isvoranu, Florin last_name: Isvoranu - first_name: Davide full_name: Pellis, Davide last_name: Pellis - first_name: Tian full_name: Chen, Tian last_name: Chen - first_name: Mark full_name: Pauly, Mark last_name: Pauly citation: ama: 'Ren Y, Kusupati U, Panetta J, et al. Umbrella meshes: Elastic mechanisms for freeform shape deployment. ACM Transactions on Graphics. 2022;41(4):1-15. doi:10.1145/3528223.3530089' apa: 'Ren, Y., Kusupati, U., Panetta, J., Isvoranu, F., Pellis, D., Chen, T., & Pauly, M. (2022). Umbrella meshes: Elastic mechanisms for freeform shape deployment. ACM Transactions on Graphics. Association for Computing Machinery. https://doi.org/10.1145/3528223.3530089' chicago: 'Ren, Yingying, Uday Kusupati, Julian Panetta, Florin Isvoranu, Davide Pellis, Tian Chen, and Mark Pauly. “Umbrella Meshes: Elastic Mechanisms for Freeform Shape Deployment.” ACM Transactions on Graphics. Association for Computing Machinery, 2022. https://doi.org/10.1145/3528223.3530089.' ieee: 'Y. Ren et al., “Umbrella meshes: Elastic mechanisms for freeform shape deployment,” ACM Transactions on Graphics, vol. 41, no. 4. Association for Computing Machinery, pp. 1–15, 2022.' ista: 'Ren Y, Kusupati U, Panetta J, Isvoranu F, Pellis D, Chen T, Pauly M. 2022. Umbrella meshes: Elastic mechanisms for freeform shape deployment. ACM Transactions on Graphics. 41(4), 1–15.' mla: 'Ren, Yingying, et al. “Umbrella Meshes: Elastic Mechanisms for Freeform Shape Deployment.” ACM Transactions on Graphics, vol. 41, no. 4, Association for Computing Machinery, 2022, pp. 1–15, doi:10.1145/3528223.3530089.' short: Y. Ren, U. Kusupati, J. Panetta, F. Isvoranu, D. Pellis, T. Chen, M. Pauly, ACM Transactions on Graphics 41 (2022) 1–15. date_created: 2024-08-05T06:30:07Z date_published: 2022-07-22T00:00:00Z date_updated: 2024-08-12T09:40:49Z day: '22' doi: 10.1145/3528223.3530089 extern: '1' intvolume: ' 41' issue: '4' language: - iso: eng month: '07' oa_version: None page: 1-15 publication: ACM Transactions on Graphics publication_identifier: eissn: - 1557-7368 issn: - 0730-0301 publication_status: published publisher: Association for Computing Machinery quality_controlled: '1' scopus_import: '1' status: public title: 'Umbrella meshes: Elastic mechanisms for freeform shape deployment' type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 41 year: '2022' ... --- _id: '17501' abstract: - lang: eng text: "Low-level systems code often needs to interact with data, such as page table entries or network packet headers, in which multiple pieces of information are packaged together as bitfield components of a single machine integer and accessed via bitfield manipulations (e.g., shifts and masking). Most existing approaches to verifying such code employ SMT solvers, instantiated with theories for bit vector reasoning: these provide a powerful hammer, but also significantly increase the trusted computing base of the verification toolchain.\r\nIn this work, we propose an alternative approach to the verification of bitfield-manipulating systems code, which we call BFF. Building on the RefinedC framework, BFF is not only highly automated (as SMT-based approaches are) but also foundational---i.e., it produces a machine-checked proof of program correctness against a formal semantics for C programs, fully mechanized in Coq. Unlike SMT-based approaches, we do not try to solve the general problem of arbitrary bit vector reasoning, but rather observe that real systems code typically accesses bitfields using simple, well-understood programming patterns: the layout of a bit vector is known up front, and its bitfields are accessed in predictable ways through a handful of bitwise operations involving bit masks. Correspondingly, we center our approach around the concept of a structured bit vector---i.e., a bit vector with a known bitfield layout---which we use to drive simple and predictable automation. We validate the BFF approach by verifying a range of bitfield-manipulating C functions drawn from real systems code, including page table manipulation code from the Linux kernel and the pKVM hypervisor." article_processing_charge: No article_type: original author: - first_name: Fengmin full_name: Zhu, Fengmin last_name: Zhu - first_name: Michael Joachim full_name: Sammler, Michael Joachim id: 510d3901-2a03-11ee-914d-d9ae9011f0a7 last_name: Sammler - first_name: Rodolphe full_name: Lepigre, Rodolphe last_name: Lepigre - first_name: Derek full_name: Dreyer, Derek last_name: Dreyer - first_name: Deepak full_name: Garg, Deepak last_name: Garg citation: ama: 'Zhu F, Sammler MJ, Lepigre R, Dreyer D, Garg D. BFF: Foundational and automated verification of bitfield-manipulating programs. Proceedings of the ACM on Programming Languages. 