bluuebunny/crossref_metadata_2025 huggingface dataset:
The Balancing and Dynamic Rail Pressure of Locomotives
Authors: Eksergian R.
Published: January 2024

The problem of counterbalancing for minimum dynamic loading and rail stress is a basic-design limitation for modern locomotives with limited axle loads. Two methods of balance are ordinarily used: static balancing, where the difference in planes of the revolving weights is not taken into consideration, and dynamic balancing, where the planes of action are considered as well. As the former method is extensively used, the estimation of maximum rail pressure with the heavy overhanging revolving weights is of considerable importance. An analysis is made, resulting in formulas and general methods for the determination of the maximum rail pressure and the corresponding position of the crank for systems of revolving weights. Also, a complete outline of balancing methods is included. The balancing of the reciprocating parts introduces unbalanced vertical components. A general study is made of the dynamic effect of the reciprocating parts and revolving parts on the locomotive itself, both for two- and three-cylinder locomotives, counterbalanced statically and dynamically. Next, comparative studies are made of the relative effects when statically and dynamically balanced for two-cylinder locomotives; that is, as to rail pressure and the vibration of the locomotive itself. A similar comparison is made of the dynamic loadings for two- and three-cylinder locomotives. A brief survey is made of the nature of rail stress and the effect of counterbalance and wheel spacing in augmenting the bending moment in the rail. Calculations are included for the rail and track loading of a Mountain type, an eight-coupled, and a three-cylinder compound locomotive. Finally, a study of weight transfer under maximum traction is made, including calculations for it with a Santa Fe type locomotive. The appendix contains special problems, as the general formula for the vertical thrust of the connecting rod on the main pin, and an estimation of revolving weight, with experimental methods of determining the constants of a rod. The general dynamical equation of a locomotive for the fore-and-aft and nosing oscillations is also included. The conclusions are that the cross or dynamic balance of main drivers should be made with modern power and the allowable axle loading should be based on the maximum rail and track loading at the average operating speeds.
Lubrication of Ball-Bearing Woodworking Spindles
Authors: Reynolds Harry R.
Published: January 2024

The purpose of this paper is to bring out methods of lubrication especially suitable for speeds of 4000 to 7500 r.p.m. which is about the range of woodworking spindles.

The author sums up by stating that where oil is used its level should not be over the center of the lowest ball if speeds are higher than 500 r.p.m. At 5000 to 5700 r.p.m. a very light spindle oil should be used, and it should be fed either by wick, or circulation from pump as any depth of oil around the balls will cause tremendous churning. Too much oil should not be used as it will cause heating, and the higher the speed the greater the heat.

If grease of the proper consistency is used, the housing can be filled. At high speed there will be a path cut through the grease by the balls, and if temperature develops, just enough melting will occur to furnish the lubrication required. Greases soft enough to churn should be avoided for high-speed applications as the heat generated will melt them so fast that conditions will duplicate those of too much oil. Failure is generally due to dirt, so the bearings must be kept clean. Especial care should be taken in renewing the lubricant, as this is when most of the dirt gets in.
The Coordination of Production and Distribution of Wood Products
Authors: Bigelow Carle M. , Perry Thomas D.
Published: January 2024

After noting that rarely have the qualities of attractive woodworking craftsmanship and methods of aggressive distribution been found in profitable combination, the authors take up problems invoiced in production, dealing successively with sales-dollar analysis, labor utilization, material yield, planning and budgeting, and standard costs. They then consider the distribution of wood products and discuss respectively marketing the commodity product, selling to distributors, and marketing the style product. Following this they deal briefly with the coordination of production and distribution, and in conclusion point out the great demand at present existing for a transfer of some of the already achieved manufacturing skill into the merchandising field.
Making Animal Glue Water Resistant
Authors: Browne F. L.
Published: January 2024

In this paper the author gives a formula for making animal glue water resistant. Graphs are given which show the relation between the temperature and the working life of a batch of glue when prepared by the recommended formula, and also for a glue containing paraformaldehyde without oxalic acid. Rapid decrease in the working life of both glues at high temperatures makes it necessary to control the heating of the glue carefully. Characteristics of a water-resistant animal glue are given, together with the effect of varying the content of oxalic acid and paraformaldehyde.
Wood Bending
Authors: Wilson T. R. C.
Published: January 2024

Wood softened by the action of moisture and heat or by other agencies can be upset or shortened very considerably, but can be stretched or lengthened but little. Hence, since the concave and convex faces of a bent piece differ in length, it is necessary in bending to prevent stretch and to cause the entire difference in length to take place as upset, this upset being a maximum at the concave face and decreasing to zero near the convex face. This can be accomplished by supplying a metal strap with securely attached end fittings through which the compressive force, or end pressure, can be applied. The end pressure must be distributed over the ends of the stock so that localized crushing does not occur, and the rotation of the end fitting must be restrained to obviate release of the end pressure. The common arrangement of parts of wood-bending apparatus does not fulfill these requirements. The requirements can be attained, however, by utilizing the principle of the reversed lever.

The distance between end fittings cannot be made exactly the same for a number of straps and cannot be kept constant, neither can pieces of wood be cut exactly to the required length. Hence, means for adjusting the distance between end fittings is necessary. Pieces whose width is considerably less than their depth must be restrained to prevent sidewise bending and the formation of lateral crooks and buckling.

This paper, which is based on studies at the Forest Products Laboratory, deals only with the requirements of bending apparatus and manipulation, emphasizes their importance, and points out that they must be correct before the large breakage losses incurred in the bending of wood can be reduced materially.
Source motion via a time-frequency representation at a single sensor
Authors: Gendron Paul
Published: January 2024

The Reflections series takes a look back on historical articles from The Journal of the Acoustical Society of America that have had a significant impact on the science and practice of acoustics.
Mapping palatal shape to electromagnetic articulography data: An approach using 3D scanning and sensor matching
Authors: Nota Yukiko , Kitamura Tatsuya , Takemoto Hironori , Maekawa Kikuo
Published: January 2024

A method for superimposing the shape of the palate on three-dimensional (3D) electromagnetic articulography (EMA) data is proposed. A biteplate with a dental impression tray and EMA sensors is used to obtain the palatal shape and record the sensor positions. The biteplate is then 3D scanned, and the scanned palate is mapped to the EMA data by matching the sensor positions on the scanned image with those in the EMA readings. The average distance between the mapped palate and the EMA palate traces is roughly 1 mm for nine speakers and is comparable to the measurement error of the EMA.
The expanding footprint of basic biology research in India
Authors: Shukla Arun K.
Published: January 2024

