cometadata/datacite-rtg-text-other-reclassification-records huggingface dataset:
Enabling Genetic Code Expansion and Peptide Macrocyclization in mRNA Display via a Promiscuous Orthogonal Aminoacyl-tRNA Synthetase
Creators: name: Baldwin, Albert S.
name: Iskandar, Sabrina E.
name: Pelton, Jarrett M.
name: Brown, Nicholas G.
name: Wick, Elizaveta T.
name: Emanuele, Michael J.
name: Bowers, Albert A.
name: Bolhuis, Derek L.
Publisher: name: American Chemical Society (ACS)
Year: 2023

description:
mRNA display is revolutionizing peptide drug discovery through its ability to quickly identify potent peptide binders of therapeutic protein targets. Methods to expand the chemical diversity of display libraries are continually needed to increase the likelihood of identifying clinically relevant peptide ligands. Orthogonal aminoacyl-tRNA synthetases (ORSs) have proven utility in cellular genetic code expansion, but are relatively underexplored for in vitro translation (IVT) and mRNA display. Herein, we demonstrate that the promiscuous ORS p-CNF-RS can incorporate noncanonical amino acids at amber codons in IVT, including the novel substrate p-cyanopyridylalanine (p-CNpyrA), to enable a pyridine-thiazoline (pyr-thn) macrocyclization in mRNA display. Pyr-thn-based selections against the deubiquitinase USP15 yielded a potent macrocyclic binder that exhibits good selectivity for USP15 and close homologues over other ubiquitin-specific proteases (USPs). Overall, this work exemplifies how promiscuous ORSs can both expand side chain diversity and provide structural novelty in mRNA display libraries through a heterocycle forming macrocyclization.
Theratta shola Anilkumar & Wesener & Moritz 2022, n. sp.
Creators: name: Anilkumar, Pooja Avinipully
name: Wesener, Thomas
name: Moritz, Leif
Publisher: name: Zenodo
Year: 2022
Subjects: Biodiversity
Taxonomy
Animalia
Arthropoda
Diplopoda
Polyzoniida
Siphonotidae
Theratta
Theratta shola

description: Theratta shola n. sp. Anilkumar, Wesener & Moritz
Figs 10, 11
Diagnosis. In T. shola n. sp. the head is smaller, broader and stouter (Fig. 10A) than in T. mannavan n. sp., where it is long and pointed. Ozopore of the 5th body-ring is thicker, elevated and located slightly under the preceding metazonite (Fig. 10F), while the ozopores are not elevated in T. eravikulam n. sp., and not under the preceding metazonite in any other species of Theratta. All antennomeres with a row of striae on their anterior margin (Figs 10A, B), while they are present only on antennomeres 6 and 7 in T. mannavan n. sp. and completely absent in T. eravikulam n. sp.. T. shola n. sp. differs from T. mannavan n. sp. and T. eravikulam n. sp. by the presence of a thick line fold at the anterior region of the head, separating the labrum from the rest of the head (Fig. 10C). Prozonites devoid of striations in T. shola n. sp. (Fig. 10E) while they are present in T. mannavan n. sp. and T. eravikulam n. sp.. T. shola n. sp. legs slender (Fig. 10G) than in T. mannavan n. sp. and T. eravikulam n. sp. (Fig. 8H). Sternite of anterior gonopod folded centrally on anterior side. Posterior gonopods with six podomeres. Podomere VI with three spine-like processes (Fig. 11E).
Etymology. Species epithet, shola, noun in apposition, after the name of the vegetation type at the type locality, the Shola forest.
Material examined. 1 immature M holotype (ZFMK-MYR 9767 A), 1 F paratype (ZFMK-MYR 9767), India, Province Kerala, Idukki District, Munnar, Eravikulam National Park, Erechipetta shola, Waterfalls, 10º10’28.0”N, 77º05’20.1”E, 1929 m, high altitude montane forest, hand collection, leg. A. A. Pooja, J. Jithin, 13 Dec 2019.
Note. The holotype is an immature male.
description: Published as part of Anilkumar, Pooja Avinipully, Wesener, Thomas & Moritz, Leif, 2022, First record of the order Polyzoniida from the Indian subcontinent with an integrative description of a new genus (Diplopoda, Colobognatha, Siphonotidae), pp. 401-428 in Zootaxa 5182 (5) on pages 417-420, DOI: 10.11646/zootaxa.5182.5.1, http://zenodo.org/record/7059565
Punctuation in Greek and Latin papyri and inscriptions
Creators: name: Marichal, Robert
Publisher: name: NAKALA - https://nakala.fr (Huma-Num - CNRS)
publisherIdentifier: https://ror.org/04ces3204
publisherIdentifierScheme: ROR
Year: 2015

description: vue 67
description: "In spite of the title written on the cover page of the folder ('Diplé'), the material collected inside concerns, more in general, punctuation and abbreviations in Greek and Latin papyri. A detailed list of (Greek?) papyri from Oxyrynchus papyri collection showing signs of punctuation; sheets collected in a folder called 'Ponctuation'. - Detailed annotations on abbreviations and punctuation on Tabula Banasitana and P. Mich. 442; transcription of Tabula Banasitana with handwritten corrections. List of Greek papyri showing abbreviatoins and punctuations, and bibliographical references. - Private letter on the meaning of an abbreviation found in a Roman inscription."
description: Source: 4MAR_8_2_5-13.3
description: created: n.d., 1958
Stochastic Approximation with Decision-Dependent Distributions: Asymptotic Normality and Optimality
Creators: name: Cutler, Joshua
name: Díaz, Mateo
name: Drusvyatskiy, Dmitriy
Publisher: name: arXiv
Year: 2022
Subjects: subject: Optimization and Control (math.OC)
subject: Machine Learning (cs.LG)
subject: Machine Learning (stat.ML)
subject: FOS: Mathematics
subject: FOS: Computer and information sciences
subject: 90C15, 90C25

description: We analyze a stochastic approximation algorithm for decision-dependent problems, wherein the data distribution used by the algorithm evolves along the iterate sequence. The primary examples of such problems appear in performative prediction and its multiplayer extensions. We show that under mild assumptions, the deviation between the average iterate of the algorithm and the solution is asymptotically normal, with a covariance that clearly decouples the effects of the gradient noise and the distributional shift. Moreover, building on the work of Hájek and Le Cam, we show that the asymptotic performance of the algorithm with averaging is locally minimax optimal.
description: 49 pages, 1 figure. v2: revised asymptotic optimality results and reworked exposition. v3: minor updates
Sorex (Otisorex) fumeus G. M. Miller 1895
Creators: name: Wilson, Don E.
name: Reeder, DeeAnn
Publisher: name: The Johns Hopkins University Press
Year: 2005
Subjects: Biodiversity
Taxonomy
Animalia
Chordata
Mammalia
Soricomorpha
Soricidae
Sorex
Sorex fumeus

