bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract IA11: Developing and improving personalized neoantigen-targeting cancer vaccines
Authors: Wu Catherine J. 
Published: February 2019

Abstract
At the heart of any cancer and host immune cell response is the tumor antigen and host antigen-specific T-cell interaction. The cytotoxic T cell-cognate antigen interaction forms the mechanistic basis for immune-mediated recognition and the killing of malignant cells. While the search for immunogenic tumor antigens has been the subject of decades-long studies, multiple lines of evidence have convincingly demonstrated tumor neoantigens as an important class of immunogenic tumor antigens. Neoantigens arise from amino acid changes encoded by somatic mutations in the tumor cell and have the potential to bind to and be presented by personal HLA molecules. Using next-generation sequencing approaches, we can now systematically identify mutations leading to amino acid changes that can be potentially recognized immunologically through the implementation of neoantigen discovery pipelines. In recent studies, we have tested the feasibility and immunogenicity of a vaccine that targets up to 20 personal neoantigens predicted to be presented by autologous patient tumor. This approach can expand the repertoire of neoantigen-specific T cells, providing a strong rationale for the further development of this approach, alone and in combination with checkpoint therapies.
Citation Format: Catherine J. Wu. Developing and improving personalized neoantigen-targeting cancer vaccines [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr IA11.
Abstract IA29: Novel insights into the dose-dependency of radiation immunogenicity
Authors: Demaria Sandra 
Published: February 2019

Abstract
Recruitment to the tumor of a Batf3-dependent subset of dendritic cells (DCs) specialized in cross-presentation of tumor-derived antigens to CD8+ cytotoxic T cells is driven by type I interferon (IFN-I) and is essential for activation of antitumor CD8+ T cells. We have recently found that in tumors refractory to treatment with immune checkpoint blockers (ICBs), radiotherapy induces cancer cell-intrinsic activation of IFN-I pathway and release of interferon-beta, mimicking a viral infection, and resulting in recruitment of Batf3-dependent DCs (Vanpouille-Box et al., Nat Commun 2017). This process is mediated by the accumulation of dsDNA in the cancer cell cytoplasm, which is sensed by cGAS and leads to downstream activation of STING. Importantly, the dose and fractionation of radiation are critical for optimal induction of IFN-I production by irradiated cancer cells. For most carcinoma cells there is a single radiation dose threshold of 12-15 Gy above which the DNA exonuclease TREX1 is upregulated. The latter degrades cytoplasmic dsDNA precluding IFN-I activation. Fractionation, i.e., repeated (three times) daily delivery of radiation therapy at doses below this threshold, amplifies the IFN-I pathway activation in the carcinoma cells, an effect that requires upregulation of IFNRA. Furthermore, the synergy of RT with ICBs (anti-CTLA-4 or anti-PD-1) and the induction of abscopal effects (i.e., immune-mediated rejection of nonirradiated synchronous tumors) are completely dependent on the ability of radiotherapy to induce cancer cell-intrinsic IFN-I.
These findings have critical implications for the use of radiotherapy to increase the response to ICBs in the clinic, a strategy currently being tested in over one hundred ongoing and planned trials.
Supported by NIH 1R01CA201246, Breast Cancer Research Foundation BCRF-016-054, and The Chemotherapy Foundation.
Citation Format: Sandra Demaria. Novel insights into the dose-dependency of radiation immunogenicity [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr IA29.
Abstract IA30: Immune checkpoint blockade in cancer therapy: New insights and opportunities, and prospects for cures
Authors: Allison James P. 
Published: February 2019

