bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-Empiricist Naturalism
Authors: Kuusela Oskari 
Published: February 2019

Abstract
This chapter elucidates Wittgenstein’s later non-empiricist naturalism. This novel kind of naturalism makes it possible to recognize the relevance of natural historical considerations concerning humans and language use for logic, while retaining the traditional conception of logic as a non-empirical discipline. The justification and generality of the employment of natural history based logical models is explained, and distinguished from the justification and generality of empirical statements. The different ways in which Wittgenstein makes use of natural historical considerations in logical or grammatical clarification are discussed, and the difference of Wittgenstein’s approach from broadly Kantian philosophical anthropology clarified. The correctness or truth of logical accounts is explained and a method of multidimensional logical descriptions introduced.
Bureaucratic Geographies of the State
Authors: Ross Anna 
Published: February 2019

Abstract
This chapter explores the nature of the Prussian state on the eve of 1848 and the administrative challenges it posed to officials. This includes an overview of Prussia’s territories and administrative structures. Within this bureaucratic geography, the Prussian Central Statistical Office comes to the fore as an institution that would be of great importance to state-building in the post-revolutionary decade. The chapter examines the activities undertaken by the director of this office and the bureaucrats who worked with him. It also establishes their role in facilitating an exchange of government materials with other states in the 1850s. The Prussian Ministry of State would rely on many of these statistical materials in exacting reforms, as will be indicated in the chapters that follow.
Crime and Punishment
Authors: Ross Anna 
Published: February 2019

Abstract
This chapter sets out to chart the reforms to criminal and penal affairs undertaken in Prussia in the 1850s. Both Manteuffel and the Justice Minister Ludwig Simons believed that revolutionary unrest could be countered by completing unattended work from the Vormärz era pertaining to criminal justice. But realizing a reform agenda was no easy task. On the political extremes it elicited opposition, especially in the symbolically charged terrain of substantive criminal law. To avoid such complications, both ministers worked hard to shift debate to the realm of procedural reform in the 1850s, creating a surprising and largely integrating space for state-building. In doing so, the post-revolutionary ministries pursued reform without slipping into parochialism. That is, they did not permanently close avenues for the creation of a set of unified national codes to regulate criminal and penal affairs.
Public Opinion and Press Management
Authors: Ross Anna 
Published: February 2019

Abstract
This chapter explores the adoption of a system of press management by the Brandenburg–Manteuffel and Manteuffel Ministries of State in the 1850s. Press management included the institutionalization of a press office, which was responsible for the production of daily reports on the state of the news. It also included the production of official newspapers, circulation of government friendly articles, and granting of subventions to non-oppositional papers. Yet it soon became clear that the office could not shape public debate, as had been hoped. The disappointing results of official press measures in Prussia and other German states meant that governments had increasingly to show themselves willing to open up the workings of the state to greater scrutiny through a circulation of state materials. This would shift the relationship between the state and public sphere, especially after the unification of the German states.
Necessity, Between Tragedy and Predestination
Authors: Leo Russ 
Published: February 2019

Abstract
Chapter 4 examines how Daniel Heinsius’ path-breaking treatise De Tragoediae Constitutione (1611) belongs not only to the Arminian Controversy but also to larger debates concerning providence and predestination in early modernity. Theologies of election and reprobation necessarily traffic in mystery, taxing the limits of the human understanding. Tragedy, however, enables readers to comprehend actions in terms of natural cause and effect; in this sense Heinsius renders divinity intelligible, even tentatively, when he develops Aristotle’s comments concerning necessity and probability (or verisimilitude) as well as his strictures regarding devices and dei ex machinis. In his tragedy Herodes Infanticida, moreover, Heinsius reframes Scripture as a tragedy, eschewing miracles and theological explanations, demonstrating instead how this key evangelical episode—Herod’s massacre of the innocents—is an all-too-human story of fear, power, ignorance, and interpretation.
The Beginnings of the Cult of Relics
Authors: Wiśniewski Robert 
Published: February 2019