Basic biology research in India has expanded in recent years, and addressing key challenges should enable this momentum to continue.
Climate Change, Landscape Fires, and Human Health: A Global Perspective
Authors: Johnston Fay H. , Williamson Grant , Borchers-Arriagada Nicolas , Henderson Sarah B. , Bowman David M.J.S.
Published: January 2024

Landscape fires are an integral component of the Earth system and a feature of prehistoric, subsistence, and industrial economies. Specific spatiotemporal patterns of landscape fire occur in different locations around the world, shaped by the interactions between environmental and human drivers of fire activity. Seven distinct types of landscape fire emerge from these interactions: remote area fires, wildfire disasters, savanna fires, Indigenous burning, prescribed burning, agricultural burning, and deforestation fires. All can have substantial impacts on human health and well-being directly and indirectly through (a) exposure to heat flux (e.g., injuries and destructive impacts), (b) emissions (e.g., smoke-related health impacts), and (c) altered ecosystem functioning (e.g., biodiversity, amenity, water quality, and climate impacts). Minimizing the adverse effects of landscape fires on population health requires understanding how human and environmental influences on fire impacts can be modified through interventions targeted at individual, community, and regional levels.
Enhanced Multiobjective Optimization Algorithm for Intelligent Grid Management of Renewable Energy Sources
Authors: Han Xue , Ding JiKe , Cheng Honglin
Published: January 2024

Optimal scheduling of microgrids (MGs) is a crucial component of smart grid optimization, playing a vital role in minimizing energy consumption and environmental degradation. However, existing methods tend to consider only a single optimization and do not consider the multiobjective optimization problem of MGs in a comprehensive and integrated way. This study proposes a comprehensive multiobjective optimal scheduling methodology for renewable energy MGs, incorporating demand-side management (DSM) considerations. Initially, a DSM multiobjective optimization model is formulated, focusing on the load shifting of controllable devices within the MG to refine the electricity consumption structure. This model contemplates the renewable energy consumption of the MG, customer electricity purchase costs, and load smoothness. Subsequently, a multiobjective optimization model for grid-connected MGs, encompassing wind and photovoltaic power generation, is constructed with the dual objectives of economic and environmental optimization for the MG. Ultimately, a multimodal multiobjective optimization algorithm, amalgamating a local convergence index and an environment selection strategy, is proposed to solve the model. The experimental results show that compared with other methods, the proposed method in this paper can reduce the integrated cost by 32.6% and 38.9% in summer and 19.4% and 40.2% in winter. This stands out as a unique contribution in the field of MG optimization, as it integrates DSM considerations into a multiobjective optimization model. This methodology achieves a balance between minimizing energy consumption and environmental degradation while also enhancing economic efficiency.
Effects of Different Ratios of Fly Ash and River Sand on Mechanical Properties of Cemented Paste Backfill Materials
Authors: Li Jiang , Cao Shenggen , Liu Yang , Che Chiyuan , Zhao Changzheng , Du Shuyu , Wang Kaifei , Ma Ruiting
Published: January 2024

The mechanical properties of cemented paste backfill (CPB) are crucial for stope safety. Some mining areas in the Yellow River basin face a shortage of coal gangue, and these areas have abundant river sand (RS) resources. The use of RS as a fine aggregate can optimize the particle gradation of the material and improve the strength of the material. The effects of different fly ash (FA) and RS ratios on uniaxial compressive strength (UCS), elastic modulus, and microstructure of CPB were studied using uniaxial compression test and scanning electron microscopy. The results showed that with increasing FA content, UCS gradually increased at 7 and 14 days of CPB. However, at 28 days, the UCS of CPB first increased and then decreased. When the FA content was 40%, UCS at 28 days of backfill material reached its highest value of 14.76 MPa. The elastic modulus decreased as FA content increased and reached its maximum value of 1.54 GPa when FA content was 40%. FA optimized particle composition, promoted hydration reaction, and improved CPB strength; however, when FA content was more than 40%, it hindered cement hydration, thus deteriorating UCS. Based on Weibull distribution and prepeak correction factor, a damage constitutive model was established to describe the stress–strain process of CPB under load. The results of this research will provide a theoretical and experimental basis for CPB engineering design.
Supplementary Data from Autotaxin Secretion Is a Stromal Mechanism of Adaptive Resistance to TGFβ Inhibition in Pancreatic Ductal Adenocarcinoma
Authors: Pietrobono Silvia , Sabbadini Fabio , Bertolini Monica , Mangiameli Domenico , De Vita Veronica , Fazzini Federica , Lunardi Giulia , Casalino Simona , Scarlato Enza , Merz Valeria , Zecchetto Camilla , Quinzii Alberto , Di Conza Giusy , Lahn Michael , Melisi Davide
Published: January 2024

Figures S1-5, Tables S1-3
Supplementary Data from Hypoxia-Responsive CAR-T Cells Exhibit Reduced Exhaustion and Enhanced Efficacy in Solid Tumors
Authors: Zhu Xiuxiu , Chen Jun , Li Wuling , Xu Yanmin , Shan Juanjuan , Hong Juan , Zhao Yongchun , Xu Huailong , Ma Jiabin , Shen Junjie , Qian Cheng
Published: January 2024

12 supplementary figures and 2 supplementary tables
Supplementary Table S9 from Leveraging Tissue-Specific Enhancer–Target Gene Regulatory Networks Identifies Enhancer Somatic Mutations That Functionally Impact Lung Cancer
Authors: Hariprakash Judith Mary , Salviato Elisa , La Mastra Federica , Sebestyén Endre , Tagliaferri Ilario , Silva Raquel Sofia , Lucini Federica , Farina Lorenzo , Cinquanta Mario , Rancati Ilaria , Riboni Mirko , Minardi Simone Paolo , Roz Luca , Gorini Francesca , Lanzuolo Chiara , Casola Stefano , Ferrari Francesco
Published: January 2024

