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682 results on '"Yang, Fusheng"'

1. High-dimensional quantum XYZ product codes for biased noise

Author

Liang, Zhipeng, Yi, Zhengzhong, Yang, Fusheng, Chen, Jiahan, Wang, Zicheng, and Wang, Xuan

Subjects
Quantum Physics
Abstract

Three-dimensional (3D) quantum XYZ product can construct a class of non-CSS codes by using three classical codes. However, their error-correcting performance has not been studied in depth so far and whether this code construction can be generalized to higher dimension is an open question. In this paper, we first study the error-correcting performance of the 3D Chamon code, which is an instance of 3D XYZ product of three repetition codes. Next, we show that 3D XYZ product can be generalized to four dimension and propose four-dimensional (4D) XYZ product code construction, which constructs a class of non-CSS codes by using either four classical codes or two CSS codes. Compared with 4D homological product, we show that 4D XYZ product can construct non-CSS codes with higher code dimension or code distance. Finally, we consider two instances of 4D XYZ product, to which we refer as 4D Chamon code and 4D XYZ product concatenated code, respectively. Our simulation results show that, 4D XYZ product can construct non-CSS codes with better error-correcting performance for $Z$-biased noise than CSS codes constructed by 4D homological product.

Published
2024

2. Clinical Efficacy of ONC201 in H3K27M-Mutant Diffuse Midline Gliomas Is Driven by Disruption of Integrated Metabolic and Epigenetic Pathways.

Author

Sweha, Stefan, Mota, Mateus, Pun, Matthew, Deogharkar, Akash, Chung, Chan, Tarapore, Rohinton, Ramage, Samuel, Chi, Andrew, Wen, Patrick, Arrillaga-Romany, Isabel, Batchelor, Tracy, Butowski, Nicholas, Sumrall, Ashley, Shonka, Nicole, Harrison, Rebecca, de Groot, John, Mehta, Minesh, Hall, Matthew, Daghistani, Doured, Cloughesy, Timothy, Ellingson, Benjamin, Beccaria, Kevin, Varlet, Pascale, Kim, Michelle, Umemura, Yoshie, Garton, Hugh, Franson, Andrea, Schwartz, Jonathan, Jain, Rajan, Kachman, Maureen, Baum, Heidi, Burant, Charles, Mottl, Sophie, Cartaxo, Rodrigo, John, Vishal, Messinger, Dana, Qin, Tingting, Peterson, Erik, Sajjakulnukit, Peter, Ravi, Karthik, Waugh, Alyssa, Walling, Dustin, Ding, Yujie, Xia, Ziyun, Schwendeman, Anna, Hawes, Debra, Yang, Fusheng, Judkins, Alexander, Wahl, Daniel, Lyssiotis, Costas, de la Nava, Daniel, Alonso, Marta, Eze, Augustine, Spitzer, Jasper, Schmidt, Susanne, Duchatel, Ryan, Dun, Matthew, Cain, Jason, Jiang, Li, Stopka, Sylwia, Baquer, Gerard, Regan, Michael, Filbin, Mariella, Agar, Nathalie, Zhao, Lili, Kumar-Sinha, Chandan, Mody, Rajen, Chinnaiyan, Arul, Kurokawa, Ryo, Pratt, Drew, Yadav, Viveka, Grill, Jacques, Kline, Cassie, Venneti, Sriram, Kawakibi, Abed, Ji, Sunjong, Resnick, Adam, Nazarian, Javad, Allen, Joshua, Odia, Yazmin, Gardner, Sharon, Koschmann, Carl, Mueller, Sabine, and Waszak, Sebastian

Subjects
Humans, Glioma, Brain Neoplasms, Histones, Treatment Outcome, Epigenesis, Genetic, Mutation
Abstract

UNLABELLED: Patients with H3K27M-mutant diffuse midline glioma (DMG) have no proven effective therapies. ONC201 has recently demonstrated efficacy in these patients, but the mechanism behind this finding remains unknown. We assessed clinical outcomes, tumor sequencing, and tissue/cerebrospinal fluid (CSF) correlate samples from patients treated in two completed multisite clinical studies. Patients treated with ONC201 following initial radiation but prior to recurrence demonstrated a median overall survival of 21.7 months, whereas those treated after recurrence had a median overall survival of 9.3 months. Radiographic response was associated with increased expression of key tricarboxylic acid cycle-related genes in baseline tumor sequencing. ONC201 treatment increased 2-hydroxyglutarate levels in cultured H3K27M-DMG cells and patient CSF samples. This corresponded with increases in repressive H3K27me3 in vitro and in human tumors accompanied by epigenetic downregulation of cell cycle regulation and neuroglial differentiation genes. Overall, ONC201 demonstrates efficacy in H3K27M-DMG by disrupting integrated metabolic and epigenetic pathways and reversing pathognomonic H3K27me3 reduction. SIGNIFICANCE: The clinical, radiographic, and molecular analyses included in this study demonstrate the efficacy of ONC201 in H3K27M-mutant DMG and support ONC201 as the first monotherapy to improve outcomes in H3K27M-mutant DMG beyond radiation. Mechanistically, ONC201 disrupts integrated metabolic and epigenetic pathways and reverses pathognomonic H3K27me3 reduction. This article is featured in Selected Articles from This Issue, p. 2293.