Abstract
The existence of multiple nonredundant inhibitory pathways that limit T-cell responses offers novel strategies for mobilizing the immune system to attack cancer cells. The best characterized of these immune checkpoints is CTLA-4, which inhibits T cell proliferation by interfering with the interaction of the costimulatory molecule CD28 with its ligands B7-1 and B7-2 on the surface of antigen-presenting cells. Antibodies to CTLA-4 have proved effective against multiple tumor types in both preclinical and clinical studies. Ipilimumab, an antibody to human CTLA-4, showed long-term (&gt;4 years) survival benefit in about 20% of patients in a randomized, placebo-controlled trial in late-stage melanoma. In 2011 it was approved by the FDA for treatment of late-stage melanoma and is now a standard of care for that disease.
PD-1, another checkpoint, recruits a phosphatase and seems to interfere with T-cell antigen receptor-mediated signaling. It has two ligands, PD-L1 and PD-L2, which are both expressed on dendritic cells. However, many tumor cells also express PD-L1. Antibodies to PD-1 and PD-L1 have both shown objective responses against several tumor types in clinical trials with response rates of about 25%. A recent phase II trial of a combination of anti-PD-1 and anti-CTLA-4 in melanoma showed objective responses in about 50% of late-stage melanoma patients. Altogether, the FDA has approved 17 checkpoint antibodies/indications for melanoma and lung cancer.
Emerging data suggest that T-cell responses are largely directed toward neoantigens arising as a result of mutational events associated with the carcinogenesis. While all tumors with antigens recognizable by the immune system should be targets for checkpoint blockade, it is becoming clear that certain types of tumors with lower burdens of mutations (e.g., prostate, breast, and kidney cancer) present special challenges for immune therapy. Strategies for effective treatment of such tumors will be discussed.
We have also used high-parameter flow cytometry to identify the cellular mechanisms of CTLA-4 and PD-1 blockade. These are mostly nonoverlapping, which may be a partial explanation for the enhanced effect of the combination.
Citation Format: James P. Allison. Immune checkpoint blockade in cancer therapy: New insights and opportunities, and prospects for cures [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr IA30.
Abstract PR08: Metabolic adaptations establish immunotherapy resistance in melanoma
Authors: Jaiswal Ashvin R. , Pudakalakatti Shivanand , Dutta Prasanta , Liu Arthur , Bartkowiak Todd , Ager Casey , Ivan Cristina , Davis Richard Eric , Davies Michael A. , Wargo Jennifer , Allison James P. , Bhattacharya Pratip K. , Hong David , Curran Michael A. 
Published: February 2019

Abstract
Background: Despite the success of T-cell checkpoint blockade antibodies in treating an array of cancers, the majority of patients still fail to respond to these therapies, or respond transiently and then relapse. The molecular mechanisms that drive lack of response to checkpoint blockade, whether pre-existing or evolved on therapy, remain unclear.
Materials and Methods: To address this critical gap in clinical knowledge, we established a mouse model of melanoma designed to elucidate the molecular mechanisms underlying immunotherapy resistance. Through multiple in vivo passages, we selected a B16 melanoma tumor line that evolved complete resistance to combination blockade of CTLA-4, PD-1, and PD-L1, which cures ~80% of mice of the parental tumor. Using gene expression analysis, proteomics, and immunogenomics, we determined the adaptations engaged by this melanoma to become completely immunotherapy resistant. NMR spectroscopy, Seahorse XF analysis, flow cytometry, confocal microscopy, and Western blot analysis provided further insight into the mechanisms driving checkpoint blockade resistance.
Results: Acquisition of immunotherapy resistance by these melanomas was driven by coordinate upregulation of the glycolytic and aldose reductase pathways to create a metabolically hostile microenvironment in which T-cell function is profoundly suppressed. When reintroduced into the parental tumor, the genes most closely associated with these metabolic adaptations confer enhanced immunotherapy resistance. We have validated upregulation of these pathways in a unique cohort of melanoma patients who failed dual checkpoint blockade. Additionally, we employed MRI imaging to visualize metabolic changes acquired by resistant tumors in live mice. Clinical application of this technique could provide a much-needed noninvasive tool to predict immunotherapeutic sensitivity of patients.
Conclusion: Upregulation of glycolytic metabolism and the aldose reductase pathway by melanoma tumor cells cripples T cells in the microenvironment and confers resistance to checkpoint blockade.
This abstract is also being presented as Poster A71.
Citation Format: Ashvin R. Jaiswal, Shivanand Pudakalakatti, Prasanta Dutta, Arthur Liu, Todd Bartkowiak, Casey Ager, Cristina Ivan, Richard Eric Davis, Michael A. Davies, Jennifer Wargo, James P. Allison, Pratip K. Bhattacharya, David Hong, Michael A. Curran. Metabolic adaptations establish immunotherapy resistance in melanoma [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr PR08.
Being Soviet, Muslim, Modernist, and Fundamentalist in 1950s Central Asia
Authors: Sartori Paolo , Babajanov Bakhtiyar 
Published: February 2019