CDH13 enhancer regression: Generalised linear model
Table S7 from Genomic and Evolutionary Characterization of Concurrent Intraductal Carcinoma and Adenocarcinoma of the Prostate
Authors: Zhao Jinge , Xu Nanwei , Zhu Sha , Nie Ling , Zhang Mengni , Zheng Linmao , Cai Diming , Sun Xiaomeng , Chen Junru , Dai Jindong , Ni Yuchao , Wang Zhipeng , Zhang Xingming , Liang Jiayu , Chen Yuntian , Hu Xu , Pan Xiuyi , Yin Xiaoxue , Liu Haoyang , Zhao Fengnian , Zhang Bei , Chen Hao , Miao Jiashun , Qin Cong , Zhao Xiaochen , Yao Jin , Liu Zhenhua , Liao Banghua , Wei Qiang , Li Xiang , Liu Jiyan , Gao Allen C. , Huang Haojie , Shen Pengfei , Chen Ni , Zeng Hao , Sun Guangxi
Published: January 2024

Table S7
Supplementary Table S7 from Leveraging Tissue-Specific Enhancer–Target Gene Regulatory Networks Identifies Enhancer Somatic Mutations That Functionally Impact Lung Cancer
Authors: Hariprakash Judith Mary , Salviato Elisa , La Mastra Federica , Sebestyén Endre , Tagliaferri Ilario , Silva Raquel Sofia , Lucini Federica , Farina Lorenzo , Cinquanta Mario , Rancati Ilaria , Riboni Mirko , Minardi Simone Paolo , Roz Luca , Gorini Francesca , Lanzuolo Chiara , Casola Stefano , Ferrari Francesco
Published: January 2024

Gene set enrichment analysis on C6 oncogenic dataset from MsigDB
Supplementary Table S6 from Leveraging Tissue-Specific Enhancer–Target Gene Regulatory Networks Identifies Enhancer Somatic Mutations That Functionally Impact Lung Cancer
Authors: Hariprakash Judith Mary , Salviato Elisa , La Mastra Federica , Sebestyén Endre , Tagliaferri Ilario , Silva Raquel Sofia , Lucini Federica , Farina Lorenzo , Cinquanta Mario , Rancati Ilaria , Riboni Mirko , Minardi Simone Paolo , Roz Luca , Gorini Francesca , Lanzuolo Chiara , Casola Stefano , Ferrari Francesco
Published: January 2024

Enhancer target gene prediction results
Table S3 from Genomic and Evolutionary Characterization of Concurrent Intraductal Carcinoma and Adenocarcinoma of the Prostate
Authors: Zhao Jinge , Xu Nanwei , Zhu Sha , Nie Ling , Zhang Mengni , Zheng Linmao , Cai Diming , Sun Xiaomeng , Chen Junru , Dai Jindong , Ni Yuchao , Wang Zhipeng , Zhang Xingming , Liang Jiayu , Chen Yuntian , Hu Xu , Pan Xiuyi , Yin Xiaoxue , Liu Haoyang , Zhao Fengnian , Zhang Bei , Chen Hao , Miao Jiashun , Qin Cong , Zhao Xiaochen , Yao Jin , Liu Zhenhua , Liao Banghua , Wei Qiang , Li Xiang , Liu Jiyan , Gao Allen C. , Huang Haojie , Shen Pengfei , Chen Ni , Zeng Hao , Sun Guangxi
Published: January 2024

Table S3
Supplementary Table S3 from Leveraging Tissue-Specific Enhancer–Target Gene Regulatory Networks Identifies Enhancer Somatic Mutations That Functionally Impact Lung Cancer
Authors: Hariprakash Judith Mary , Salviato Elisa , La Mastra Federica , Sebestyén Endre , Tagliaferri Ilario , Silva Raquel Sofia , Lucini Federica , Farina Lorenzo , Cinquanta Mario , Rancati Ilaria , Riboni Mirko , Minardi Simone Paolo , Roz Luca , Gorini Francesca , Lanzuolo Chiara , Casola Stefano , Ferrari Francesco
Published: January 2024

Number of enhancers associated with genes and the number of mutations in the lower right quadrant of figure 4c Overlap with Msigdb C2 dataset
Table S2-revised from Genomic and Evolutionary Characterization of Concurrent Intraductal Carcinoma and Adenocarcinoma of the Prostate
Authors: Zhao Jinge , Xu Nanwei , Zhu Sha , Nie Ling , Zhang Mengni , Zheng Linmao , Cai Diming , Sun Xiaomeng , Chen Junru , Dai Jindong , Ni Yuchao , Wang Zhipeng , Zhang Xingming , Liang Jiayu , Chen Yuntian , Hu Xu , Pan Xiuyi , Yin Xiaoxue , Liu Haoyang , Zhao Fengnian , Zhang Bei , Chen Hao , Miao Jiashun , Qin Cong , Zhao Xiaochen , Yao Jin , Liu Zhenhua , Liao Banghua , Wei Qiang , Li Xiang , Liu Jiyan , Gao Allen C. , Huang Haojie , Shen Pengfei , Chen Ni , Zeng Hao , Sun Guangxi
Published: January 2024

Table S2-revised
Supplementary Table S1 from Leveraging Tissue-Specific Enhancer–Target Gene Regulatory Networks Identifies Enhancer Somatic Mutations That Functionally Impact Lung Cancer
Authors: Hariprakash Judith Mary , Salviato Elisa , La Mastra Federica , Sebestyén Endre , Tagliaferri Ilario , Silva Raquel Sofia , Lucini Federica , Farina Lorenzo , Cinquanta Mario , Rancati Ilaria , Riboni Mirko , Minardi Simone Paolo , Roz Luca , Gorini Francesca , Lanzuolo Chiara , Casola Stefano , Ferrari Francesco
Published: January 2024

Primer details
Supplementary Data from Genomic and Evolutionary Characterization of Concurrent Intraductal Carcinoma and Adenocarcinoma of the Prostate
Authors: Zhao Jinge , Xu Nanwei , Zhu Sha , Nie Ling , Zhang Mengni , Zheng Linmao , Cai Diming , Sun Xiaomeng , Chen Junru , Dai Jindong , Ni Yuchao , Wang Zhipeng , Zhang Xingming , Liang Jiayu , Chen Yuntian , Hu Xu , Pan Xiuyi , Yin Xiaoxue , Liu Haoyang , Zhao Fengnian , Zhang Bei , Chen Hao , Miao Jiashun , Qin Cong , Zhao Xiaochen , Yao Jin , Liu Zhenhua , Liao Banghua , Wei Qiang , Li Xiang , Liu Jiyan , Gao Allen C. , Huang Haojie , Shen Pengfei , Chen Ni , Zeng Hao , Sun Guangxi
Published: January 2024

