bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Bayesian Framework for Inferring the Influence of Sequence Context on Point Mutations
Authors: Ling Guy , Miller Danielle , Nielsen Rasmus , Stern Adi 
Published: October 2019

AbstractThe probability of point mutations is expected to be highly influenced by the flanking nucleotides that surround them, known as the sequence context. This phenomenon may be mainly attributed to the enzyme that modifies or mutates the genetic material, because most enzymes tend to have specific sequence contexts that dictate their activity. Here, we develop a statistical model that allows for the detection and evaluation of the effects of different sequence contexts on mutation rates from deep population sequencing data. This task is computationally challenging, as the complexity of the model increases exponentially as the context size increases. We established our novel Bayesian method based on sparse model selection methods, with the leading assumption that the number of actual sequence contexts that directly influence mutation rates is minuscule compared with the number of possible sequence contexts. We show that our method is highly accurate on simulated data using pentanucleotide contexts, even when accounting for noisy data. We next analyze empirical population sequencing data from polioviruses and HIV-1 and detect a significant enrichment in sequence contexts associated with deamination by the cellular deaminases ADAR 1/2 and APOBEC3G, respectively. In the current era, where next-generation sequencing data are highly abundant, our approach can be used on any population sequencing data to reveal context-dependent base alterations and may assist in the discovery of novel mutable sites or editing sites.
Incorporation and influence of Leishmania histone H3 in chromatin
Authors: Dacher Mariko , Tachiwana Hiroaki , Horikoshi Naoki , Kujirai Tomoya , Taguchi Hiroyuki , Kimura Hiroshi , Kurumizaka Hitoshi 
Published: October 2019

Abstract
Immunopathologies caused by Leishmania cause severe human morbidity and mortality. This protozoan parasite invades and persists inside host cells, resulting in disease development. Leishmania modifies the epigenomic status of the host cells, thus probably averting the host cell defense mechanism. To accomplish this, Leishmania may change the host cell chromatin structure. However, the mechanism by which the parasite changes the host cell chromatin has not been characterized. In the present study, we found that ectopically produced Leishmania histone H3, LmaH3, which mimics the secreted LmaH3 in infected cells, is incorporated into chromatin in human cells. A crystallographic analysis revealed that LmaH3 forms nucleosomes with human histones H2A, H2B and H4. We found that LmaH3 was less stably incorporated into the nucleosome, as compared to human H3.1. Consistently, we observed that LmaH3–H4 association was remarkably weakened. Mutational analyses revealed that the specific LmaH3 Trp35, Gln57 and Met98 residues, which correspond to the H3.1 Tyr41, Arg63 and Phe104 residues, might be responsible for the instability of the LmaH3 nucleosome. Nucleosomes containing LmaH3 resisted the Mg2+-mediated compaction of the chromatin fiber. These distinct physical characteristics of LmaH3 support the possibility that histones secreted by parasites during infection may modulate the host chromatin structure.
Evolution-guided engineering of small-molecule biosensors
Authors: Snoek Tim , Chaberski Evan K , Ambri Francesca , Kol Stefan , Bjørn Sara P , Pang Bo , Barajas Jesus F , Welner Ditte H , Jensen Michael K , Keasling Jay D 
Published: October 2019

Abstract
Allosteric transcription factors (aTFs) have proven widely applicable for biotechnology and synthetic biology as ligand-specific biosensors enabling real-time monitoring, selection and regulation of cellular metabolism. However, both the biosensor specificity and the correlation between ligand concentration and biosensor output signal, also known as the transfer function, often needs to be optimized before meeting application needs. Here, we present a versatile and high-throughput method to evolve prokaryotic aTF specificity and transfer functions in a eukaryote chassis, namely baker's yeast Saccharomyces cerevisiae. From a single round of mutagenesis of the effector-binding domain (EBD) coupled with various toggled selection regimes, we robustly select aTF variants of the cis,cis-muconic acid-inducible transcription factor BenM evolved for change in ligand specificity, increased dynamic output range, shifts in operational range, and a complete inversion-of-function from activation to repression. Importantly, by targeting only the EBD, the evolved biosensors display DNA-binding affinities similar to BenM, and are functional when ported back into a prokaryotic chassis. The developed platform technology thus leverages aTF evolvability for the development of new host-agnostic biosensors with user-defined small-molecule specificities and transfer functions.
Localization of Drosophila CENP-A to non-centromeric sites depends on the NuRD complex
Authors: Demirdizen Engin , Spiller-Becker Matthias , Förtsch Arion , Wilhelm Alexander , Corless Samuel , Bade Debora , Bergner Andrea , Hessling Bernd , Erhardt Sylvia 
Published: October 2019

