bluuebunny/crossref_metadata_2025_split huggingface dataset:
India and the Comprehensive Test Ban Treaty
Authors: Nachiappan Karthik 
Published: January 2020

Abstract
In this chapter, I unpack how India negotiates the Comprehensive Test Ban Treaty, recounting the transnational pressures pushing toward test ban negotiations and why those developments served India’s interests having pulled for such an agreement for decades. This legacy of disarmament diplomacy strongly influenced the approach adopted by the overseeing institution Ministry of External Affairs at CTBT negotiations where Indian diplomats strove to negotiate an agreement that placed uniform constraints vis-à-vis nuclear tests on both nuclear and non-nuclear weapon states. And finally, I distil how domestic interest groups, namely security and nuclear experts, shaped public debates concerning the CTBT which, in turn, gave MEA officials more space to determine whether to ratify or reject the treaty once it became clear that India’s strategy would not have produced the agreement they desired.
A Renaissance Marriage
Authors: James Carolyn 
Published: January 2020

Abstract
Drawing extensively on unpublished archival sources, this book analyses the marriage of Isabella d’Este, one of the most famous figures of the Italian Renaissance, and her less well-known husband, Francesco Gonzaga, ruler of the small northern Italian principality of Mantua (r. 1484–1519). It offers fresh insights into the nature of political marriages during the early modern period by investigating the forces which shaped the lives of an aristocratic couple who, within several years of their wedding, had to deal with the political challenges posed by the first conflicts of the Italian Wars (1494–1559) and, later, the scourge of the Great Pox. The study humanizes a relationship that was organized for entirely strategic reasons, but had to be inhabited emotionally if it was to produce the political and dynastic advantages that had inspired the match. The letter exchanges of Isabella and Francesco over twenty-nine years, as well as their correspondence with relatives and courtiers, show how their personal rapport evolved and how they cooperated in the governance of a princely state. Hitherto examined mainly from literary and religious perspectives and on the basis of legal evidence and prescriptive literature, early modern marriage emerges here in vivid detail, offering the reader access to aspects of the lived experience of an elite Renaissance spousal relationship. The book also contributes to our understanding of the history of emotions, of politics and military conflict, of childbirth, childhood, and family life, and of the history of disease and medicine.
Our Gigantic Zoo
Authors: Lekan Thomas M. 
Published: January 2020

Abstract
This book examines the troubled relationship between Europe’s greatest wildlife conservationist, the former Frankfurt Zoo director and Oscar-winning documentarian Bernhard Grzimek, and the landscape he saw as a “gigantic zoo” for the earth’s last great mammals: the Serengeti National Park in Tanzania. It analyzes the fissures that emerged between Grzimek and his son Michael’s self-appointed quest to save the Serengeti from modernization and “overpopulation” and the rights of rural Africans and their livestock to inhabit the landscape on their own terms during the era of decolonization around 1960. Grzimek is beloved in Germany as an animal whisperer. He rebuilt the Frankfurt Zoo from a bombed-out shell and sensitized a generation of young people to environmental issues on his long-running television program, A Place for Animals. Yet his advocacy abroad exposed the danger of thinking locally and acting globally. The Grzimeks projected European anxieties about war, Americanization, race, and environmental destruction onto Africa, sidestepping the uncomfortable imperialist legacies of exploitation that had endangered animals in the first place. After independence, Bernhard tried to make wildlife pay for Tanzania by promoting package tours from Europe and soliciting West German development aid for national parks. These efforts created an important alliance between Grzimek, West German diplomats, and Tanzanian leader Julius Nyerere. Grzimek’s conservation priorities soon clashed against Nyerere’s nationalist ones, as a more self-assertive Tanzania resented failed promises and incessant meddling. The Africanization of the national park system in the early 1970s ended the Grzimek quest: the fate of the Serengeti lay in Nyerere’s hands, not Grzimek’s.
Crystal Eastman
Authors: Aronson Amy 
Published: January 2020

