bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A10: Exploring the interplay between the purinosome, a multienzyme, purine biosynthetic machine, and the Rheb-mTORC1 signaling axis
Authors: Emmanuel Natasha , Bernfeld Elyssa , Ragunathan Shoba , Wang Fang , Shan Qin , Giannakou Andreas , Huser Nanni , Jin Guixian , Myers Jeremy , Unsal-Kacmaz Keziban , Abraham Robert T. 
Published: December 2020

Abstract
Pharmacologic agents that interfere with nucleotide metabolism constitute an important class of anticancer agents. Recent studies demonstrated that mTOR complex 1 (mTORC1) inhibitors suppress de novo biosynthesis of pyrimidine and purine nucleotides. We have previously demonstrated that mTORC1 itself is suppressed by drugs that reduce intracellular purine nucleotide pools. Cellular treatment with AG2037, an inhibitor of the purine biosynthetic enzyme, GARFT, profoundly inhibits mTORC1 activity via a reduction in the level of GTP-bound Rheb, an obligate upstream activator of mTORC1, in part due to a reduction in intracellular guanine nucleotides. Purines are synthesized intracellularly in dynamic metabolic structures known as the purinosome. Our emerging data suggest that Rheb associates with the purinosome and treatment with AG2037 disrupts this interaction. We hypothesize that Rheb senses the availability of purines at the site of the purinosome and communicates purine sufficiency to activate mTORC1. The results of this project will increase our understanding of the regulation of purine biosynthesis and mTORC1 activation, two key processes in cell proliferation and cancer.
Citation Format: Natasha Emmanuel, Elyssa Bernfeld, Shoba Ragunathan, Fang Wang, Qin Shan, Andreas Giannakou, Nanni Huser, Guixian Jin, Jeremy Myers, Keziban Unsal-Kacmaz, Robert T. Abraham. Exploring the interplay between the purinosome, a multienzyme, purine biosynthetic machine, and the Rheb-mTORC1 signaling axis [abstract]. In: Proceedings of the AACR Special Conference on Targeting PI3K/mTOR Signaling; 2018 Nov 30-Dec 8; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(10_Suppl):Abstract nr A10.
Abstract B26: Role of AKT3 in EGFR-TKI resistance of non-small cell lung cancer
Authors: Huang Shih-Hsiang , Shih Jin-Yuan , Chen Ching-Chow 
Published: December 2020

Abstract
Lung cancer is the leading cause of cancer deaths worldwide, and EGFR-TKI is the first-line treatment for non-small cell lung cancer (NSCLC) harboring EGFR activation mutation. However, most patients develop acquired resistance within 9–14 months. Exploring the mechanisms of drug resistance is critical to improve treatment efficacy. Two resistant cells, HCC827/IR (IRESSA resistance) and H1975/AR (AZD9291 resistance), exhibiting EMT phenotypes were generated to investigate the molecular and cellular characteristics of the EGFR-TKI acquired resistance. HCC827/IR (without T790M) and H1975/AR (without C797S) showed “off-target resistance”. Upregulation of AXL and FGFR1 in HCC827/IR but not H1975/AR cells was found. AKT activation (p-AKT) in parental cells was more sensitive to EGFR-TKI than that in resistant cells. RNA-seq revealed the upregulation of AKT3 in both resistant cells. High expression of AKT3 was predicted to correlate with the poor survival of lung adenocarcinoma patients. Knockdown of AKT3 in HCC827/IR cells inhibited cell migration and increased the protein expression of E-cadherin, as well as inhibited S phase population to reduce cell proliferation. Knockdown of AKT3 in H1975/AR cells enhanced AZD9291-induced inhibition on AKT activation (p-AKT). Immunoprecipitation of AKT3 in both resistant cells demonstrated its involvement in AKT activation, and AKT3 activation (p-AKT3) was insensitive to gefitinib and AZD9291 inhibition in resistant cells. Protein but not mRNA of AKT3 was upregulated in gefitinib-treated HCC827/IR and AZD9291-treated H1975/AR cells. AKT3 might serve as a predictive biomarker for EGFR-TKIs therapy. Its upregulation might be one of the mechanisms for EGFR-TKIs acquired resistance.
Citation Format: Shih-Hsiang Huang, Jin-Yuan Shih, Ching-Chow Chen. Role of AKT3 in EGFR-TKI resistance of non-small cell lung cancer [abstract]. In: Proceedings of the AACR Special Conference on Targeting PI3K/mTOR Signaling; 2018 Nov 30-Dec 8; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(10_Suppl):Abstract nr B26.
Abstract B33: Targeting PI3K/mTOR signaling with potent, selective and orally-available small-molecule inhibitors of eIF4E
Authors: Parker Gregory S. , Hung Ivy N.J. , Staunton Jocelyn , Barrera Maria , Sung Eric , Parra Ana , Stumpf Craig R. , Chen Joan , Thompson Peggy A. , Nevarez Andreas , Wegerski Christopher J. , Clarine Jeff , Sperry Samuel , Xiang Alan , Nilewski Christian , Packard Garrick K. , Urklalan Kaveri , Mukaiyama Takasuke , Michels Theo , Ernst Justin T. , Sprengeler Paul A. , Reich Siegfried H. , Chiang Gary G. , Webster Kevin R. 
Published: December 2020

