bluuebunny/crossref_metadata_2025_split huggingface dataset:
Large-scale analysis of human gene expression variability associates highly variable drug targets with lower drug effectiveness and safety
Authors: Simonovsky Eyal , Schuster Ronen , Yeger-Lotem Esti 
Published: January 2019

Abstract

Motivation
The effectiveness of drugs tends to vary between patients. One of the well-known reasons for this phenomenon is genetic polymorphisms in drug target genes among patients. Here, we propose that differences in expression levels of drug target genes across individuals can also contribute to this phenomenon.

Results
To explore this hypothesis, we analyzed the expression variability of protein-coding genes, and particularly drug target genes, across individuals. For this, we developed a novel variability measure, termed local coefficient of variation (LCV), which ranks the expression variability of each gene relative to genes with similar expression levels. Unlike commonly used methods, LCV neutralizes expression levels biases without imposing any distribution over the variation and is robust to data incompleteness. Application of LCV to RNA-sequencing profiles of 19 human tissues and to target genes of 1076 approved drugs revealed that drug target genes were significantly more variable than protein-coding genes. Analysis of 113 drugs with available effectiveness scores showed that drugs targeting highly variable genes tended to be less effective in the population. Furthermore, comparison of approved drugs to drugs that were withdrawn from the market showed that withdrawn drugs targeted significantly more variable genes than approved drugs. Last, upon analyzing gender differences we found that the variability of drug target genes was similar between men and women. Altogether, our results suggest that expression variability of drug target genes could contribute to the variable responsiveness and effectiveness of drugs, and is worth considering during drug treatment and development.

Availability and implementation
LCV is available as a python script in GitHub (https://github.com/eyalsim/LCV).

Supplementary information
Supplementary data are available at Bioinformatics online.
KORP: knowledge-based 6D potential for fast protein and loop modeling
Authors: López-Blanco José Ramón , Chacón Pablo 
Published: January 2019

Abstract

Motivation
Knowledge-based statistical potentials constitute a simpler and easier alternative to physics-based potentials in many applications, including folding, docking and protein modeling. Here, to improve the effectiveness of the current approximations, we attempt to capture the six-dimensional nature of residue–residue interactions from known protein structures using a simple backbone-based representation.

Results
We have developed KORP, a knowledge-based pairwise potential for proteins that depends on the relative position and orientation between residues. Using a minimalist representation of only three backbone atoms per residue, KORP utilizes a six-dimensional joint probability distribution to outperform state-of-the-art statistical potentials for native structure recognition and best model selection in recent critical assessment of protein structure prediction and loop-modeling benchmarks. Compared with the existing methods, our side-chain independent potential has a lower complexity and better efficiency. The superior accuracy and robustness of KORP represent a promising advance for protein modeling and refinement applications that require a fast but highly discriminative energy function.

Availability and implementation
http://chaconlab.org/modeling/korp.

Supplementary information
Supplementary data are available at Bioinformatics online.
Public Procurement versus Laissez-Faire: Evidence from Household Waste Collection
Authors: Meriläinen Jaakko , Tukiainen Janne 
Published: January 2019

AbstractWe document that switching from laissez-faire production to public procurement in residential waste collection in Finland reduces the number of firms active in the local market, but induces a statistically significant and large decrease in unit prices on average. While public procurement, thus, seems to be desirable from the citizens’ perspective, not all municipalities adopt public procurement. We provide descriptive evidence that municipal council composition is associated with the chosen regime. This suggests that local politics may be one obstacle for the efficient provision of local public goods. (JEL codes: C23, D72, H76, L13, and L85).
The renoprotective effect of concomitant fosfomycin in the treatment of pulmonary exacerbations in cystic fibrosis
Authors: Al-Aloul Mohamed , Nazareth Dilip , Walshaw Martin 
Published: January 2019