description: Sorex (Otisorex) fumeus G. M. Miller 1895
Sorex (Otisorex) fumeus G. M. Miller 1895, N. Amer. Fauna, 10: 50.
Type Locality: USA, "Peterboro [Madison Co.], New York.".
Vernacular Names: Smoky Shrew.
Subspecies::
Subspecies Sorex (Otisorex) fumeus subsp. fumeus G. M. Miller 1895
Subspecies Sorex (Otisorex) fumeus subsp. umbrosus Jackson 1917
Distribution: S Ontario, S Quebec, New Brunswick, and Nova Scotia (Canada); all of New England and Appalachian Mtns and adjacent areas to NE Georgia (USA).
Conservation: IUCN – Lower Risk (lc).
Discussion: Subgenus Otisorex. Reviewed by Owen (1984, Mammalian Species No. 215). Karyotype has 2n = 66, FN = 98. Overlaps in distribution and may be easily confused with arcticus in part of its range (Junge and Hoffmann, 1981).
description: Published as part of Wilson, Don E. & Reeder, DeeAnn, 2005, Order Soricomorpha, pp. 220-311 in Mammal Species of the World: a Taxonomic and Geographic Reference (3 rd Edition), Volume 1, Baltimore :The Johns Hopkins University Press on page 288, DOI: 10.5281/zenodo.7316519
A Bivalent Human Norovirus Vaccine Induces Homotypic and Heterotypic Neutralizing Antibodies
Creators: name: Ramani, Sasirekha
name: Ettayebi, Khalil
name: Sherwood, James
name: Atmar, Robert L
name: Estes, Mary K
name: Neill, Frederick H
name: Lindesmith, Lisa
name: Baric, Ralph S
name: Brinkman, Amanda
name: Braun, Ralph
Publisher: name: Oxford University Press (OUP)
Year: 2023

description:
A GII.2 outbreak in an efficacy study of a bivalent virus-like particle norovirus vaccine, TAK-214, in healthy US adults provided an opportunity to examine GII.4 homotypic vs GII.2 heterotypic responses to vaccination and infection. Three serologic assays-virus-like particle binding, histoblood group antigen blocking, and neutralizing-were performed for each genotype. Results were highly correlated within a genotype but not between genotypes. Although the vaccine provided protection from GII.2-associated disease, little GII.2-specific neutralization occurred after vaccination. Choice of antibody assay can affect assessments of human norovirus vaccine immunogenicity.
A living ex vivo platform for functional, personalized brain cancer diagnosis
Creators: name: Kram, David
name: Rego, Stephen
name: Vaziri, Cyrus
name: Satterlee, Andrew B.
name: Graves, Lee M.
name: Valdivia, Alain
name: Corcoran, David L.
name: Adefolaju, Adebimpe
name: Thang, Morrent
name: Hingtgen, Shawn
name: Quinsey, Carolyn
name: Mann, Breanna
name: Bell, Noah
name: Rauf, Yasmeen
name: Cassidy, Noah
name: Floyd, Scott
name: Baldwin, Albert
name: Dunn, Denise
name: Zhang, Xiaopei
name: Lettry, Vivien
name: Jiang, Yuchao
name: Dasari, Rajaneekar
name: Kanchi, Krishna
name: Buckley, Andrew
name: Yang, Yang
Publisher: name: Elsevier
Year: 2023

description:
Functional precision medicine platforms are emerging as promising strategies to improve pre-clinical drug testing and guide clinical decisions. We have developed an organotypic brain slice culture (OBSC)-based platform and multi-parametric algorithm that enable rapid engraftment, treatment, and analysis of uncultured patient brain tumor tissue and patient-derived cell lines. The platform has supported engraftment of every patient tumor tested to this point: high- and low-grade adult and pediatric tumor tissue rapidly establishes on OBSCs among endogenous astrocytes and microglia while maintaining the tumor's original DNA profile. Our algorithm calculates dose-response relationships of both tumor kill and OBSC toxicity, generating summarized drug sensitivity scores on the basis of therapeutic window and allowing us to normalize response profiles across a panel of U.S. Food and Drug Administration (FDA)-approved and exploratory agents. Summarized patient tumor scores after OBSC treatment show positive associations to clinical outcomes, suggesting that the OBSC platform can provide rapid, accurate, functional testing to ultimately guide patient care.
Cheiloneurus Westwood 1833
Creators: name: Wang, Haiyang
name: Zhang, Chenghui
name: Xue, Hao
name: Xi, Chunxiang
name: Yang, Zening
name: Zu, Guohao
Publisher: name: Zenodo
Year: 2023
Subjects: Biodiversity
Taxonomy
Animalia
Arthropoda
Insecta
Hymenoptera
Encyrtidae
Cheiloneurus

description: Genus Cheiloneurus Westwood, 1833
6. Cheiloneurus chinensis Si & Wang, 1994
7. Cheiloneurus elegans (Dalman, 1820)
description: Published as part of Wang, Haiyang, Zhang, Chenghui, Xue, Hao, Xi, Chunxiang, Yang, Zening & Zu, Guohao, 2023, Encyrtidae (Hymenoptera: Chalcidoidea) from China, with the description of two new species, pp. 237-251 in Zootaxa 5361 (2) on page 248, DOI: 10.11646/zootaxa.5361.2.5, http://zenodo.org/record/10150921
Trifolium lappaceum Linnaeus 1753
Creators: name: Jarvis, Charlie
Publisher: name: Linnaean Society of London in association with the Natural History Museum
Year: 2007
Subjects: Biodiversity
Taxonomy
Plantae
Tracheophyta
Magnoliopsida
Fabales
Fabaceae
Trifolium
Trifolium lappaceum

