bluuebunny/crossref_metadata_2025 huggingface dataset:
Interconnected roles of fungal nuclear- and intron-encoded maturases: at the crossroads of mitochondrial intron splicing
Authors: Mukhopadhyay Jigeesha , Hausner Georg
Published: June 2024

Group I and II introns are large catalytic RNAs (ribozymes) that are frequently encountered in fungal mitochondrial genomes. The discovery of respiratory mutants linked to intron splicing defects demonstrated that for the efficient removal of organellar introns there appears to be a requirement of protein splicing factors. These splicing factors can be intron-encoded proteins with maturase activities that usually promote the splicing of the introns that encode them ( cis-acting) and/or nuclear-encoded factors that can promote the splicing of a range of different introns ( trans-acting). Compared to plants organellar introns, fungal mitochondrial intron splicing is still poorly explored, especially in terms of the synergy of nuclear factors with intron-encoded maturases that has direct impact on splicing through their association with intron RNA. In addition, nuclear-encoded accessory factors might drive the splicing impetus through translational activation, mitoribosome assembly, and phosphorylation-mediated RNA turnover. This review explores protein-assisted splicing of introns by nuclear and mitochondrial-encoded maturases as a means of mitonuclear interplay that could respond to environmental and developmental factors promoting phenotypic adaptation and potentially speciation. It also highlights key evolutionary events that have led to changes in structure and ATP-dependence to accommodate the dual functionality of nuclear and organellar splicing factors.
Conditions for the existence of positive operator valued measures
Authors: Schumacher Maximilian , Alber Gernot
Published: June 2024

Sufficient and necessary conditions are presented for the existence of ( N, M)-positive operator valued measures (( N, M)-POVMs) valid for arbitrary-dimensional quantum systems. Firstly, a sufficient condition for the existence of ( N, M)-POVMs is presented. It yields a simple relation determining an upper bound on the continuous parameter of an arbitrary ( N, M)-POVM, below which all its POVM elements are guaranteed to be positive semidefinite. Secondly, for arbitrary optimal ( N, M)-POVMs conditions on their existence are derived, which exhibit a close connection to the existence of sets of ( M − 1) N isospectral, traceless, orthonormal, and hermitian operators with particular common spectra. The specific form of the two possible types of spectra depends on whether M is smaller than the dimension of the quantum system under consideration or not. For the special case of M = 2 and dimensions, which are powers of two, these sets of operators always exist and can be expressed in terms of the Clifford algebra of tensor products of Pauli operators.
Superconformal blocks for stress-tensor and chiral operators for 4D $${\mathcal {N}}=2$$ superconformal field theories
Authors: Rakshit Subhadeep , Mukhopadhyay Subir
Published: June 2024

We have computed the superconformal partial wave for the mixed correlators involving J, $$\phi $$
ϕ
, and $$\phi ^\dagger $$

ϕ
†

, where J is the superconformal primary of 4D $${{\mathcal {N}}} = 2$$

N
=
2

stress-tensor multiplet, $$\phi $$
ϕ
, and $$\phi ^\dagger $$

ϕ
†

are chiral and anti-chiral scalars, respectively in the channel $$\langle {J J}\phi \phi ^{\dagger }\rangle $$

⟨

JJ

ϕ

ϕ
†

⟩

. We have used the superembedding formalism and computed the conformal partial wave corresponding to the exchange of long multiplet using the supershadow approach. This study provides part of the ingredients necessary for the study of conformal bootstrap for mixed correlator in 4D $${{\mathcal {N}}} = 2$$

N
=
2

superconformal field theories.
Quasinormal modes of a regular black hole with sub-Planckian curvature
Authors: Zhang Dan , Gong Huajie , Fu Guoyang , Wu Jian-Pin , Pan Qiyuan
Published: June 2024

This paper explores the properties of the quasinormal modes (QNMs) of a regular black hole (BH) characterized by a Minkowski core and sub-Planckian curvature. When focusing on a special case, this regular BH exhibits identical large-scale behavior with the Hayward BH and some loop quantum gravity corrected (LQG-corrected) BH. A notable characteristic of the QNMs in this regular BH is the pronounced outburst of overtones when compared to the Schwarzschild BH (SS-BH). This outburst can be attributed to the deviation from the SS-BH in the near-horizon geometry region due to the quantum gravity effect. Furthermore, we compare the QNM properties of the regular BH with those of the Hayward BH and the LQG-corrected BH. A similar phenomenon of overtone outburst is observed in the modes of the overtone. As a conclusion, the QNMs may be a powerful tool for detecting the quantum gravity effect and distinguishing different BH models.
Holographic RG flows and boundary conditions in a 3D gauged supergravity
Authors: Arkhipova Ksenia , Astrakhantsev Lev , Deger Nihat Sadik , Golubtsova Anastasia A. , Gubarev Kirill , Musaev Edvard T.
Published: June 2024

In this work we focus on the study of RG flows of conformal field theories that are holographically dual to Poincaré domain wall solutions in $$D=3$$

D
=
3

, $$\mathcal {N}=(2,0)$$

N
=
(
2
,
0
)

gauged supergravity coupled to a sigma model with target space $$\textrm{SU}(1, 1)/\textrm{U}(1) = \mathbb {H}^2$$

SU

(
1
,
1
)

/
U

(
1
)

=

H

2

. This theory is truncated to a subsector where the vector field and phase of the scalar field vanish and we consider different boundary conditions for the remaining real scalar field. The RG flows, which are mostly non-superysymmetric, are analyzed by treating the supergravity field equations as a dynamical system for the scalar field and its derivative with respect to the scale factor. Phase diagrams are constructed for different values of the parameter $$a^2$$

a
2

, which is related to the curvature of the scalar manifold. The behavior of solutions near the boundary is used to determine their type based on the expansion of the corresponding fake superpotential. By incorporating information on the boundary conditions, the obtained RG flows are interpreted using the holographic dictionary. Numerical solutions and plots of the fake superpotential are also provided.
A KPI framework to standardize the measurement of a country’s progress in bringing quantum computing into application
Authors:   Quantum Technology and Application Consortium – QUTAC, Binder Julia , Hachmann Lara , Luber Sebastian
Published: June 2024