AbstractBackgroundFosfomycin, effective in Cystic Fibrosis (CF), competes with aminoglycosides at renal binding sites and may therefore afford a renoprotective effect when used in combination therapy. We explored this by using markers of acute renal tubular damage [N-acetyl-β-d-glucose-aminidase (NAG), alanine amino-peptidase (AAP) and β2-microglobulin].MethodsUsing a prospective randomized crossover trial design, at an acute pulmonary exacerbation, 18 adult CF patients received either 14 days of intravenous (IV) tobramycin or IV tobramycin and IV fosfomycin, both in combination with a second IV antibiotic (colomycin).ResultsUrinary NAG (P = 0.003) and AAP (P = 0.03) following treatment with concomitant fosfomycin were lower than those after treatment with tobramycin and colomycin alone. Fosfomycin attenuated the total 24-h urinary protein leak (P = 0.0001). The 14-day improvements in all surrogate markers of exacerbation resolution (FEV1% predicted, FVC, white cell count and C-reactive protein) were similar for both treatment regimens.ConclusionThe addition of fosfomycin reduces acute renal injury caused by IV aminoglycoside therapy in CF pulmonary exacerbations.
Comparative analysis of life history traits and trends of abundance in coral reefs of the orange-spotted grouper (Epinephelus coioides) from two regions of the Arabian Gulf
Authors: Lin Yu-Jia , Grandcourt Edwin M , Rabaoui Lotfi , Maneja Rommel H , Qurban Mohammad A , Al-Abdulkader Khaled , Roa-Ureta Rubén H 
Published: January 2019

AbstractThe orange-spotted grouper Epinephelus coioides is one of the most important commercially exploited fish species in the Arabian Gulf. Studies to establish the basic biological knowledge necessary for sustainable exploitation are few and of limited spatial extent. We carry out a comparative analysis of life history traits of this sequential hermaphrodite and of trends of abundance in coral reefs, northern vs. southern Gulf. We found remarkable differences in sex proportion by length and age, rates of somatic growth, size at maturity and production of gonadic biomass, and no differences in the age composition, mode of growth, timing and duration of spawning, natural mortality rate, and trends of abundance. In the northern Gulf, the reproductive tactics could be diandric protogyny or protandric because males disappear at higher size and later age. In the southern Gulf, the strategy is protogyny, with full predominance of females in early life and full predominance of males in late life. In the northern Gulf, the orange-spotted grouper could exhibit bidirectional sex change. We suggest that fisheries policies should be versatile, consisting of regional-wide as well as local management measures, to account for local differences and regional-wide commonalities in life history traits and trends of abundance.
A probabilistic disease progression modeling approach and its application to integrated Huntington’s disease observational data
Authors: Sun Zhaonan , Ghosh Soumya , Li Ying , Cheng Yu , Mohan Amrita , Sampaio Cristina , Hu Jianying 
Published: January 2019

AbstractObjectiveChronic diseases often have long durations with slow, nonlinear progression and complex, and multifaceted manifestation. Modeling the progression of chronic diseases based on observational studies is challenging. We developed a framework to address these challenges by building probabilistic disease progression models to enable better understanding of chronic diseases and provide insights that could lead to better disease management.Materials and MethodsWe developed a framework to build probabilistic disease progression models using observational medical data. The framework consists of two steps. The first step determines the number of disease states. The second step builds a probabilistic disease progression model with the determined number of states. The model discovers typical states along the trajectory of the target disease, learns the characteristics of these states, and transition probabilities between the states. We applied the framework to an integrated observational HD dataset curated from four recent observational HD studies.ResultsThe resulting HD progression model identified nine disease states. Compared to state-of-art HD staging system, the model 1) covers wider range of HD progression; 2) is able to quantitatively describe complex changes around the time of clinical diagnosis; 3) discovers multiple potential HD progression pathways; and 4) reveals expected time durations of the identified states.Discussion and ConclusionThe proposed framework addresses practical challenges in observational data and can help enhance the understanding of progression of chronic diseases. The framework could be applied to other chronic diseases with the help of clinical knowledge.
Social Networks and Mobility in Time and Space: Integration Processes of Burmese Karen Resettled Refugees in Sweden
Authors: Suter Brigitte 
Published: January 2019