2022;6(OOPSLA2):1613-1638. doi:10.1145/3563345' apa: 'Zhu, F., Sammler, M. J., Lepigre, R., Dreyer, D., & Garg, D. (2022). BFF: Foundational and automated verification of bitfield-manipulating programs. Proceedings of the ACM on Programming Languages. Association for Computing Machinery. https://doi.org/10.1145/3563345' chicago: 'Zhu, Fengmin, Michael Joachim Sammler, Rodolphe Lepigre, Derek Dreyer, and Deepak Garg. “BFF: Foundational and Automated Verification of Bitfield-Manipulating Programs.” Proceedings of the ACM on Programming Languages. Association for Computing Machinery, 2022. https://doi.org/10.1145/3563345.' ieee: 'F. Zhu, M. J. Sammler, R. Lepigre, D. Dreyer, and D. Garg, “BFF: Foundational and automated verification of bitfield-manipulating programs,” Proceedings of the ACM on Programming Languages, vol. 6, no. OOPSLA2. Association for Computing Machinery, pp. 1613–1638, 2022.' ista: 'Zhu F, Sammler MJ, Lepigre R, Dreyer D, Garg D. 2022. BFF: Foundational and automated verification of bitfield-manipulating programs. Proceedings of the ACM on Programming Languages. 6(OOPSLA2), 1613–1638.' mla: 'Zhu, Fengmin, et al. “BFF: Foundational and Automated Verification of Bitfield-Manipulating Programs.” Proceedings of the ACM on Programming Languages, vol. 6, no. OOPSLA2, Association for Computing Machinery, 2022, pp. 1613–38, doi:10.1145/3563345.' short: F. Zhu, M.J. Sammler, R. Lepigre, D. Dreyer, D. Garg, Proceedings of the ACM on Programming Languages 6 (2022) 1613–1638. date_created: 2024-09-05T08:27:17Z date_published: 2022-10-31T00:00:00Z date_updated: 2024-09-10T09:49:18Z day: '31' doi: 10.1145/3563345 extern: '1' intvolume: ' 6' issue: OOPSLA2 language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1145/3563345 month: '10' oa: 1 oa_version: Published Version page: 1613-1638 publication: Proceedings of the ACM on Programming Languages publication_identifier: issn: - 2475-1421 publication_status: published publisher: Association for Computing Machinery quality_controlled: '1' scopus_import: '1' status: public title: 'BFF: Foundational and automated verification of bitfield-manipulating programs' type: journal_article user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345 volume: 6 year: '2022' ... --- _id: '17502' abstract: - lang: eng text: "Recent years have seen great advances towards verifying large-scale systems code. However, these verifications are usually based on hand-written assembly or machine-code semantics for the underlying architecture that only cover a small part of the instruction set architecture (ISA). In contrast, other recent work has used Sail to establish formal models for large real-world architectures, including Armv8-A and RISC-V, that are comprehensive (complete enough to boot an operating system or hypervisor) and authoritative (automatically derived from the Arm internal model and validated against the Arm validation suite, and adopted as the official formal specification by RISC-V International, respectively). But the scale and complexity of these models makes them challenging to use as a basis for verification.\r\nIn this paper, we propose Islaris, the first system to support verification of machine code above these complete and authoritative real-world ISA specifications. Islaris uses a novel combination of SMT-solver-based symbolic execution (the Isla symbolic executor) and automated reasoning in a foundational program logic (a new separation logic we derive using Iris in Coq). We show that this approach can handle Armv8-A and RISC-V machine code exercising a wide range of systems features, including installing and calling exception vectors, code parametric on a relocation address offset (from the production pKVM hypervisor); unaligned access faults; memory-mapped IO; and compiled C code using inline assembly and function pointers." article_processing_charge: No author: - first_name: Michael Joachim full_name: Sammler, Michael Joachim id: 510d3901-2a03-11ee-914d-d9ae9011f0a7 last_name: Sammler - first_name: Angus full_name: Hammond, Angus last_name: Hammond - first_name: Rodolphe full_name: Lepigre, Rodolphe last_name: Lepigre - first_name: Brian full_name: Campbell, Brian last_name: Campbell - first_name: Jean full_name: Pichon-Pharabod, Jean last_name: Pichon-Pharabod - first_name: Derek full_name: Dreyer, Derek last_name: Dreyer - first_name: Deepak full_name: Garg, Deepak last_name: Garg - first_name: Peter full_name: Sewell, Peter last_name: Sewell citation: ama: 'Sammler MJ, Hammond A, Lepigre R, et al. Islaris: Verification of machine code against authoritative ISA semantics. In: Proceedings of the 43rd ACM SIGPLAN International Conference on Programming Language Design and Implementation. Association for Computing Machinery; 2022:825-840. doi:10.1145/3519939.3523434' apa: 'Sammler, M. J., Hammond, A., Lepigre, R., Campbell, B., Pichon-Pharabod, J., Dreyer, D., … Sewell, P. (2022). Islaris: Verification of machine code against authoritative ISA semantics. In Proceedings of the 43rd ACM SIGPLAN International Conference on Programming Language Design and Implementation (pp. 825–840). San Diego, CA, United States: Association for Computing Machinery. https://doi.org/10.1145/3519939.3523434' chicago: 'Sammler, Michael Joachim, Angus Hammond, Rodolphe Lepigre, Brian Campbell, Jean Pichon-Pharabod, Derek Dreyer, Deepak Garg, and Peter Sewell. “Islaris: Verification of Machine Code against Authoritative ISA Semantics.” In Proceedings of the 43rd ACM SIGPLAN International Conference on Programming Language Design and Implementation, 825–40. Association for Computing Machinery, 2022. https://doi.org/10.1145/3519939.3523434.' ieee: 'M. J. Sammler et al., “Islaris: Verification of machine code against authoritative ISA semantics,” in Proceedings of the 43rd ACM SIGPLAN International Conference on Programming Language Design and Implementation, San Diego, CA, United States, 2022, pp. 825–840.' ista: 'Sammler MJ, Hammond A, Lepigre R, Campbell B, Pichon-Pharabod J, Dreyer D, Garg D, Sewell P. 2022. Islaris: Verification of machine code against authoritative ISA semantics. Proceedings of the 43rd ACM SIGPLAN International Conference on Programming Language Design and Implementation. PLDI: Conference on Programming Language Design and Implementation, 825–840.' mla: 'Sammler, Michael Joachim, et al. “Islaris: Verification of Machine Code against Authoritative ISA Semantics.” Proceedings of the 43rd ACM SIGPLAN International Conference on Programming Language Design and Implementation, Association for Computing Machinery, 2022, pp. 825–40, doi:10.1145/3519939.3523434.' short: M.J. Sammler, A. Hammond, R. Lepigre, B. Campbell, J. Pichon-Pharabod, D. Dreyer, D. Garg, P. Sewell, in:, Proceedings of the 43rd ACM SIGPLAN International Conference on Programming Language Design and Implementation, Association for Computing Machinery, 2022, pp. 825–840. conference: end_date: 2022-06-17 location: San Diego, CA, United States name: 'PLDI: Conference on Programming Language Design and Implementation' start_date: 2022-06-13 date_created: 2024-09-05T08:29:08Z date_published: 2022-06-09T00:00:00Z date_updated: 2024-09-10T11:08:03Z day: '09' doi: 10.1145/3519939.3523434 extern: '1' language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1145/3519939.3523434 month: '06' oa: 1 oa_version: Published Version page: 825-840 publication: Proceedings of the 43rd ACM SIGPLAN International Conference on Programming Language Design and Implementation publication_status: published publisher: Association for Computing Machinery quality_controlled: '1' scopus_import: '1' status: public title: 'Islaris: Verification of machine code against authoritative ISA semantics' type: conference user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345 year: '2022' ... --- _id: '17503' abstract: - lang: eng text: "Systems code often requires fine-grained control over memory layout and pointers, expressed using low-level (e.g., bitwise) operations on pointer values. Since these operations go beyond what basic pointer arithmetic in C allows, they are performed with the help of integer-pointer casts. Prior work has explored increasingly realistic memory object models for C that account for the desired semantics of integer-pointer casts while also being sound w.r.t. compiler optimisations, culminating in PNVI, the preferred memory object model in ongoing discussions within the ISO WG14 C standards committee. However, its complexity makes it an unappealing target for verification, and no tools currently exist to verify C programs under PNVI.