Quantum computing (QC) is a new and disruptive technology with large economic potential especially in application and downstream value creation stages. Hence, it is important for an economy to understand the current implementation state and to know the ecosystem to support the successful industrial application of this technology. Regularly identifying potential areas of improvement and then defining appropriate actions is necessary to ensure a leading position. Therefore, the Quantum Technology and Application Consortium (QUTAC) has developed a Key Performance Indicator (KPI) framework consisting of 24 KPIs that represent a country’s performance in applying QC. Detailed measurement guidelines and clear data sources ensure transparency of measurement, reproducibility of KPI values and comparability over time. An aggregation method allows summarizing the results of all KPIs. Thus, it is possible to assess the performance of each stakeholder involved and to calculate a single composite indicator that represents the country’s performance. The KPI framework can be adapted to any country and enables the comparison of the performance of different countries. It is a proposal for standardizing the evaluation of QC and its ecosystem on a national level. Thus, strengths and weaknesses can be identified and measurements for improvement derived. The paper highlights the development of the framework, its main features and the application of the framework to Germany. Based on the results, we will discuss the current state of QC application in Germany and make possible suggestions for improvement.
DIGITAL CAPABILITIES, FIRM PERFORMANCE, AND INNOVATION CAPABILITIES: A COMBINED APPROACH OF PLS-SEM AND ANN
Authors: HOANG DINH VAN , HIEN NGUYEN THI
Published: June 2024

This study, rooted in the dynamic capabilities view, examines the influence of digital capabilities on the performance and innovation capabilities of manufacturing small and medium-sized enterprises (SMEs) in an emerging market. Surveying 297 manufacturing SMEs in Vietnam, the research employed partial least squares-structural equation modelling (PLS-SEM) and artificial neural network (ANN) to test hypotheses. The results show a positive effect of digital capabilities on process and product innovation capabilities. Despite an insignificant direct impact of digital capabilities on firm performance, technological uncertainty moderates this relationship positively. Notably, process innovation capability has no direct impact on firm performance, while product innovation capability’s impact on it is negatively significant. The study explored the roles of digital culture and digital leadership, offering novel contributions to understanding a firm’s digital and innovation capabilities. It provides practical implications for managers aiming to enhance firm performance by leveraging digital capabilities for innovation.
Nonlinear optimal control for free-floating space robotic manipulators
Authors: Rigatos G. , Pomares J. , Abbaszadeh M. , Busawon K. , Gao Z. , Zouari F.
Published: June 2024

Free-floating space robotic manipulators (FSRMs) are robotic arms mounted on space platforms, such as spacecraft or satellites which are used for the repair of space vehicles or the removal of noncooperating targets such as inactive material remaining in orbit. In this paper, a novel nonlinear optimal control method is applied to the dynamic model of FSRMs. First, the state-space model of a 3-DOF free-floating space robot is formulated and its differential flatness properties are proven. This model undergoes approximate linearization around a temporary operating point that is recomputed at each time-step of the control method. The linearization relies on Taylor series expansion and on the associated Jacobian matrices. For the linearized state-space model of the free-floating space robot a stabilizing optimal (H-infinity) feedback controller is designed. This controller stands for the solution of the nonlinear optimal control problem under model uncertainty and external perturbations. To compute the controller’s feedback gains an algebraic Riccati equation is repetitively solved at each iteration of the control algorithm. The stability properties of the control method are proven through Lyapunov analysis. The proposed nonlinear optimal control approach achieves fast and accurate tracking of setpoints under moderate variations of the control inputs and a minimum dispersion of energy by the actuators of the free-floating space robot.
Study on Intelligent Scoring of English Composition Based on Machine Learning from the Perspective of Natural Language Processing
Authors: Tang Jing
Published: June 2024

Knowledge management is crucial to the teaching and learning process in the current era of digitalization. The idea of "learning via working together" is making Natural Language Processing a popular tool to improve the learning process based on the intelligent system for evaluating the composition. English language learning is highly dependent on the composition written by the students under various topics. Teachers are facing huge difficulties in the evaluation of the composition as the level of writing by the students will vary for individual. In this research, Natural Language Processing concept is utilized for getting trained with the student's writing skills and Multiprocessor Learning Algorithm (MLA) combined with Convolutional Neural Network (CNN) (MLA-CNN) for evaluating the composition and declaring the scores for the students. The model's composition scoring rate is validated using a range of learning rate settings. Some theoretical notions for smart teaching are proposed, and it is hoped that this automatic composition scoring model would be used to grade student writing in English classes. When applied to the automatic scoring of students' English composition in schools, the suggested composition scoring system trained by the MLP-CNN has great performance and lays the groundwork for the educational applications of ML inside AI. The study results proved that the proposed model has provided an accuracy of 98%.
Using Reinforcement Learning and Error Models for Drone Precise Landing
Authors: Saryazdi Sepehr , Alkouz Balsam , Bouguettaya Athman , Lakhdari Abdallah
Published: June 2024

We propose a novel framework for achieving precision landing in drone services. The proposed framework consists of two distinct decoupled modules, each designed to address a specific aspect of landing accuracy. The first module is concerned with intrinsic errors, where new error models are introduced. This includes a spherical error model that takes into account the orientation of the drone. Additionally, we propose a live position correction algorithm that employs the error models to correct for intrinsic errors in real time. The second module focuses on external wind forces and presents an aerodynamics model with wind generation to simulate the drone’s physical environment. We utilize reinforcement learning to train the drone in simulation with the goal of landing precisely under dynamic wind conditions. Experimental results, conducted through simulations and validated in the physical world, demonstrate that our proposed framework significantly increases landing accuracy while maintaining a low onboard computational cost.
Supplementary Figure S4 from A Histone Methylation–MAPK Signaling Axis Drives Durable Epithelial–Mesenchymal Transition in Hypoxic Pancreatic Cancer
Authors: Brown Brooke A. , Myers Paul J. , Adair Sara J. , Pitarresi Jason R. , Sah-Teli Shiv K. , Campbell Logan A. , Hart William S. , Barbeau Michelle C. , Leong Kelsey , Seyler Nicholas , Kane William , Lee Kyoung Eun , Stelow Edward , Jones Marieke , Simon M. Celeste , Koivunen Peppi , Bauer Todd W. , Stanger Ben Z. , Lazzara Matthew J.
Published: June 2024