AbstractAlthough there are exceptions, refugees from protracted refugee situations generally experience an overall slower integration process into the new country than other refugees and immigrants. Often the circumstances in the refugee camps, including lacking education and social networks, are used to explain this. This article looks at the post-resettlement integration process of Burmese Karen refugees in Sweden through a capital approach. Consequently, the analysis is concerned with the accumulation of resources—such as social networks—both in the pre- and post-resettlement contexts. Mobility is acknowledged as a decisive factor in this process and, as such, mobility practices from both before and after resettlement are highlighted to better understand the refugees’ social, cultural and economic embeddedness. As this article argues, social and cultural capital acquired before resettlement is of crucial importance to create social networks after resettlement and hence to the overall integration process in Sweden.
Experimental Candida albicans osteomyelitis: Microbiologic, antigenic, histologic, and 18FDG-PET-CT imaging characteristics in a newly established rabbit model
Authors: Gamaletsou Maria N , Meletiadis Joseph , Chatziioannou Sofia , Panayiotides Ioannis G , Agadakos Euthimios , Katsimpoulas Michalis , Kostomitsopoulos Nikolaos , Petraitis Vidmantas , Walsh Thomas J , Sipsas Nikolaos V 
Published: January 2019

Abstract
Candida osteomyelitis is a debilitating disease that is difficult to diagnose and treat. As there are no animal models or prospective studies for this uncommon infection, little is known about the pathogenesis, diagnosis, or treatment. We therefore sought to establish an animal model for the study of the pathophysiology, diagnostic modalities, and therapeutic interventions of Candida osteomyelitis. We developed a modified version of the Norden rabbit model of tibial osteomyelitis, in which the right tibia was inoculated intraoperatively with different inocula of C. albicans or normal saline as control. On days 7, 14, and 21 after inoculation, the animals underwent bone radiography, 18-fluoro-2-deoxy-D-glucose positron emission tomography combined with computed tomography (PET/CT) scan, and blood sampling for blood cultures, blood counts, erythrocyte sedimentation rate, and Candida mannan antigen serum levels. On day 21, animals were euthanized, and infected tibias harvested for culture and histology. Among eight evaluable animals inoculated with 1 × 106 to 1 × 107 cfu, histology and bone cultures established the presence of Candida osteomyelitis in seven, with a host response of neutrophils, mononuclear cells, multinucleate giant cells, fibrosis, and necrosis. Infected animals demonstrated radiological signs of osteomyelitis with significantly increased tracer uptake in 18FDG-PET/CT scans (P < .01) and elevated serum mannan levels (P < .01). All blood cultures were negative. Indices of inflammation were only slightly increased. In conclusion, we report successful establishment of a new animal model of Candida albicans osteomyelitis that may be applicable to advancing our understanding of the pathophysiology, diagnostic modalities, and treatment of this debilitating infection.
Aging, Gender, and the Body
Authors: Hurd Laura 
Published: January 2019

AbstractIn this chapter, the author considers some of the theoretical and methodological conundrums that she encountered in her qualitative research that has focused on later life experiences of the aging body as a site of inequality. Western culture is replete with deeply entrenched ageist stereotypes, which position old bodies as inherently asexual, dependent, frail, obsolete, senile, unproductive, and undesirable. Negative cultural constructions of old bodies are further reflected in and buttressed by masculinity and femininity ideals as well as societal assumptions concerning personal responsibility for health. Collectively, these cultural norms shape research in powerful ways as they lead to the avoidance of certain topics, taken-for-granted assumptions that are difficult to elicit or interrogate, and complex power dynamics between researchers and study participants. Reflecting on the intricacies of researching later life body image and embodiment, I offer some suggestions about how the challenges might be reframed as opportunities.
Ellipsis In Natural Language
Authors: van Craenenbroeck Jeroen , Temmerman Tanja 
Published: January 2019