AbstractCentromere function requires the presence of the histone H3 variant CENP-A in most eukaryotes. The precise localization and protein amount of CENP-A are crucial for correct chromosome segregation, and misregulation can lead to aneuploidy. To characterize the loading of CENP-A to non-centromeric chromatin, we utilized different truncation- and localization-deficient CENP-A mutant constructs in Drosophila melanogaster cultured cells, and show that the N-terminus of Drosophila melanogaster CENP-A is required for nuclear localization and protein stability, and that CENP-A associated proteins, rather than CENP-A itself, determine its localization. Co-expression of mutant CENP-A with its loading factor CAL1 leads to exclusive centromere loading of CENP-A whereas co-expression with the histone-binding protein RbAp48 leads to exclusive non-centromeric CENP-A incorporation. Mass spectrometry analysis of non-centromeric CENP-A interacting partners identified the RbAp48-containing NuRD chromatin remodeling complex. Further analysis confirmed that NuRD is required for ectopic CENP-A incorporation, and RbAp48 and MTA1-like subunits of NuRD together with the N-terminal tail of CENP-A mediate the interaction. In summary, our data show that Drosophila CENP-A has no intrinsic specificity for centromeric chromatin and utilizes separate loading mechanisms for its incorporation into centromeric and ectopic sites. This suggests that the specific association and availability of CENP-A interacting factors are the major determinants of CENP-A loading specificity.
Elusive Impartiality
Authors: Pittard John 
Published: October 2019

Abstract
This chapter considers what implications a commitment to rigorous epistemic impartiality has for one’s religious beliefs and credences. It is argued that epistemic impartiality in the religious domain proves to be elusive for two reasons. First, a commitment to epistemic impartiality appears to be self-undermining, and arguably the best response to this self-undermining problem is incompatible with an unqualified commitment to epistemic impartiality in the religious domain. Second, the most plausible methods for identifying an impartial doxastic stance on religious matters require that one settle various questions that are themselves implicated in religious controversy. In particular, one must take a stand on questions concerning rational bias on religious matters, and these questions cannot be settled in a religiously impartial way. In light of this problem, it is far from obvious that religious skepticism is the attitude that best comports with a commitment to epistemic impartiality.
Mimicry as Rivalry
Authors: Belvadi Anilkumar 
Published: October 2019

Abstract
Chapter 6 is a detailed study of Sunday schools as sites of pedagogical practice in India. Guided by “tact” as a principle of conducting their work, Anglo-American Protestant missionaries, in order to secure and retain enrollment in their Sunday schools, jettisoned or substantially modified a number of clearly held Christian principles. They denounced racism, but closely allied themselves with a colonial militarist power that would not brook racial integration, and correspondingly instituted racial segregation in their Sunday schools. A second manifestation of “tact” was their borrowing of a number of schooling and cultural practices of the “idolatrous” Hindus, resulting in a type of Christian institution that began to look casteized even to Christian observers. Highly Sanskritized Sunday school hymns, Hindu religious musical forms, visual arts, and festive observances were made a part of the Christian Sunday school. All this benefited a number of Christian converts from the “lower castes” of Hindu society, inasmuch as they were able to acquire those symbolic resources traditionally denied them by the “upper castes.” But at the same time, the mimicking of such practices by Christian institutions underscored the prestige that certain Hindu traditions enjoyed. Also, and worryingly for missionaries, the “upper castes” began to organize their own Sunday schools without Christian doctrine, but mimicking elements of Anglicized, Christian Sunday schools that had seemed attractive to them to begin with. Further, to counter competition, missionaries expanded the Sunday school curriculum, but in the process mimicked secular institutions and undermined the evangelical thrust of their program. And finally, to solicit funds back home, missionaries sensationalized accounts of their work in India. Instrumental reasoning pervaded all aspects of their management of Sunday schools.
From Lists to Literature
Authors: Schniedewind William M. 
Published: October 2019