Supplementary Methods
Supplementary Data from Progressively Enhancing Stemness of Adoptively Transferred T Cells with PI3Kδ Blockade Improves Metabolism and Antitumor Immunity
Authors: Rangel Rivera Guillermo O. , Dwyer Connor J. , Knochelmann Hannah M. , Smith Aubrey S. , Aksoy Bülent Arman , Cole Anna C. , Wyatt Megan M. , Kumaresan Soundharya , Thaxton Jessica E. , Lesinski Gregory B. , Paulos Chrystal M.
Published: January 2024

Supplemental data related to main figures 1-7
Supplementary Figure S1 from Targeting Transcriptional Regulation with a CDK9 Inhibitor Suppresses Growth of Endocrine- and Palbociclib-Resistant ER+ Breast Cancers
Authors: Soosainathan Arany , Iravani Marjan , El-Botty Rania , Alexander John , Sourd Laura , Morisset Ludivine , Painsec Pierre , Orha Rebecca , Nikitorowicz-Buniak Joanna , Pancholi Sunil , Haider Syed , Dowsett Mitch , Marangoni Elisabetta , Martin Lesley-Ann , Isacke Clare M.
Published: January 2024

Supplementary Figure S1
Supplementary Data from Targeting Transcriptional Regulation with a CDK9 Inhibitor Suppresses Growth of Endocrine- and Palbociclib-Resistant ER+ Breast Cancers
Authors: Soosainathan Arany , Iravani Marjan , El-Botty Rania , Alexander John , Sourd Laura , Morisset Ludivine , Painsec Pierre , Orha Rebecca , Nikitorowicz-Buniak Joanna , Pancholi Sunil , Haider Syed , Dowsett Mitch , Marangoni Elisabetta , Martin Lesley-Ann , Isacke Clare M.
Published: January 2024

Supplementary Methods
Supplementary Data from Hypoxic Bone Marrow Stromal Cells Secrete miR-140–5p and miR-28–3p That Target SPRED1 to Confer Drug Resistance in Multiple Myeloma
Authors: Zhang Hui , Du Zhimin , Tu Chenggong , Zhou Xinyan , Menu Eline , Wang Jinheng
Published: January 2024

Supplementary methods and figures
Data from Autotaxin Secretion Is a Stromal Mechanism of Adaptive Resistance to TGFβ Inhibition in Pancreatic Ductal Adenocarcinoma
Authors: Pietrobono Silvia , Sabbadini Fabio , Bertolini Monica , Mangiameli Domenico , De Vita Veronica , Fazzini Federica , Lunardi Giulia , Casalino Simona , Scarlato Enza , Merz Valeria , Zecchetto Camilla , Quinzii Alberto , Di Conza Giusy , Lahn Michael , Melisi Davide
Published: January 2024

Abstract
The TGFβ receptor inhibitor galunisertib demonstrated efficacy in patients with pancreatic ductal adenocarcinoma (PDAC) in the randomized phase II H9H-MC-JBAJ study, which compared galunisertib plus the chemotherapeutic agent gemcitabine with gemcitabine alone. However, additional stromal paracrine signals might confer adaptive resistance that limits the efficacy of this therapeutic strategy. Here, we found that autotaxin, a secreted enzyme that promotes inflammation and fibrosis by generating lysophosphatidic acid (LPA), mediates adaptive resistance to TGFβ receptor inhibition. Blocking TGFβ signaling prompted the skewing of cancer-associated fibroblasts (CAF) toward an inflammatory (iCAF) phenotype. iCAFs were responsible for a significant secretion of autotaxin. Paracrine autotaxin increased LPA-NFκB signaling in tumor cells that triggered treatment resistance. The autotaxin inhibitor IOA-289 suppressed NFκB activation in PDAC cells and overcame resistance to galunisertib and gemcitabine. In immunocompetent orthotopic murine models, IOA-289 synergized with galunisertib in restoring sensitivity to gemcitabine. Most importantly, treatment with galunisertib significantly increased plasma levels of autotaxin in patients enrolled in the H9H-MC-JBAJ study, and median progression-free survival was significantly longer in patients without an increase of autotaxin upon treatment with galunisertib compared with those with increased autotaxin. These results establish that autotaxin secretion by CAFs is increased by TGFβ inhibition and that circulating autotaxin levels predict response to the combination treatment approach of gemcitabine plus galunisertib.
Significance:
TGFβ inhibition skews cancer-associated fibroblasts toward an inflammatory phenotype that secretes autotaxin to drive adaptive resistance in PDAC, revealing autotaxin as a therapeutic target and biomarker of galunisertib response.
Data from Hypoxia-Responsive CAR-T Cells Exhibit Reduced Exhaustion and Enhanced Efficacy in Solid Tumors
Authors: Zhu Xiuxiu , Chen Jun , Li Wuling , Xu Yanmin , Shan Juanjuan , Hong Juan , Zhao Yongchun , Xu Huailong , Ma Jiabin , Shen Junjie , Qian Cheng
Published: January 2024

Abstract
Expanding the utility of chimeric antigen receptor (CAR)-T cells in solid tumors requires improving their efficacy and safety. Hypoxia is a feature of most solid tumors that could be used to help CAR-T cells discriminate tumors from normal tissues. In this study, we developed hypoxia-responsive CAR-T cells by engineering the CAR to be under regulation of hypoxia-responsive elements and selected the optimal structure (5H1P-CEA CAR), which can be activated in the tumor hypoxic microenvironment to induce CAR-T cells with high polyfunctionality. Hypoxia-responsive CAR T cells were in a “resting” state with low CAR expression under normoxic conditions. Compared with conventional CAR-T cells, hypoxia-responsive CAR-T cells maintained lower differentiation and displayed enhanced oxidative metabolism and proliferation during cultivation, and they sowed a capacity to alleviate the negative effects of hypoxia on T-cell proliferation and metabolism. Furthermore, 5H1P-CEA CAR-T cells exhibited decreased T-cell exhaustion and improved T-cell phenotype in vivo. In patient-derived xenograft models, hypoxia-responsive CAR-T cells induced more durable antitumor activity than their conventional counterparts. Overall, this study provides an approach to limit CAR expression to the hypoxic tumor microenvironment that could help to enhance CAR T-cell efficacy and safety in solid tumors.
Significance:
Engineering CAR-T cells to upregulate CAR expression under hypoxic conditions induces metabolic reprogramming, reduces differentiation, and increases proliferation to enhance their antitumor activity, providing a strategy to improve efficacy and safety.
Data from Gain-of-Function p53 Mutation Acts as a Genetic Switch for TGFβ Signaling–Induced Epithelial-to-Mesenchymal Transition in Intestinal Tumors
Authors: Wang Dong , Nakayama Mizuho , Hong Chang Pyo , Oshima Hiroko , Oshima Masanobu
Published: January 2024