Abstract
Aberrant protein translation plays a role in the pathogenesis of multiple solid tumors and hematologic malignancies. The translation initiation factor eIF4E is essential for the translation of m7G-capped mRNA and is a key point of convergence for several signaling pathways, such as PI3K/mTOR and MAPK, which are intimately involved in tumor cell growth and survival. As such, eIF4E has generated intense interest as a target for anticancer drug discovery. We have designed a series of potent, selective, and orally available m7G cap-competitive inhibitors of eIF4E (eFT-4Ei) with favorable drug-like properties. These inhibitors bind free eIF4E, eIF4E-4EBP and eIF4E-eIF4F complexes within tumor cells. Ribosomal profiling of eIF4E inhibitor-treated tumor cells has identified a subset of translationally regulated target genes that overlap with mTORC1/2 regulated genes, but also include a larger set of unique translationally regulated target mRNAs that are enriched for 5'-TOP, PRTE and CERT sequence elements in their 5'-untranslated regions. eIF4E inhibition results in potent antiproliferative activity and induction of apoptosis in a subset of tumor cell lines. Consistent with this observation, our eIF4E inhibitors show some similarities, yet several important differences from existing mTORC1 or mTORC1/2 dual inhibitors in both cellular and physiologic assays. Finally, significant antitumor efficacy was observed with eIF4E inhibition in both solid tumor and hematologic xenografts in vivo. Taken together, these results highlight the potential of targeting eIF4E as a novel and differentiated therapeutic strategy to treat cancer.
Citation Format: Gregory S. Parker, Ivy N.J. Hung, Jocelyn Staunton, Maria Barrera, Eric Sung, Ana Parra, Craig R. Stumpf, Joan Chen, Peggy A. Thompson, Andreas Nevarez, Christopher J. Wegerski, Jeff Clarine, Samuel Sperry, Alan Xiang, Christian Nilewski, Garrick K. Packard, Kaveri Urklalan, Takasuke Mukaiyama, Theo Michels, Justin T. Ernst, Paul A. Sprengeler, Siegfried H. Reich, Gary G. Chiang, Kevin R. Webster. Targeting PI3K/mTOR signaling with potent, selective and orally-available small-molecule inhibitors of eIF4E [abstract]. In: Proceedings of the AACR Special Conference on Targeting PI3K/mTOR Signaling; 2018 Nov 30-Dec 8; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(10_Suppl):Abstract nr B33.
Abstract IA02: The PI3K-mTOR signaling network and tumor cell metabolism
Authors: Manning Brendan D. 
Published: December 2020