Abstract
Spelling and vocabulary were taught though lexical lists. Fragments of at least two, perhaps three, of these lists are present at Kuntillet ʿAjrud. The standardization of spelling reflects the growth and centralization in government and bureaucracy, which were the primary consumers of writing. Fragments of cuneiform lists found in Israel dating to the Late Bronze Age give direct evidence of a vector of transmission for the cuneiform lexical tradition into early Israel. In fact, they provide a key for interpreting the Gezer Calendar as well as biblical texts. Lexical lists taught standardized spelling, but they also classified knowledge. In everyday commerce, lists were critical to administration and bureaucracy. In biblical literature, lists were adapted in a number of ways and incorporated into biblical literature.
Proverbial Sayings
Authors: Schniedewind William M. 
Published: October 2019

Abstract
Scribes learned many sayings, wisdom sayings and proverbial sayings, that could be used for and adapted to a variety of contexts. From the comparative cuneiform evidence in “lentil” texts, proverbs were copied and memorized individually. To be sure, there are also collections of proverbs, but the individual sayings were their primary context. We then have evidence that these individual sayings were employed in letters, narratives, and liturgy. All these literary contexts provide parallels for the one example of this is a reciprocity statement used at Kuntillet ʿAjrud. This one example finds parallels in Ugarit, the Amarna letters, Aramaic inscriptions, and even Papyrus Amherst 63. This variety is also paralleled in biblical literature where the reciprocality formula appears in both biblical narratives and liturgy. More generally, the concept of individual sayings (as opposed to larger collections) that were memorized and used by scribes in different contexts is also evident in biblical literature.
Creating Wealth
Authors: Polèse Mario 
Published: October 2019

Abstract
This chapter returns to the question at the heart of economics as a social science since Adam Smith and his seminal work on the origins of wealth. Why are some nations rich and others poor? The focus here is on the role of cities, on “agglomeration” in the jargon of economics. We find little evidence in support of Jane Jacobs’s thesis that agglomeration is sufficient to independently trigger economic growth. After explaining the concept of “agglomeration economies,” the gains from spatial concentration, various obstacles to their realization are examined: deficient urban transport; insecurity; arbitrary governance; informality; and so on. Their full realization requires solid institutions, which all too often are lacking. Starting with the origins of the Industrial Revolution, we conclude that the impact of urbanization (greater agglomeration) is essentially allocational, shifting labor to more productive endeavors. The roots of technological innovation, which is at the heart of economic progress, run much deeper, taking us back to national cultures and institutions.
Diverging Neighbors
Authors: Polèse Mario 
Published: October 2019

Abstract
This chapter compares Buffalo, New York, and Toronto, Ontario, two urban areas located on the Great Lakes with similar populations (one million) in 1950. Toronto has since passed the six million mark, while Buffalo seems trapped in a seemingly irreversible cycle of economic decline. The diverging destiny of the two cities has many roots (e.g., the St. Lawrence Seaway, the collapse of Big Steel) but invariably sends us back to the different political cultures of the United States and Canada. The government of Ontario stepped in early in the urbanization process to impose a model of metropolitan governance on the Toronto region, with the explicit aim of deterring the emergence of deep social divides, specifically between city and suburb, and ensuring the maintenance of a strong central core. The state of New York did no such thing in Buffalo, for which Buffalo continues to pay a price.
Speech on Campus
Authors: Baer Ulrich 
Published: October 2019