Supplementary Figure S4
Supplementary Figure S2 from A Histone Methylation–MAPK Signaling Axis Drives Durable Epithelial–Mesenchymal Transition in Hypoxic Pancreatic Cancer
Authors: Brown Brooke A. , Myers Paul J. , Adair Sara J. , Pitarresi Jason R. , Sah-Teli Shiv K. , Campbell Logan A. , Hart William S. , Barbeau Michelle C. , Leong Kelsey , Seyler Nicholas , Kane William , Lee Kyoung Eun , Stelow Edward , Jones Marieke , Simon M. Celeste , Koivunen Peppi , Bauer Todd W. , Stanger Ben Z. , Lazzara Matthew J.
Published: June 2024

Supplementary Figure S2
Supplementary Fig. S5 from Whole-Genome DNA Methylation Profiling of Intrahepatic Cholangiocarcinoma Reveals Prognostic Subtypes with Distinct Biological Drivers
Authors: Liao Haotian , Chen Xing , Wang Haichuan , Lin Youpei , Chen Lu , Yuan Kefei , Liao Mingheng , Jiang Hanyu , Peng Jiajie , Wu Zhenru , Huang Jiwei , Li Jiaxin , Zeng Yong
Published: June 2024

Supplementary Fig. S5
Supplementary Fig. S15 from Whole-Genome DNA Methylation Profiling of Intrahepatic Cholangiocarcinoma Reveals Prognostic Subtypes with Distinct Biological Drivers
Authors: Liao Haotian , Chen Xing , Wang Haichuan , Lin Youpei , Chen Lu , Yuan Kefei , Liao Mingheng , Jiang Hanyu , Peng Jiajie , Wu Zhenru , Huang Jiwei , Li Jiaxin , Zeng Yong
Published: June 2024

Supplementary Fig. S15
Supplementary Figure 6 from SPARC Stabilizes ApoE to Induce Cholesterol-Dependent Invasion and Sorafenib Resistance in Hepatocellular Carcinoma
Authors: Wan Shan , He Quan-Yao , Yang Yun , Liu Feng , Zhang Xue , Guo Xin , Niu Hui , Wang Yi , Liu Yi-Xuan , Ye Wen-Long , Li Xiu-Ming , ZhuanSun Xue-Mei , Sun Pu , He Xiao-Shun , Hu Guang , Breuhahn Kai , Zhao Hua , Wu Guo-Qiang , Wu Hua
Published: June 2024

SPARC is upregulated and maintains the cholesterol-dependent EMT phenotype in sorafenib-resistant HCC cells.
Supplementary Figure 1 from SPARC Stabilizes ApoE to Induce Cholesterol-Dependent Invasion and Sorafenib Resistance in Hepatocellular Carcinoma
Authors: Wan Shan , He Quan-Yao , Yang Yun , Liu Feng , Zhang Xue , Guo Xin , Niu Hui , Wang Yi , Liu Yi-Xuan , Ye Wen-Long , Li Xiu-Ming , ZhuanSun Xue-Mei , Sun Pu , He Xiao-Shun , Hu Guang , Breuhahn Kai , Zhao Hua , Wu Guo-Qiang , Wu Hua
Published: June 2024

SPARC expression in HCC cell lines, tissue samples and HCC tumoroids.
Supplementary Table S2 from The Deep Learning Framework iCanTCR Enables Early Cancer Detection Using the T-cell Receptor Repertoire in Peripheral Blood
Authors: Cai Yideng , Luo Meng , Yang Wenyi , Xu Chang , Wang Pingping , Xue Guangfu , Jin Xiyun , Cheng Rui , Que Jinhao , Zhou Wenyang , Pang Boran , Xu Shouping , Li Yu , Jiang Qinghua , Xu Zhaochun
Published: June 2024

Information of benchmark testing set
Supplementary Figure S2 from Oncogenic Cell Tagging and Single-Cell Transcriptomics Reveal Cell Type–Specific and Time-Resolved Responses to Vhl Inactivation in the Kidney
Authors: Kurlekar Samvid , Lima Joanna D.C.C. , Li Ran , Lombardi Olivia , Masson Norma , Barros Ayslan B. , Pontecorvi Virginia , Mole David R. , Pugh Christopher W. , Adam Julie , Ratcliffe Peter J.
Published: June 2024

Biallelic Vhl loss entrains early cell-specific transcriptomic changes in renal tubular cells
Figure 6 from Oncogenic Cell Tagging and Single-Cell Transcriptomics Reveal Cell Type–Specific and Time-Resolved Responses to Vhl Inactivation in the Kidney
Authors: Kurlekar Samvid , Lima Joanna D.C.C. , Li Ran , Lombardi Olivia , Masson Norma , Barros Ayslan B. , Pontecorvi Virginia , Mole David R. , Pugh Christopher W. , Adam Julie , Ratcliffe Peter J.
Published: June 2024

Vhl-null cells exhibit time-dependent proliferation and association with ccRCC-like gene expression. A, Representative dual IHC for tdTomato (brown) and Ki67 (purple) counterstained with hematoxylin in kidneys of KO mice harvested early after recombination. Scale bar, 25 μm. Magnification, ×40. Black arrow, dual-positive cell; red arrow, tdTomato-negative Ki67-positive cell. B, Proportion of tdTomato-positive (top) or tdTomato-negative (bottom) cells that are positive for Ki67 by dual IHC in kidneys of Control and KO mice harvested early and late after recombination (n = 2F, 6M for Control early; n = 4F, 2M for KO early; n = 4F, 5M for Control late; n = 1F, 6M for KO late). Pairwise comparisons by Kruskal–Wallis test with Dunn correction. C, UMAP plot depicting RTE cells from Control and KO mice at the early and late time points. Orange, cells expressing Mki67. D, Proportion of tdTomato-positive (top) or tdTomato-negative (bottom) RTE cells that express Mki67 in different conditions. Pairwise comparisons tested by one-way ANOVA with Holm–Šídák correction. E, Proportion of tdTomato-positive cells of different PT identities that express Mki67 in different conditions. Pairwise comparisons tested by two-way ANOVA with Holm–Šídák correction. F, Violin plot overlaid with boxplot depicting expression score for genes upregulated in ccRCC cells known to be HIF targets (left) and not known to be HIF targets (right) in tdTomato-positive cells from Control and KO mice harvested at early or late time points. G, Scatter plot depicting changes in mean expression scores for HIF-target (top) and non-HIF-target (bottom) genes specifically upregulated in ccRCC, in tdTomato-positive cells of different PT identities from different conditions when compared with those from Control mice at the early time point. B, D, and E, Median and interquartile range plotted. Only significant (P < 0.05) comparisons shown. C–G, scRNA-seq data shown for n = 3F, 1M mice for tdTomato-positive and tdTomato-negative Control early and Control late samples; n = 2F, 1M mice for tdTomato-negative KO early samples; n = 2F, 2M mice for tdTomato-positive KO early samples; n = 2F, 2M mice for tdTomato-positive and tdTomato-negative KO late samples.
Supplementary Figure S6 from Repolarization of Immunosuppressive Macrophages by Targeting SLAMF7-Regulated CCL2 Signaling Sensitizes Hepatocellular Carcinoma to Immunotherapy
Authors: Weng Jialei , Wang Zheng , Hu Zhiqiu , Xu Wenxin , Sun Jia-Lei , Wang Fu , Zhou Qiang , Liu Shaoqing , Xu Min , Xu Minghao , Gao Dongmei , Shen Ying-Hao , Yi Yong , Shi Yi , Dong Qiongzhu , Zhou Chenhao , Ren Ning
Published: June 2024