Abstract
Crystal Eastman was a central figure in many of the defining social movements of the twentieth century—labor, feminism, internationalism, free speech, peace. She drafted America’s first serious workers’ compensation law. She helped found the National Woman’s Party and is credited as coauthor of the Equal Rights Amendment (ERA). She helped found the Woman’s Peace Party—today, the Women’s International League for Peace and Freedom (WILPF)—and the American Union against Militarism. She copublished the Liberator magazine. And she engineered the founding the American Civil Liberties Union (ACLU). Eastman worked side by side with national and international suffrage leaders, renowned Progressive reformers and legislators, birth control advocates, civil rights champions, and revolutionary writers and artists. She traveled with a transatlantic crowd of boundary breakers and innovators. And in virtually every arena she entered, she was one of the most memorable women known to her allies and adversaries alike. Yet today, her legacy is oddly ambiguous. She is commemorated, paradoxically, as one of the most neglected feminist leaders in American history. This first full-length biography recovers the revealing story of a woman who attained rare political influence and left a thought-provoking legacy in ongoing struggles. The social justice issues she cared about—gender equality and human rights, nationalism and globalization, political censorship and media control, worker benefits and family balance, and the monumental questions of war, sovereignty, force, and freedom—remain some of the most consequential questions of our own time.
Working Memory Training From an Individual Differences Perspective
Authors: Borella Erika , Carretti Barbara , Cornoldi Cesare , Beni Rossana De 
Published: January 2020

Abstract
This chapter presents and discusses a verbal WM training developed for older adults. The model of working memory (WM) proposed by Cornoldi and Vecchi, which is based on an analysis of individual and age-related differences, is used as a framework for discussing the efficacy of the WM training procedure proposed and developed for older adults. The model (a) assumes that different WM tasks (and underlying processes) may be located along two continua that describe the type of content to be processed and the degree of active control required by the task and (b) considers metacognitive/motivational aspects, which also have a role in determining WM performance. The WM training procedure presented here takes into account not only the capacity to use WM resources and attentional control by adopting an adaptive procedure, but also the importance of including variations in the training task demands to produce a challenging and engaging task that sustains motivation and favor the training’s short- and long-term efficacy, at least in older adults. These aspects seem crucial in explaining the results obtained with this verbal WM training program in aging.
Sulfur Deficiency-Induced Glucosinolate Catabolism Attributed to Two β-Glucosidases, BGLU28 and BGLU30, is Required for Plant Growth Maintenance under Sulfur Deficiency
Authors: Zhang Liu , Kawaguchi Ryota , Morikawa-Ichinose Tomomi , Allahham Alaa , Kim Sun-Ju , Maruyama-Nakashita Akiko 
Published: January 2020

Abstract
Sulfur (S) is an essential element for plants, and S deficiency causes severe growth retardation. Although the catabolic process of glucosinolates (GSLs), the major S-containing metabolites specific to Brassicales including Arabidopsis, has been recognized as one of the S deficiency (−S) responses in plants, the physiological function of this metabolic process is not clear. Two β-glucosidases (BGLUs), BGLU28 and BGLU30, are assumed to be responsible for this catabolic process as their transcript levels were highly upregulated by −S. To clarify the physiological function of BGLU28 and BGLU30 and their roles in GSL catabolism, we analyzed the accumulation of GSLs and other S-containing compounds in the single and double mutant lines of BGLU28 and BGLU30 and in wild-type plants under different S conditions. GSL levels were highly increased, while the levels of sulfate, cysteine, glutathione and protein were decreased in the double mutant line of BGLU28 and BGLU30 (bglu28/30) under −S. Furthermore, transcript level of Sulfate Transporter1;2, the main contributor of sulfate uptake from the environment, was increased in bglu28/30 mutants under −S. With these metabolic and transcriptional changes, bglu28/30 mutants displayed obvious growth retardation under −S. Overall, our results indicate that BGLU28 and BGLU30 are required for −S-induced GSL catabolism and contribute to sustained plant growth under −S by recycling sulfate to primary S metabolism.
Cognitive Functional Therapy for People with Nonspecific Persistent Low Back Pain in a Secondary Care Setting—A Propensity Matched, Case–Control Feasibility Study
Authors: Ussing Kasper , Kjaer Per , Smith Anne , Kent Peter , Jensen Rikke K , Schiøttz-Christensen Berit , O’Sullivan Peter Bruce 
Published: January 2020