Abstract
How can we find rules that respect the university’s commitment to academic freedom while creating an environment where everyone can contribute to teaching and research in truly equal ways? A first step is to recognize that the campus controversies are not about offended feelings but about truth and equality in our democracy. A second step is not to overplay these controversies but realize the speakers are turned down routinely who lack qualifications or standing. The line can be drawn at speech that denies the humanity of some groups because it is non-scientific and advocates illegal actions under our nation’s laws.
Introduction
Authors: Katz Mark 
Published: October 2019

Abstract
The introduction explains why the partnership between hip hop diplomacy is unlikely and risky but also potentially productive. Hip hop is a powerful platform for US cultural diplomacy because it is globally popular, widely accessible, readily combined with a variety of artistic styles and practices, and immediately and positively associated with the United States. Hip hop diplomacy can serve US foreign policy objectives by enhancing the image of the United States and promoting US interests abroad. The introduction concludes with a reflection on the author’s identity as a white man and considers its implications for working in hip hop, a genre and culture that arose out of African American communities.
Non-Opioid Alternatives to Managing Chronic Pain
Authors: Singh Vanila , Katonak Rachel 
Published: October 2019

Abstract
While public health practitioners generally focus on the primary prevention of illness and disease by developing programs and policies that promote health and well-being, an understanding of chronic pain and its treatment is important for public health professionals working to address the opioid crisis. There are unintended consequences of well-intentioned policies that may restrict prescribing behavior or otherwise interrupt or change access to opioids. For example, one consequence of expanding state prescription drug monitoring programs has been concern by providers that “legitimate” pain patients may be subjected to increased suspicion and stigma and not able to obtain needed medications. State and federal efforts to shut down “pill mills” are vital to addressing diversion and criminal behavior, but pain patients who are also seen in these clinics may have an interruption in their treatment or access to medication. Understanding chronic pain treatment and non-opioid alternatives to pain management is an important part of developing sound public health policies to prevent opioid use disorder and its sequelae. This chapter presents these alternatives and the evidence base for each.
Redeeming Eden: A Priestly Dialogue in Genesis–Leviticus
Authors: Brett Mark G. 
Published: October 2019

Abstract
The Priestly compositions in Genesis–Leviticus turned away from the national vision, emphasizing wider filial connections with other kinship groups and, in effect, proposed that Eden could be redeemed as a sacred space. Yhwh is certainly the God of Israel, but the ancestors never knew that divine name. Combining an interpretation of Abraham as a non-Yahwist, a distinctive exodus account, cultic laws, and the social ethics of the Holiness Code, this paradigm provided hope for a renewed divine communion within which Yhwh may once again “walk about” among the people (Lev 26:11–12), even if the same Creator is known as Elohim or El by other nations. Instead of emerging from a royal court, the Priestly laws were promulgated by Moses in the desert, without the benefit of royal power or territory, and there is no conquest legislation in this material.
Heresies, Forgeries, Novelties
Authors: Klawans Jonathan 
Published: October 2019

Abstract
The fundamental goal of this chapter is to present the dynamic to be explored in this book, relating heresy, forgery, and novelty. In its first sections, this chapter probes the contestability of religious novelty and the roles that condemnations of novelty played in Christian heresiological discourse. Then the chapter examines and also chips away at the various perspectives and biases that have prevented exploring the Jewish origins of Christian heresiology. The chapter next considers the extent to which second temple period Jewish writers went to conceal innovations, often by deceitfully disguising recent writings as much more ancient ones. The threads tie together with a restatement of the key dynamic at play: Heresy involves the condemnation of novelty; forgery entails the feigning of antiquity. Novelty ensues with the valorization of innovation, which can harden into supersessionism—the inverse of heresy.
In the Shadow of Trump
Authors: Boatright Robert G. , Sperling Valerie 
Published: October 2019