(A) Flow cytometry analyses of CD80 and CD206 expressions in THP-1-differentiated macrophages cocultured with the indicated HCC cells. (B) Flow cytometry analyses of MHC-II and CD206 expressions in BMDMs cocultured with the indicated HCC cells. (C) qPCR analyses of M1 and M2 marker genes transcription levels in BMDMs cocultured with the indicated HCC cells. (D-E) Chemotaxis assays showing the effect of supernatants from the indicated coculture systems on the migration ability of THP-1-differentiated macrophages and BMDMs. Scale bar: 100 μm. (F) The correlations of intra-tumoral SLAMF7 expression with CXCL10, CXCL9, and ARG1 expression in TCGA-LIHC cohort. (G) The prognostic prediction performances of SLAMF7 in combination with CD68, CD80, and CD206 for OS in our Fudan LCI HCC cohort. *P<0.05, **P<0.01, and ***P<0.001, Student’s t test. Experiments were repeated three time and results were present as the mean ± SD.
Supplementary Figure S11 from Repolarization of Immunosuppressive Macrophages by Targeting SLAMF7-Regulated CCL2 Signaling Sensitizes Hepatocellular Carcinoma to Immunotherapy
Authors: Weng Jialei , Wang Zheng , Hu Zhiqiu , Xu Wenxin , Sun Jia-Lei , Wang Fu , Zhou Qiang , Liu Shaoqing , Xu Min , Xu Minghao , Gao Dongmei , Shen Ying-Hao , Yi Yong , Shi Yi , Dong Qiongzhu , Zhou Chenhao , Ren Ning
Published: June 2024

(A) The liver and kidney functions of C57BL/6 mice with orthotopic Hepa1-6 tumors receiving RS102895 and anti-PD-1 antibody monotherapy or combination therapy at the study endpoint. (B) Gross appearance of the liver bearing Hepa1-6-shSlamf7 tumors in the indicated treatment groups. (C) The tumor weight and tumor volume of each group at the study endpoint (5 mice per group). (D) Gross appearance of the liver bearing Hepa1-6-Slamf7 tumors in the indicated treatment groups. (E) The tumor weight and tumor volume of each group at the study endpoint (5 mice per group). (F) Schematic showing the schedule of elotuzumab treatment in mice bearing MM and HCC subcutaneous tumors. (G) Gross appearance of the subcutaneous tumors from the indicated groups. (H) The tumor weight of each group at the endpoint. (I) Volumes of subcutaneous tumors in each group during treatment. NS, not significant, ***P<0.001, one-way ANOVA with a post hoc LSD test (or Student’s t test in part H and I).
Supplementary Figure S1 from Repolarization of Immunosuppressive Macrophages by Targeting SLAMF7-Regulated CCL2 Signaling Sensitizes Hepatocellular Carcinoma to Immunotherapy
Authors: Weng Jialei , Wang Zheng , Hu Zhiqiu , Xu Wenxin , Sun Jia-Lei , Wang Fu , Zhou Qiang , Liu Shaoqing , Xu Min , Xu Minghao , Gao Dongmei , Shen Ying-Hao , Yi Yong , Shi Yi , Dong Qiongzhu , Zhou Chenhao , Ren Ning
Published: June 2024

(A) The mRNA expression of SLAMF7 between peri-tumor (PT) and tumor (TT) tissues of GSE14520 cohort (n=247). (B) qPCR and immunoblot assays of SLAMF7 expression in hepatic cell line L-02 and HCC cell lines. (C) qPCR and immunoblot assays verifying the knockdown and overexpression efficiency of SLAMF7 in HCC cells. (D-E) CCK8 and migration assays showing the effect of SLAMF7 on the proliferative and migration abilities of HCC cells. (F-G) Left: Gross appearance of the liver bearing orthotopic Hepa1-6 tumors with and without Slamf7 overexpression from C57BL/6 and NOG mice. Right: The tumor weight and tumor volume of each group (5 mice per group). (H-I) Representative H&E staining images of lungs (left) and the incidence of lung metastasis (right) in the indicated orthotopic HCC mouse models from C57BL/6 and NOG mice. Scale bar: 500 μm (top) and 100 μm (bottom). ***P<0.001, and NS, not significant. Student’s t test (or one-way ANOVA with a post hoc LSD test in part A). Experiments were repeated three time and results were present as the mean ± SD.
Supplementary Movie 1 from Cigarette Smoking and E-cigarette Use Induce Shared DNA Methylation Changes Linked to Carcinogenesis
Authors: Herzog Chiara , Jones Allison , Evans Iona , Raut Janhavi R. , Zikan Michal , Cibula David , Wong Andrew , Brenner Hermann , Richmond Rebecca C. , Widschwendter Martin
Published: June 2024

Supplementary Movie 1
Figure S6 from Cigarette Smoking and E-cigarette Use Induce Shared DNA Methylation Changes Linked to Carcinogenesis
Authors: Herzog Chiara , Jones Allison , Evans Iona , Raut Janhavi R. , Zikan Michal , Cibula David , Wong Andrew , Brenner Hermann , Richmond Rebecca C. , Widschwendter Martin
Published: June 2024

Supplementary Figure 6
Figure S13 from Cigarette Smoking and E-cigarette Use Induce Shared DNA Methylation Changes Linked to Carcinogenesis
Authors: Herzog Chiara , Jones Allison , Evans Iona , Raut Janhavi R. , Zikan Michal , Cibula David , Wong Andrew , Brenner Hermann , Richmond Rebecca C. , Widschwendter Martin
Published: June 2024

