bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preclinical Characterization of Linrodostat Mesylate, a Novel, Potent, and Selective Oral Indoleamine 2,3-Dioxygenase 1 Inhibitor
Authors: Balog Aaron , Lin Tai-an , Maley Derrick , Gullo-Brown Johnni , Kandoussi Enzo Hamza , Zeng Jianing , Hunt John T. 
Published: December 2020

Abstract
Tumors can exploit the indoleamine 2,3-dioxygenase 1 (IDO1) pathway to create an immunosuppressive microenvironment. Activated IDO1 metabolizes tryptophan into immunosuppressive kynurenine, leading to suppressed effector T-cell (Teff) proliferation, allowing for tumor escape from host immune surveillance. IDO1 inhibition counteracts this immunosuppressive tumor microenvironment and may improve cancer outcomes, particularly when combined with other immunotherapies. Linrodostat mesylate (linrodostat) is a potent, selective oral IDO1 inhibitor that occupies the heme cofactor–binding site to prevent further IDO1 activation and is currently in multiple clinical trials for treatment of patients with advanced cancers. Here, we assess the in vitro potency, in vivo pharmacodynamic (PD) activity, and preclinical pharmacokinetics (PKs) of linrodostat. Linrodostat exhibited potent cellular activity, suppressing kynurenine production in HEK293 cells overexpressing human IDO1 and HeLa cells stimulated with IFNγ, with no activity against tryptophan 2,3-dioxygenase or murine indoleamine 2,3-dioxygenase 2 detected. Linrodostat restored T-cell proliferation in a mixed-lymphocyte reaction of T cells and allogeneic IDO1-expressing dendritic cells. In vivo, linrodostat reduced kynurenine levels in human tumor xenograft models, exhibiting significant PD activity. Linrodostat demonstrated a PK/PD relationship in the xenograft model, preclinical species, and samples from patients with advanced cancers, with high oral bioavailability in preclinical species and low to moderate systemic clearance. Our data demonstrate that linrodostat potently and specifically inhibits IDO1 to block an immunosuppressive mechanism that could be responsible for tumor escape from host immune surveillance with favorable PK/PD characteristics that support clinical development.
Predicting Tumor Killing and T-Cell Activation by T-Cell Bispecific Antibodies as a Function of Target Expression: CombiningIn VitroExperiments with Systems Modeling
Authors: Van De Vyver Arthur J. , Weinzierl Tina , Eigenmann Miro J. , Frances Nicolas , Herter Sylvia , Buser Regula B. , Somandin Jitka , Diggelmann Sarah , Limani Florian , Lehr Thorsten , Bacac Marina , Walz Antje-Christine 
Published: December 2020

AbstractTargeted T-cell redirection is a promising field in cancer immunotherapy. T-cell bispecific antibodies (TCB) are novel antibody constructs capable of binding simultaneously to T cells and tumor cells, allowing cross-linking and the formation of immunologic synapses. This in turn results in T-cell activation, expansion, and tumor killing. TCB activity depends on system-related properties such as tumor target antigen expression as well as antibody properties such as binding affinities to target and T cells. Here, we developed a systems model integrating in vitro data to elucidate further the mechanism of action and to quantify the cytotoxic effects as the relationship between targeted antigen expression and corresponding TCB activity. In the proposed model, we capture relevant processes, linking immune synapse formation to T-cell activation, expansion, and tumor killing for TCBs in vitro to differentiate the effect between tumor cells expressing high or low levels of the tumor antigen. We used cibisatamab, a TCB binding to carcinoembryonic antigen (CEA), to target different tumor cell lines with high and low CEA expression in vitro. We developed a model to capture and predict our observations, as a learn-and-confirm cycle. Although full tumor killing and substantial T-cell activation was observed in high expressing tumor cells, the model correctly predicted partial tumor killing and minimal T-cell activation in low expressing tumor cells when exposed to cibisatamab. Furthermore, the model successfully predicted cytotoxicity across a wide range of tumor cell lines, spanning from very low to high CEA expression.
ABBV-085, Antibody–Drug Conjugate Targeting LRRC15, Is Effective in Osteosarcoma: A Report by the Pediatric Preclinical Testing Consortium
Authors: Hingorani Pooja , Roth Michael E. , Wang Yifei , Zhang Wendong , Gill Jonathan B. , Harrison Douglas J. , Teicher Beverly , Erickson Stephen , Gatto Gregory , Smith Malcolm A. , Kolb Edward A. , Gorlick Richard 
Published: December 2020