AbstractThis chapter introduces the general topic of the handbook: the linguistic study of elliptical phenomena in natural language. In addition, it outlines the general structure of the handbook, with a subdivision into four parts (the theory of ellipsis; ellipsis as a diagnostic tool; the taxonomy of elliptical constructions; case studies exploring the elliptical inventory of a single language), and explains the philosophy behind and rationale for this structure. Finally, the chapter also highlights (a selection of) the main results and generalizations that emerge from contributions to the handbook, and briefly reflects on the future of linguistic research into ellipsis.
Ellipsis and Prosody
Authors: Winkler Susanne 
Published: January 2019

AbstractThis chapter investigates the relation between ellipsis and prosody. Prosody is most frequently described as “the organizational structure of speech” (Beckman 1996). It has been defined in terms of three independent factors of the phonological representation: “intonation, phrasal rhythmic patterning and prosodic phrasing” (Selkirk 1995: 550). Prosody plays an important role in the interpretation of elliptical utterances and bridges the gap between what is overtly expressed and what is understood. There are three specific research areas where prosody has been claimed to be relevant: first, prosody-related licensing of ellipsis; second, prosody-related conditions of recoverability of deletion; third, prosodic effects with respect to the question of whether there is structure in the ellipsis site. In this area, research has focused on prosodic conditions on extraction and locality. This chapter is structured accordingly. It first summarizes the prosodic system of English and then reviews the research on how prosody bears on the central issues of the theory of ellipsis (licensing, recoverability, structure in the ellipsis site). The discussion shows that the interaction of prosody and the absence of sound contributes to the understanding of the theories of sound–meaning correspondence.
Nominal Ellipsis
Authors: Saab Andrés 
Published: January 2019

AbstractThis chapter centers on nominal ellipsis phenomena from a broad perspective. First, several diagnostics are provided in order to make a basic distinction between empty nouns and true instances of nominal ellipses. One set of such diagnostics is related to uniformity considerations; i.e. the parallelism between elliptical and non-elliptical nominal phrases with respect to thematic assignment, matching effects, and extraction. Another set has to do with the specific conditions that distinguish empty nouns from nominal ellipses with respect to the need for an antecedent, identity effects, productivity, and lexical meaning. Second, the chapter also focuses on the recoverability conditions that regulate the distribution of nominal anaphora. It is shown why lexical identity is unavoidable in nominal ellipses. Moreover, some putative instances of pragmatically controlled nominal ellipses are, in reality, conceived of as empty nouns requiring contextual salience. Finally, the chapter addresses the problem of licensing nominal ellipses. On the one hand, it is argued that there is no licensing by inflection of any sort. Instead, the morphological effects we observe are epiphenomena resulting from the way in which morphology resolves different stranded affix scenarios. On the other hand, a typology of nominal ellipses is proposed based on the different sizes that the elided constituents might have, depending on some selectional properties of functional heads.
Null Complement Anaphora
Authors: Depiante Marcela 
Published: January 2019

AbstractIn this chapter, the different positions regarding NCA in the literature are discussed and the analysis proposed in Hankamer and Sag (1976) is favored. NCA is taken to be a type of deep anaphor as opposed to a surface anaphor, in Hankamer and Sag’s proposed typology. It behaves like a deep anaphor in that it can take pragmatic antecedents, missing antecedents, and does not seem to require strict syntactic parallelism with its antecedent. In addition, NCA does not allow overt or covert extraction out of it, which provides evidence in favor of the view that NCA is to be represented as an element with no internal syntactic structure. It is also shown that the types of predicates that select NCA seem to be lexically determined, since no reliable pattern has yet been found to be able to predict which predicates select it.
Hungarian
Authors: Lipták Anikó 
Published: January 2019