Supplementary Figure 13
Data from Regular Use of Aspirin and Statins Reduces the Risk of Cancer in Individuals with Systemic Inflammatory Diseases
Authors: Lin Jia-Run , Han Duan-Duan , Wei Wei , Zeng Qin , Rong Zi-Xuan , Bai Xue , Zhang Yan-Pei , Wang Jian , Cai Xiao-Ting , Rao Xu-Guang , Ma Si-Cong , Dong Zhong-Yi
Published: June 2024

Abstract
Aspirin has shown potential for cancer prevention, but a recent large randomized controlled trial found no evidence for a reduction in cancer risk. Given the anti-inflammatory effects of aspirin, systemic inflammatory diseases (SID), such as osteoporosis, cardiovascular diseases, and metabolic diseases, could potentially modify the aspirin-cancer link. To investigate the impact of aspirin in people with SIDs, we conducted an observational study on a prospective cohort of 478,615 UK Biobank participants. Individuals with at least one of the 41 SIDs displayed a higher cancer risk than those without SIDs. Regular aspirin use showed protective effects exclusively in patients with SID, contrasting an elevated risk among their non-SID counterparts. Nonetheless, aspirin use demonstrated preventative potential only for 9 of 21 SID-associated cancer subtypes. Cholesterol emerged as another key mediator linking SIDs to cancer risk. Notably, regular statin use displayed protective properties in patients with SID but not in their non-SID counterparts. Concurrent use of aspirin and statins exhibited a stronger protective association in patients with SID, covering 14 common cancer subtypes. In summary, patients with SIDs may represent a population particularly responsive to regular aspirin and statin use. Promoting either combined or individual use of these medications within the context of SIDs could offer a promising chemoprevention strategy.
Significance:
Individuals with systemic inflammatory diseases derive chemoprotective benefits from aspirin and statins, providing a precision cancer prevention approach to address the personal and public challenges posed by cancer.
Obesogenic High-Fat Diet and MYC Cooperate to Promote Lactate Accumulation and Tumor Microenvironment Remodeling in Prostate Cancer
Authors: Boufaied Nadia , Chetta Paolo , Hallal Tarek , Cacciatore Stefano , Lalli Daniela , Luthold Carole , Homsy Kevin , Imada Eddie L. , Syamala Sudeepa , Photopoulos Cornelia , Di Matteo Anna , de Polo Anna , Storaci Alessandra Maria , Huang Ying , Giunchi Francesca , Sheridan Patricia A. , Michelotti Gregory , Nguyen Quang-De , Zhao Xin , Liu Yang , Davicioni Elai , Spratt Daniel E. , Sabbioneda Simone , Maga Giovanni , Mucci Lorelei A. , Ghigna Claudia , Marchionni Luigi , Butler Lisa M. , Ellis Leigh , Bordeleau François , Loda Massimo , Vaira Valentina , Labbé David P. , Zadra Giorgia
Published: June 2024

Cancer cells exhibit metabolic plasticity to meet oncogene-driven dependencies while coping with nutrient availability. A better understanding of how systemic metabolism impacts the accumulation of metabolites that reprogram the tumor microenvironment (TME) and drive cancer could facilitate development of precision nutrition approaches. Using the Hi-MYC prostate cancer mouse model, we demonstrated that an obesogenic high-fat diet (HFD) rich in saturated fats accelerates the development of c-MYC–driven invasive prostate cancer through metabolic rewiring. Although c-MYC modulated key metabolic pathways, interaction with an obesogenic HFD was necessary to induce glycolysis and lactate accumulation in tumors. These metabolic changes were associated with augmented infiltration of CD206+ and PD-L1+ tumor-associated macrophages (TAM) and FOXP3+ regulatory T cells, as well as with the activation of transcriptional programs linked to disease progression and therapy resistance. Lactate itself also stimulated neoangiogenesis and prostate cancer cell migration, which were significantly reduced following treatment with the lactate dehydrogenase inhibitor FX11. In patients with prostate cancer, high saturated fat intake and increased body mass index were associated with tumor glycolytic features that promote the infiltration of M2-like TAMs. Finally, upregulation of lactate dehydrogenase, indicative of a lactagenic phenotype, was associated with a shorter time to biochemical recurrence in independent clinical cohorts. This work identifies cooperation between genetic drivers and systemic metabolism to hijack the TME and promote prostate cancer progression through oncometabolite accumulation. This sets the stage for the assessment of lactate as a prognostic biomarker and supports strategies of dietary intervention and direct lactagenesis blockade in treating advanced prostate cancer.

Significance:

Lactate accumulation driven by high-fat diet and MYC reprograms the tumor microenvironment and promotes prostate cancer progression, supporting the potential of lactate as a biomarker and therapeutic target in prostate cancer.

See related commentary by Frigo, p. 1742
The DNA Methyltransferase Inhibitor 5-Aza-4′-thio-2′-Deoxycytidine Induces C>G Transversions and Acute Lymphoid Leukemia Development
Authors: Bertoli Ryan M. , Chung Yang Jo , Difilippantonio Michael J. , Wokasch Anthony , Marasco Madison R.B. , Klimaszewski Haley , Gammell Susannah , Zhu Yuelin J. , Walker Robert L. , Cao Dengchao , Khanna Ajay , Walter Matthew J. , Doroshow James H. , Meltzer Paul S. , Aplan Peter D.
Published: June 2024

DNA methyltransferase inhibitors (DNMTi), most commonly cytidine analogs, are compounds that decrease 5′-cytosine methylation. DNMTi are used clinically based on the hypothesis that cytosine demethylation will lead to re-expression of tumor suppressor genes. 5-Aza-4′-thio-2′-deoxycytidine (Aza-TdCyd or ATC) is a recently described thiol-substituted DNMTi that has been shown to have anti-tumor activity in solid tumor models. In this study, we investigated the therapeutic potential of ATC in a murine transplantation model of myelodysplastic syndrome. ATC treatment led to the transformation of transplanted wild-type bone marrow nucleated cells into lymphoid leukemia, and healthy mice treated with ATC also developed lymphoid leukemia. Whole-exome sequencing revealed 1,000 acquired mutations, almost all of which were C>G transversions in a specific 5′-NCG-3′ context. These mutations involved dozens of genes involved in human lymphoid leukemia, such as Notch1, Pten, Pax5, Trp53, and Nf1. Human cells treated in vitro with ATC showed 1,000 acquired C>G transversions in a similar context. Deletion of Dck, the rate-limiting enzyme for the cytidine salvage pathway, eliminated C>G transversions. Taken together, these findings demonstrate a highly penetrant mutagenic and leukemogenic phenotype associated with ATC.

