bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiotherapy and cisplatin increase immunotherapy efficacy by enabling local and systemic intratumoral T-cell activity
Authors: Kroon Paula , Frijlink Elselien , Iglesias-Guimarais Victoria , Volkov Andriy , van Buuren Marit M , Schumacher Ton N , Verheij Marcel , Borst Jannie , Verbrugge Inge 
Published: June 2018

AbstractTo increase cancer immunotherapy success, PD-1 blockade must be combined with rationally selected treatments. Here, we examined in a poorly immunogenic mouse breast cancer model the potential of antibody-based immunomodulation and conventional anti-cancer treatments to collaborate with anti-PD-1 treatment. One important requirement to improve anti-PD-1-mediated tumor control was to promote tumor-specific cytotoxic T cell (CTL) priming, which was achieved by stimulating the CD137 costimulatory receptor. A second requirement was to overrule PD-1-unrelated mechanisms of CTL suppression in the tumor micro-environment (TME). This was achieved by radiotherapy and cisplatin treatment. In the context of CD137/PD-1-targeting immunotherapy, radiotherapy allowed for tumor elimination by altering the TME, rather than intrinsic CTL functionality. Combining this radioimmunotherapy regimen with low-dose cisplatin improved CTL-dependent regression of a contralateral tumor outside the radiation field. Thus, systemic tumor control may be achieved by combining immunotherapy protocols that promote T cell priming with (chemo)radiation protocols that permit CTL activity in both the irradiated tumor and (occult) metastases.Summary statementThis study reveals that radiotherapy and cisplatin can be ‘re-purposed’ to improve antibody-based immunotherapy success in poorly immunogenic breast cancer by overruling PD-1 unrelated mechanisms of T cell suppression in the tumor micro-environment.
The evolution of a beneficial association between an animal and a microbial community
Authors: Rebar D. , Leggett H. C. , Aspinall S.M.L. , Duarte A. , Kilner R.M. 
Published: June 2018

ABSTRACTAnimals are now known to be intimately associated with microbial communities, some of which enhance animal fitness. Yet relatively little is known about how these beneficial associations initially arose. We investigated this problem with an experiment on burying beetles, Nicrophorus vespilloides, which breed on the body of a small dead vertebrate. We found that burying beetles breeding on germ-free mice produced smaller larvae, with lower fitness, than those breeding on conventional germ-laden mice. Thus, burying beetles gain benefits from the microbial community associated with their carrion breeding resource, because they lose fitness when this community is removed experimentally. Our experiment suggests that a symbiosis between an animal and a microbial community might begin as an adaptation to the microbial ecosystem in which the animal lives, even when these microbes exist outside the animal, are transiently associated with it at each generation and are not directly transmitted from parents to offspring.
Improving peptide-spectrum matching by fragmentation prediction using Hidden Markov Models
Authors: Kirik Ufuk , Refsgaard Jan C. , Jensen Lars J. 
Published: June 2018

AbstractTandem mass-spectrometry has become the method of choice for high-throughput, quantitative analysis in proteomics. However, since the link between the peptides and the proteins they originate from is typically broken, identification of the analyzed peptides relies on matching of the fragmentation spectra (MS2) to theoretical spectra of possible candidate peptides, often filtered for precursor ion mass. To this end, peptide-spectrum matching algorithms score the concordance between the experimental and the theoretical spectra of candidate peptides, by evaluating the number (or proportion) of theoretically possible fragment ions observed in the experimental spectra, without any discrimination. However, the assumption that each theoretical fragment is just as likely to be observed is inaccurate. On the contrary, MS2 spectra often have few dominant fragments.We propose a novel prediction algorithm based on a hidden Markov model, which allow for the training process to be carried out very efficiently. Using millions of MS/MS spectra generated in our lab, we found an overall good reproducibility across different fragmentation spectra, given the precursor peptide and charge state. This result implies that there is indeed a pattern to fragmentation that justifies using machine learning methods. Furthermore, the overall agreement between spectra of the same peptide at the same charge state serves as an upper limit on how well prediction algorithms can be expected to perform.We have investigated the performance of a third order HMM model, trained on several million MS2 spectra, in various ways. Compared to a mock model, in which the fragment ions and their intensities are shuffled, we see a clear difference in prediction accuracy using our model. This result indicates that our model can pick up meaningful patterns, i.e. we can indeed learn the fragmentation process. Secondly, looking at the variability of the prediction performance by varying the train/test data split, in a K-fold cross validation scheme, we observed an overall robust model that performs well independent of the specific peptides that are present in the training data.Last but not least, we propose that the real value of this model is as a pre-processing step in the peptide identification process, by discerning fragment ions that are unlikely to be intense for a given candidate peptide, rather than using the actual predicted intensities. As such, probabilistic measures of concordance between experimental and theoretical spectra, would leverage better statistics.
The effects on neutral variability of recurrent selective sweeps and background selection
Authors: Campos José Luis , Charlesworth Brian 
Published: June 2018