AbstractHow far, if at all, did the intellectual legacy of early 20th-century Muslim reformism inform the transformative process which Islam underwent in Soviet Central Asia, especially after WWII? Little has been done so far to analyze the output of Muslim scholars (ʿulamāʾ) operating under Soviet rule from the perspective of earlier Islamic intellectual traditions. The present essay addresses this problem and sheds light on manifestations of continuity among Islamic intellectual practices—mostly puritanical—from the period immediately before the October Revolution to the 1950s. Such a continuity, we argue, profoundly informed the activity of the Spiritual Administration of the Muslims of Central Asia and Kazakhstan (SADUM) established in Tashkent in 1943 and, more specifically, the latter’s attack against manifestations of religiosity deemed “popular,” which were connected to the cult of saints. Thus, this essay posits that the juristic output of Soviet ʻulamā’ in Central Asia originates from and further develops an Islamic reformist thinking, which manifested itself in the region in the late 19th- and early 20th-century. By establishing such an intellectual genealogy, we seek in this article to revise a historiographical narrative which has hitherto tended to decouple scripturalist sensibilities from Islamic reformism and modernism.
The Text and Metre of Sapph. fr. 114 V.
Authors: Meister Felix J. 
Published: February 2019

AbstractThis article aims to address the problems posed by Sappho’s difficult fr. 114 V. It first revises the assumption that both lines need to display the same metrical profile and concludes that this assumption is unreliable. Then it offers a reconstruction of the fragment that is not restricted by the alleged need for metrical homogeneity.
Royal Wet Nurses in Seventh- and Early Eighth-Century China: Historiographical Evaluation and Narrative Construction
Authors: Doran Rebecca 
Published: February 2019

AbstractThe women who served as wet nurses to powerful and in some cases notorious members of the Tang royal family appear in written materials in various capacities in relation to prominent historical actors. An analysis of historical narratives involving these women indicates that their portrayals were strongly influenced by the historian’s mode of moral assessment, in particular, the historical judgment meted out upon their controversial charges. The manipulation in historical narrative of royal wet nurses thus elucidates a fascinating example of the operation of “praise and blame” in traditional historiography. Wet nurses are used as narrative pawns to emphasize the historical judgment of their famous former charges and become a vehicle or mouthpiece for historical evaluation.
Aristotle on Virtue of Character and the Authority of Reason
Authors: Müller Jozef 
Published: February 2019

AbstractI argue that, for Aristotle, virtue of character is a state of the non-rational part of the soul that makes one prone to making and acting on decisions in virtue of that part’s standing in the right relation to (correct) reason, namely, a relation that qualifies the agent as a true self-lover. In effect, this central feature of virtue of character is nothing else than love of practical wisdom. As I argue, it not only explains how reason can hold direct authority over non-rational desires but also why Aristotle defines virtue of character as hexis prohairetikē.
Some Cases of Root Exegesis of Hebrew Forms in Peshitta Ezekiel
Authors: Lund Jerome A. 
Published: February 2019

AbstractThe new translation of Peshitta Ezekiel by Gillian Greenberg and Donald M. Walter in the Bible of Antioch series raises issues with regard to the interpretation of the Syriac text and its relationship to the Hebrew. The Syriac translator used root exegesis of Hebrew forms as a translation tool. This study will examine a number of cases of root exegesis in Peshitta Ezekiel with the aim of better understanding the Peshitta translation. This research was undertaken as part of the Bible of Edessa project.
The Helpful God: A Reevaluation of the Etymology and Character of (ˀēl) šadday
Authors: Wilson-Wright Aren M. 
Published: February 2019