Significance: Treatment with a DNA methyltransferase inhibitor generates a distinct mutation signature and triggers leukemic transformation, which has important implications for the research and clinical applications of these inhibitors.
A Hypoxia-Epigenetics Axis Drives EMT in Pancreatic Cancer
Authors: Wirth Matthias , Schneider Günter
Published: June 2024

Epithelial-to-mesenchymal transition (EMT) is a classical cellular plasticity process induced by various cell-intrinsic and -extrinsic triggers. Although prominent factors, such as TGFβ, mediate EMT via well-characterized pathways, alternative avenues are less well understood. Transcriptomic subtyping of pancreatic ductal adenocarcinoma (PDAC) has demonstrated that basal-like PDACs enrich a mesenchymal-like expression program, emphasizing the relevance of EMT in the disease. In this issue of Cancer Research, Brown and colleagues demonstrate the tight connection of EMT to hypoxia. Through a detailed mechanistic analysis, the authors deciphered that hypoxia-induced signals are integrated by the histone H3 lysine 36 di-methylation (H3K36me2) mark. On the one hand, hypoxia decreased activity of the H3K36me2 eraser KDM2A, while on the other hand promoting stabilization of the H3K36me2 writer NSD2. Hypoxia diminished the expression of a set of serine-threonine phosphatases, subsequently resulting in SRC kinase family-dependent activation of canonical MEK, ERK, and JNK signaling to impinge on NSD2 expression. In addition, reduced expression of the protein phosphatase PP2Cδ was linked to increased NSD2 protein expression. These discoveries illuminate the close relationship of hypoxia signaling to the epigenetic machinery and cellular plasticity processes.

See related article by Brown et al., p. 1764
Case-Case Genome-Wide Analyses Identify Subtype-Informative Variants That Confer Risk for Breast Cancer
Authors: Sun Xiaohui , Verma Shiv P. , Jia Guochong , Wang Xinjun , Ping Jie , Guo Xingyi , Shu Xiao-Ou , Chen Jianhong , Derkach Andriy , Cai Qiuyin , Liang Xiaolin , Long Jirong , Offit Kenneth , Oh Jung H. , Reiner Anne S. , Watt Gordon P. , Woods Meghan , Yang Yaohua , Ambrosone Christine B. , Ambs Stefan , Chen Yu , Concannon Patrick , Garcia-Closas Montserrat , Gu Jian , Haiman Christopher A. , Hu Jennifer J. , Huo Dezheng , John Esther M. , Knight Julia A. , Li Christopher I. , Lynch Charles F. , Mellemkjær Lene , Nathanson Katherine L. , Nemesure Barbara , Olopade Olufunmilayo I. , Olshan Andrew F. , Pal Tuya , Palmer Julie R. , Press Michael F. , Sanderson Maureen , Sandler Dale P. , Troester Melissa A. , Zheng Wei , Bernstein Jonine L. , Buas Matthew F. , Shu Xiang
Published: June 2024

Breast cancer includes several subtypes with distinct characteristic biological, pathologic, and clinical features. Elucidating subtype-specific genetic etiology could provide insights into the heterogeneity of breast cancer to facilitate the development of improved prevention and treatment approaches. In this study, we conducted pairwise case–case comparisons among five breast cancer subtypes by applying a case–case genome-wide association study (CC-GWAS) approach to summary statistics data of the Breast Cancer Association Consortium. The approach identified 13 statistically significant loci and eight suggestive loci, the majority of which were identified from comparisons between triple-negative breast cancer (TNBC) and luminal A breast cancer. Associations of lead variants in 12 loci remained statistically significant after accounting for previously reported breast cancer susceptibility variants, among which, two were genome-wide significant. Fine mapping implicated putative functional/causal variants and risk genes at several loci, e.g., 3q26.31/TNFSF10, 8q22.3/NACAP1/GRHL2, and 8q23.3/LINC00536/TRPS1, for TNBC as compared with luminal cancer. Functional investigation further identified rs16867605 at 8q22.3 as a SNP that modulates the enhancer activity of GRHL2. Subtype-informative polygenic risk scores (PRS) were derived, and patients with a high subtype-informative PRS had an up to two-fold increased risk of being diagnosed with TNBC instead of luminal cancers. The CC-GWAS PRS remained statistically significant after adjusting for TNBC PRS derived from traditional case–control GWAS in The Cancer Genome Atlas and the African Ancestry Breast Cancer Genetic Consortium. The CC-GWAS PRS was also associated with overall survival and disease-specific survival among patients with breast cancer. Overall, these findings have advanced our understanding of the genetic etiology of breast cancer subtypes, particularly for TNBC.

Significance: The discovery of subtype-informative genetic risk variants for breast cancer advances our understanding of the etiologic heterogeneity of breast cancer, which could accelerate the identification of targets and personalized strategies for prevention and treatment.
Dietary Commensal Wrestles Iron from Tumor Microenvironment to Activate Antitumoral Macrophages
Authors: Lee Amanda H. , Randhawa Simran K. , Meisel Marlies
Published: June 2024

The microbiome dictates the response to cancer immunotherapy efficacy. However, the mechanisms of how the microbiota impacts therapy efficacy remain poorly understood. In a recent issue of Nature Immunology, Sharma and colleagues elucidate a multifaceted, macrophage-driven mechanism exerted by a specific strain of fermented food commensal plantarum strain IMB19, LpIMB19. LpIMB19 activates tumor macrophages, resulting in the enhancement of cytotoxic cluster differentiation 8 (CD8) T cells. LpIMB19 administration led to an expansion of tumor-infiltrating CD8 T cells and improved the efficacy of anti-PD-L1 therapy. Rhamnose-rich heteropolysaccharide, a strain-specific cell wall component, was identified as the primary effector molecule of LplMB19. Toll-like receptor 2 signaling and the ability of macrophages to sequester iron were both critical for rhamnose-rich heteropolysaccharide–mediated macrophage activation upstream of the CD8 T-cell effector response and contributed to tumor cell apoptosis through iron deprivation. These findings reveal a well-defined mechanism connecting diet and health outcomes, suggesting that diet-derived commensals may warrant further investigation. Additionally, this work emphasizes the importance of strain-specific differences in studying microbiome-cancer interactions and the concept of “nutritional immunity” to enhance microbe-triggered antitumor immunity.
Supplementary Figure S6 from Discovery of a Long Half-Life AURKA Inhibitor to Treat MYC-Amplified Solid Tumors as a Monotherapy and in Combination with Everolimus
Authors: Chang Chun-Ping , Yeh Teng-Kuang , Chen Chiung-Tong , Wang Wan-Ping , Chen Yen-Ting , Tsai Chia-Hua , Chen Yan-Fu , Ke Yi-Yu , Wang Jing-Ya , Chen Ching-Ping , Hsieh Tsung-Chih , Wu Mine-Hsine , Huang Chen-Lung , Chen Ya-Ping , Zhuang Hong , Chi Ya-Hui
Published: June 2024