\r\nIn this paper, we introduce VIP, a new memory object model aimed at supporting C verification. VIP sidesteps the complexities of PNVI with a simple but effective idea: a new construct that lets programmers express the intended provenances of integer-pointer casts explicitly. At the same time, we prove VIP compatible with PNVI, thus enabling verification on top of VIP to benefit from PNVI’s validation with respect to practice. In particular, we build a verification tool, RefinedC-VIP, for verifying programs under VIP semantics. As the name suggests, RefinedC-VIP extends the recently developed RefinedC tool, which is automated yet also produces foundational proofs in Coq. We evaluate RefinedC-VIP on a range of systems-code idioms, and validate VIP’s expressiveness via an implementation in the Cerberus C semantics." article_processing_charge: No article_type: original author: - first_name: Rodolphe full_name: Lepigre, Rodolphe last_name: Lepigre - first_name: Michael Joachim full_name: Sammler, Michael Joachim id: 510d3901-2a03-11ee-914d-d9ae9011f0a7 last_name: Sammler - first_name: Kayvan full_name: Memarian, Kayvan last_name: Memarian - first_name: Robbert full_name: Krebbers, Robbert last_name: Krebbers - first_name: Derek full_name: Dreyer, Derek last_name: Dreyer - first_name: Peter full_name: Sewell, Peter last_name: Sewell citation: ama: 'Lepigre R, Sammler MJ, Memarian K, Krebbers R, Dreyer D, Sewell P. VIP: Verifying real-world C idioms with integer-pointer casts. Proceedings of the ACM on Programming Languages. 2022;6(POPL):1-32. doi:10.1145/3498681' apa: 'Lepigre, R., Sammler, M. J., Memarian, K., Krebbers, R., Dreyer, D., & Sewell, P. (2022). VIP: Verifying real-world C idioms with integer-pointer casts. Proceedings of the ACM on Programming Languages. Association for Computing Machinery. https://doi.org/10.1145/3498681' chicago: 'Lepigre, Rodolphe, Michael Joachim Sammler, Kayvan Memarian, Robbert Krebbers, Derek Dreyer, and Peter Sewell. “VIP: Verifying Real-World C Idioms with Integer-Pointer Casts.” Proceedings of the ACM on Programming Languages. Association for Computing Machinery, 2022. https://doi.org/10.1145/3498681.' ieee: 'R. Lepigre, M. J. Sammler, K. Memarian, R. Krebbers, D. Dreyer, and P. Sewell, “VIP: Verifying real-world C idioms with integer-pointer casts,” Proceedings of the ACM on Programming Languages, vol. 6, no. POPL. Association for Computing Machinery, pp. 1–32, 2022.' ista: 'Lepigre R, Sammler MJ, Memarian K, Krebbers R, Dreyer D, Sewell P. 2022. VIP: Verifying real-world C idioms with integer-pointer casts. Proceedings of the ACM on Programming Languages. 6(POPL), 1–32.' mla: 'Lepigre, Rodolphe, et al. “VIP: Verifying Real-World C Idioms with Integer-Pointer Casts.” Proceedings of the ACM on Programming Languages, vol. 6, no. POPL, Association for Computing Machinery, 2022, pp. 1–32, doi:10.1145/3498681.' short: R. Lepigre, M.J. Sammler, K. Memarian, R. Krebbers, D. Dreyer, P. Sewell, Proceedings of the ACM on Programming Languages 6 (2022) 1–32. date_created: 2024-09-05T08:31:09Z date_published: 2022-01-12T00:00:00Z date_updated: 2024-09-10T09:48:57Z day: '12' doi: 10.1145/3498681 extern: '1' intvolume: ' 6' issue: POPL language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1145/3498681 month: '01' oa: 1 oa_version: Published Version page: 1-32 publication: Proceedings of the ACM on Programming Languages publication_identifier: issn: - 2475-1421 publication_status: published publisher: Association for Computing Machinery quality_controlled: '1' scopus_import: '1' status: public title: 'VIP: Verifying real-world C idioms with integer-pointer casts' type: journal_article user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345 volume: 6 year: '2022' ... --- _id: '17504' abstract: - lang: eng text: "Today’s compilers employ a variety of non-trivial optimizations to achieve good performance. One key trick compilers use to justify transformations of concurrent programs is to assume that the source program has no data races: if it does, they cause the program to have undefined behavior (UB) and give the compiler free rein. However, verifying correctness of optimizations that exploit this assumption is a non-trivial problem. In particular, prior work either has not proven that such optimizations preserve program termination (particularly non-obvious when considering optimizations that move instructions out of loop bodies), or has treated all synchronization operations as external functions (losing the ability to reorder instructions around them).