Abstract
Christians always admired and venerated martyrs who died for their faith, but for a long time thought that the bodies of martyrs should remain undisturbed in their graves. Initially, the Christian attitude toward the bones of the dead, whether a saint’s or not, was that of respectful distance. This book tells how, in the mid-fourth century, this attitude started to change, swiftly and dramatically. The first chapters show the rise of new beliefs. They study how, when, and why Christians began to believe in the power of relics, first, over demons, then over physical diseases and enemies; how they sought to reveal hidden knowledge at the tombs of saints and why they buried the dead close to them. An essential element of this new belief was a strong conviction that the power of relics was transferred in a physical way and so subsequent chapters study relics as material objects. The book seeks to show what the contact with relics looked like and how close it was. Did people touch, kiss, or look at the very bones, or just at reliquaries which contained them? When did the custom of dividing relics appear? Finally, the book deals with discussions and polemics concerning relics and tries to find out how strong was the opposition which this new phenomenon had to face, both within and outside Christianity on the way to relics becoming an essential element of medieval religiosity.
Discussions and Theology
Authors: Wiśniewski Robert 
Published: February 2019

Abstract
This chapter deals with polemics about the cult of relics. It studies pagan, Jewish, and Christian attitudes, trying to answer the question of how strong the hostility toward the new phenomenon was and discussing its sources (whether ritual pollution, disgust, an association with magic, or lack of a biblical model). It also deals with the doctrinal implications of the cult of relics, such us the problem of the relation between the soul and the body after death, and describes attempts at creating a theology of relics. It studies more closely the debate on the cult of relics which was under way in the West at the turn of the fifth century and involved a group of promoters of the new religiosity to which Victricius of Rouen, Jerome of Stridon, Paulinus of Nola, and Augustine of Hippo belonged.
Conclusions
Authors: Wiśniewski Robert 
Published: February 2019

Abstract
This part of the book summarizes the findings presented in the preceding chapters and in particular traces the chronological development of the cult of relics. It also shows this phenomenon against a wide background of the new Christian religiosity which started to emerge in the Mediterranean in the fourth century and which profoundly changed Christian attitudes to space and time and the material world. The cult of relics was an element of this new religiosity, but it can be fully understood only when studied together with its other aspects, such as the idea of the Holy Land and the practice of pilgrimages, the rise of monasticism and monastic holiness, the development of the Christian calendar, and the habit of feasting.
Dietary Ingredients Requiring Further Research Before Evidence-Based Recommendations Can Be Made for Their Use as an Approach to Mitigating Pain
Authors: Crawford Cindy , Boyd Courtney , Berry Kevin , Deuster Patricia ,   HERB Working Group
Published: February 2019

Abstract

Objective
Approximately 55–76% of Service members use dietary supplements for various reasons; although such use has become popular, decisions are often driven by information that is not evidence-based. This work evaluates whether current research on dietary ingredients for chronic musculoskeletal pain provides sufficient evidence to inform decisions for practice and self-care, specifically for Special Operations Forces personnel.

Methods
A steering committee convened to develop research questions and factors required for decision-making. Key databases were searched through August 2016. Eligible systematic reviews and randomized controlled trials were assessed for methodological quality. Meta-analysis was applied where feasible. Grading of Recommendations, Assessment, Development and Evaluation was used to determine confidence in the effect estimates. The committee used a decision table to make evidence-informed judgments across decision-making factors and recommendations for practice and self-care use.

Results
Nineteen dietary ingredients were assessed. No recommendations were given for boswellia, ginger, rose hip, or s-adenosyl-L-methionine (SAMe); specifically, although ginger can be obtained via food, no recommendation is provided for use as a supplement due to unclear research. Further, there were insufficient strong research on boswellia and SAMe and possible compliance issues (i.e., high number of capsules required daily) associated with rose hip.

