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  1. Article ; Online: Intranasal delivery of low-dose anti-CD124 antibody enhances treatment of chronic rhinosinusitis with nasal polyps.

    Wu, Jiamin / Jones, Natalie / Chao, Po-Han / Chan, Vanessa / Hohenwarter, Lukas / Wu, Angeline / Bergamo, Marta / Rodríguez-Rodríguez, Cristina / Saatchi, Katayoun / Liang, Alex / Häfeli, Urs O / Tan, Zheng / Hedtrich, Sarah / Andrew, Lucas J / Li, Shyh-Dar

    Biomaterials

    2024  Volume 308, Page(s) 122567

    Abstract: Frequent injections of anti-CD124 monoclonal antibody (αCD124) over long periods of time are used to treat chronic rhinosinusitis with nasal polyps (CRSwNP). Needle-free, intranasal administration (i.n.) of αCD124 is expected to provide advantages of ... ...

    Abstract Frequent injections of anti-CD124 monoclonal antibody (αCD124) over long periods of time are used to treat chronic rhinosinusitis with nasal polyps (CRSwNP). Needle-free, intranasal administration (i.n.) of αCD124 is expected to provide advantages of localized delivery, improved efficacy, and enhanced medication adherence. However, delivery barriers such as the mucus and epithelium in the nasal tissue impede penetration of αCD124. Herein, two novel protamine nanoconstructs: allyl glycidyl ether conjugated protamine (Nano-P) and polyamidoamine-linked protamine (Dendri-P) were synthesized and showed enhanced αCD124 penetration through multiple epithelial layers compared to protamine in mice. αCD124 was mixed with Nano-P or Dendri-P and then intranasally delivered for the treatment of severe CRSwNP in mice. Micro-CT and pathological changes in nasal turbinates showed that these two nano-formulations achieved ∼50 % and ∼40 % reductions in nasal polypoid lesions and eosinophil count, respectively. Both nano-formulations provided enhanced efficacy in suppressing nasal and systemic Immunoglobulin E (IgE) and nasal type 2 inflammatory biomarkers, such as interleukin 13 (IL-13) and IL-25. These effects were superior to those in the protamine formulation group and subcutaneous (s.c.) αCD124 given at a 12.5-fold higher dose. Intranasal delivery of protamine, Nano-P, or Dendri-P did not induce any measurable toxicities in mice.
    MeSH term(s) Animals ; Female ; Mice ; Administration, Intranasal ; Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal/pharmacology ; Chronic Disease ; Mice, Inbred BALB C ; Nasal Polyps/drug therapy ; Nasal Polyps/pathology ; Protamines/chemistry ; Rhinosinusitis/drug therapy
    Chemical Substances Antibodies, Monoclonal ; Protamines
    Language English
    Publishing date 2024-04-06
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 603079-8
    ISSN 1878-5905 ; 0142-9612
    ISSN (online) 1878-5905
    ISSN 0142-9612
    DOI 10.1016/j.biomaterials.2024.122567
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Perm1 Protects the Heart From Pressure Overload-Induced Dysfunction by Promoting Oxidative Metabolism.

    Tachibana, Shizuko / Yu, Nam-Kyung / Li, Ruixia / Fernandez-Costa, Carolina / Liang, Alex / Choi, Janet / Jung, Dayoen / Xiao, Changchun / Kralli, Anastasia / Yates, John R / Ross, Robert S / Cho, Yoshitake

    Circulation

    2023  Volume 147, Issue 11, Page(s) 916–919

    MeSH term(s) Animals ; Mice ; Cell Respiration ; Heart ; Heart Failure ; Mice, Inbred C57BL ; Muscle Proteins/metabolism ; Myocardium/metabolism ; Oxidative Stress
    Chemical Substances Muscle Proteins ; PERM1 protein, mouse
    Language English
    Publishing date 2023-03-13
    Publishing country United States
    Document type Letter ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80099-5
    ISSN 1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
    ISSN (online) 1524-4539
    ISSN 0009-7322 ; 0069-4193 ; 0065-8499
    DOI 10.1161/CIRCULATIONAHA.122.060173
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Book ; Online: FedML Parrot

    Tang, Zhenheng / Chu, Xiaowen / Ran, Ryan Yide / Lee, Sunwoo / Shi, Shaohuai / Zhang, Yonggang / Wang, Yuxin / Liang, Alex Qiaozhong / Avestimehr, Salman / He, Chaoyang

    A Scalable Federated Learning System via Heterogeneity-aware Scheduling on Sequential and Hierarchical Training

    2023  

    Abstract: Federated Learning (FL) enables collaborations among clients for train machine learning models while protecting their data privacy. Existing FL simulation platforms that are designed from the perspectives of traditional distributed training, suffer from ... ...