Abstract
Membrane protein leucine–rich repeat containing 15 (LRRC15) is known to be expressed in several solid tumors including osteosarcoma. ABBV-085, an antibody–drug conjugate against LRRC15, conjugated to monomethyl auristatin E (MMAE), was studied in osteosarcoma patient-derived xenografts (PDXs) by the Pediatric Preclinical Testing Consortium (PPTC). LRRC15 expression data were obtained from PPTC RNA-sequencing data for the PDX models. The TARGET database was mined for LRRC15 expression in human osteosarcoma. Protein expression was confirmed via IHC in three PDX models. Seven osteosarcoma PDX models (OS1, OS9, OS33, OS34, OS42, OS55, and OS60) with varying LRRC15 gene expression were studied. ABBV-085 was administered at 3 mg/kg (OS33), 6 mg/kg (all seven PDXs), and 12 mg/kg (OS60) weekly for 4 consecutive weeks via intraperitoneal injection. Control cohorts included vehicle and an isotype MMAE-linked antibody. Tumor volumes and responses were reported using PPTC statistical analysis. OS1, OS33, OS42, OS55, and OS60 had high LRRC15 expression while OS9 and OS34 had low LRRC15 expression. ABBV-085 inhibited tumor growth in six of seven PDX models as compared with vehicle control and significantly improved event-free survival in five of seven models as compared with isotype controls. Two models showed maintained complete responses while all others showed progressive disease. Response correlated with LRRC15 expression. ABBV-085’s antitumor activity against osteosarcoma PDX suggests LRRC15 may be a rational target for pursuing clinical trials in patients with this disease.
Inhibition of Intermedin (Adrenomedullin 2) Suppresses the Growth of Glioblastoma and Increases the Antitumor Activity of Temozolomide
Authors: Huang Luping , Wang Denian , Feng Zhongxue , Zhao Huan , Xiao Fei , Wei Yong'gang , Zhang Heng , Li Hongyu , Kong Lingmiao , Li Min , Liu Fei , Zhang Haili , Zhang Wei 
Published: December 2020

Abstract
Glioblastoma multiforme (GBM; grade IV glioma) is the most malignant type of primary brain tumor and is characterized by rapid proliferation and invasive growth. Intermedin (IMD) is an endogenous peptide belonging to the calcitonin gene-related peptide family and has been reported to play an important role in cell survival and invasiveness in several types of cancers. In this study, we found that the expression level of IMD was positively related to the malignancy grade of gliomas. The highest expression of IMD was found in GBM, indicating that IMD may play an important role in glioma malignancy. IMD increased the invasive ability of glioma cells by promoting filopodia formation, which is dependent on ERK1/2 activation. IMD-induced ERK1/2 phosphorylation also promoted GBM cell proliferation. In addition, IMD enhanced mitochondrial function and hypoxia-induced responses in GBM cells. Treatment with anti-IMD monoclonal antibodies not only inhibited tumor growth in both ectopic and orthotopic models of GBM but also significantly enhanced the antitumor activity of temozolomide. Our study may provide novel insights into the mechanism of GBM cell invasion and proliferation and provide an effective strategy to improve the therapeutic effect of GBM treatments.
G9a Promotes Invasion and Metastasis of Non–Small Cell Lung Cancer through Enhancing Focal Adhesion Kinase Activation via NF-κB Signaling Pathway
Authors: Sun Ting , Zhang Keqiang , Pangeni Rajendra P. , Wu Jun , Li Wendong , Du Yong , Guo Yuming , Chaurasiya Shyambabu , Arvanitis Leonidas , Raz Dan J. 
Published: December 2020