\r\nIn this work we present Simuliris, the first simulation technique to establish termination preservation (under a fair scheduler) for a range of concurrent program transformations that exploit UB in the source language. Simuliris is based on the idea of using ownership to reason modularly about the assumptions the compiler makes about programs with well-defined behavior. This brings the benefits of concurrent separation logics to the space of verifying program transformations: we can combine powerful reasoning techniques such as framing and coinduction to perform thread-local proofs of non-trivial concurrent program optimizations. Simuliris is built on a (non-step-indexed) variant of the Coq-based Iris framework, and is thus not tied to a particular language. In addition to demonstrating the effectiveness of Simuliris on standard compiler optimizations involving data race UB, we also instantiate it with Jung et al.’s Stacked Borrows semantics for Rust and generalize their proofs of interesting type-based aliasing optimizations to account for concurrency." article_processing_charge: No article_type: original author: - first_name: Lennard full_name: Gäher, Lennard last_name: Gäher - first_name: Michael Joachim full_name: Sammler, Michael Joachim id: 510d3901-2a03-11ee-914d-d9ae9011f0a7 last_name: Sammler - first_name: Simon full_name: Spies, Simon last_name: Spies - first_name: Ralf full_name: Jung, Ralf last_name: Jung - first_name: Hoang-Hai full_name: Dang, Hoang-Hai last_name: Dang - first_name: Robbert full_name: Krebbers, Robbert last_name: Krebbers - first_name: Jeehoon full_name: Kang, Jeehoon last_name: Kang - first_name: Derek full_name: Dreyer, Derek last_name: Dreyer citation: ama: 'Gäher L, Sammler MJ, Spies S, et al. Simuliris: A separation logic framework for verifying concurrent program optimizations. Proceedings of the ACM on Programming Languages. 2022;6(POPL):1-31. doi:10.1145/3498689' apa: 'Gäher, L., Sammler, M. J., Spies, S., Jung, R., Dang, H.-H., Krebbers, R., … Dreyer, D. (2022). Simuliris: A separation logic framework for verifying concurrent program optimizations. Proceedings of the ACM on Programming Languages. Association for Computing Machinery. https://doi.org/10.1145/3498689' chicago: 'Gäher, Lennard, Michael Joachim Sammler, Simon Spies, Ralf Jung, Hoang-Hai Dang, Robbert Krebbers, Jeehoon Kang, and Derek Dreyer. “Simuliris: A Separation Logic Framework for Verifying Concurrent Program Optimizations.” Proceedings of the ACM on Programming Languages. Association for Computing Machinery, 2022. https://doi.org/10.1145/3498689.' ieee: 'L. Gäher et al., “Simuliris: A separation logic framework for verifying concurrent program optimizations,” Proceedings of the ACM on Programming Languages, vol. 6, no. POPL. Association for Computing Machinery, pp. 1–31, 2022.' ista: 'Gäher L, Sammler MJ, Spies S, Jung R, Dang H-H, Krebbers R, Kang J, Dreyer D. 2022. Simuliris: A separation logic framework for verifying concurrent program optimizations. Proceedings of the ACM on Programming Languages. 6(POPL), 1–31.' mla: 'Gäher, Lennard, et al. “Simuliris: A Separation Logic Framework for Verifying Concurrent Program Optimizations.” Proceedings of the ACM on Programming Languages, vol. 6, no. POPL, Association for Computing Machinery, 2022, pp. 1–31, doi:10.1145/3498689.' short: L. Gäher, M.J. Sammler, S. Spies, R. Jung, H.-H. Dang, R. Krebbers, J. Kang, D. Dreyer, Proceedings of the ACM on Programming Languages 6 (2022) 1–31. date_created: 2024-09-05T08:32:16Z date_published: 2022-01-12T00:00:00Z date_updated: 2024-09-10T09:48:37Z day: '12' doi: 10.1145/3498689 extern: '1' intvolume: ' 6' issue: POPL language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1145/3498689 month: '01' oa: 1 oa_version: Published Version page: 1-31 publication: Proceedings of the ACM on Programming Languages publication_identifier: issn: - 2475-1421 publication_status: published publisher: Association for Computing Machinery quality_controlled: '1' scopus_import: '1' status: public title: 'Simuliris: A separation logic framework for verifying concurrent program optimizations' type: journal_article user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345 volume: 6 year: '2022' ...