    Abstract Federated Learning (FL) enables collaborations among clients for train machine learning models while protecting their data privacy. Existing FL simulation platforms that are designed from the perspectives of traditional distributed training, suffer from laborious code migration between simulation and production, low efficiency, low GPU utility, low scalability with high hardware requirements and difficulty of simulating stateful clients. In this work, we firstly demystify the challenges and bottlenecks of simulating FL, and design a new FL system named as FedML \texttt{Parrot}. It improves the training efficiency, remarkably relaxes the requirements on the hardware, and supports efficient large-scale FL experiments with stateful clients by: (1) sequential training clients on devices; (2) decomposing original aggregation into local and global aggregation on devices and server respectively; (3) scheduling tasks to mitigate straggler problems and enhance computing utility; (4) distributed client state manager to support various FL algorithms. Besides, built upon our generic APIs and communication interfaces, users can seamlessly transform the simulation into the real-world deployment without modifying codes. We evaluate \texttt{Parrot} through extensive experiments for training diverse models on various FL datasets to demonstrate that \texttt{Parrot} can achieve simulating over 1000 clients (stateful or stateless) with flexible GPU devices setting ($4 \sim 32$) and high GPU utility, 1.2 $\sim$ 4 times faster than FedScale, and 10 $\sim$ 100 times memory saving than FedML. And we verify that \texttt{Parrot} works well with homogeneous and heterogeneous devices in three different clusters. Two FL algorithms with stateful clients and four algorithms with stateless clients are simulated to verify the wide adaptability of \texttt{Parrot} to different algorithms.
    Keywords Computer Science - Machine Learning ; Computer Science - Distributed ; Parallel ; and Cluster Computing
    Subject code 006
    Publishing date 2023-03-03
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Correction: Perm1 promotes cardiomyocyte mitochondrial biogenesis and protects against hypoxia/reoxygenation-induced damage in mice.

    Cho, Yoshitake / Tachibana, Shizuko / Lam, Kayla / Arita, Yoh / Khosrowjerdi, Shamim / Zhang, Oliver / Liang, Alex / Li, Ruixia / Andreyev, Aleksander / Kralli, Anastasia / Murphy, Anne N / Ross, Robert S

    The Journal of biological chemistry

    2021  Volume 297, Issue 3, Page(s) 101121

    Language English
    Publishing date 2021-08-28
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1016/j.jbc.2021.101121
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Perm1 promotes cardiomyocyte mitochondrial biogenesis and protects against hypoxia/reoxygenation-induced damage in mice.

    Cho, Yoshitake / Tachibana, Shizuko / Lam, Kayla / Arita, Yoh / Khosrowjerdi, Shamim / Zhang, Oliver / Liang, Alex / Li, Ruixia / Andreyev, Aleksander / Murphy, Anne N / Ross, Robert S

    The Journal of biological chemistry

    2021  Volume 297, Issue 1, Page(s) 100825

    Abstract: Normal contractile function of the heart depends on a constant and reliable production of ATP by cardiomyocytes. Dysregulation of cardiac energy metabolism can result in immature heart development and disrupt the ability of the adult myocardium to adapt ... ...

    Abstract Normal contractile function of the heart depends on a constant and reliable production of ATP by cardiomyocytes. Dysregulation of cardiac energy metabolism can result in immature heart development and disrupt the ability of the adult myocardium to adapt to stress, potentially leading to heart failure. Further, restoration of abnormal mitochondrial function can have beneficial effects on cardiac dysfunction. Previously, we identified a novel protein termed Perm1 (PGC-1 and estrogen-related receptor (ERR)-induced regulator, muscle 1) that is enriched in skeletal and cardiac-muscle mitochondria and transcriptionally regulated by PGC-1 (peroxisome proliferator-activated receptor gamma coactivator 1) and ERR. The role of Perm1 in the heart is poorly understood and is studied here. We utilized cell culture, mouse models, and human tissue, to study its expression and transcriptional control, as well as its role in transcription of other factors. Critically, we tested Perm1's role in cardiomyocyte mitochondrial function and its ability to protect myocytes from stress-induced damage. Our studies show that Perm1 expression increases throughout mouse cardiogenesis, demonstrate that Perm1 interacts with PGC-1α and enhances activation of PGC-1 and ERR, increases mitochondrial DNA copy number, and augments oxidative capacity in cultured neonatal mouse cardiomyocytes. Moreover, we found that Perm1 reduced cellular damage produced as a result of hypoxia and reoxygenation-induced stress and mitigated cell death of cardiomyocytes. Taken together, our results show that Perm1 promotes mitochondrial biogenesis in mouse cardiomyocytes. Future studies can assess the potential of Perm1 to be used as a novel therapeutic to restore cardiac dysfunction induced by ischemic injury.
    MeSH term(s) Animals ; Cell Hypoxia ; DNA, Mitochondrial/genetics ; Down-Regulation/genetics ; Heart/embryology ; Heart Failure/genetics ; Heart Ventricles/metabolism ; Humans ; Intracellular Signaling Peptides and Proteins/genetics ; Intracellular Signaling Peptides and Proteins/metabolism ; Mice, Inbred C57BL ; Mitochondria, Heart/metabolism ; Muscle Proteins/genetics ; Muscle Proteins/metabolism ; Myocytes, Cardiac/metabolism ; Organelle Biogenesis ; Oxidation-Reduction ; Oxidative Phosphorylation ; Oxygen/metabolism ; Promoter Regions, Genetic/genetics ; Protein Biosynthesis ; Protein Isoforms/genetics ; Protein Isoforms/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Receptors, Estrogen/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Transcription, Genetic ; ERRalpha Estrogen-Related Receptor ; Mice
    Chemical Substances DNA, Mitochondrial ; Intracellular Signaling Peptides and Proteins ; Muscle Proteins ; PERM1 protein, human ; PERM1 protein, mouse ; Protein Isoforms ; RNA, Messenger ; Receptors, Estrogen ; Transcription Factors ; peroxisome-proliferator-activated receptor-gamma coactivator-1 ; Oxygen (S88TT14065)
    Language English
    Publishing date 2021-05-23
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1016/j.jbc.2021.100825
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Uc I Zs.108: Show issues Location:
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