Abstract
This chapter explores the impact of presidential primary campaigns on House and Senate primary races, looking at the relationship between presidential and nonpresidential primaries, and evaluating the effect Donald Trump had on candidate emergence and strategy. Few candidates wished to associate themselves with Trump, yet the Republican presidential primary so dominated media and public attention that Republican primary candidates who might have flourished in any other year, such as conservative, Tea Party–style candidates, were unable to garner attention or raise as much money as they might otherwise have. Moreover, even in the handful of primary races featuring so-called “mini-Trumps,” there were few in which attention to gender issues or misogynist rhetoric played a role. The chapter documents these findings by comparing 2016 to prior election years with regard to primary competition, turnout, and spending, and examining congressional primaries in which Republican candidates were overtly compared to or endorsed Donald Trump.
Being a Good Samaritan Requires You to Vote
Authors: Maskivker Julia 
Published: October 2019

Abstract
This chapter expands on the notion of a Samaritan duty of justice to aid society. It dispels the possible objection that only physical emergencies can count as the object of Samaritan assistance, and it explains why a natural duty of justice to help others can be discharged via elections—as elections are the only method to install governments, which affect the quality of governance nontrivially. The chapter proceeds to explain why justice and the erection of governments are uniquely related, which makes voting morally special, and morally mandated if not unduly burdensome for the citizen. The chapter elaborates on the idea that the duty to aid society via the vote is a duty to engage in cooperation with others, by participating in elections. Voting is, then, an instance of collectively rational Samaritanism.
Is Proportionality in Punishment Possible, and Achievable?
Authors: Tonry Michael 
Published: October 2019

Abstract
Proportionality theory’s influence is waning. It is beset by challenges. Some, such as difficulties in scaling crime seriousness and punishment severity, and linking them, are primarily analytical and of interest mostly to theorists. Others, such as trade-offs between proportionality and crime prevention, relate to real world applications. The big question is whether the challenges are epiphenomenal and portend displacement of retribution as the most intellectually influential normative frame of reference for thinking about punishment. My best guess is yes. The lesser question is whether proportionality theory can provide satisfactory answers to core questions about crime seriousness, punishment severity, and links between them. Alas, it cannot. Proportionality theory does, however, support two injunctions with which most people, citizens, scholars, and professionals alike, would say they agree. First, no one should be punished more severely than he or she deserves. Second, all else being equal, people who commit more serious crimes should be punished more severely than people who commit less serious ones, and vice versa. Converting that principled agreement into real-world policies and practices is not easy. The post-Enlightenment values of fairness, equality, justice, and parsimony, however, that underlie proportionality theory, are widely accepted and are likely to remain influential even if punishment paradigms once again shift. Proportionality theory is likely to be eclipsed but not to disappear.
Outposts of the Law: The Frontier and the Civil-Law Fringe
Authors: Friedman Lawrence M. 
Published: October 2019

Abstract
This chapter discusses the history of American frontier law. The new nation faced the problem of how to deal with the western lands. Some of the states had huge, vague, and vast claims to chunks of western land, stretching out far beyond the pale of settlement; other states did not. The Ordinance of 1787 dealt with the issue of governance and the future of the western lands. It set basic law for a huge area of forest and plain that became the states of Ohio, Indiana, Illinois, Michigan, and Wisconsin. The Ordinance of 1790 extended the influence of the Northwest Ordinance into what became the state of Tennessee.
Blood and Gold: Some Main Themes in the Law in the Last Half of the Nineteenth Century
Authors: Friedman Lawrence M. 
Published: October 2019

Abstract
This chapter discusses changes in American law during the second half of the nineteenth century, covering organic law, state constitutions, and the West. The last half of the nineteenth century was crowded with events and evolutions, the most dramatic of which was the great Civil War. In many ways, wars fundamentally disrupt the operation of the legal system. The Civil War was unusually violent, and it did unusual violence to the ordinary course of justice. It was also a constitutional crisis: the Confederate states had renounced the union, declared themselves independent, and drafted their own constitution. But the war was, in a way, only an interlude. Underneath and around it and before it and after it, vast processes were changing society in fundamental ways. Changes in American law, between 1850 and 1900, were little short of revolutionary. In many fields, the law or the practice looked very different at the end of this period, compared to the beginning.