Abstract

Potential roles of euchromatic histone methyltransferase 2 (EHMT2 or G9a) in invasion and metastasis are not well understood in non–small cell lung cancer (NSCLC). Here, we investigated the effect and underlying mechanisms of G9a and therapeutic implications of targeting G9a in the invasion and metastasis of NSCLC. Overexpression of G9a significantly enhanced in vitro proliferation and invasion, while knockdown of G9a drastically suppressed in vivo growth and metastasis of A549 and H1299 NSCLC cells. Knockdown or inhibition of G9a significantly decreased the expression of focal adhesion kinase (FAK) protein and activation of FAK pathway. In addition, defactinib, a potent FAK inhibitor, partially abolished the G9a-enhanced invasion in these NSCLC cells. Furthermore, targeting G9a was found to suppress NF-κB transcriptional activity in NSCLC cells through stabilizing NF-κB inhibitor alpha (IκBα), while an NF-κB inhibitor Parthenilide partially abolished the G9a-enhanced FAK activation, which suggests that G9a-enhanced invasion and activation of FAK is mediated by elevated NF-κB activity. Notably, a strong positive correlation between the IHC staining of G9a and phosphorylated FAK proteins was identified in H1299 xenografts and 159 cases of NSCLC tissues (R = 0.408).

Implications:
The findings of this study strongly demonstrate that G9a may promote invasion and metastasis of NSCLC cells by enhancing FAK signaling pathway via elevating NF-κB transcriptional activity, indicating potential significance and therapeutic implications of these pathways in the invasion and metastasis of NSCLCs that overexpress G9a protein.
Pallas and a Female Pyrrhic Dance for Athena in Attica
Authors: Valdés Guía Miriam 
Published: December 2020

Abstract
In Attica, Pallas was a giant apparently related to the sanctuary of Athena at Pallene. Pallene recalled the eponymous Chalcidian region and thus echoed the myth of the Gigantomachy. In some versions, Athena performed the Pyrrhic dance after defeating the giants. In other versions, however, Pallas was also a Titan, the father of Athena and another young woman. This maiden was the alter ego of the goddess and died at the hands of Athena in an hoplomachia. In this paper, I explore the possibility that some representations of a female Pyrrhic dance relating to Athena on red-figure vases may reflect a ritual in fifth-century Athens. This ritual was presumably associated with the Pallenian sanctuary where the Gigantomachy was evoked and a mimêsis of the goddess in arms seems to have taken place.
Animals and Beauties: Zoomorphic Inscriptions of a Modern Gender Hierarchy
Authors: Edwards Louise 
Published: December 2020

Abstract
At the turn of the nineteenth and twentieth centuries, along with myriad other foundational changes taking place in China, attitudes to the role and significance of women and animals were also changing. This evolution is apparent in the artistic realm where both had featured in imperial-era Chinese art for centuries and continued to appear in the new Republic after 1911. This article examines animals and their paired depiction with women within one genre of art – the Baimei tu (One hundred beauties) – as it evolved from the late 1800s until the end of the 1910s. An examination of the works of leading commercial artists of this form reveals the importance of animals in the creation of a gendered modernity for China’s Republic – one that established a clear hierarchy of men over women. This article argues that the species-ist othering of animals was integral to the othering of women in the early Republican world of commercial art. It contributes to the literature on human-animal studies that shows the links between species-ism and sexism through the identical processes of variously othering animals and women. Identifying animals and women as special and different, reinforces a species hierarchy that places humans above other animals and a sex hierarchy that places men above women.
Materialität und Spiritualität im altisraelitischen Opferkult: Religionsgeschichtliche Abstraktionsprozesse
Authors: Dietrich Jan 
Published: December 2020

Abstract
In the ancient near East, including ancient Israel, the material value of sacrifice was held in high esteem. In the sacrificial system of Leviticus 1-5, however, we find modes of abstraction from the material value of offerings which have parallels to the invention of money in ancient Greece. Here, money as an accepted medium of exchange, was invented with the value of the coin not totally dependent on its metal weight. While in ancient Greece this form of abstraction developed in the economic sphere, in ancient Israel it developed in the religious sphere and paved the way to regard prayers or confessions of faith as equivalent substitutions of material sacrifice.
Proverbs 21:1 and Ancient Near Eastern Hydrology
Authors: Keefer Arthur Jan 
Published: December 2020

Abstract
Proverbs 21:1 says that “The king’s heart is a stream of water in the hand of the Lord; he turns it to all whom he will.” The reference to “stream(s) of water” (פלגי־מים) is largely assumed to have a Palestinian agricultural background, and suggestions that the phrase bears any relation to foreign irrigation practices remain undeveloped. I argue, first, that these streams are artificial irrigation waterways and, second, that they connote royal ideologies which were linked to the hydrological procedures of Egypt and Mesopotamia. Most of all, their association with kingship in Prov 21:1 bears a deliberate relation to the Exodus Narrative. Based on a fresh look at written, iconographic, geographical, and archeological evidence from the wider ancient Near Eastern world, this article brings new interpretive insights to Prov 21:1 in several areas: its geographical background, its meaning, its origin, and its connection with other portions of the Hebrew Bible.
Creating the Coloured Other in South Africa in Light of the “Jewish Question” in Germany
Authors: Walters Handri , van der Waal C.S. (Kees) 
Published: December 2020