AbstractBoth the role of the deity (El) Shadday in the religions of ancient Israel and the etymology of the name šadday remain poorly understood. In this article, I will propose a new etymology for the name šadday and then leverage this etymology into a better understanding of (El) Shadday’s character. I argue that šadday is a nomen agentis from the root sdy ‘to help’ and originated as an epithet of the deity El, which highlighted his benevolent qualities. A comparison of El in the Ugaritic epics and El Shadday in the Priestly Source (P) suggests that El Shadday was thought to help his worshippers by providing them with children. El Shadday thus represents one way in which the deity El survived in the religions of ancient Israel.
Testing the causal understanding of water displacement by kea (Nestor notabilis)
Authors: Schwing R. , Weiss F. , Tichy A. , Gajdon G. 
Published: February 2019

Abstract
Rooks, Eurasian jays and NC crows have already solved the Aesop’s fable paradigm, using stones to raise a water level to get a previously out of reach reward. Here we test kea parrots on their understanding of water displacement. In Experiment 1, they preferentially chose the water-filled tube over two solid substrates (sand, rocks) within 5 trials. In Experiment 2, they generalised to novel coloured substrates in the first trial. In Experiment 3, confronted with two water-filled tubes, one of which was made unsolvable by preventing the water from rising, none of the kea managed to solve the task. This suggests that their performance in Experiments 1 and 2 was reward association with the liquid-filled tube, without attendance to changes in water level. These results therefore provide no evidence of causal understanding of water displacement and highlight that such an understanding is not required for solving Aesop’s Fable.
Fusion Politics from the Poor People’s Campaign to the Rainbow Coalition to the New Poor People’s Campaign
Authors: Sinclair-Chapman Valeria , Targ Harry 
Published: February 2019

Abstract
This article examines a model of fusion politics that connects activism to end poverty, and addresses a constellation of social injustices across more than a half century in the United States. We consider an articulation of fusion politics that highlights the actions of disparate groups and individuals, including youth, racial and ethnic minorities, women, LGBT activists, teachers, and union members who have joined in a cooperative effort to address independent but linked concerns such as quality public schools, livable wages, affordable healthcare, environmental justice, immigrant rights, women’s reproductive rights, fair elections, and criminal justice. Our analysis points out the historical links between the 1968 Poor People’s Campaign, the Rainbow Coalition of the 1980s, and the new Poor People’s Campaign launched in 2018. It draws heavily on the words and writings of Reverend Martin Luther King, Jr. and the Reverend William Barber, II in understanding the organizing, objectives, and transformative potential of these movements.
A Global and Inclusive Agreement? Participation of Armed Actors in the Inter-Congolese Dialogue and Its Impact on Local Violence
Authors: Hellmüller Sara 
Published: February 2019

Abstract
This article provides an analytical framework to understand how participation of armed actors in peace negotiations influences local violence. It argues that the link between violence and exclusion or inclusion of armed actors is often indirect and depends on armed actors’ underlying motivations to be included and their corresponding strategies. Based on an analysis of the Congolese peace process from 1999 to 2003, the article assesses how the mandate of the peace process influenced armed groups’ motivations to be included. It then analyzes the strategies that armed actors used to be included and examines their impact on local violence. Thereby, it allows for a more nuanced understanding of how participation of armed actors in a mediation process influences prospects for peace.
“Sticky Faith” in Australian Baptist Churches: Surveying Generational Participation and Ministry Priorities
Authors: Cronshaw Darren 
Published: February 2019