description: Trifolium lappaceum Linnaeus, Species Plantarum 2: 768. 1753.
"Habitat Monspelii." RCN: 5655.
Type not designated.
Original material: none traced.
Current name: Trifolium lappaceum L. (Fabaceae: Faboideae).
Note: Many authors have followed Zohary (in Candollea 27: 144. 1972) in treating 930.28 (LINN) as the type. However, this sheet is not annotated in a way to link it to this name, and is indeed the lectotype of another species, T. alpestre L. Although it is possible that Zohary cited sheet 930.28 in error for 930.23 (apparently original material for this name), this cannot be safely assumed, and the name remains at present untypified.
description: Published as part of Jarvis, Charlie, 2007, Chapter 7: Linnaean Plant Names and their Types (part T), pp. 878-905 in Order out of Chaos. Linnaean Plant Types and their Types, London :Linnaean Society of London in association with the Natural History Museum on page 898, DOI: 10.5281/zenodo.291971
Paraclius parenti Capellari & Amorim, 2009, sp. nov.
Creators: name: Capellari, Renato Soares
name: Amorim, Dalton De Souza
Publisher: name: Zenodo
Year: 2009
Subjects: Biodiversity
Taxonomy
Animalia
Arthropoda
Insecta
Diptera
Dolichopodidae
Paraclius
Paraclius parenti

description: Paraclius parenti, sp. nov.
(Figs. 3–4, 15–16)
Diagnosis. First flagellomere almost rectangular, not pointed at apex; basal article of stylus about half the length of distal article. Two short black setae dorsally on proepisternum and scattered white setulae. Phallus without ornamentation except serrate ventral surface of apex; hypandrium harpoon-shaped in lateral view.
Material examined. Holotype 3, BRAZIL, Pernambuco, Recife, Parque dos Dois Irmãos, 1 3, track 3, Malaise trap, 17–20.vii.2002, S. T. P. Amarante e eq. cols. Paratypes: 1 3, same data as holotype, except track 5; same, but 1 3, track 3; same, but 2 3, track 1.
Description. Very similar to P. amphiatheratus except by the features listed in the diagnosis and the following details. Male. Body length, 2.9–3.1. Wing (Fig. 16), 2.5–2.7 long, 0.9–1.0 wide. Male antennae as in Fig. 15. Leg measures: I: 0.9, 0.9, 0.4, 0.1, 0.1, 0.1, 0.1. II: 1.2, 1.2, 0.5, 0.3, 0.2, 0.2, 0.1. III: 1.2, 1.3, 0.4, 0.5, 0.3, 0.2, 0.1. Hypopygium as in Figs. 3–4. Sperm pump slightly enlarged and weakly folded back over itself
Etymology. This species is named after the French abbot and dipterist Octave Parent (1882–1942), who extensively contributed to the development of the taxonomy of Dolichopodidae.
Comments. This species resembles Paraclius dicrophallus, sp. nov. in the rectangular male first flagellomere, but can be easily separated from it by the shape of the phallus (simple, not furcated in P. parenti, sp. nov., Figs. 3–4, and divided mesally at apex into a pair of stems in P. dicrophallus, sp. nov., Figs. 7–8) and of the hypandrium (harpoon-shaped in P. parenti, sp. nov., Fig. 3, and laterally forked into two stems in P. dicrophallus, sp. nov., Figs. 7–8).
description: Published as part of Capellari, Renato Soares & Amorim, Dalton De Souza, 2009, Four new species of Paraclius Loew (Diptera: Dolichopodidae) from the Brazilian Atlantic Forest, and notes on the systematic position of Cheiromyia Dyte, pp. 51-61 in Zootaxa 2274 on pages 54-55, DOI: 10.5281/zenodo.191040
title: EU-Taxonomie in der Bauabwicklung
Creators: name: Raab, Jacqueline
name: Kapeller, Markus
name: Weigert, Maximilian
Publisher: name: TU Wien
Year: 2024
Subjects: Bauwirtschaft
EU-Taxonomie-Verordnung
Umweltschutz
Ressourcenschonendes Bauen
Klimaschutz

description: Veranstaltungsbericht zu den 14. Wiener Gesprächen
description: Das Institut für Baubetrieb und Bauwirtschaft der TU Wien veranstaltete Mitte November 2024 bereits zum 14. Mal die Wiener Gespräche. In diesem Jahr drehte sich alles um das in der Baubranche brennende Thema der EU-Taxonomie in der Bauabwicklung. Dieser Beitrag erläutert Kernthemen und wesentliche Anforderungen für die Branche und reflektiert die zentralen Ereignisse der Abendveranstaltung.
Eotopus Noyes & Hayat 1984
Creators: name: Wang, Haiyang
name: Zhang, Chenghui
name: Xue, Hao
name: Xi, Chunxiang
name: Yang, Zening
name: Zu, Guohao
Publisher: name: Zenodo
Year: 2023
Subjects: Biodiversity
Taxonomy
Animalia
Arthropoda
Insecta
Hymenoptera
Encyrtidae
Eotopus

description: Genus Eotopus Noyes & Hayat, 1984
12. Eotopus beneficus (Shafee, 1981)
description: Published as part of Wang, Haiyang, Zhang, Chenghui, Xue, Hao, Xi, Chunxiang, Yang, Zening & Zu, Guohao, 2023, Encyrtidae (Hymenoptera: Chalcidoidea) from China, with the description of two new species, pp. 237-251 in Zootaxa 5361 (2) on page 248, DOI: 10.11646/zootaxa.5361.2.5, http://zenodo.org/record/10150921
An EZH2-NF-κB regulatory axis drives expression of pro-oncogenic gene signatures in triple negative breast cancer
Creators: name: Dardis, Gabrielle J
name: Wang, Jun
name: Wang, Gang Greg
name: Baldwin, Albert S
name: Simon, Jeremy M
Publisher: name: Elsevier
Year: 2023

description:
The histone methyltransferase EZH2 has been studied most extensively in the context of PRC2-dependent gene repression. Accumulating evidence indicates non-canonical functions for EZH2 in cancer contexts including promoting paradoxical gene expression through interactions with transcription factors, including NF-κB in triple negative breast cancer (TNBC). We profile EZH2 and NF-κB factor co-localization and positive gene regulation genome-wide, and define a subset of NF-κB targets and genes associated with oncogenic functions in TNBC that is enriched in patient datasets. We demonstrate interaction between EZH2 and RelA requiring the recently identified transactivation domain (TAD) which mediates EZH2 recruitment to, and activation of certain NF-κB-dependent genes, and supports downstream migration and stemness phenotypes in TNBC cells. Interestingly, EZH2-NF-κB positive regulation of genes and stemness does not require PRC2. This study provides new insight into pro-oncogenic regulatory functions for EZH2 in breast cancer through PRC2-independent, and NF-κB-dependent regulatory mechanisms.
Asymmetric Claisen-Cope rearrangements
Creators: name: Breinsperger, Johanna
name: Kaiser, Maximilian
name: Gärtner, Peter
Publisher: name: TU Wien
Year: 2024
Subjects: Rearrangement
Asymmetric Synthesis
Claisen-Cope