Abstract
Signaling by TGFβ family cytokines plays a tumor-suppressive role by inducing cell differentiation, while it promotes malignant progression through epithelial-to-mesenchymal transition (EMT). Identification of the mechanisms regulating the switch from tumor suppression to tumor promotion could identify strategies for cancer prevention and treatment. To identify the key genetic alterations that determine the outcome of TGFβ signaling, we used mouse intestinal tumor-derived organoids carrying multiple driver mutations in various combinations to examine the relationship between genotypes and responses to the TGFβ family cytokine activin A. KrasG12D mutation protected organoid cells from activin A–induced growth suppression by inhibiting p21 and p27 expression. Furthermore, Trp53R270H gain-of-function (GOF) mutation together with loss of wild-type Trp53 by loss of heterozygosity (LOH) promoted activin A–induced partial EMT with formation of multiple protrusions on the organoid surface, which was associated with increased metastatic incidence. Histologic analysis confirmed that tumor cells at the protrusions showed loss of apical–basal polarity and glandular structure. RNA sequencing analysis indicated that expression of Hmga2, encoding a cofactor of the SMAD complex that induces EMT transcription factors, was significantly upregulated in organoids with Trp53 GOF/LOH alterations. Importantly, loss of HMGA2 suppressed expression of Twist1 and blocked activin A–induced partial EMT and metastasis in Trp53 GOF/LOH organoids. These results indicate that TP53 GOF/LOH is a key genetic state that primes for TGFβ family-induced partial EMT and malignant progression of colorectal cancer. Activin signaling may be an effective therapeutic target for colorectal cancer harboring TP53 GOF mutations.
Significance:
KRAS and TP53 mutations shift activin-mediated signaling to overcome growth inhibition and promote partial EMT, identifying a subset of patients with colorectal cancer that could benefit from inhibition of TGFβ signaling.
Data from Leveraging Tissue-Specific Enhancer–Target Gene Regulatory Networks Identifies Enhancer Somatic Mutations That Functionally Impact Lung Cancer
Authors: Hariprakash Judith Mary , Salviato Elisa , La Mastra Federica , Sebestyén Endre , Tagliaferri Ilario , Silva Raquel Sofia , Lucini Federica , Farina Lorenzo , Cinquanta Mario , Rancati Ilaria , Riboni Mirko , Minardi Simone Paolo , Roz Luca , Gorini Francesca , Lanzuolo Chiara , Casola Stefano , Ferrari Francesco
Published: January 2024

Abstract
Enhancers are noncoding regulatory DNA regions that modulate the transcription of target genes, often over large distances along with the genomic sequence. Enhancer alterations have been associated with various pathological conditions, including cancer. However, the identification and characterization of somatic mutations in noncoding regulatory regions with a functional effect on tumorigenesis and prognosis remain a major challenge. Here, we present a strategy for detecting and characterizing enhancer mutations in a genome-wide analysis of patient cohorts, across three lung cancer subtypes. Lung tissue–specific enhancers were defined by integrating experimental data and public epigenomic profiles, and the genome-wide enhancer–target gene regulatory network of lung cells was constructed by integrating chromatin three-dimensional architecture data. Lung cancers possessed a similar mutation burden at tissue-specific enhancers and exons but with differences in their mutation signatures. Functionally relevant alterations were prioritized on the basis of the pathway-level integration of the effect of a mutation and the frequency of mutations on individual enhancers. The genes enriched for mutated enhancers converged on the regulation of key biological processes and pathways relevant to tumor biology. Recurrent mutations in individual enhancers also affected the expression of target genes, with potential relevance for patient prognosis. Together, these findings show that noncoding regulatory mutations have a potential relevance for cancer pathogenesis and can be exploited for patient classification.
Significance:
Mapping enhancer–target gene regulatory interactions and analyzing enhancer mutations at the level of their target genes and pathways reveal convergence of recurrent enhancer mutations on biological processes involved in tumorigenesis and prognosis.
Data from Progressively Enhancing Stemness of Adoptively Transferred T Cells with PI3Kδ Blockade Improves Metabolism and Antitumor Immunity
Authors: Rangel Rivera Guillermo O. , Dwyer Connor J. , Knochelmann Hannah M. , Smith Aubrey S. , Aksoy Bülent Arman , Cole Anna C. , Wyatt Megan M. , Kumaresan Soundharya , Thaxton Jessica E. , Lesinski Gregory B. , Paulos Chrystal M.
Published: January 2024