Published
2023

11. Targeting integrated epigenetic and metabolic pathways in lethal childhood PFA ependymomas

Author

Panwalkar, Pooja, Tamrazi, Benita, Dang, Derek, Chung, Chan, Sweha, Stefan, Natarajan, Siva Kumar, Pun, Matthew, Bayliss, Jill, Ogrodzinski, Martin P, Pratt, Drew, Mullan, Brendan, Hawes, Debra, Yang, Fusheng, Lu, Chao, Sabari, Benjamin R, Achreja, Abhinav, Heon, Jin, Animasahun, Olamide, Cieslik, Marcin, Dunham, Christopher, Yip, Stephen, Hukin, Juliette, Phillips, Joanna J, Bornhorst, Miriam, Griesinger, Andrea M, Donson, Andrew M, Foreman, Nicholas K, Garton, Hugh JL, Heth, Jason, Muraszko, Karin, Nazarian, Javad, Koschmann, Carl, Jiang, Li, Filbin, Mariella G, Nagrath, Deepak, Kool, Marcel, Korshunov, Andrey, Pfister, Stefan M, Gilbertson, Richard J, Allis, C David, Chinnaiyan, Arul M, Lunt, Sophia Y, Blüml, Stefan, Judkins, Alexander R, and Venneti, Sriram

Subjects
Cancer, Biotechnology, Genetics, Rare Diseases, Orphan Drug, Neurosciences, Brain Disorders, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Animals, Child, Ependymoma, Epigenesis, Genetic, Epigenomics, Histones, Humans, Metabolic Networks and Pathways, Mice, Biological Sciences, Medical and Health Sciences
Abstract

Childhood posterior fossa group A ependymomas (PFAs) have limited treatment options and bear dismal prognoses compared to group B ependymomas (PFBs). PFAs overexpress the oncohistone-like protein EZHIP (enhancer of Zeste homologs inhibitory protein), causing global reduction of repressive histone H3 lysine 27 trimethylation (H3K27me3), similar to the oncohistone H3K27M. Integrated metabolic analyses in patient-derived cells and tumors, single-cell RNA sequencing of tumors, and noninvasive metabolic imaging in patients demonstrated enhanced glycolysis and tricarboxylic acid (TCA) cycle metabolism in PFAs. Furthermore, high glycolytic gene expression in PFAs was associated with a poor outcome. PFAs demonstrated high EZHIP expression associated with poor prognosis and elevated activating mark histone H3 lysine 27 acetylation (H3K27ac). Genomic H3K27ac was enriched in PFAs at key glycolytic and TCA cycle–related genes including hexokinase-2 and pyruvate dehydrogenase. Similarly, mouse neuronal stem cells (NSCs) expressing wild-type EZHIP (EZHIP-WT) versus catalytically attenuated EZHIP-M406K demonstrated H3K27ac enrichment at hexokinase-2 and pyruvate dehydrogenase, accompanied by enhanced glycolysis and TCA cycle metabolism. AMPKα-2, a key component of the metabolic regulator AMP-activated protein kinase (AMPK), also showed H3K27ac enrichment in PFAs and EZHIP-WT NSCs. The AMPK activator metformin lowered EZHIP protein concentrations, increased H3K27me3, suppressed TCA cycle metabolism, and showed therapeutic efficacy in vitro and in vivo in patient-derived PFA xenografts in mice. Our data indicate that PFAs and EZHIP-WT–expressing NSCs are characterized by enhanced glycolysis and TCA cycle metabolism. Repurposing the antidiabetic drug metformin lowered pathogenic EZHIP, increased H3K27me3, and suppressed tumor growth, suggesting that targeting integrated metabolic/epigenetic pathways is a potential therapeutic strategy for treating childhood ependymomas.