description: The Claisen rearrangement of allylic aryl ethers typically results in the formation of ortho-allylated phenols. However, if the ortho positions are substituted, a Cope-rearrangement occurs to the para position, concluding the Claisen-Cope reaction. These [3,3]-sigmatropic rearrangements feature a transition state comprising a cyclic array of continuously bonded atoms, which enables high predictability in terms of connectivity and configuration. The aforementioned ability for stereocontrol has led to the development of a limited number of methods for the ortho Claisen rearrangement in recent years. In contrast, the asymmetric para Claisen-Cope rearrangement has been largely overlooked until now.
title: Irrigation
title: Irrigation
titleType: AlternativeTitle
title: Irrigated argriculture
titleType: AlternativeTitle
Creators: name: Charbonnier, Julien
Publisher: name: NAKALA - https://nakala.fr (Huma-Num - CNRS)
publisherIdentifier: https://ror.org/04ces3204
publisherIdentifierScheme: ROR
Year: 2023
Subjects: Irrigation
Arabia
Pre-Islamic period
Agriculture
Hydraulic engineering
Water management
Land use

description: Charbonnier, Julien, 2023. "Irrigation". Thematic Dictionary of Ancient Arabia. Online edition 2023.
description: Source: https://doi.org/10.60667/tdaa-0066
description: Charbonnier, Julien, 2023. "Irrigation". Thematic Dictionary of Ancient Arabia. Online edition 2023.
AGC kinase inhibitors regulate STING signaling through SGK-dependent and SGK-independent mechanisms
Creators: name: Li, Kelin
name: Aubé, Jeff
name: Castillo Cabrera, Johnny
name: Dang, Hong
name: Damania, Blossom
name: King, Zayna
name: Bear, James E
name: Torres-Castillo, Jose
name: Zhang, Zhigang
name: Hagan, Robert S
name: Graves, Adam
name: Baldwin, Albert S
name: Liu, Pengda
Publisher: name: Elsevier
Year: 2023

description:
Type 1 IFN expression is critical in the innate immune response, but aberrant expression is associated with autoimmunity and cancer. Here, we identify N-[4-(1H46 pyrazolo[3,4-b] pyrazin-6-yl)-phenyl]-sulfonamide (Sanofi-14h), a compound with preference for inhibition of the AGC family kinase SGK3, as an inhibitor of Ifnb1 gene expression in response to STING stimulation of macrophages. Sanofi-14h abrogated SGK activity and also impaired activation of the critical TBK1/IRF3 pathway downstream of STING activation, blocking interaction of STING with TBK1. Deletion of SGK1/3 in a macrophage cell line did not block TBK1/IRF3 activation but decreased expression of transcription factors, such as IRF7 and STAT1, required for the innate immune response. Other AGC kinase inhibitors blocked TBK1 and IRF3 activation suggesting common action on a critical regulatory node in the STING pathway. These studies reveal both SGK-dependent and SGK-independent mechanisms in the innate immune response and indicate an approach to block aberrant Ifnb1 expression.
Mid-Term Technical Report. Part B. Version 1.0
Creators: name: Rouhani, Amir
name: Jomaa, Seifeddine
Publisher: name: Zenodo
Year: 2025

description: The Mid-Term Technical Report summarizes the progress of work carried out by 15 partners from ten countries, Germany, Spain, France, Greece, Italy, Jordan, Morocco, Portugal, Tunisia, and Türkiye, between June 2023 and December 2024. The report analyses the project objectives and the degree of fulfilment for each. Additionally, it includes progress updates for each work package (WP), a review of the expected impacts, and details on the Exploitation and Dissemination Plan, as well as the Data Management Plan. Finally, it outlines any deviations from the original proposal. 
description: This project is part of the PRIMA Programme supported by the European Union’s Horizon 2020 Research and Innovation Programme under Grant Agreement No 2222
Production of a p65fl/fl/LysMCre mouse model with dysfunctional NF-κB signaling in bone marrow-derived macrophages
Creators: name: Peppers, Anthony
name: Baldwin, Albert S.
name: Korkaya, Ahmet K.
name: Miao, Edward A.
name: Rayamajhi, Manira
name: Crosson, Sean M.
name: Bradford, Jennifer W.
name: Fischer, Jeffrey
Publisher: name: SAGE Publications
Year: 2023

description:
Here, we describe the production and characterization of a novel p65fl/fl/LysMCre mouse model, which lacks canonical nuclear factor-kappaB member RelA/p65 (indicated as p65 hereafter) in bone marrow-derived macrophages. Cultured bone marrow-derived macrophages that lack p65 protein reveal NF-κB signaling deficiencies, a reduction in phagocytic ability, and reduced ability to produce nitrites. Despite abnormal bone marrow-derived macrophage function, p65fl/fl/LysMCre mice do not exhibit differences in naïve systemic immune profiles or colony forming units and time to death following Salmonella infection as compared to controls. Additionally, p65fl/fl/LysMCre mice, especially females, display splenomegaly, but no other obvious physical or behavioral differences as compared to control animals. As bone marrow-derived macrophages from this transgenic model are almost completely devoid of canonical nuclear factor-kappaB pathway member p65, this model has the potential for being very useful in investigating bone marrow-derived macrophage NF-kappaB signaling in diverse biological and biomedical studies.
Dynamics of qudit gates and effects of spectator modes on optimal control pulses
Creators: name: Özgüler, A. Barış
name: Job, Joshua A.
Publisher: name: arXiv
Year: 2022
Subjects: subject: Quantum Physics (quant-ph)
subject: Emerging Technologies (cs.ET)
subject: FOS: Physical sciences
subject: FOS: Computer and information sciences

description: Qudit gates for high-dimensional quantum computing can be synthesized with high precision using numerical quantum optimal control techniques. Large circuits are broken down into modules and the tailored pulses for each module can be used as primitives for a qudit compiler. Application of the pulses of each module in the presence of extra modes may decrease their effectiveness due to crosstalk. In this paper, we address this problem by simulating qudit dynamics for circuit quantum electrodynamics (cQED) systems. As a test case, we take pulses for single-qudit SWAP gates optimized in isolation and then apply them in the presence of spectator modes each of which are in Fock states. We provide an experimentally relevant scaling formula that can be used as a bound on the fidelity decay. Our results show that frequency shift from spectator mode populations has to be $\lesssim 0.1\%$ of the qudit's nonlinearity in order for high-fidelity single-qudit gates to be useful in the presence of occupied spectator modes.
description: 6 pages, 1 figure. Published in Physical Review A
Suntsova O. SOME ASPECTS OF MODELLING IMPACT OF PPP'S ASSETS ON ECONOMIC GROWTH: CASE OF UKRAINE'S RESTORE PROGRAMMS // ХХ International Scientific Conference «Problems of management of enterprises in modern conditions»: Book of abstracts. – 17-18 April 2024. – K.: National University of Food Technologies, 2024. – P. 187-191
Creators: name: Suntsova, Olesia
Publisher: name: Zenodo
Year: 2024

description: Public-private partnerships (PPPs) have emerged as an increasingly popular strategy for the implementation of diverse public policies, including marketing policies aimed at managing territorial economies. These partnerships facilitate collaboration between the public sector and private businesses, harnessing the respective strengths and resources of each to pursue common objectives. The PPP model has been widely adopted across various sectors such as infrastructure, education, health, and environmental conservation.