Supplementary Figure S6. Synergistic effect of DBPR728 in combination with PI3K/mTOR inhibitors. (A) Dose matrix of 6K465 in combination with copanlisib (a pan-PI3K inhibitor), alpelisib (a PI3Kalpha inhibitor) and idelalisib (a PI3Kdelta inhibitor) in NCI-H69 and NCI-H446 cells. Percent growth inhibition at each dose assessed at 72 hr after drug treatment was shown on the left. Synergy distribution based on a ZIP model was shown on the right. (B) Individual tumor growth curve of NCI-H69 and NCI-H446 xenografts in mice as presented in Fig. 6, C-D.
Kinase Panel 2 from A Novel Dual ATM/DNA-PK Inhibitor, XRD-0394, Potently Radiosensitizes and Potentiates PARP and Topoisomerase I Inhibitors
Authors: Gilmer Tona M. , Lai Chun-Hsiang , Guo Kexiao , Deland Katherine , Ashcraft Kathleen A. , Stewart Amy E. , Wang Yaode , Fu Jianmin , Wood Kris C. , Kirsch David G. , Kastan Michael B.
Published: June 2024

Results of Kinase Panel Screen-2
Supplementary Table 2 from Proton FLASH Radiotherapy Ameliorates Radiation-induced Salivary Gland Dysfunction and Oral Mucositis and Increases Survival in a Mouse Model of Head and Neck Cancer
Authors: Chowdhury Priyanka , Velalopoulou Anastasia , Verginadis Ioannis I. , Morcos George , Loo Phoebe E. , Kim Michele M. , Motlagh Seyyedeh Azar Oliaei , Shoniyozov Khayrullo , Diffenderfer Eric S. , Ocampo Emilio A. , Putt Mary , Assenmacher Charles-Antoine , Radaelli Enrico , Lu Jiawei , Qin Ling , Liu Hengxi , Leli Nektaria Maria , Girdhani Swati , Denef Nicolas , Vander Stappen Francois , Cengel Keith A. , Busch Theresa M. , Metz James M. , Dong Lei , Lin Alexander , Koumenis Constantinos
Published: June 2024

The list of antibodies used for the immunofluorescence and the western blot assay.
Supplementary Table 1 from Proton FLASH Radiotherapy Ameliorates Radiation-induced Salivary Gland Dysfunction and Oral Mucositis and Increases Survival in a Mouse Model of Head and Neck Cancer
Authors: Chowdhury Priyanka , Velalopoulou Anastasia , Verginadis Ioannis I. , Morcos George , Loo Phoebe E. , Kim Michele M. , Motlagh Seyyedeh Azar Oliaei , Shoniyozov Khayrullo , Diffenderfer Eric S. , Ocampo Emilio A. , Putt Mary , Assenmacher Charles-Antoine , Radaelli Enrico , Lu Jiawei , Qin Ling , Liu Hengxi , Leli Nektaria Maria , Girdhani Swati , Denef Nicolas , Vander Stappen Francois , Cengel Keith A. , Busch Theresa M. , Metz James M. , Dong Lei , Lin Alexander , Koumenis Constantinos
Published: June 2024

The TaqMan primer list for RT–qPCR.
Supplementary Table 2 from Thio-2 Inhibits Key Signaling Pathways Required for the Development and Progression of Castration-resistant Prostate Cancer
Authors: Neeb Antje , Figueiredo Ines , Bogdan Denisa , Cato Laura , Stober Jutta , Jiménez-Vacas Juan M. , Gourain Victor , Lee Irene I. , Seeger Rebecca , Muhle-Goll Claudia , Gurel Bora , Welti Jonathan , Nava Rodrigues Daniel , Rekowski Jan , Qiu Xintao , Jiang Yija , Di Micco Patrizio , Mateos Borja , Bielskutė Stasė , Riisnaes Ruth , Ferreira Ana , Miranda Susana , Crespo Mateus , Buroni Lorenzo , Ning Jian , Carreira Suzanne , Bräse Stefan , Jung Nicole , Gräßle Simone , Swain Amanda , Salvatella Xavier , Plymate Stephen R. , Al-Lazikani Bissan , Long Henry W. , Yuan Wei , Brown Myles , Cato Andrew C.B. , de Bono Johann S. , Sharp Adam
Published: June 2024

TaqMan probes for qRT-PCR analyses.
Supplementary Figure 8 from Thio-2 Inhibits Key Signaling Pathways Required for the Development and Progression of Castration-resistant Prostate Cancer
Authors: Neeb Antje , Figueiredo Ines , Bogdan Denisa , Cato Laura , Stober Jutta , Jiménez-Vacas Juan M. , Gourain Victor , Lee Irene I. , Seeger Rebecca , Muhle-Goll Claudia , Gurel Bora , Welti Jonathan , Nava Rodrigues Daniel , Rekowski Jan , Qiu Xintao , Jiang Yija , Di Micco Patrizio , Mateos Borja , Bielskutė Stasė , Riisnaes Ruth , Ferreira Ana , Miranda Susana , Crespo Mateus , Buroni Lorenzo , Ning Jian , Carreira Suzanne , Bräse Stefan , Jung Nicole , Gräßle Simone , Swain Amanda , Salvatella Xavier , Plymate Stephen R. , Al-Lazikani Bissan , Long Henry W. , Yuan Wei , Brown Myles , Cato Andrew C.B. , de Bono Johann S. , Sharp Adam
Published: June 2024