ABSTRACTLevels of variability and rates of adaptive evolution may be affected by hitchhiking, the effect of selection on evolution at linked sites. Hitchhiking can be caused either by selective sweeps or by background selection, involving the spread of new favorable alleles or the elimination of deleterious mutations, respectively. Recent analyses of population genomic data have fitted models where both these processes act simultaneously, in order to infer the parameters of selection. Here, we investigate the consequences of relaxing a key assumption of some of these studies – that the time occupied by a selective sweep is negligible compared with the neutral coalescent time. We derive a new expression for the expected level of neutral variability in the presence of recurrent selective sweeps and background selection. We also derive approximate integral expressions for the effects of recurrent selective sweeps. The accuracy of the theoretical predictions was tested against multilocus simulations, with selection, recombination and mutation parameters that are realistic forDrosophila melanogaster. In the presence of crossing over, there is approximate agreement between the theoretical and simulation results. We show that the observed relations between the rate of crossing over and the level of synonymous site diversity and rate of adaptive evolution in Drosophila are probably mainly caused by background selection, whereas selective sweeps and population size changes are needed to produce the observed distortions of the site frequency spectrum.
Efficient coding of subjective value
Authors: Polanía Rafael , Woodford Michael , Ruff Christian C. 
Published: June 2018

AbstractPreference-based decisions are essential for survival, for instance when deciding what we should (not) eat. Despite their importance, choices based on preferences are surprisingly variable and can appear irrational in ways that have defied mechanistic explanations. Here we propose that subjective valuation results from an inference process that accounts for the information structure of values in the environment and that maximizes information in value representations in line with demands imposed by limited coding resources. A model of this inference process explains the variability in both subjective value reports and preference-based choices, and predicts a new preference illusion that we validate with empirical data. Interestingly, the same model also explains the level of confidence associated with these reports. Our results imply that preference-based decisions reflect information-maximizing transmission and statistically optimal decoding of subjective values by a limited-capacity system. These findings provide a unified account of how humans perceive and valuate the environment to optimally guide behavior.
Nanopore sequencing of long ribosomal DNA amplicons enables portable and simple biodiversity assessments with high phylogenetic resolution across broad taxonomic scale
Authors: Krehenwinkel Henrik , Pomerantz Aaron , Henderson James B. , Kennedy Susan R. , Lim Jun Ying , Swamy Varun , Shoobridge Juan Diego , Patel Nipam H. , Gillespie Rosemary G. , Prost Stefan 
Published: June 2018

AbstractBackgroundIn light of the current biodiversity crisis, DNA barcoding is developing into an essential tool to quantify state shifts in global ecosystems. Current barcoding protocols often rely on short amplicon sequences, which yield accurate identification of biological entities in a community, but provide limited phylogenetic resolution across broad taxonomic scales. However, the phylogenetic structure of communities is an essential component of biodiversity. Consequently, a barcoding approach is required that unites robust taxonomic assignment power and high phylogenetic utility. A possible solution is offered by sequencing long ribosomal DNA (rDNA) amplicons on the MinION platform (Oxford Nanopore Technologies).ResultsUsing a dataset of various animal and plant species, with a focus on arthropods, we assemble a pipeline for long rDNA barcode analysis and introduce a new software (MiniBar) to demultiplex dual indexed nanopore reads. We find excellent phylogenetic and taxonomic resolution offered by long rDNA sequences across broad taxonomic scales. We highlight the simplicity of our approach by field barcoding with a miniaturized, mobile laboratory in a remote rainforest. We also test the utility of long rDNA amplicons for analysis of community diversity through metabarcoding and find that they recover highly skewed diversity estimates.ConclusionsSequencing dual indexed, long rDNA amplicons on the MinION platform is a straightforward, cost effective, portable and universal approach for eukaryote DNA barcoding. Long rDNA amplicons scale up DNA barcoding by enabling the accurate recovery of taxonomic and phylogenetic diversity. However, bulk community analyses using long-read approaches may introduce biases and will require further exploration.
Functional and genetic characterization of anincF-type multidrug resistance plasmid isolated from fresh spinach
Authors: Ajayi Adeyinka O. , Perry Benjamin J. , Yost Christopher K. 
Published: June 2018