Abstract
The mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) is a key signaling node, universal to eukaryotic cells, which links the sensing of nutrients to the coordinated regulation of nutrient metabolism. mTORC1 has the ability to integrate signals from a variety of sources, including intracellular nutrients and secreted growth factors. The activation state of mTORC1 is tightly controlled through a small G protein switch involving the TSC1-TSC2-TBC1D7 complex (the TSC complex) and the Ras-related small G protein Rheb. The direct phosphorylation and inhibition of the TSC complex by the protein kinase Akt provides the major mechanistic link between growth factor signaling and mTORC1. Current evidence indicates that this signal is integrated with amino acid sensing pathways upstream of mTORC1 through independent spatial control over the subcellular localization of the TSC complex and mTORC1 to the surface of the lysosome. This talk will include unpublished data on additional signals that regulate mTORC1 through the TSC-Rheb circuit. Our data suggest that both physiologic growth signals and common oncogenic events in cancer activate mTORC1 through mechanisms leading to dissociation of the TSC protein complex from the lysosomal subpopulation of Rheb, which is required for mTORC1 activation.
Physiologic and pathologic activation of PI3K-mTOR signaling results in a shift from catabolic processes to anabolic biosynthetic processes. This pathway acutely responds to feeding and is also frequently and aberrantly activated in human cancers. Through unbiased genomic and metabolomic approaches, we have found that, in addition to its established roles in promoting protein synthesis and inhibiting autophagy, mTORC1 stimulates changes in specific metabolic pathways through transcriptional and post-translational effects on metabolic enzymes. In this manner, mTORC1 serves to link growth signals to metabolic processes that promote the growth of cells, tissues, and tumors, including the de novo synthesis of proteins, lipids, and nucleotides. Research in our lab is focused on understanding the coordinated anabolic program downstream of PI3K-mTOR signaling and identifying metabolic vulnerabilities stemming from uncontrolled pathway activation that can be targeted in tumors. I will discuss our latest data on additional metabolic enzymes under control of the PI3K-mTOR network that contribute to an integrated metabolic program underlying cell growth in both normal and cancer cells.
Citation Format: Brendan D. Manning. The PI3K-mTOR signaling network and tumor cell metabolism [abstract]. In: Proceedings of the AACR Special Conference on Targeting PI3K/mTOR Signaling; 2018 Nov 30-Dec 8; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(10_Suppl):Abstract nr IA02.
Abstract IA03: Regulation of growth by the mTOR pathway
Authors: Sabatini David M. 
Published: December 2020

Abstract
mTOR is the target of the immunosuppressive and anticancer drug rapamycin and the central component of a nutrient- and hormone-sensitive signaling pathway that regulates cell growth and proliferation. We now appreciate that this pathway becomes deregulated in many human cancers and has key roles in the control of metabolism, cell and organ size, and aging. We have identified two distinct mTOR-containing proteins complexes, one of which regulates growth through S6K and another that regulates cell survival and metabolism through Akt. These complexes, called mTORC1 and mTORC2, define both rapamycin-sensitive and -insensitive branches of the mTOR pathway. Over the last few years we have focused on how nutrients, particularly amino acids, regulate mTORC1. We have identified a complex signaling pathway that relays amino acid availability to mTORC1 through the heterodimeric Rag GTPases. We recently discovered several of the amino acid sensors for the pathway. I will discuss new results from our lab on the regulation and functions of mTORC1.
Citation Format: David M. Sabatini. Regulation of growth by the mTOR pathway [abstract]. In: Proceedings of the AACR Special Conference on Targeting PI3K/mTOR Signaling; 2018 Nov 30-Dec 8; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(10_Suppl):Abstract nr IA03.
Troubling Habits
Authors: Lankewish Vincent A. 
Published: December 2020

Abstract
Against the backdrop of a new progressivism ushered into existence in the Roman Catholic Church by the Vatican II Council initiated by Pope John XXIII in 1962 and concluded by Pope Paul VI in 1965, this essay examines nuns’ resistance to and eventual adoption of new professional garb as a site of sometimes contentious debates about the changing roles of women ecclesiastics. Within the context of passionate and, at times, violent fights for civil and women’s rights and of protests against U.S. involvement in Vietnam, two popular films from this decade—The Trouble with Angels (1966) and its sequel, Where Angels Go, Trouble Follows (1968)—stage a competition between tradition and innovation in both theological and sartorial arenas. Ultimately, the nuns in these films follow a calling to become public advocates for a more humane and charitable world.
The Transformation of Monastic Habits
Authors: Pyun Kyunghee 
Published: December 2020