Thio-2 downregulates androgen receptor signaling and inhibits growth of prostate cancer cell lines through a BAG-1 independent mechanism.
Supplementary Figure S9 from Structural Basis for Multivalent MUC16 Recognition and Robust Anti-Pancreatic Cancer Activity of Humanized Antibody AR9.6
Authors: Aguilar Eric N. , Sagar Satish , Murray Brandy R. , Rajesh Christabelle , Lei Eric K. , Michaud Sarah A. , Goodlett David R. , Caffrey Thomas C. , Grandgenett Paul M. , Swanson Benjamin , Brooks Teresa M. , Black Adrian R. , van Faassen Henk , Hussack Greg , Henry Kevin A. , Hollingsworth Michael A. , Brooks Cory L. , Radhakrishnan Prakash
Published: June 2024

Fig. S9. Evaluation of huAR9.6’s potential toxicity. Liver enzyme profile showing (A) ALT and (B) AST measured in vehicle control (PBS), huIgG and huAR9.6 (500 µg/25 g bodyweight, i.p. for 4 doses) treated orthotopic PDAC tumor-bearing mice (n=5). (C) Representative H&E staining of liver, lung, spleen, and kidney collected from the vehicle control (PBS), huIgG and huAR9.6-treated orthotopic PDAC tumor-bearing mice (n=7) on day 28. (D) Schematic of a single-dose toxicity model in athymic nude mice (n=6). Blood collection was done on day 0 (pre-treatment), after which mice were treated with a single dose of vehicle (PBS) or huAR9.6 (1 mg/25 g bodyweight, i.p.), followed by blood collection on days 3 and 14. Body weight measurements were done daily. At the experimental endpoint (day 14), mice were euthanized. (E) Body weight measurements in grams (g) for mice treated with single-dose vehicle (PBS) or huAR9.6 (1 mg/mL). Day 0 serves as the pre-treatment timepoint. Liver enzyme profile showing (F) ALT and (G) AST measured in serum at pre-treated, 3- and 14-days post treatment timepoints. (H) Representative H&E staining of pancreas, liver, lung, spleen, and kidney collected from mice 14 days after single-dose treatment with vehicle or huAR9.6 (1 mg/mL).
Supplementary Figure 12 from Thio-2 Inhibits Key Signaling Pathways Required for the Development and Progression of Castration-resistant Prostate Cancer
Authors: Neeb Antje , Figueiredo Ines , Bogdan Denisa , Cato Laura , Stober Jutta , Jiménez-Vacas Juan M. , Gourain Victor , Lee Irene I. , Seeger Rebecca , Muhle-Goll Claudia , Gurel Bora , Welti Jonathan , Nava Rodrigues Daniel , Rekowski Jan , Qiu Xintao , Jiang Yija , Di Micco Patrizio , Mateos Borja , Bielskutė Stasė , Riisnaes Ruth , Ferreira Ana , Miranda Susana , Crespo Mateus , Buroni Lorenzo , Ning Jian , Carreira Suzanne , Bräse Stefan , Jung Nicole , Gräßle Simone , Swain Amanda , Salvatella Xavier , Plymate Stephen R. , Al-Lazikani Bissan , Long Henry W. , Yuan Wei , Brown Myles , Cato Andrew C.B. , de Bono Johann S. , Sharp Adam
Published: June 2024

Thio-2 solubility.
Supplementary Figure 1 from Thio-2 Inhibits Key Signaling Pathways Required for the Development and Progression of Castration-resistant Prostate Cancer
Authors: Neeb Antje , Figueiredo Ines , Bogdan Denisa , Cato Laura , Stober Jutta , Jiménez-Vacas Juan M. , Gourain Victor , Lee Irene I. , Seeger Rebecca , Muhle-Goll Claudia , Gurel Bora , Welti Jonathan , Nava Rodrigues Daniel , Rekowski Jan , Qiu Xintao , Jiang Yija , Di Micco Patrizio , Mateos Borja , Bielskutė Stasė , Riisnaes Ruth , Ferreira Ana , Miranda Susana , Crespo Mateus , Buroni Lorenzo , Ning Jian , Carreira Suzanne , Bräse Stefan , Jung Nicole , Gräßle Simone , Swain Amanda , Salvatella Xavier , Plymate Stephen R. , Al-Lazikani Bissan , Long Henry W. , Yuan Wei , Brown Myles , Cato Andrew C.B. , de Bono Johann S. , Sharp Adam
Published: June 2024

Development and characterization of BAG-1 knockout mice.
Supplementary Figure S3 from Structural Basis for Multivalent MUC16 Recognition and Robust Anti-Pancreatic Cancer Activity of Humanized Antibody AR9.6
Authors: Aguilar Eric N. , Sagar Satish , Murray Brandy R. , Rajesh Christabelle , Lei Eric K. , Michaud Sarah A. , Goodlett David R. , Caffrey Thomas C. , Grandgenett Paul M. , Swanson Benjamin , Brooks Teresa M. , Black Adrian R. , van Faassen Henk , Hussack Greg , Henry Kevin A. , Hollingsworth Michael A. , Brooks Cory L. , Radhakrishnan Prakash
Published: June 2024

Fig. S3. MUC16 expression in PDAC cells and PDAC patients’ samples using huAR9.6 mAb. (A) Western blotting for MUC16 (with huAR9.6) in normal HPDE cells and AsPC-1, T3M4, Capan-2, Panc-1, MiaPaCa-2, Capan-1, BxPC-3, S2-013, FG and SU86.86 PDAC cells. Loading control: α-tubulin. (B) Immunofluorescent staining for MUC16 (AF647-huAR9.6, red) and α-tubulin (AF488, green) in T3M4-WT and T3M4-MUC16KO cells. (C) Representative image of immunofluorescent staining for MUC16 (AF647-huAR9.6, red) in normal pancreas (n=7) and PDAC tissue (n=32) obtained from the Rapid Autopsy Program at UNMC. (D) Representative images of immunohistochemistry for MUC16 on a patient-derived xenograft (PDX) microarray using huAR9.6; (E) Graphical representation of varying histoscores; (F) Graphical representation of consistency between histoscore (huAR9.6-based MUC16 detection) and RNA sequencing of MUC16 gene expression in PDX microarray samples (n = 31). (G) Western blotting for MUC16 (with huAR9.6) in ascites fluids (n = 34) obtained from PDAC patients via the Rapid Autopsy Program at UNMC. Western blot of N-glycanase, O-glycanase and sialidase treated (H) T3M4 cell lysates and (I) MUC16 TR1.2 glycopeptides probed with huAR9.6 mAb. Detection of α-tubulin served as the loading control.