Abstract
Generating stem-like memory T cells (TSCM) is a potential strategy to improve adoptive immunotherapy. Elucidating optimal ways to modulate signaling pathways that enrich TSCM properties could identify approaches to achieve this goal. We discovered herein that blocking the PI3Kδ pathway pharmaceutically to varying degrees can generate T cells with increasingly heightened stemness properties, based on the progressive enrichment of the transcription factors Tcf1 and Lef1. T cells with enhanced stemness features exhibited metabolic plasticity, marked by improved mitochondrial function and glucose uptake after tumor recognition. Conversely, T cells with low or medium stemness were less metabolically dynamic, vulnerable to antigen-induced cell death, and expressed more inhibitory checkpoint receptors. Only T-cell receptor–specific or chimeric antigen receptor (CAR)-specific T cells with high stemness persisted in vivo and mounted protective immunity to tumors. Likewise, the strongest level of PI3Kδ blockade in vitro generated human tumor-infiltrating lymphocytes and CAR T cells with elevated stemness properties, in turn bolstering their capacity to regress human solid tumors. The stemness level of T cells in vitro was important, ultimately impacting their efficacy in mice bearing three distinct solid tumors. Lef1 and Tcf1 sustained antitumor protection by donor high CD8+ TSCM or CD4+ Th17SCM, as deletion of either one compromised the therapeutic efficacy. Collectively, these findings highlight the importance of strategic modulation of PI3Kδ signaling in T cells to induce stemness and lasting protective responses to solid tumors.
Significance:
Elevating T-cell stemness by progressively blocking PI3Kδ signaling during ex vivo manufacturing of adoptive cell therapies alters metabolic and functional properties to enhance antitumor immunity dependent on Tcf1 and Lef1.
Figure S4 from Phase I Dose-Escalation Trial of MIW815 (ADU-S100), an Intratumoral STING Agonist, in Patients with Advanced/Metastatic Solid Tumors or Lymphomas
Authors: Meric-Bernstam Funda , Sweis Randy F. , Hodi F. Stephen , Messersmith Wells A. , Andtbacka Robert H.I. , Ingham Matthew , Lewis Nancy , Chen Xinhui , Pelletier Marc , Chen Xueying , Wu Jincheng , Dubensky Thomas W. , McWhirter Sarah M. , Müller Thomas , Nair Nitya , Luke Jason J.
Published: January 2024

On-treatment changes in NK-cell lineage markers in injected and noninjected lesions
Figure S3 from Phase I Dose-Escalation Trial of MIW815 (ADU-S100), an Intratumoral STING Agonist, in Patients with Advanced/Metastatic Solid Tumors or Lymphomas
Authors: Meric-Bernstam Funda , Sweis Randy F. , Hodi F. Stephen , Messersmith Wells A. , Andtbacka Robert H.I. , Ingham Matthew , Lewis Nancy , Chen Xinhui , Pelletier Marc , Chen Xueying , Wu Jincheng , Dubensky Thomas W. , McWhirter Sarah M. , Müller Thomas , Nair Nitya , Luke Jason J.
Published: January 2024

Immunohistochemistry of injected and noninjected lesions
Figure S1 from Phase I Dose-Escalation Trial of MIW815 (ADU-S100), an Intratumoral STING Agonist, in Patients with Advanced/Metastatic Solid Tumors or Lymphomas
Authors: Meric-Bernstam Funda , Sweis Randy F. , Hodi F. Stephen , Messersmith Wells A. , Andtbacka Robert H.I. , Ingham Matthew , Lewis Nancy , Chen Xinhui , Pelletier Marc , Chen Xueying , Wu Jincheng , Dubensky Thomas W. , McWhirter Sarah M. , Müller Thomas , Nair Nitya , Luke Jason J.
Published: January 2024

Time on MIW815 treatment according to dose level and indication
Table S2 from Metabolic Hallmarks for Purine Nucleotide Biosynthesis in Small Cell Lung Carcinoma
Authors: Tabata Sho , Umemura Shigeki , Narita Miyu , Udagawa Hibiki , Ishikawa Takamasa , Tsuboi Masahiro , Goto Koichi , Ishii Genichiro , Tsuchihara Katsuya , Ochiai Atsushi , Kobayashi Susumu S. , Soga Tomoyoshi , Makinoshima Hideki
Published: January 2024

Level of metabolites in tumors from HPRT1-deleted DMS273 cells
Figure S6 from Metabolic Hallmarks for Purine Nucleotide Biosynthesis in Small Cell Lung Carcinoma
Authors: Tabata Sho , Umemura Shigeki , Narita Miyu , Udagawa Hibiki , Ishikawa Takamasa , Tsuboi Masahiro , Goto Koichi , Ishii Genichiro , Tsuchihara Katsuya , Ochiai Atsushi , Kobayashi Susumu S. , Soga Tomoyoshi , Makinoshima Hideki
Published: January 2024

Metabolic flux analysis for purine nucleotide biosynthesis in DMS273 cells with or without HPRT1 expression
Figure S4 from Metabolic Hallmarks for Purine Nucleotide Biosynthesis in Small Cell Lung Carcinoma
Authors: Tabata Sho , Umemura Shigeki , Narita Miyu , Udagawa Hibiki , Ishikawa Takamasa , Tsuboi Masahiro , Goto Koichi , Ishii Genichiro , Tsuchihara Katsuya , Ochiai Atsushi , Kobayashi Susumu S. , Soga Tomoyoshi , Makinoshima Hideki
Published: January 2024

Western blot analysis of HPRT1 expression in retrovirally transduced cells
Supplementary Table 2 from SP4 Facilitates Esophageal Squamous Cell Carcinoma Progression by Activating PHF14 Transcription and Wnt/Β-Catenin Signaling
Authors: Wei Li , Deng Chaowei , Zhang Bo , Wang Guanghui , Meng Yan , Qin Hao
Published: January 2024

Association of PHF14 mRNA expression with clinicopathological characteristics of EC (n = 73).
Supplementary Figure 2 from SP4 Facilitates Esophageal Squamous Cell Carcinoma Progression by Activating PHF14 Transcription and Wnt/Β-Catenin Signaling
Authors: Wei Li , Deng Chaowei , Zhang Bo , Wang Guanghui , Meng Yan , Qin Hao
Published: January 2024

High expression of PHF14 occurred in ESCC and is associated with the clinicopathologic feature.
Supplementary Figure 1 from SP4 Facilitates Esophageal Squamous Cell Carcinoma Progression by Activating PHF14 Transcription and Wnt/Β-Catenin Signaling
Authors: Wei Li , Deng Chaowei , Zhang Bo , Wang Guanghui , Meng Yan , Qin Hao
Published: January 2024

SP4 are closely associated with cancer cell apoptosis.
Supplementary Table 3 from Whole-Exome Sequencing Identifies Mutation Profile and Mutation Signature-Based Clustering Associated with Prognosis in Appendiceal Pseudomyxoma Peritonei
Authors: Lin Yu-Lin , Zhu Jun-Qi , Ma Rui-Qing , Meng Wei , Wang Zi-Yue , Li Xin-Bao , Ma Ru , Wu He-Liang , Xu Hong-Bin , Gao Ying , Li Yan
Published: January 2024