Conclusions
No recommendations were made when the evidence was low quality or trade-offs were so closely balanced that any recommendation would be too speculative. Research recommendations are provided to enhance the quality and body of evidence for the most promising ingredients. Clinicians and those with chronic pain can rely on evidence-based recommendations to inform their decisions.
“Self-inactivating” rabies viruses are susceptible to loss of their intended attenuating modification
Authors: Jin Lei , Matsuyama Makoto , Sullivan Heather A. , Zhu Mulangma , Lavin Thomas K. , Hou YuanYuan , Lea Nicholas E. , Pruner Maxwell T. , Dam Ferdínez María Lucía , Wickersham Ian R. 
Published: February 2019

ABSTRACTMonosynaptic tracing using rabies virus is an important technique in neuroscience, allowing brain- wide labeling of neurons directly presynaptic to a targeted neuronal population. A 2017 article reported development of a noncytotoxic version – a major advance – based on attenuating the rabies virus by addition of a destabilization domain to the C-terminus of a viral protein. However, this modification did not appear to hinder the ability of the virus to spread between neurons. We analyzed two viruses provided by the authors and show here that both were mutants that had lost the intended modification, explaining the paper’s paradoxical results. We then made a virus that actually did have the intended modification in at least the majority of virions and found that it did not spread efficiently under the conditions described in the original paper, namely, without an exogenous protease being expressed in order to remove the destabilization domain. We found that it did spread when the protease was supplied, although this also appeared to result in the deaths of most source cells by three weeks postinjection. We conclude that the new approach is not robust but that it could become a viable technique given further optimization and validation.SIGNIFICANCE STATEMENTRabies virus, which spreads between synaptically-connected neurons, has been one of the primary tools used by neuroscientists to reveal the organization of the brain. A new modification to rabies virus was recently reported to allow the mapping of connected neurons without adverse effects on the cells’ health, unlike earlier versions. Here we show that the conclusions of that study were probably incorrect and based on having used viruses that had lost the intended modification because of mutations. We also show that a rabies virus that does retain the intended modification does not spread efficiently between neurons under the conditions reported previously; however, it does spread between neurons under different conditions, suggesting that the approach may be successful if refined further.
Similar patterns of background mortality across Europe are mostly driven by drought in European beech and a combination of drought and competition in Scots pine
Authors: Archambeau Juliette , Benito Paloma Ruiz , Ratcliffe Sophia , Fréjaville Thibaut , Changenet Alexandre , Muñoz Castañeda Jose M. , Lehtonen Aleksi , Dahlgren Jonas , Zavala Miguel A. , Garzón Marta Benito 
Published: February 2019

ABSTRACTAimBackground tree mortality is a complex demographic process that affects forest structure and long-term dynamics. We aimed to test how drought intensity interacts with interspecific and intraspecific competition (or facilitation) in shaping individual mortality patterns across tree species ranges.LocationEuropean latitudinal gradient (Spain to Finland).Time period1985 – 2014.Major taxa studiedScots pine (Pinus sylvestrisL.) and European beech (Fagus sylvaticaL.).MethodsWe performed logistic regression models based on individual tree mortality recorded in five European National Forest Inventories. We computed the relative importance of climatic drought intensity, basal area of conspecific and heterospecific trees (proxy of indirect intra- and interspecific competition or facilitation) and the effects of their interactions on mortality along the latitudinal gradient of both species range.ResultsIncrease in drought intensity over the study period was associated with higher mortality rates in both species. Drought was the most important driver of beech mortality at almost all latitudes while Scots pine mortality was mainly driven by basal area. High conspecific basal area was associated with high mortality rates in both species while high heterospecific basal area was correlated with mortality rates that were high in Scots pine but low in beech.Main conclusionsBeech mortality was directly affected by drought while Scots pine mortality was indirectly affected by drought through interactions with basal area. Despite their different sensitivity to drought and basal area, the highest predicted mortality rates for both species were at the ecotone between Mediterranean and cool temperate biomes, which can be explained by the combined effect of drought and competition. In the context of global warming, which is expected to be particularly strong in the Mediterranean biome, our results suggest that populations at the southern limit of species ranges may experience increased mortality rates in the near future.BIOSKETCHThe authors’ research is focused on functional trait ecology and global change, with special attention to mortality and demography processes. The authors use modelling multidisciplinary approaches to understand complex processes in ecology on a large geographical scale.
The tortoise strategy as an arbovirus fitness phenotype within the mosquito as revealed by a novel formulation of age-structured vectorial capacity
Authors: Mayton E. Handly , Tramonte A. Ryan , Wearing Helen J. , Christofferson Rebecca C. 
Published: February 2019