 

In the context of territorial economy management, PPPs present unique opportunities for implementing marketing policies that foster economic growth and development in specific regions. This model involves collaboration between government entities and private firms in delivering public services, with both parties sharing risks and rewards. PPPs can facilitate investment attraction, infrastructure development, and economic expansion, necessitating effective communication, cooperation, and contractual arrangements between public and private entities.
Trifolium lupinaster Linnaeus 1753
Creators: name: Jarvis, Charlie
Publisher: name: Linnaean Society of London in association with the Natural History Museum
Year: 2007
Subjects: Biodiversity
Taxonomy
Plantae
Tracheophyta
Magnoliopsida
Fabales
Fabaceae
Trifolium
Trifolium lupinaster

description: Trifolium lupinaster Linnaeus, Species Plantarum 2: 766. 1753.
"Habitat in Sibiria." RCN: 5645.
Lectotype (Gillett in Canad. J. Bot. 50: 1985. 1972): Herb. Linn. No. 930.13 (LINN).
Current name: Trifolium lupinaster L. (Fabaceae: Faboideae).
description: Published as part of Jarvis, Charlie, 2007, Chapter 7: Linnaean Plant Names and their Types (part T), pp. 878-905 in Order out of Chaos. Linnaean Plant Types and their Types, London :Linnaean Society of London in association with the Natural History Museum on page 898, DOI: 10.5281/zenodo.291971
Paraclius sagittatus Capellari & Amorim, 2009, sp. nov.
Creators: name: Capellari, Renato Soares
name: Amorim, Dalton De Souza
Publisher: name: Zenodo
Year: 2009
Subjects: Biodiversity
Taxonomy
Animalia
Arthropoda
Insecta
Diptera
Dolichopodidae
Paraclius
Paraclius sagittatus

description: Paraclius sagittatus, sp. nov.
(Figs. 5–6)
Diagnosis. First flagellomere pointed at apex; stylus articles about equal in length. A single tiny seta dorsally on proepisternum. Phallus without ornamentation; hypandrium with two lateral projections at apex, arrow-like in dorsal view.
Material examined. Holotype 3: BRAZIL, Espírito Santo, Linhares, Reserva Biológica de Sooterama, 18º58'02.7'' S 40º08'06.8'' W, track 5, Malaise trap, 24–27.iii.2002, C.O. Azevedo e eq. col.
Description. Very similar to P. amphiatheratus except by the features listed in the diagnosis and the following details. Male. Body length, 2.3. Wing 2.1 long, 0.8 wide. Leg measures: I: 0.6, 0.6, 0.3, 0.2, 0.1, 0.1, 0.1. II: 0.8, 0.9, 0.4, 0.3, 0.2, 0.1, 0.1. III: 1.0, 1.1, 0.3, 0.4, 0.2, 0.2, 0.1. Hypopygium as in Figs. 5 and 6. Sperm pump slightly enlarged, with an almost spherical shape, and greatly folded back over itself.
Etymology. From Greek “sagitta” (arrow), referring to the shape of hypandrium.
Comments. This species superficially resembles P. amphiatheratus, sp. nov. by the pointed male first flagellomere, but differs by the shape both of the phallus and hypandrium, as noted above.
description: Published as part of Capellari, Renato Soares & Amorim, Dalton De Souza, 2009, Four new species of Paraclius Loew (Diptera: Dolichopodidae) from the Brazilian Atlantic Forest, and notes on the systematic position of Cheiromyia Dyte, pp. 51-61 in Zootaxa 2274 on page 55, DOI: 10.5281/zenodo.191040
Mid-Term Technical Report. Part B. Version 1.4
Creators: name: Rouhani, Amir
name: Jomaa, Seifeddine
Publisher: name: Zenodo
Year: 2025

description: The Mid-Term Technical Report summarizes the progress of work carried out by 15 partners from ten countries, Germany, Spain, France, Greece, Italy, Jordan, Morocco, Portugal, Tunisia, and Türkiye, between June 2023 and December 2024. The report analyses the project objectives and the degree of fulfilment for each. Additionally, it includes progress updates for each work package (WP), a review of the expected impacts, and details on the Exploitation and Dissemination Plan, as well as the Data Management Plan. Finally, it outlines any deviations from the original proposal. 
description: This project is part of the PRIMA Programme supported by the European Union’s Horizon 2020 Research and Innovation Programme under Grant Agreement No 2222
Sorex (Otisorex) fumeus subsp. fumeus G. M. Miller 1895
Creators: name: Wilson, Don E.
name: Reeder, DeeAnn
Publisher: name: The Johns Hopkins University Press
Year: 2005
Subjects: Biodiversity
Taxonomy
Animalia
Chordata
Mammalia
Soricomorpha
Soricidae
Sorex
Sorex fumeus
Sorex (otisorex) fumeus subsp. fumeus g. m. miller 1895

description: Sorex (Otisorex) fumeus subsp. fumeus G. M. Miller 1895
Sorex (Otisorex) fumeus subsp. fumeus G. M. Miller 1895, N. Amer. Fauna, 10: 50.
Type Locality: USA, "Peterboro [Madison Co.], New York.".
description: Published as part of Wilson, Don E. & Reeder, DeeAnn, 2005, Order Soricomorpha, pp. 220-311 in Mammal Species of the World: a Taxonomic and Geographic Reference (3 rd Edition), Volume 1, Baltimore :The Johns Hopkins University Press on page 288, DOI: 10.5281/zenodo.7316519
Noncanonical HPV carcinogenesis drives radiosensitization of head and neck tumors
Creators: name: Hayward, Michele C.
name: Wu, Di
name: Xie, Yue
name: Flamand, Yael
name: Weir, William H.
name: Stepp, Wesley H.
name: Tasoulas, Jason
name: Kim, Sulgi
name: Yarbrough, Gray
name: Baldwin, Albert S.
name: Burtness, Barbara
name: Sewell, Andrew
name: Yarbrough, Wendell G.
name: Li, Xue
name: Rehmani, Hina
name: Schrank, Travis P.
name: Marur, Shanthi
name: Liu, Xinyi
name: Kothari, Aditi
name: Anderson, Karen S.
name: Wang, Xiaowei
name: Issaeva, Natalia
Publisher: name: Proceedings of the National Academy of Sciences
Year: 2023