The correlation between clinicopathological factors and two MSC groups
Supplementary Table 9 from Distinct microRNA Signature and Suppression of ZFP36L1 Define ASCL1-Positive Lung Adenocarcinoma
Authors: Enokido Takayoshi , Horie Masafumi , Yoshino Seiko , Suzuki Hiroshi I. , Matsuki Rei , Brunnström Hans , Micke Patrick , Nagase Takahide , Saito Akira , Miyashita Naoya
Published: January 2024

Genes downregulated by ectopic ZFP36L1 expression.
Supplementary Figure 8 from Whole-Exome Sequencing Identifies Mutation Profile and Mutation Signature-Based Clustering Associated with Prognosis in Appendiceal Pseudomyxoma Peritonei
Authors: Lin Yu-Lin , Zhu Jun-Qi , Ma Rui-Qing , Meng Wei , Wang Zi-Yue , Li Xin-Bao , Ma Ru , Wu He-Liang , Xu Hong-Bin , Gao Ying , Li Yan
Published: January 2024

Hypothesis model of mutation-cluster-based molecular pathogenesis and prognosis of PMP.
Supplementary Figure 7 from Whole-Exome Sequencing Identifies Mutation Profile and Mutation Signature-Based Clustering Associated with Prognosis in Appendiceal Pseudomyxoma Peritonei
Authors: Lin Yu-Lin , Zhu Jun-Qi , Ma Rui-Qing , Meng Wei , Wang Zi-Yue , Li Xin-Bao , Ma Ru , Wu He-Liang , Xu Hong-Bin , Gao Ying , Li Yan
Published: January 2024

The cophenetic coefficient for selecting optimal NMF rank.
Supplementary Table 5 from Distinct microRNA Signature and Suppression of ZFP36L1 Define ASCL1-Positive Lung Adenocarcinoma
Authors: Enokido Takayoshi , Horie Masafumi , Yoshino Seiko , Suzuki Hiroshi I. , Matsuki Rei , Brunnström Hans , Micke Patrick , Nagase Takahide , Saito Akira , Miyashita Naoya
Published: January 2024

miRNAs downregulated by ASCL1 knockdown in VMRC-LCD cells.
Supplementary Figure 5 from Whole-Exome Sequencing Identifies Mutation Profile and Mutation Signature-Based Clustering Associated with Prognosis in Appendiceal Pseudomyxoma Peritonei
Authors: Lin Yu-Lin , Zhu Jun-Qi , Ma Rui-Qing , Meng Wei , Wang Zi-Yue , Li Xin-Bao , Ma Ru , Wu He-Liang , Xu Hong-Bin , Gao Ying , Li Yan
Published: January 2024

Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of appendiceal PMP. A: Biological process; B: Cellular component; C: Molecular function;D: KEGG pathway.
Supplementary Table 3 from Distinct microRNA Signature and Suppression of ZFP36L1 Define ASCL1-Positive Lung Adenocarcinoma
Authors: Enokido Takayoshi , Horie Masafumi , Yoshino Seiko , Suzuki Hiroshi I. , Matsuki Rei , Brunnström Hans , Micke Patrick , Nagase Takahide , Saito Akira , Miyashita Naoya
Published: January 2024

Differentially expressed miRNAs in ASCL1-high lung adenocarcinomas of the CPTAC dataset.
Supplementary Table 2 from Distinct microRNA Signature and Suppression of ZFP36L1 Define ASCL1-Positive Lung Adenocarcinoma
Authors: Enokido Takayoshi , Horie Masafumi , Yoshino Seiko , Suzuki Hiroshi I. , Matsuki Rei , Brunnström Hans , Micke Patrick , Nagase Takahide , Saito Akira , Miyashita Naoya
Published: January 2024

Primers, siRNA sequences, and primary antibodies.
Supplementary Figure 1 from Whole-Exome Sequencing Identifies Mutation Profile and Mutation Signature-Based Clustering Associated with Prognosis in Appendiceal Pseudomyxoma Peritonei
Authors: Lin Yu-Lin , Zhu Jun-Qi , Ma Rui-Qing , Meng Wei , Wang Zi-Yue , Li Xin-Bao , Ma Ru , Wu He-Liang , Xu Hong-Bin , Gao Ying , Li Yan
Published: January 2024

Flow-chart of sample processing and subsequent analyses.
Supplementary Figure 5 from Distinct microRNA Signature and Suppression of ZFP36L1 Define ASCL1-Positive Lung Adenocarcinoma
Authors: Enokido Takayoshi , Horie Masafumi , Yoshino Seiko , Suzuki Hiroshi I. , Matsuki Rei , Brunnström Hans , Micke Patrick , Nagase Takahide , Saito Akira , Miyashita Naoya
Published: January 2024

ZFP36L1 expression in relation to TP53 or RB1 mutation status
Supplementary Figure 4 from Distinct microRNA Signature and Suppression of ZFP36L1 Define ASCL1-Positive Lung Adenocarcinoma
Authors: Enokido Takayoshi , Horie Masafumi , Yoshino Seiko , Suzuki Hiroshi I. , Matsuki Rei , Brunnström Hans , Micke Patrick , Nagase Takahide , Saito Akira , Miyashita Naoya
Published: January 2024

Epigenetic regulation of ZFP36L1 in lung adenocarcinomas
Supplementary Table 2 from RNF185 Control of COL3A1 Expression Limits Prostate Cancer Migration and Metastatic Potential
Authors: Van Espen Benjamin , Oo Htoo Zarni , Collins Colin , Fazli Ladan , Molinolo Alfredo , Yip Kevin , Murad Rabi , Gleave Martin , Ronai Ze'ev A.
Published: January 2024

List of genes driving the enrichment score for HALLMARL_EMT in MPC3.shRNF185#1 compared to MPC3.pLKO in GSEA analysis.
Supplementary Figure 3 from Distinct microRNA Signature and Suppression of ZFP36L1 Define ASCL1-Positive Lung Adenocarcinoma
Authors: Enokido Takayoshi , Horie Masafumi , Yoshino Seiko , Suzuki Hiroshi I. , Matsuki Rei , Brunnström Hans , Micke Patrick , Nagase Takahide , Saito Akira , Miyashita Naoya
Published: January 2024