AbstractBackgroundEffective, inexpensive, and low-risk interventions are needed for patients with nonspecific persistent low back pain (NS-PLBP) who are unresponsive to primary care interventions. Cognitive functional therapy (CFT) is a multidimensional behavioral self-management approach that has demonstrated promising results in primary care and has not been tested in secondary care.ObjectiveTo investigate the effect of CFT and compare it with usual care for patients with NS-PLBP.DesignCase–control study.SettingA secondary care spine center.SubjectsThirty-nine patients received a CFT intervention and were matched using propensity scoring to 185 control patients receiving usual care.MethodsThe primary outcome was Roland Morris Disability Questionnaire (0–100 scale) score. Group-level differences at six- and 12-month follow-up were estimated using mixed-effects linear regression.ResultsAt six-month follow-up, a statistically significant and clinically relevant difference in disability favored the CFT group (–20.7, 95% confidence interval [CI] = –27.2 to –14.2, P &lt; 0.001). Significant differences also occurred for LBP and leg pain, fear, anxiety, and catastrophizing in favor of CFT. At 12-month follow-up, the difference in disability was smaller and no longer statistically significant (–8.1, 95% CI = –17.4 to 1.2, P = 0.086). Differences in leg pain intensity and fear remained significantly in favor of CFT. Treatment satisfaction was significantly higher in the CFT group at six- (93% vs 66%) and 12-month (84% vs 52%) follow-up.ConclusionsThese findings support that CFT is beneficial for patients with NS-PLBP who are unresponsive to primary care interventions. Subsequent randomized controlled trials could incorporate booster sessions, which may result in larger effects at 12-month follow-up.
A Targeted Metabolomics-Based Assay Using Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Identifies Structural and Functional Cardiotoxicity Potential
Authors: Palmer Jessica A , Smith Alan M , Gryshkova Vitalina , Donley Elizabeth L R , Valentin Jean-Pierre , Burrier Robert E 
Published: January 2020

Abstract
Implementing screening assays that identify functional and structural cardiotoxicity earlier in the drug development pipeline has the potential to improve safety and decrease the cost and time required to bring new drugs to market. In this study, a metabolic biomarker-based assay was developed that predicts the cardiotoxicity potential of a drug based on changes in the metabolism and viability of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). Assay development and testing was conducted in 2 phases: (1) biomarker identification and (2) targeted assay development. In the first phase, metabolomic data from hiPSC-CM spent media following exposure to 66 drugs were used to identify biomarkers that identified both functional and structural cardiotoxicants. Four metabolites that represent different metabolic pathways (arachidonic acid, lactic acid, 2′-deoxycytidine, and thymidine) were identified as indicators of cardiotoxicity. In phase 2, a targeted, exposure-based biomarker assay was developed that measured these metabolites and hiPSC-CM viability across an 8-point concentration curve. Metabolite-specific predictive thresholds for identifying the cardiotoxicity potential of a drug were established and optimized for balanced accuracy or sensitivity. When predictive thresholds were optimized for balanced accuracy, the assay predicted the cardiotoxicity potential of 81 drugs with 86% balanced accuracy, 83% sensitivity, and 90% specificity. Alternatively, optimizing the thresholds for sensitivity yields a balanced accuracy of 85%, 90% sensitivity, and 79% specificity. This new hiPSC-CM-based assay provides a paradigm that can identify structural and functional cardiotoxic drugs that could be used in conjunction with other endpoints to provide a more comprehensive evaluation of a drug’s cardiotoxicity potential.
Privacy-preserving biomedical database queries with optimal privacy-utility trade-offs
Authors: Cho Hyunghoon , Simmons Sean , Kim Ryan , Berger Bonnie 
Published: January 2020