description:
We analyzed transcriptional data from 104 HPV+ (Human papillomavirus) HNSCC (head and neck squamous cell carcinoma) tumors together with two publicly available sources to identify highly robust transcriptional programs (modules) which could be detected consistently despite heterogeneous sequencing and quantification methodologies. Among 22 modules identified, we found a single module that naturally subclassifies HPV+ HNSCC tumors based on a bimodal pattern of gene expression, clusters all atypical features of HPV+ HNSCC biology into a single subclass, and predicts patient outcome in four independent cohorts. The subclass-defining gene set was strongly correlated with Nuclear factor kappa B (NF-κB) target expression. Tumors with high expression of this NF-κB module were rarely associated with activating PIK3CA alterations or viral integration, and also expressed higher levels of HPHPV E2 and had decreased APOBEC mutagenesis. Alternatively, they harbored inactivating alterations of key regulators of NF-κB, TNF receptor associated factor 3 (TRAF3), and cylindromatosis (CYLD), as well as retinoblastoma protein (RB1). HPV+ HNSCC cells in culture with experimental depletion of TRAF3 or CYLD displayed increased expression of the subclass-defining genes, as well as robust radio-sensitization, thus recapitulating both the tumor transcriptional state and improved treatment response observed in patient data. Across all gene sets investigated, methylation to expression correlations were the strongest for the subclass-defining, NF-κB-related genes. Increased tumor-infiltrating CD4+ T cells and increased Estrogen receptors alpha (ERα) expression were identified in NF-κB active tumors. Based on the relatively high rates of cure in HPV+ HNSCC, deintensification of therapy to reduce treatment-related morbidity is being studied at many institutions. Tumor subclassification based on oncogenic subtypes may help guide the selection of therapeutic intensity or modality for patients with HPV+ HNSCC.
Trifolium medium Linnaeus 1759
Creators: name: Jarvis, Charlie
Publisher: name: Linnaean Society of London in association with the Natural History Museum
Year: 2007
Subjects: Biodiversity
Taxonomy
Plantae
Tracheophyta
Magnoliopsida
Fabales
Fabaceae
Trifolium
Trifolium medium

description: Trifolium medium Linnaeus, Amoenitates Academicae 4: 105. 1759.
"Habitat [in Anglia.]" RCN: 5658.
Lectotype (Zohary in Candollea 27: 118. 1972): Herb. Linn. No. 930.27 (LINN).
Current name: Trifolium medium L. (Fabaceae: Faboideae).
description: Published as part of Jarvis, Charlie, 2007, Chapter 7: Linnaean Plant Names and their Types (part T), pp. 878-905 in Order out of Chaos. Linnaean Plant Types and their Types, London :Linnaean Society of London in association with the Natural History Museum on page 898, DOI: 10.5281/zenodo.291971
ҲУҚУҚБУЗАРЛИКЛАР ПРОФИЛАКТИКАСИДА АХБОРОТ ТЕХНОЛОГИЯЛАРИ ЁРДАМИДА СОДИР ЭТИЛАДИГАН ҲУҚУҚБУЗАРЛИКЛАРНИНГ ОЛДИНИ ОЛИШ ФАОЛИЯТИ
Creators: name: ИИВ Академияси курсанти Рузиева Мубинабону Содикжон кизи
Publisher: name: Zenodo
Year: 2024

description: Ушбу маколада Ҳуқуқбузарликлар профилактикасида ахборот технологиялари ёрдамида содир этиладиган ҳуқуқбузарликлар тушунчаси ва унинг асосий турлари, шунингдек, шу турдаги ҳуқуқбузарликларнинг замонавий кўриниши ҳамда олдини олишнинг ўзига хос хусусиятлари. Бундан ташкари, ҳуқуқбузарликлар профилактикасида ахборот технологиялари ёрдамида содир этиладиган ҳуқуқбузарликларнинг олдини олиш фаолиятининг ҳуқуқий асослари, айрим турдаги мавжуд муаоммо ва камчиликларни бартараф этиш бўйича бир қатор таклифлар. Ҳуқуқбузарликлар профилактикасида ахборот технологиялари ёрдамида содир этиладиган ҳуқуқбузарликларнинг олдини олиш бўйича илғор хориж тажрибаси тахлили ҳамда фаолиятини такомилаштириш йўналишлари ёритиб ўтилган.

Калит сузлар:  хукукбузарликлар прафилактикаси, ахборот техналогиялар, кибер жиноятчилар, пароларни мустахкамлаш, 2022-2023 йилар статистикалари, хавфсизлик тушунчалари, ахборот технологиялари ёрдамида содир этиладиган ҳуқуқбузарликларнинг олдини олиш бўйича илғор хориж тажрибаси, ахборотлаштириш миллий тизимини шакллантириш, компютер техникаси ва телекоммуникациялар, фуқароларнинг ахборотга нисбатан ўсиб бораётган эҳтиёжларини иложи борича тўлиқ қондириш,
BCG vaccination stimulates integrated organ immunity by feedback of the adaptive immune response to imprint prolonged innate antiviral resistance
Creators: name: Powers, John M.
name: Leist, Sarah R.
name: Nolan, Garry P.
name: Pavenko, Anna
name: Lee, Audrey
name: Liang, Yan
name: Tan, Tze Kai
name: Froggatt, Heather M.
name: Gully, Kendra L.
name: Li, Chunfeng
name: Ruggiero, Alistaire D.
name: Hui, Harold
name: Scoville, David
name: Fang, Zhuoqing
name: Suthar, Mehul S.
name: Arunachalam, Prabhu S.
name: Baric, Ralph S.
name: Lujan, Victor
name: Floyd, Katharine
name: Wu, Shengyang
name: Pulendran, Bali
name: Hubbard, Miranda L.
Publisher: name: Springer Nature
Year: 2023