AbstractThe transmission dynamics of arboviruses like Zika virus (ZIKV) are most often evaluated by vector competence and the related extrinsic incubation period (EIP), which represent the proportion of vectors that become infectious given exposure and the time it takes for a vector to become infectious given exposure, respectively. Thus, EIP is the temporality of vector competence, and these measures have been used to evaluate the relative fitness of arbovirus systems. However, another temporal process critical to assessing arbovirus transmission dynamics is the age-structure of vector populations, as studies have demonstrated how vector mortality interplays with vector competence and EIP to alter transmission system efficiency. These and other parameters are critical to vectorial capacity (VC), a measure of transmission potential of a vector-pathogen system. However, how these three components – EIP, vector competence, and age – affect VC still needs to be addressed. We first compared experimentally how vector competence/EIP and mosquito age at the time of infection acquisition (Ageacquisition) interacted in an Aedes aegypti-ZIKV model system. We found that Ageacquisition did not alter the vector competence/EIP using traditional analyses, except in the context of mortality. To capture and quantify this age-dependent context, we developed an age-structured vectorial capacity framework (VCage) by experimentally determining daily mortality and probability of biting, as well as vector competence/EIP parameterized as EIPMin and EIPMax. Like previous studies, we found that arbovirus phenotypes leading to outbreaks are not straightforward and may follow a tortoise and the hare (TotH), whereby slow and steady is as or better than fast and furious phenotypes. Understanding the contributions of these age-dependent life traits as well as VCage allows for quantification and visualization of both the magnitude and temporality of transmission dynamics in an age-dependent manner, which reveals this TotH model that should change how compare and rank arbovirus phenotypes, and perhaps even how we identify ‘highly’ or ‘negligibly’ competent vectors.
De novo diploid genome assembly for genome-wide structural variant detection
Authors: Zhang Lu , Zhou Xin , Weng Ziming , Sidow Arend 
Published: February 2019

AbstractStructural variants (SVs) in a personal genome are important but, for all practical purposes, impossible to detect comprehensively by standard short-fragment sequencing. De novo assembly, traditionally used to generate reference genomes, offers an alternative means for variant detection and phasing but has not been applied broadly to human genomes because of fundamental limitations of short-fragment approaches and high cost of long-read technologies. We here show that 10x linked-read sequencing, which has been applied to assemble human diploid genomes into high quality contigs, supports accurate SV detection. We examined variants in six de novo 10x assemblies with diverse experimental parameters from two commonly used human cell lines, NA12878 and NA24385. The assemblies are effective in detecting mid-size SVs, which were discovered by simple pairwise alignment of the assemblies’ contigs to the reference (hg38). Our study also shows that the accuracy of SV breakpoint at base-pair level is high, with a majority (80% for deletion and 70% for insertion) of SVs having precisely correct sizes and breakpoints (<2bp difference). Finally, setting the ancestral state of SV loci by comparing to ape orthologs allows inference of the actual molecular mechanism (insertion or deletion) causing the mutation, which in about half of cases is opposite to that of the reference-based call. Interestingly, we uncover 214 SVs that may have been maintained as polymorphisms in the human lineage since before our divergence from chimp. Overall, we show that de novo assembly of 10x linked-read data can achieve cost-effective SV detection for personal genomes.
DRAFT - Robotic automation of production and the recovery of cell spheroids
Authors: Langer Krzysztof , Jönsson Håkan 
Published: February 2019