AbstractSharing data across research groups is an essential driver of biomedical research. In particular, biomedical databases with interactive query-answering systems allow users to retrieve information from the database using restricted types of queries (e.g. number of subjects satisfying certain criteria). While these systems aim to facilitate the sharing of aggregate biomedical insights without divulging sensitive individual-level data, they can still leak private information about the individuals in the database through the query answers. Existing strategies to mitigate such risks either provide insufficient levels of privacy or greatly diminish the usefulness of the database. Here, we draw upon recent advances in differential privacy to introduce privacy-preserving query-answering mechanisms for biomedical databases that provably maximize the expected utility of the system while achieving formal privacy guarantees. We demonstrate the accuracy improvement of our methods over existing approaches for a range of use cases, including count, membership, and association queries. Notably, our new theoretical results extend the proof of optimality of the underlying mechanism, previously known only for count queries with symmetric utility functions, to asymmetric utility functions needed for count queries in cohort discovery workflows as well as membership queries—a core functionality of the Beacon Project recently launched by the Global Alliance for Genomics and Health (GA4GH). Our work presents a path towards biomedical query-answering systems that achieve the best privacy-utility trade-offs permitted by the theory of differential privacy.
Construction of Nanobody Library in Mammalian Cells by Linear-double-stranded DNA Based AND Gate Genetic Circuit
Authors: Zhao Yanjie , Tong Xin , Zhang Chunze , Li Shuai 
Published: January 2020

AbstractNanobody is one special type of single-domain antibody fragment with multiple advantages over traditional antibody. Our previous work established linear-double-stranded DNA (ldsDNA, or PCR amplicon) as novel biological parts for building AND gate genetic circuits in mammalian cells. During this AND-gate circuit formation process, the co-transfected up- and down-stream ldsDNAs could be linked together to form intact gene expression cassette. Here, we employed thisldsDNA-basedAND-gate (LBAG) strategy to construct nanobody library in mammalian cells. The sequence complexity of complementary determining regions (CDRs) was introduced into ldsDNA by PCR amplification. After being co-transfected into mammalian cells, the up- and down-stream ldsDNAs undergo AND gate linkage and form full nanobody coding regions, containing CDR1-3. High throughput sequencing identified 22,173 unique oligonucleotide sequences in total generated by this strategy. Thus, we developed a novel method to construct nanobody library, which is a start point for building high content nanobody library in mammalian cells.
Prepronociceptin expressing neurons in the extended amygdala encode and promote rapid arousal responses to motivationally salient stimuli
Authors: Rodriguez-Romaguera Jose , Ung Randall L , Nomura Hiroshi , Otis James M , Basiri Marcus L , Namboodiri Vijay MK , Zhu Xueqi , Robinson J Elliott , McHenry Jenna A , Kosyk Oksana , Jhou Thomas C , Kash Thomas L , Bruchas Michael R , Stuber Garret D 
Published: January 2020