Published
2021

37. Abstract PR-007: H3.3K27M diffuse midline gliomas are sensitive to SWI/SNF chromatin remodeler degradation

Author

Mota, Mateus, primary, Sweha, Stefan, additional, Pun, Matt, additional, Natarajan, Siva Kumar, additional, Ding, Yujie, additional, Chung, Chan, additional, Hawes, Debra, additional, Yang, Fusheng, additional, Judkins, Alexander, additional, Samajdar, Susanta, additional, Cao, Xuhong, additional, Xiao, Lanbo, additional, Parolia, Abhijit, additional, Chinnaiyan, Arul, additional, and Venneti, Sriram, additional

Published
2024
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45. Immunohistochemical analysis of H3K27me3 demonstrates global reduction in group-A childhood posterior fossa ependymoma and is a powerful predictor of outcome

Author

Panwalkar, Pooja, Clark, Jonathan, Ramaswamy, Vijay, Hawes, Debra, Yang, Fusheng, Dunham, Christopher, Yip, Stephen, Hukin, Juliette, Sun, Yilun, Schipper, Matthew J, Chavez, Lukas, Margol, Ashley, Pekmezci, Melike, Chung, Chan, Banda, Adam, Bayliss, Jill M, Curry, Sarah J, Santi, Mariarita, Rodriguez, Fausto J, Snuderl, Matija, Karajannis, Matthias A, Saratsis, Amanda M, Horbinski, Craig M, Carret, Anne-Sophie, Wilson, Beverly, Johnston, Donna, Lafay-Cousin, Lucie, Zelcer, Shayna, Eisenstat, David, Silva, Marianna, Scheinemann, Katrin, Jabado, Nada, McNeely, P Daniel, Kool, Marcel, Pfister, Stefan M, Taylor, Michael D, Hawkins, Cynthia, Korshunov, Andrey, Judkins, Alexander R, and Venneti, Sriram

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Brain Disorders, Genetics, Brain Cancer, Rare Diseases, Neurosciences, Clinical Research, Pediatric Cancer, Cancer, Clinical Trials and Supportive Activities, Pediatric, Child, Child, Preschool, Disease-Free Survival, Ependymoma, Female, Humans, Infant, Infratentorial Neoplasms, Jumonji Domain-Containing Histone Demethylases, Male, Prognosis, Registries, Survival Rate, Childhood ependymoma, Epigenetics, H3K27me3, Molecular subgrouping, Neurology & Neurosurgery
Abstract

Posterior fossa ependymomas (EPN_PF) in children comprise two morphologically identical, but biologically distinct tumor entities. Group-A (EPN_PFA) tumors have a poor prognosis and require intensive therapy. In contrast, group-B tumors (EPN_PFB) exhibit excellent prognosis and the current consensus opinion recommends future clinical trials to test the possibility of treatment de-escalation in these patients. Therefore, distinguishing these two tumor subtypes is critical. EPN_PFA and EPN_PFB can be distinguished based on DNA methylation signatures, but these assays are not routinely available. We have previously shown that a subset of poorly prognostic childhood EPN_PF exhibits global reduction in H3K27me3. Therefore, we set out to determine whether a simple immunohistochemical assay for H3K27me3 could be used to segregate EPN_PFA from EPN_PFB tumors. We assembled a cohort of 230 childhood ependymomas and H3K27me3 immunohistochemistry was assessed as positive or negative in a blinded manner. H3K27me3 staining results were compared with DNA methylation-based subgroup information available in 112 samples [EPN_PFA (n = 72) and EPN_PFB tumors (n = 40)]. H3K27me3 staining was globally reduced in EPN_PFA tumors and immunohistochemistry showed 99% sensitivity and 100% specificity in segregating EPN_PFA from EPN_PFB tumors. Moreover, H3K27me3 immunostaining was sufficient to delineate patients with worse prognosis in two independent, non-overlapping cohorts (n = 133 and n = 97). In conclusion, immunohistochemical evaluation of H3K27me3 global reduction is an economic, easily available and readily adaptable method for defining high-risk EPN_PFA from low-risk posterior fossa EPN_PFB tumors to inform prognosis and to enable the design of future clinical trials.

Published
2017

50. AlH 3 as High-Energy Fuels for Solid Propellants: Synthesis, Thermodynamics, Kinetics, and Stabilization.

Author

Liu, Youhai, Yang, Fusheng, Zhang, Yang, Wu, Zhen, and Zhang, Zaoxiao

Subjects
SOLID propellants, THERMODYNAMICS, ALUMINUM hydride, DEHYDROGENATION, THERMAL stability
Abstract

Aluminum hydride (AlH3) has attracted wide attention due to its high gravimetric and volumetric hydrogen capacity. AlH3 can easily release hydrogen when heated at relatively low temperature. Such high hydrogen density and low dehydrogenation temperature make it one of the most promising high-energy fuels for solid propellants. In particular, AlH3 as a component of solid propellants may greatly increase the specific impulse of rocket engines. However, AlH3 exhibits low chemical and thermal stability in an ambient atmosphere. In this paper, the research progress about the synthesis, dehydrogenation thermodynamics, and kinetics, the stabilization of AlH3 over the past decades are reviewed, with the aim of exploring more a economical synthesis and suitable stabilization methods for large-scale use in solid propellants. Finally, some suggestions regarding future research directions in this filed are proposed. [ABSTRACT FROM AUTHOR]

Published
2024
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