Abstract
In this paper, I posit that the transformation of monastic habits is observed and maintained in East Asian school uniforms. School uniforms at the schools founded by religious orders, mainly by Protestant and Catholic missionaries, could have manifested faith and religious identity. These religious authorities, who acted as managers of civic education, coincided with other public and private schools founded in secular contexts, unlike the religious emblems of those groups in their home countries. Many schools founded by Christian missionaries in East Asia in the early twentieth century eliminated a “sacred versus profane” dichotomy in their school uniforms and school symbols. In the formulation of a nation state in East Asia, homogeneity among inhabitants was more important than a faith-based religious identity by each Christian missionary group. Wearers of school uniforms in East Asia were taught to nurture civic identity along with the faith.
Erasing the Marks of Domination: Economic Sovereignty, Decolonization, and International Lawmaking in the 1950s and 1960s
Authors: Dietrich Christopher 
Published: December 2020

Abstract
This article tells a legal and intellectual history of oil and decolonization in the 1950s and 1960s through the projects of international institutions including the UN Permanent Sovereignty Commission and the Organization of Petroleum Exporting Countries and the work of anti-colonial lawyers Hasan Zakariya and Nicolas Sarkis. It examines the ideas and infrastructure of decolonization as they related to the question of how international law could be used to win economic sovereignty.
A Fully Compressible Nonhydrostatic Deep-Atmosphere Equations Solver for MPAS
Authors: Skamarock William C. , Ong Hing , Klemp Joseph B. 
Published: December 2020

AbstractA solver for the nonhydrostatic deep-atmosphere equations of motion is described that extends the capabilities of the Model for Prediction Across Scales-Atmosphere (MPAS-A) beyond the existing shallow-atmosphere equations solver. The discretization and additional terms within this extension maintain the C-grid staggering, hybrid height vertical coordinate, and spherical centroidal Voronoi mesh used by MPAS, and also preserve the solver’s conservation properties. Idealized baroclinic wave test results, using Earth-radius and reduced-radius sphere configurations, verify the correctness of the solver and compare well with published results from other models. For these test cases, the time evolution of the maximum horizontal wind speed, and the total energy and its components, are presented as additional solution metrics that may allow for further discrimination in model comparisons. The test case solutions are found to be sensitive to the configuration of dissipation mechanisms in MPAS-A, and many of the differences among models in previously published test case solutions appear to arise because of their differing dissipation configurations. For the deep-atmosphere reduced-radius sphere test case, small-scale noise in the numerical solution was found to arise from the analytic initialization that contains unstable lapse rates in the tropical lower troposphere. By adjusting a parameter in this initialization, the instability is removed and the unphysical large-scale overturning no longer occurs. Inclusion of the deep-atmosphere capability in the MPAS-A solver increases the dry dynamics cost by less than 5% on CPU-based architectures, and configuration of either the shallow- or deep-atmosphere equations is controlled by a simple switch.
Practicing What We Preach: Incorporating Team-Based Learning into the Pre-Service Teaching Curriculum for Improved Outcomes
Authors: Vogler Jane S. , Fu Jun , Finney Emily A. 
Published: December 2020

Background: Prior research has shown that pre-service teachers’ learning of theory is enhanced when teacher educators model the instructional approaches that they advocate as effective. Objective: The purpose of this study was to compare undergraduate learning outcomes in a course using Team-based Learning (TBL) with those in a traditional, lecture-based approach. Method: Occurring across two consecutive semesters, we recruited students ( n = 43) enrolled in an educational psychology course serving primarily pre-service teachers for this quasi-experimental study. In addition to final grades, data sources included responses to essay prompts administered at the beginning and end of the semester, which were qualitatively analyzed and coded. Results: Independent samples t-tests showed significant differences in favor of students in the TBL condition for course grades, but not on the final exam. χ2 tests of independence revealed significant differences for two of the seven essay codes, again in favor of TBL. Conclusion: These results provide further evidence that when placed in a context that emphasizes collaborative learning, students demonstrate more nuanced understanding and fewer misconceptions. Teaching Implications: The opportunity to experience TBL may provide pre-service teachers with better theoretical understanding and an effective model for translating socio-constructive theory into collaborative learning practices.
The determinants of the intensity of home-based informal care among cancer patients in receipt of home-based palliative care
Authors: Cai Jiaoli , Zhang Li , Guerriere Denise , Coyte Peter C 
Published: December 2020