Abstract
This article offers a response to Warren Goldstein’s analysis of the racialisation of the “Jewish Question.” By analysing the role of Scripture, Afrikaner nationalism and racial science in the production of apartheid, we argue that the insights shared by Goldstein as related to the “Jewish Question” sparks a fertile reflection on the “Coloured Question” in South Africa. While the outcomes differed, the correlations are to be found in the processes of othering that preceded and accompanied them. We explore the entangled nature of theology, biology, and politics in the racialisation, and subsequent othering, of the coloured category (where resonances with the Jewish example are to be found). By illustrating the similarities and differences between the “Jewish Question” and the “Coloured Question,” what is offered here is a piece to think with as the process of othering finds new targets in an increasingly polarised world.
A Theological Statement on the Coronavirus Pandemic
Authors: Pityana N. Barney 
Published: December 2020

Abstract
This Statement is a response to the challenge that the church and Christian communities around the world face as a result of the spread of the coronavirus pandemic and the regulations that have been imposed in order to control the spread of infections. The paper starts off by explaining that pandemics may be a challenge and an opportunity to the faith. Special attention is paid to the coronavirus pandemic, its origins, the effect on public health systems around the world, and its impact on the socio-economic livelihoods; the role of medical health scientists and the breakdown and disruption of communities, the economic arrangements of states. It also raises questions about the possibility of a new world order that seeks a more equal, compassionate and humane world. On that basis, the paper raises some pertinent theological questions that arise for the church and for faith communities. It explores and examines theological questions that arise out of a world that is broken and suffering, beset by devastation and yet called to live the faith responsibly and truthfully. The questions that arise are pre-eminently about God and the meaning of the divine and how God manifests Good during dark times. The paper raises some of the dilemmas that traditional faith practices are confronted by the pandemic especially in areas like worship, the sacraments and understanding the value of technology in the practice of the faith. Finally, the paper explores implications for the life of the church, especially in the moral life of the Christian community and the dilemmas posed by public ethics.
Giat: A community-based periodical for Koto Gadang society
Authors: Sudarmoko  
Published: December 2020

This paper discusses the contents and roles of the bulletin Giat (June 1953 to December 1957), a community-based periodical published in Jakarta by a Koto Gadang foundation to support development in Koto Gadang, West Sumatra. Giat played a role as a communication medium linking people from Koto Gadang who lived outside their home area (rantau) to their original villages. In describing and analysing the bulletin, I explore its content and focus on its collecting of funds for the clean water pipeline project in Koto Gadang and on its distribution of information, especially information about Minangkabau customary law, culture, literature, and the women’s movement. The bulletin also facilitated the sharing of family news among people from Koto Gadang in the village and the rantau. Giat became a medium for maintaining interpersonal connections and accommodated initiatives to develop the village. It is shown that, as a community-based publication, Giat played a role in developing village infrastructure as well as its social and cultural fields.
The Factors Regulating the Use of the Hebrew-Aramaic Component in Judeo-Spanish
Authors: Schwarzwald Ora (Rodrigue) 
Published: December 2020

Abstract
This article focuses on the quantitative and qualitative weight of the Hebrew-Aramaic (HA) component in Judeo-Spanish (JS) by examining three characteristics of language usage: 1. linguistic features of HA words: morphological—nouns vs. other categories (e.g., mazál ‘luck.N’ vs. maxamá ‘because of.PREP’); semantic—HA words and phrases related to Jewish religious concepts as opposed to other HA words and phrases (e.g., rošaná ‘New Year’ vs. xavér ‘friend, partner’), and syntactic. 2. The HA inventory in JS: which sources and texts produced HA words and expressions used in JS (e.g., the Passover Haggadah)? 3. The actual distribution of the HA component as it appears in various sociolinguistic circumstances and literary texts (e.g., male vs. female, spoken vs. written, Halakhic vs. non-Halakhic). These characteristics suggest a hierarchy of factors that influence the quantity and quality of the HA component in JS.
Translation in a Multilingual Context: The Mixture of Sanskrit and Tamil Languages in Medieval South Indian Śrīvaiṣṇava Religious Tradition
Authors: Akeyipapornchai Manasicha 
Published: December 2020