Abstract
Australian Baptist Churches share a demographic aging trend with many Western churches — they engage proportionately more older and less young people. Moreover, a significant proportion of children and youth lack “sticky faith” and leave church. The 2016 National Church Life Survey identifies trends in generational participation and ministry priorities. Interviewed Baptist young adults and leaders suggest as reasons youth disengage from church: external societal pressures, “siloed” programs and lack of discipleship, relationships and service opportunities. Many Australian Baptist churches are adopting a more “generational” and less “siloed” approach, but there is room for improvement in resourcing churches for “sticky” faith formation.
Does Sharīʿa Need to Be Restored? The Legislative Predicament of the Sunnī Doctrinal Theories
Authors: Sewilam Heba 
Published: February 2019

Abstract
The post-colonialist academic discourse blames colonialism for the marginalisation of Sharī‘a in the legal systems of Sunnī Muslim-majority countries. However, an analysis of some juristic debates around the Sunnī doctrinal theories of uṣūl al-fiqh and maqāṣid al-sharīʿa exposes few of the theories’ internal problems accounting for the marginalisation. In uṣūl al-fiqh, disputes regarding ijmāʿ and qiyās virtually bring their effectiveness as legal doctrines for positive law legislation to a halt. With regard to maqāṣid al-sharīʿa, an Ašʿarī adherence to a literal reading of the text reduces its potential to produce new Sharī‘a-compliant laws. Such problems render uṣūl al-fiqh and maqāṣid al-sharīʿa ineffective instruments for regulating accelerated legal changes demanded by fast-paced societal and scientific developments and deem the application of Sharīʿa in Sunnī Muslim-majority countries a task neither possible nor even recommended.
World-Wide Comparative Evidence for Calquing of Valency Patterns in Creoles
Authors: Michaelis Susanne Maria 
Published: February 2019

Creole languages consistently show valency patterns that cannot be traced back to their lexifier languages, but derive from their substrate languages. In this paper, I start out from the observation that a convincing case for substrate influence can be made by adopting a world-wide comparative approach. If there are recurrent matches between substrate and creole structures in a given construction type, in creoles of different world regions and with different substrates, then we can exclude the possibility of an accident, and substrate influence is the only explanation. The construction types that I will look at are ditransitive constructions (Section 3), weather constructions (Section 4), experiencer constructions (Section 5), and motion constructions (Section 6). I will draw on the unique typological data source from the Atlas of Pidgin and Creole Language Structures (Michaelis et al., 2013a; 2013b). My conclusion is that the data provided in AP
i
CS support the claim that during creolization, valency patterns have been systematically calqued into the nascent creoles.
On Divine Providence
Authors: Badakhchani S.J. 
Published: February 2019

Abstract
Naṣīr al-Dīn al-Ṭūsī (1201–1274), the most eminent Muslim thinker of thirteenth-century Iran occupies a unique place among the Muslim polymaths of the Middle Ages who have gained recognition both in the East and West. In the West, he is recognised as a scientist whose contribution to astronomy, trigonometry and mathematics influenced the course of scientific developments, and in the East as a supreme teacher who contributed significantly to the application of metaphysical argumentation and philosophical terminology in Sufism, Ismaili and Twelver Shiʿi theology, bringing the Ismaili humanistic and ethical tradition of philosophers into the centre of Islamic ethical discourse. The renown of his commentary on Avicenna’s “Hints and Indications” (al-Išārāt wa-l-tanbīhāt) seems to have gained him the position of the foremost master of Avicennian philosophy. From another aspect al-Ṭūsī can be considered a partisan of Nizārī Ismaili theological thinking, a doctrine that in his opinion was somehow in harmony with Avicennan philosophy when he equates Necessary Existence with God. However, while commenting on Avicenna’s theorem of Divine Providence, al-Ṭūsī finds the Avicennan position unacceptable. The conclusions reached in this paper uphold the influence of Nizārī Ismaili philosophical deliberations on the nature of the Divine and His knowledge, not only on al-Ṭūsī and al-Šahrastānī but also on Avicenna himself. Needless to say, the wide scope of the subject prevents us from reaching definitive answers to all the questions raised and this attempt endeavours to lay the ground for further investigations to reach a clearer understanding of the subject.