Background: Understanding the determinants of the intensity of informal care may assist policy makers in the identification of supports for informal caregivers. Little is known about the utilization of informal care throughout the palliative care trajectory. Aim: The purpose of this study was to analyze the intensity and determinants of the use of informal care among cancer patients over the palliative care trajectory. Design: This was a longitudinal, prospective cohort design conducted in Canada. Regression analysis using instrumental variables was applied. Setting/participants: From November 2013 to August 2017, a total of 273 caregivers of cancer patients were interviewed biweekly over the course of the care recipient’s palliative care trajectory. The outcome was the number of hours of informal care provided by unpaid caregivers, that is, hours of informal care. Results: The number of hours of informal care increased as patients approached death. Home-based nursing care complemented, and hence, increased the provision of informal care. Patients living alone and caregivers who were employed were associated with the provision of fewer hours of informal care. Spousal caregivers provided more hours of informal care. Patient’s age, sex, and marital status, and caregiver’s age, sex, marital status, and education were associated with the number of hours of informal care. Conclusions: The intensity of informal care was determined by predisposing, enabling, and needs-based factors. This study provides a reference for the planning and targeting of supports for the provision of informal care.
Application of near-infrared fluorescent cholangiography using indocyanine green in laparoscopic cholecystectomy
Authors: Wang Chusi , Peng Wenguang , Yang Jiarui , Li Yuxuan , Yang Jiawei , Hu Xueqiao , Xia Long , Zhang Lei , Zhong Yuesi , Qiao Liang , Pan Weidong 
Published: December 2020

Objective Near-infrared fluorescence cholangiography (NIRF-C) can help to identify the bile duct during laparoscopic cholecystectomy. This retrospective study was performed to investigate the effect of NIRF-C in laparoscopic cholecystectomy. Methods Consecutive patients who underwent NIRF-C-assisted laparoscopic cholecystectomy (n = 34) or conventional laparoscopic cholecystectomy (n = 36) were enrolled in this study. Identification of biliary structures, the operation time, intraoperative blood loss, and postoperative complications were analyzed. Results Laparoscopic cholecystectomy was completed in all patients without conversion to laparotomy. The median operation time and intraoperative blood loss were not significantly different between the two groups. No intraoperative injuries or postoperative complications occurred in either group. In the NIRF-C group, the visualization rate of the cystic duct, common bile duct, and common hepatic duct prior to dissection was 91%, 79%, and 53%, respectively. The success rate of cholangiography was 100% in the NIRF-C group. NIRF-C was more effective for visualizing biliary structures in patients with a BMI of <25 than >25 kg/m2. Conclusions NIRF-C is a safe and effective technique that enables real-time identification of the biliary anatomy during laparoscopic cholecystectomy. NIRF-C helps to improve the efficiency of dissection.
Survivors of Acute Lung Injury Have Greater Impairments in Strength and Exercise Capacity Than Survivors of Other Critical Illnesses as Measured Shortly After ICU Discharge
Authors: Mackney Jennifer , Harrold Meg , Jenkins Sue , Fehlberg Rachel , Thomas Lauren , Havill Ken , Jacques Angela , Hill Kylie 
Published: December 2020

Purpose: To compare the physical function on ICU discharge in adults who survived an ICU admission for acute lung injury (ALI) with those admitted for a critical illness other than ALI. Materials and Methods: Two groups were recruited, (i) those who survived an ICU admission for ALI and, (ii) those who survived an ICU admission for a critical illness other than ALI. Within 7 days of discharge from ICU, in all participants, measures were collected of peripheral muscle strength, balance, walking speed and functional exercise capacity. Results: Recruitment was challenging and ceased prior to achieving the desired sample size. Participants with ALI (n = 22) and critical illness (n = 33) were of similar median age (50 vs. 57 yr, p = 0.09), sex proportion (males %, 45 vs. 58, p = 0.59) and median APACHE II score (21.5 vs. 23.0, p = 0.74). Compared with the participants with critical illness, those with ALI had lower hand grip (mean ± SD, 18 ± 9 vs. 13 ± 8 kg, p = 0.018) and shoulder flexion strength (10 ± 4 vs. 7 ± 3 kg, p = 0.047), slower 10-meter walk speed (median [IQR], 1.03 [0.78 to 1.14] vs. 0.78 [0.67 to 0.94] m/s, p = 0.039) and shorter 6-minute walk distance (265 [71 to 328] vs. 165 [53 to 220] m, p = 0.037). The Berg balance scores were similar in both groups. Conclusions: Compared with survivors of a critical illness that is not ALI, those with ALI are likely to have greater physical impairment when measured shortly after discharge to the ward.