AbstractDroplet microfluidics enables high throughput cell processing, analysis and screening by miniaturizing the reaction vessels to nano-or pico-liter water-in oil droplets, but like many other microfluidic formats, droplet microfluidics have not been interfaced with or automated by laboratory robotics. Here we demonstrate automation of droplet microfluidics based on an inexpensive liquid handling robot for the automated production of human scaffold-free cell spheroids, using pipette actuation and interfacing the pipetting tip with a droplet generating microfluidic chip. In this chip we produce highly mono-disperse 290μm droplets with diameter CV of 1.7%. By encapsulating cells in these droplets we produce cell spheroids in droplets and recover them to standard formats at a throughput of 85000 spheroids per microfluidic circuit per hour. The viability of the cells in spheroids remains high after recovery only decreased by 4% starting from 96% after 16 hours incubation in nanoliter droplets. Scaffold-free cell spheroids and 3D tissue constructs recapitulate many aspects of functional human tissue more accurately than 2D or single cell cultures, but assembly methods for spheroids,e.g. hanging drop micro-plates, has had limited throughput. The increased throughput and decreased cost of our method enables spheroid production at the scale needed for lead discovery drug screening and approaches the cost where these micro tissues could be used as building blocks for organ scale regenerative medicine.
Reliable analysis of clinical tumor-only whole exome sequencing data
Authors: Oh Sehyun , Geistlinger Ludwig , Ramos Marcel , Morgan Martin , Waldron Levi , Riester Markus 
Published: February 2019

AbstractBackgroundAllele-specific copy number alteration (CNA) analysis is essential to study the functional impact of single nucleotide variants (SNV) and the process of tumorigenesis. Most commonly used tools in the field rely on high quality genome-wide data with matched normal profiles, limiting their applicability in clinical settings.MethodsWe propose a workflow, based on the open-source PureCN R/Bioconductor package in conjunction with widely used variant-calling and copy number segmentation algorithms, for allele-specific CNA analysis from whole exome sequencing (WES) without matched normals. We use The Cancer Genome Atlas (TCGA) ovarian carcinoma (OV) and lung adenocarcinoma (LUAD) datasets to benchmark its performance against gold standard SNP6 microarray and WES datasets with matched normal samples. Our workflow further classifies SNVs by somatic status and then uses this information to infer somatic mutational signatures and tumor mutational burden (TMB).ResultsApplication of our workflow to tumor-only WES data produces tumor purity and ploidy estimates that are highly concordant with estimates from SNP6 microarray data and matched-normal WES data. The presence of cancer type-specific somatic mutational signatures was inferred with high accuracy. We also demonstrate high concordance of TMB between our tumor-only workflow and matched normal pipelines.ConclusionThe proposed workflow provides, to our knowledge, the only open-source option for comprehensive allele-specific CNA analysis and SNV classification of tumor-only WES with demonstrated high accuracy.
Drosophila p38 MAPK Interacts with BAG-3/starvin to Regulate Age-dependent Protein Homeostasis
Authors: Ryan Sarah M. , Almassey Michael , Burch Amelia M. , Ngo Gia , Martin Julia M. , Myers David , Compton Devin , Barbee Scott , Mortimer Nathan T. , Sanyal Subhabrata , Vrailas-Mortimer Alysia D. 
Published: February 2019

SummaryAs organisms age, they often accumulate protein aggregates that are thought to be toxic, potentially leading to age-related diseases. This accumulation of protein aggregates is partially attributed to a failure to maintain protein homeostasis. A variety of genetic factors have been linked to longevity, but how these factors also contribute to protein homeostasis is not completely understood. In order to understand the relationship between aging and protein aggregation, we tested how a gene that regulates lifespan and age-dependent locomotor behaviors, p38 MAPK (p38Kb), influences protein homeostasis as an organism ages. We find that p38Kb regulates age-dependent protein aggregation through an interaction with the Chaperone-Assisted Selective Autophagy complex. Furthermore, we have identified Lamin as an age-dependent target of p38Kb and the Chaperone-Assisted Selective Autophagy complex.