AbstractThe presence of antibiotic-resistant bacteria and clinically-relevant antibiotic resistance genes within raw foods is an on-going food safety concern. It is particularly important to be aware of the microbial quality of fresh produce because foods such as leafy greens including lettuce and spinach are minimally processed and often consumed raw therefore they often lack a microbial inactivation step. This study characterizes the genetic and functional aspects of a mobile, multidrug resistance plasmid, pLGP4, isolated from fresh spinach bought from a farmers’ market. pLGP4 was isolated using a bacterial conjugation approach. The functional characteristics of the plasmid were determined using multidrug resistance profiling and plasmid stability assays. pLGP4 was resistant to six of the eight antibiotics tested and included ciprofloxacin and meropenem. The plasmid was stably maintained within host strains in the absence of an antibiotic selection. The plasmid DNA was sequenced using an Illumina MiSeq high throughput sequencing approach and assembled into contigs using SPAdes. PCR mapping and Sanger DNA sequencing of PCR amplicons was used to complete the plasmid DNA sequence. Comparative sequence analysis determined that the plasmid was similar to plasmids that have been frequently associated with multidrug resistant clinical isolates ofKlebsiella spp. DNA sequence analysis showed pLGP4 harbouredqnrB1and several other antibiotic resistance genes including three β-lactamases:blaTEM-1,blaCTX-M-15andblaOXA-1. The detection of a multidrug-resistant, clinically-relevant plasmid on fresh spinach emphasizes the importance for vegetable producers to implement evidence-based food safety approaches into their production practises to ensure the food safety of leafy greens.
Categorized analysis of forest ecological values in the China’s conversion cropland to forest program
Authors: Yuan Wen-Ge , Zheng Jian-Wei , Gu Jian-Cai , Lu Gui-Qiao 
Published: June 2018

AbstractBackgroundThe China’s Conversion Cropland to Forest Program (CCFP) is one of the large state ecological construction programs. Up to now, the program has effectively improved the ecological environment and produced large ecological benefit. However, there were also some problems in its implementation process, the program has been sometimes less effective than the expected.MethodsBased on the data and the methods of ‘State report on monitoring ecological effects in CCFP’ and the Chinese Forest Ecosystem Research Network (CFERN) in 2013, we analyzed the categorized ‘forest ecological benefit value’ (B-V) s in the three forest restoration ways in different regions in China to provide references for CCFP construction.ResultsThe unit area B-Vs in CCFP varied between 35 000 RMBs.hm−2.a−1and 100 000 RMBs.hm−2.a−1. Water conservation B-V and species conservation B-V were the two largest constituents, nutrient accumulation B-V was the least in all the categorized B-Vs on regional and unit area scale. The rank of restoration ways on average unit area total B-Vs was—‘hillside forest conservation’ > ‘returning cropland to forest’ > ‘afforestation on suitable barren hills and wasteland’ in CCFP. Among the categorized B-Vs, some pairs were positively correlated with each other and some were negatively correlative. The correlation coefficients and some regression equations were given in the text and the attached Fig.s.ConclusionsWater conservation B-V was the highest and nutrient accumulation B-V was the lowest whether on regional or unit area scale in CCFP.Forest ecological B-Vs varied in different forest restoration ways and different regions in CCFP. The ‘hillside forest conservation’ restoration way and the water conservation B-V should be paid more attention in China’s future forest restoration. We suggest that suitable forest restoration ways should be selective according to the regional specific and ecological targets.There were correlations among the categorized B-Vs, and the correlations varied with different forest restoration ways in CCFP. Knowing about the correlations could clarify the targeted restoration ways according to the goal of ecological benefit.
Heritability Estimation and Differential Analysis with Generalized Linear Mixed Models in Genomic Sequencing Studies
Authors: Sun Shiquan , Zhu Jiaqiang , Mozaffari Sahar , Ober Carole , Chen Mengjie , Zhou Xiang 
Published: June 2018

ABSTRACTMotivationGenomic sequencing studies, including RNA sequencing and bisulfite sequencing studies, are becoming increasingly common and increasingly large. Large genomic sequencing studies open doors for accurate molecular trait heritability estimation and powerful differential analysis. Heritability estimation and differential analysis in sequencing studies requires the development of statistical methods that can properly account for the count nature of the sequencing data and that are computationally efficient for large data sets.ResultsHere, we develop such a method, PQLseq (Penalized Quasi-Likelihood for sequencing count data), to enable effective and efficient heritability estimation and differential analysis using the generalized linear mixed model framework. With extensive simulations and comparisons to previous methods, we show that PQLseq is the only method currently available that can produce unbiased heritability estimates for sequencing count data. In addition, we show that PQLseq is well suited for differential analysis in large sequencing studies, providing calibrated type I error control and more power compared to the standard linear mixed model methods. Finally, we apply PQLseq to perform gene expression heritability estimation and differential expression analysis in a large RNA sequencing study in the Hutterites.Availability and implementationPQLseq is implemented as an R package with source code freely available atwww.xzlab.org/software.htmlandhttps://cran.r-project.org/web/packages/PQLseq/index.html.ContactXZ (xzhousph@umich.edu)Supplementary informationSupplementary data are available online.
Efficient Synthesis of Mutants Using Genetic Crosses
Authors: Pratapa Aditya , Jalihal Amogh P. , Ravi S. S. , Murali T. M. 
Published: June 2018