description:
Bacille Calmette–Guérin (BCG) vaccination can confer nonspecific protection against heterologous pathogens. However, the underlying mechanisms remain mysterious. We show that mice vaccinated intravenously with BCG exhibited reduced weight loss and/or improved viral clearance when challenged with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 B.1.351) or PR8 influenza. Protection was first evident between 14 and 21 d post-vaccination and lasted ∼3 months. Notably, BCG induced a biphasic innate response and robust antigen-specific type 1 helper T cell (TH1 cell) responses in the lungs. MyD88 signaling was essential for innate and TH1 cell responses, and protection against SARS-CoV-2. Depletion of CD4+ T cells or interferon (IFN)-γ activity before infection obliterated innate activation and protection. Single-cell and spatial transcriptomics revealed CD4-dependent expression of IFN-stimulated genes in lung myeloid and epithelial cells. Notably, BCG also induced protection against weight loss after mouse-adapted SARS-CoV-2 BA.5, SARS-CoV and SHC014 coronavirus infections. Thus, BCG elicits integrated organ immunity, where CD4+ T cells feed back on tissue myeloid and epithelial cells to imprint prolonged and broad innate antiviral resistance.
Sorex (Sorex) hosonoi Imaizumi 1954
Creators: name: Wilson, Don E.
name: Reeder, DeeAnn
Publisher: name: The Johns Hopkins University Press
Year: 2005
Subjects: Biodiversity
Taxonomy
Animalia
Chordata
Mammalia
Soricomorpha
Soricidae
Sorex
Sorex hosonoi

description: Sorex (Sorex) hosonoi Imaizumi 1954
Sorex (Sorex) hosonoi Imaizumi 1954, Bull. Natl. Sci. Mus. Tokyo, 35: 94.
Type Locality: "Tokiwa Mura (Maneki, about 900 m altitude, foot of Mt. Gaki, Japan Alps), Kita-Azumi Gun, Nagano Pref., Central Honsyû [= Honshu], Japan ".
Vernacular Names: Azumi Shrew.
Synonyms: Sorex (Sorex) shiroumanus Imaizumi 1954.
Distribution: Montane forests of C Honshu (Japan).
Conservation: IUCN – Vulnerable.
Discussion: Subgenus Sorex. Imaizumi (1970 b) reported that hosonoi occurs sympatrically with shinto and therefore should be considered as separate species (Corbet, 1978 c). Ohdachi et al. (1997 a, 2001) demonstrated that the species is genetically related to minutissimus.
description: Published as part of Wilson, Don E. & Reeder, DeeAnn, 2005, Order Soricomorpha, pp. 220-311 in Mammal Species of the World: a Taxonomic and Geographic Reference (3 rd Edition), Volume 1, Baltimore :The Johns Hopkins University Press on page 289, DOI: 10.5281/zenodo.7316519
Ericydnus Haliday 1832
Creators: name: Wang, Haiyang
name: Zhang, Chenghui
name: Xue, Hao
name: Xi, Chunxiang
name: Yang, Zening
name: Zu, Guohao
Publisher: name: Zenodo
Year: 2023
Subjects: Biodiversity
Taxonomy
Animalia
Arthropoda
Insecta
Hymenoptera
Encyrtidae
Ericydnus

description: Genus Ericydnus Haliday, 1832
13. Ericydnus infuscatus Liu, Wang, Li & Zhang, 2013
description: Published as part of Wang, Haiyang, Zhang, Chenghui, Xue, Hao, Xi, Chunxiang, Yang, Zening & Zu, Guohao, 2023, Encyrtidae (Hymenoptera: Chalcidoidea) from China, with the description of two new species, pp. 237-251 in Zootaxa 5361 (2) on page 248, DOI: 10.11646/zootaxa.5361.2.5, http://zenodo.org/record/10150921
Melilotus siculus B. D. Jacks.
Creators: name: Jarvis, Charlie
Publisher: name: Linnaean Society of London in association with the Natural History Museum
Year: 2007
Subjects: Biodiversity
Taxonomy
Plantae
Tracheophyta
Magnoliopsida
Fabales
Fabaceae
Melilotus
Melilotus siculus

description: Trifolium messanense Linnaeus, Mantissa Plantarum Altera: 275. 1771.
"Habitat in Sicilia. H.U." RCN: 5644.
Lectotype (Ali in Nasir & Ali, Fl. W. Pakistan 100: 308. 1977): Jacquin 9, Herb. Linn. No. 930.11 (LINN).
Current name: Melilotus siculus (Turra) B.D. Jacks. (Fabaceae: Faboideae).
description: Published as part of Jarvis, Charlie, 2007, Chapter 7: Linnaean Plant Names and their Types (part T), pp. 878-905 in Order out of Chaos. Linnaean Plant Types and their Types, London :Linnaean Society of London in association with the Natural History Museum on page 898, DOI: 10.5281/zenodo.291971
Sorex (Sorex) excelsus G. M. Allen 1923
Creators: name: Wilson, Don E.
name: Reeder, DeeAnn
Publisher: name: The Johns Hopkins University Press
Year: 2005
Subjects: Biodiversity
Taxonomy
Animalia
Chordata
Mammalia
Soricomorpha
Soricidae
Sorex
Sorex excelsus

description: Sorex (Sorex) excelsus G. M. Allen 1923
Sorex (Sorex) excelsus G. M. Allen 1923, Am. Mus. Novit., 100: 4.
Type Locality: "summit of Ho-shan (=Xue Shan), Pae-tai, 30 miles (48 km) south of Chung-tien (=Zhongdian), Yunnan, China, altitude 13000 feet [3962 m].".
Vernacular Names: Chinese Highland Shrew.
Distribution: Yunnan and Sichuan (China), and possibly Nepal.
Conservation: IUCN – Data Deficient.
Discussion: Subgenus Sorex. Considered as a possible subspecies of asper (Corbet, 1978 c) but retained as a full species related to tundrensis by Hoffmann (1987) who also suggested that a specimen from Nepal recorded by Agrawal and Chakraborty (1971) may represent excelsus. However, mtDNA data indicate that excelsus is neither related to asper nor to tundrensis (Fumagalli et al., 1999).
description: Published as part of Wilson, Don E. & Reeder, DeeAnn, 2005, Order Soricomorpha, pp. 220-311 in Mammal Species of the World: a Taxonomic and Geographic Reference (3 rd Edition), Volume 1, Baltimore :The Johns Hopkins University Press on page 287, DOI: 10.5281/zenodo.7316519
Paraclius dicrophallus Capellari & Amorim, 2009, sp. nov.
Creators: name: Capellari, Renato Soares
name: Amorim, Dalton De Souza
Publisher: name: Zenodo
Year: 2009
Subjects: Biodiversity
Taxonomy
Animalia
Arthropoda
Insecta
Diptera
Dolichopodidae
Paraclius
Paraclius dicrophallus