ABSTRACTMotivational states are complex and consist of cognitive, emotional, and physiological components controlled by a network across multiple brain regions. An integral component of this neural circuitry is the bed nucleus of the stria terminalis (BNST). Here, we identified a subpopulation of neurons within BNST expressing the gene prepronociceptin (PnocBNST), that can modulate the rapid changes in physiological arousal that occur upon exposure to stimuli with motivational salience. Usingin vivotwo-photon calcium imaging we found that excitatory responses from individualPnocBNSTneurons directly corresponded with rapid increases in pupillary size and occurred upon exposure to both aversive and rewarding odors. Furthermore, optogenetic activation of these neurons increased pupillary size, but did not alter approach/avoidance or locomotor behaviors. These findings suggest that excitatory responses inPnocBNSTneurons encode rapid arousal responses irrespective of tested behaviors. Further histological, electrophysiological, and single-cell RNA sequencing data revealed thatPnocBNSTneurons are composed of genetically and anatomically identifiable subpopulations that can be further investigated. Taken together, our findings demonstrate a key role for aPnocBNSTneuronal ensemble in encoding the rapid arousal responses that are triggered by motivational stimuli.
Structures of three actinobacteriophage capsids: Roles of symmetry and accessory proteins
Authors: Podgorski Jennifer , Calabrese Joshua , Alexandrescu Lauren , Jacobs-Sera Deborah , Pope Welkin , Hatfull Graham , White Simon 
Published: January 2020

AbstractMycobacterium tuberculosisandabscessusare major human pathogens that are part of theActinobacteriaphylum. Increasing multiple drug resistance in these bacteria has led to a renewed interest in using viruses that infect these bacteria for therapy. In order to understand these viruses, a course-based undergraduate research experience (CURE) program run by SEA-PHAGES at the University of Pittsburgh and HHMI has isolated, sequenced, and annotated over 3000 actinobacteriophages (viruses that infectActinobacteria). Little work has been done to investigate the structural diversity of these phage, all of which are thought to use a common protein fold, the HK97-fold, in their major capsid protein. Here we describe the structure of three actinobacteriophage capsids isolated by students that infectMycobacterium smegmatis. The capsid structures were resolved to approximately 6 angstroms, which allowed confirmation that each phage uses the HK97-fold to form their capsid. One phage, Rosebush, has a novel variation of the HK97-fold. Four novel accessory proteins, that form the capsid head along with the major capsid protein, were identified that show limited or no homology to known proteins. The genes that encode the proteins were identified using SDS-PAGE and mass spectrometry. Bioinformatic analysis of the accessory proteins suggest they are used in many actinobacteriophage capsids.
Investigating the causal effect of maternal vitamin B12 and folate levels on offspring birthweight
Authors: Moen Gunn-Helen , Beaumont Robin N , Sommer Christine , Shields Beverley M. , Lawlor Deborah A , Freathy Rachel M , Evans David M , Warrington Nicole M 
Published: January 2020

AbstractLower maternal serum vitamin B12 (B12) and folate levels have been associated with lower offspring birthweight in observational studies. The aim of this study was to investigate whether this relationship is causal.We performed two-sample Mendelian Randomization (MR) using summary data on associations between genotype-B12 (10 genetic variants) or genotype-folate (4 genetic variants) levels from a genome-wide association study of 45,576 individuals (sample 1) and maternal-specific genetic effects on offspring birthweight from the latest EGG consortium meta-analysis with 297,356 individuals reporting their own birthweight and 210,248 women reporting their offspring’s birthweight (sample 2). To investigate the effect of offspring’s own B12 or folate levels on their own birthweight, we performed two-sample MR using the fetal-specific genetic effects from the latest EGG consortium meta-analysis. We used the inverse variance weighted method, and sensitivity analyses to account for pleiotropy, in addition to sensitivity analyses excluding a potentially pleiotropic variant in theFUT2gene for B12.We did not find evidence for a causal effect of maternal B12 on offspring birthweight, nor evidence for an effect of offspring B12 on their own birthweight using the fetal-specific genetic effect. The results were consistent across the different methods and in sensitivity analyses excluding theFUT2variant. We found a positive effect of maternal folate on offspring birthweight (0.146 [0.065, 0.227], which corresponds to an increase in birthweight of 71g per 1SD higher folate). We found some evidence for a small inverse effect of fetal folate on their own birthweight (−0.051 [−0.100, −0.003]).In conclusion, our results are consistent with evidence from randomized controlled trials that increased maternal folate levels increase offspring birthweight. We did not find evidence for a causal effect of B12 on offspring birthweight, suggesting previous observational studies may have been due to confounding.