Abstract
In this paper, I investigate South Asian multilinguality by focusing on the medieval South Indian Śrīvaiṣṇava religious tradition (originated in the tenth century CE), which employ Sanskrit, Tamil, and Maṇipravāḷa, a hybrid language comprising both Sanskrit and Tamil, in their composition. Through the lens of translation and hybridity, I propose to complicate the recent scholarship on the Sanskrit and vernacular languages (e.g., Pollock and interlocutors) and also respond to the scholarly call for research that addresses the distinctive history of South Asian multilinguality. In particular, it explores the use of multiple linguistic media by one of the most significant Śrīvaiṣṇava theologians, Vedāntadeśika (c. 1268–1369 CE), in his Rahasyatrayasāra. The Rahasyatrayasāra which deals with soteriological and ritual aspects of the Śrīvaiṣṇavas was composed in Maṇipravāḷa and furnished with Sanskrit and Tamil opening and concluding verses. Through the investigation of the Maṇipravāḷa content in relation to the verses in the Rahasyatrayasāra, I argue that Maṇipravāḷa can be considered translation as it brings the Sanskrit and Tamil streams of the tradition together into a single context that can accommodate both. For a multilingual community like the Śrīvaiṣṇavas, Maṇipravāḷa, which represents translation into a hybrid, makes possible the collective religious identity.
Hinduizing Nepal’s Hindus: Making Modern Hinduism in Medieval Nepal
Authors: Birkenholtz Jessica Vantine 
Published: December 2020

Abstract
This article examines Nepal’s Svasthānīvratakathā (SVK) text as a lens to explore the shift from the heterogeneity of Newar and Parbatiyā Hindu ideology and identity in premodern Nepal toward a singular, hegemonic form of Hinduism in modern Nepal. The SVK originated in the sixteenth century as a Newar folk legend and is today the most often read and heard Hindu devotional text in Nepal. Beginning in the eighteenth century, the text began to incorporate normative Sanskritic narratives and gradually transformed into an expansive Purāṇa text. These narratives expanded the SVK’s geographical, temporal, and ideological parameters in a manner that articulated, promulgated, and reinforced the emergence of a broader—but simultaneously narrower, Brahmanical—‘Hindu’ identity that became increasingly important in modern Nepal as its rulers cast Nepal as the ‘pure Hindu land.’ The SVK’s Puranicization demonstrates the ways in which the tradition privileged Nepali Hindu-ness over sectarian or ethnic affiliations to create a shared Nepali tradition among Newar and Parbatiyā Hindus and broadcast an emergent Nepali Hindu identity vis-à-vis Indian Hindu identity.
Classification of Wintertime Atmospheric Teleconnection Patterns in the Northern Hemisphere
Authors: Kim Minju , Yoo Changhyun , Sung Mi-Kyung , Lee Sukyoung 
Published: December 2020

AbstractEnergetics of the major atmospheric teleconnection patterns of the Northern Hemisphere winter are examined to investigate the role of baroclinic and barotropic energy conversions in their growth. Based on characteristics of the energetics and the horizontal structures, the patterns are classified into three general types: meridional dipole (D-type), wave (W-type), and hybrid (H-type). The primary energy conversion term that differentiates these patterns is the baroclinic energy conversion of the available potential energy from the climatology to the eddy field associated with the teleconnections. For this conversion term, D-type patterns exhibit the comparable conversion of potential energy via the eddy heat flux across the climatological thermal gradient in both the zonal and meridional directions. In contrast, baroclinic conversion for W-type patterns occurs primarily in the meridional direction, while H-type patterns exhibit a structure that combines the characteristics of the other two pattern types. An important secondary factor is barotropic conversion from the climatology to the eddy field, which takes place mainly in the regions where the climatological shear is strong. For the D-type patterns, conversion occurs on the flank of the climatological jet exit, while it occurs at the center of the jet exit for the W-type patterns. Last, for all the patterns, synoptic-time-scale eddies make a negative contribution via the baroclinic process, but a positive contribution via the barotropic process. Damping by diabatic heating weakens the temperature anomalies associated with the patterns.