description: Paraclius dicrophallus, sp. nov.
(Figs. 7–8)
Diagnosis. First flagellomere almost rectangular, not pointed at apex; basal article about half the length of distal article of stylus. Three short black setae dorsally on proepisternum, with few scattered white setulae. Phallus divided mesally at apex into a pair of stems; hypandrium laterally forked into two stems, darker to the apex.
Material examined. Holotype 3: BRAZIL, Pernambuco, Recife, Parque dos Dois Irmãos, track 5, Malaise trap, 17–20.vii.2002, S. T. P. Amarante e eq. cols.
Description. Male. Body length, 3.3. Wing, 2.7 long, 0.9 wide. Very similar to P. amphiatheratus, sp. nov. by the features listed in diagnosis. Leg measures: I: 1.0, 0.8, 0.4, 0.1, 0.1, 0.1, 0.1. II: 1.2, 1.4, 0.5, 0.4, 0.2, 0.2, 0.1. III: 1.3, 1.2, 0.4, 0.6, 0.4, 0.3, 0.1. Hypopygium as in Figs. 7 and 8. Sperm pump slightly enlarged, but greatly folded back over itself.
Etymology. From the Greek, “dikros” (forked) and “phallus” (penis), referring to the bifurcated shape of the phallus in this species.
Comments. This species superficially resembles P. p a re n t i, sp. nov. by the rectangular male first flagellomere, but can be recognized by the shape of both the phallus and hypandrium, as noted above.
description: Published as part of Capellari, Renato Soares & Amorim, Dalton De Souza, 2009, Four new species of Paraclius Loew (Diptera: Dolichopodidae) from the Brazilian Atlantic Forest, and notes on the systematic position of Cheiromyia Dyte, pp. 51-61 in Zootaxa 2274 on pages 55-58, DOI: 10.5281/zenodo.191040
Exoristobia Ashmead 1904
Creators: name: Wang, Haiyang
name: Zhang, Chenghui
name: Xue, Hao
name: Xi, Chunxiang
name: Yang, Zening
name: Zu, Guohao
Publisher: name: Zenodo
Year: 2023
Subjects: Biodiversity
Taxonomy
Animalia
Arthropoda
Insecta
Hymenoptera
Encyrtidae
Exoristobia

description: Genus Exoristobia Ashmead, 1904
14. Exoristobia dipterae (Risbec, 1951)
15. Exoristobia sinica Zu & Li, 2020
description: Published as part of Wang, Haiyang, Zhang, Chenghui, Xue, Hao, Xi, Chunxiang, Yang, Zening & Zu, Guohao, 2023, Encyrtidae (Hymenoptera: Chalcidoidea) from China, with the description of two new species, pp. 237-251 in Zootaxa 5361 (2) on page 248, DOI: 10.11646/zootaxa.5361.2.5, http://zenodo.org/record/10150921
Economy in the Roman Egypt
Creators: name: Marichal, Robert
Publisher: name: NAKALA - https://nakala.fr (Huma-Num - CNRS)
publisherIdentifier: https://ror.org/04ces3204
publisherIdentifierScheme: ROR
Year: 2015

description: vue 41
description: Annotations and bibliographical references on several aspects of the economic life in Ancient Egypt. List of the topic written on the cover page of the folder: 'Economie antique', 'Civilisation', 'Monnaie', 'Fiscalité', xxx
description: Source: 4MAR_22_4_2
description: created: n.d., 1953
title: 'The education of the modern king, the constitutional king' : raising heirs to the throne in nineteenth century Spain
Creators: name: Meyer Forsting, Richard
Publisher: name: University of St Andrews
publisherIdentifier: https://ror.org/02wn5qz54
publisherIdentifierScheme: ROR
Year: 2017

description: This thesis analyses royal education in nineteenth-century, constitutional Spain. The main subjects of this investigations are Isabel II (1830-1904), Alfonso XII (1857-1885) and Alfonso XIII (1886-1941) during their time as monarchs-in-waiting. It will be argued that their upbringing was considered an opportunity to shape the future of Spain, reflected the political struggles that emerged in the course of the construction of a liberal state, and allowed for the modernisation of the monarchy. The upbringing of royal heirs was a subject taken seriously by contemporaries and at various points in time assumed a wider political, social and cultural significance. The thesis is structured around the three powerful groups that showed an active interest, influenced, and significantly shaped the education of heirs to the throne: the court, the military, and the public. The study aims to throw new light on the position of the Spanish monarchy in the constitutional state, its ability to adapt to social, political, and cultural change and its varied sources of legitimacy, power, and attraction. One of the central aims of the thesis is to contribute to scholars’ growing interest in nineteenth-century Spain and the re-establishment of the Peninsula’s history as an integral part of European historiography.
FGFR inhibition blocks NF-ĸB-dependent glucose metabolism and confers metabolic vulnerabilities in cholangiocarcinoma
Creators: name: Bardeesy, Nabeel
name: Balasooriya, Eranga R.
name: Juric, Dejan
name: Liu, Kai
name: Xu, Qin
name: Ellis, Haley
name: Morris, Robert
name: Haas, Wilhelm
name: Shi, Lei
name: Baldwin, Albert S.
name: Shah, Simran
name: Zhen, Yuanli
name: Kreuzer, Johannes
Publisher: name: Springer Nature
Year: 2024

description:
Genomic alterations that activate Fibroblast Growth Factor Receptor 2 (FGFR2) are common in intrahepatic cholangiocarcinoma (ICC) and confer sensitivity to FGFR inhibition. However, the depth and duration of response is often limited. Here, we conduct integrative transcriptomics, metabolomics, and phosphoproteomics analysis of patient-derived models to define pathways downstream of oncogenic FGFR2 signaling that fuel ICC growth and to uncover compensatory mechanisms associated with pathway inhibition. We find that FGFR2-mediated activation of Nuclear factor-κB (NF-κB) maintains a highly glycolytic phenotype. Conversely, FGFR inhibition blocks glucose uptake and glycolysis while inciting adaptive changes, including switching fuel source utilization favoring fatty acid oxidation and increasing mitochondrial fusion and autophagy. Accordingly, FGFR inhibitor efficacy is potentiated by combined mitochondrial targeting, an effect enhanced in xenograft models by intermittent fasting. Thus, we show that oncogenic FGFR2 signaling drives NF-κB-dependent glycolysis in ICC and that metabolic reprogramming in response to FGFR inhibition confers new targetable vulnerabilities.