AbstractThis chapter reviews ellipsis in Hungarian, providing examples of the majority of ellipsis types that are discussed in this book. The discussion starts with nominal ellipsis and shows that, unlike ordinary noun phrases, possessed noun phrases do not show evidence for ellipsis, V-stranding ellipsis, and pseudogapping) and includes a section on preverb-stranding ellipsis and the analytical challenges it represents. Clausal ellipsis phenomena (sluicing, fragments, stripping) are treated with reference to single remnant ellipsis and multiple remnant ellipsis as well, the latter including a description of gapping. Separate sections are dedicated to right-node raising, null complement anaphora, and ellipsis in comparative clauses. Analytical and theory-specific details about the structure of Hungarian are introduced along the way.
Lamps
Authors: Parani Maria G. 
Published: January 2019

AbstractLamps with Christian imagery are among the earliest and most easily identifiable material witnesses to early Christian communities in the Roman Empire, but lamps employed by Christians were not confined to those adorned with religious images and symbols. This chapter presents an overview of the types of clay, metal, and glass lamps owned and used by Christians and discusses their functions in daily, funerary, ecclesiastical, and other ritual contexts. Continuities with and departures from earlier Roman practices are highlighted, while the emergence of a specifically Christian decorative repertory is associated both with the wish of early Christians to express their distinct religious identity in material terms and with the gradual elaboration of a Christian symbolism of light. The need for more focused, contextualized studies of lamps within the framework of Christian archaeology remains a desideratum for future research.
Christian Archaeology in Palestine
Authors: Taylor Joan E. 
Published: January 2019

AbstractThe first Christian archaeological evidence in Palestine dates from the third century, in the so-called Megiddo church. From 326 onward, Palestine was the focus of imperial funding, and grand basilicas were established by order of the emperor Constantine. Sacred places associated with Jesus’s ancient appearance to Abraham (Mamre), birth (Bethlehem), Crucifixion and Resurrection (Golgotha), and instruction and Ascension (the Mount of Olives) have all yielded monumental remains. There is ample material testifying to a boom in church building to service Christian pilgrimage and conversion of the population, with Christian building and rebuilding continuing through to the Persian invasion of 614 and subsequent Muslim conquest of Palestine in 638.
Kunqu Cross-dressing as Artistic and/or Queer Performance
Authors: Lam Joseph S. C. 
Published: January 2019

Abstract
Cross-dressing in kunqu, a classical genre of Chinese opera, as artistic and/or queer performance, may be understood through the Chinese aesthetic dyad of se (erotic charm) and yi (performance skill); these concepts complement or challenge international queer theories. The chapter surveys current debates about kunqu cross-dressing, illustrating with analysis of representative works/performances such as Jade Hairpin (Yuzanji), Peony Pavilion (Mudanting), and Yearning for the Secular World (Sifan) by leading impersonators like Banto Tamasaburo, Mei Lanfang, and Yue Meiti. Kunqu cross-dressing simultaneously confirms and challenges hegemonic Chinese notions of gender and sex, underscoring the need to investigate music as personal and/or social performance of gender and sex.
How to Do Things with Theory
Authors: Amico Stephen 
Published: January 2019

Abstract
This article explores the potentials and perils of reading queerness in relation to cultural products, performances, and places outside the site of the theory’s genesis. Beginning with an examination of audiovisual and discursive transgressions in the works of post-Soviet Ukrainian band Kamon!!!, putatively “stylistic” elements are shown as intimately related to a political sociocultural realm. This move to the political, and to queer politics, necessitates an interrogation of the politics of queerness, and the risks of intellectual colonialism that perpetuates cultural hierarchies and stereotypes (the “backward,” pragmatic East versus the fluid, utopian West). Approaching queer theory through the lens of performativity—a textual assimilation which “queers” the other—the dynamics of musical notation and transcription are engaged in order to highlight the possible asymmetries engendered via transcultural queering, suggesting that only through mutually transformative dialog can queerness fulfill its liberatory potential.