PCR analyses in A549 and H441 cells following ASCL1 knockdown
Supplementary Figure 1 from Distinct microRNA Signature and Suppression of ZFP36L1 Define ASCL1-Positive Lung Adenocarcinoma
Authors: Enokido Takayoshi , Horie Masafumi , Yoshino Seiko , Suzuki Hiroshi I. , Matsuki Rei , Brunnström Hans , Micke Patrick , Nagase Takahide , Saito Akira , Miyashita Naoya
Published: January 2024

Immunohistochemistry for ASCL1 and YAP1
Supplementary Figure 2 from RNF185 Control of COL3A1 Expression Limits Prostate Cancer Migration and Metastatic Potential
Authors: Van Espen Benjamin , Oo Htoo Zarni , Collins Colin , Fazli Ladan , Molinolo Alfredo , Yip Kevin , Murad Rabi , Gleave Martin , Ronai Ze'ev A.
Published: January 2024

S2. Effect of RNF185 KD in PCa cell lines and validation of in vivo phenotype.
Data from Whole-Exome Sequencing Identifies Mutation Profile and Mutation Signature-Based Clustering Associated with Prognosis in Appendiceal Pseudomyxoma Peritonei
Authors: Lin Yu-Lin , Zhu Jun-Qi , Ma Rui-Qing , Meng Wei , Wang Zi-Yue , Li Xin-Bao , Ma Ru , Wu He-Liang , Xu Hong-Bin , Gao Ying , Li Yan
Published: January 2024

Abstract
Pseudomyxoma peritonei (PMP) is a rare malignant clinical syndrome with little known about the global mutation profile. In this study, whole-exome sequencing (WES) was performed in 49 appendiceal PMP to investigate mutation profiles and mutation signatures. A total of 4,020 somatic mutations were detected, with a median mutation number of 56 (1–402). Tumor mutation burden (TMB) was generally low (median 1.55 mutations/Mb, 0.12–11.26 mutations/Mb). Mutations were mainly enriched in the function of cancer-related axonogenesis, extracellular matrix–related processes, calcium signaling pathway, and cAMP signaling pathway. Mutations in FCGBP, RBFOX1, SPEG, RTK-RAS, PI3K-AKT, and focal adhesion pathways were associated with high-grade mucinous carcinoma peritonei. These findings revealed distinct mutation profile in appendiceal PMP. Ten mutation signatures were identified, dividing patients into mutation signature cluster (MSC) 1 (N = 28, 57.1%) and MSC 2 (N = 21, 42.9%) groups. MSC (P = 0.007) was one of the four independent factors associated with 3-year survival. TMB (P = 0.003) and microsatellite instability (P = 0.002) were independent factors associated with MSC 2 grouping. Taken together, our findings provided a broader view in the understanding of molecular pathologic mechanism in appendiceal PMP and may be critical to developing an individualized approach to appendiceal PMP treatment.
Implications:
This work describes exhaustive mutation profile of PMP based on WES data and derives ten mutation signatures, which divides patients into two clusters and serve as an independent prognostic factor associated with 3-year survival.
Data from Distinct microRNA Signature and Suppression of ZFP36L1 Define ASCL1-Positive Lung Adenocarcinoma
Authors: Enokido Takayoshi , Horie Masafumi , Yoshino Seiko , Suzuki Hiroshi I. , Matsuki Rei , Brunnström Hans , Micke Patrick , Nagase Takahide , Saito Akira , Miyashita Naoya
Published: January 2024

Abstract
Achaete-scute family bHLH transcription factor 1 (ASCL1) is a master transcription factor involved in neuroendocrine differentiation. ASCL1 is expressed in approximately 10% of lung adenocarcinomas (LUAD) and exerts tumor-promoting effects. Here, we explored miRNA profiles in ASCL1-positive LUADs and identified several miRNAs closely associated with ASCL1 expression, including miR-375, miR-95–3p/miR-95–5p, miR-124–3p, and members of the miR-17∼92 family. Similar to small cell lung cancer, Yes1 associated transcriptional regulator (YAP1), a representative miR-375 target gene, was suppressed in ASCL1-positive LUADs. ASCL1 knockdown followed by miRNA profiling in a cell culture model further revealed that ASCL1 positively regulates miR-124–3p and members of the miR-17∼92 family. Integrative transcriptomic analyses identified ZFP36 ring finger protein like 1 (ZFP36L1) as a target gene of miR-124–3p, and IHC studies demonstrated that ASCL1-positive LUADs are associated with low ZFP36L1 protein levels. Cell culture studies showed that ectopic ZFP36L1 expression inhibits cell proliferation, survival, and cell-cycle progression. Moreover, ZFP36L1 negatively regulated several genes including E2F transcription factor 1 (E2F1) and snail family transcriptional repressor 1 (SNAI1). In conclusion, our study revealed that suppression of ZFP36L1 via ASCL1-regulated miR-124–3p could modulate gene expression, providing evidence that ASCL1-mediated regulation of miRNAs shapes molecular features of ASCL1-positive LUADs.
Implications:
Our study revealed unique miRNA profiles of ASCL1-positive LUADs and identified ASCL1-regulated miRNAs with functional relevance.
Leitura argumentativa em livros didáticos de Língua Portuguesa: análise da coleção Se liga na língua, PNLD/2020
Authors: Santos Aline de Santana , Novais Rosely Melo Matos de
Published: January 2024

Neste artigo, analisamos uma atividade presente no Livro Didático (LD) Se liga na língua, relacionada ao desenvolvimento da leitura argumentativa e à sua contribuição para o desenvolvimento de capacidades argumentativas. O corpus é composto por um material do 6º ano do Ensino Fundamental, adotado na rede municipal de Cícero Dantas - BA. Selecionamos uma atividade do capítulo sete, seção Entre saberes, cuja perspectiva requer a contraposição de pontos de vista. Metodologicamente, a pesquisa é de caráter documental e qualitativa. A análise terá a aplicação de um protocolo elaborado para compreender a proposta dos autores, sendo incluídas sugestões em prol da promoção da leitura argumentativa em uma perspectiva interacional (Plantin, 2008). Os resultados preliminares apontam que a atividade em análise parte dos pressupostos da leitura argumentativa, mas ainda requer adaptação e ampliação. Assim, almejamos que este estudo contribua com as discussões sobre leitura argumentativa e coopere para a efetivação do ensino da argumentação.