AbstractThe genetic cross is a fundamental, flexible, and widely-used experimental technique to create new mutant strains from existing ones. Surprisingly, the problem of how to efficiently compute a sequence of crosses that can make a desired target mutant from a set of source mutants has received scarce attention. In this paper, we make three contributions to this question.First, we formulate several natural problems related to efficient synthesis of a target mutant from source mutants. Our formulations capture experimentally-useful notions of verifiability (e.g the need to confirm that a mutant contains mutations in the desired genes) and permissibility (e.g., the requirement that no intermediate mutants in the synthesis be inviable).Second, we develop combinatorial techniques to solve these problems. We prove that checking the existence of a verifiable, permissible synthesis is NP-complete in general. We complement this result with three polynomial time or fixed-parameter tractable algorithms for optimal synthesis of a target mutant for special cases of the problem that arise in practice.Third, we apply these algorithms to simulated data and to synthetic data. We use results from simulations of a mathematical model of the cell cycle to replicate realistic experimental scenarios where a biologist may be interested in creating several mutants in order to verify model predictions. Our results show that the consideration of permissible mutants can affect the existence of a synthesis or the number of crosses in an optimal one. Our algorithms gracefully handle the restrictions that permissible mutants impose. Results on synthetic data show that our algorithms scale well with increases in the size of the input and the fixed parameters.
Qualitative job insecurity and turnover intention
Authors: Urbanaviciute Ieva , Lazauskaite-Zabielske Jurgita , Vander Elst Tinne , De Witte Hans 
Published: June 2018

PurposeThe purpose of this paper is to test two hypotheses. First, an indirect relationship between qualitative job insecurity and turnover intention through basic psychological need satisfaction was investigated. Second, a moderated mediation analysis was conducted to explore potential sectoral differences in this indirect relationship.Design/methodology/approachA cross-sectional design was used to collect and analyze the data. In total, 358 employees participated in the study (private sectorn=178, public sectorn=180). The data were collected through an online survey platform.FindingsQualitative job insecurity was indirectly related to turnover intention through the satisfaction of the basic psychological needs for autonomy, competence and relatedness. The indirect relationships were more salient in the private sector.Research limitations/implicationsBasic psychological needs may explain the relationship between qualitative job insecurity and turnover intention. Furthermore, sector differences may exist in the way job insecurity is responded to. However, a longitudinal study is necessary to confirm the sequential effects.Originality/valueThe study provides a constructive replication of the findings on basic psychological need satisfaction as a mediator between job insecurity and employee outcomes. A novel aspect is the authors’ focus on sector differences, which draws attention to contextual factors that may shape the way employees respond to job-insecure situations.
The role of geographic spillovers in employment policy planning: an empirical investigation for Russian regions
Authors: Aldieri Luigi , Kotsemir Maxim , Vinci Concetto Paolo 
Published: June 2018

PurposeThe purpose of this paper is to look at the factors driving labour creation in Russia, while paying attention to the role of innovation policy. The study considers innovation variables with indicators linked to social conditions (social filter component) and geographical spillovers for 85 regions during the period 2010-2016.Design/methodology/approachIn particular, the study uses latitude and longitude coordinates to compute the distance between Russian regions according to the Haversine formula. In this manner, it measures the spillovers as the weighted sum of R&D capital stock on the basis of computed distance, according to the accessibility index procedure.FindingsThe finding is very important in terms of policy implications for supporting employment. As the results stress that own innovation produces labour creation effects, while knowledge spillovers are labour-saving, the study could conclude that regional innovation policy may have undetermined the objective of an efficient level of absorptive capacity able to benefit positively from external innovation.Originality/valueThe study contributes to the literature by exploring whether geographical spillovers are labour-friendly or labour-saving in Russia.
Trust, commitment, customer intimacy and customer loyalty in Islamic banking relationships
Authors: Tabrani Mirza , Amin Muslim , Nizam Ahmad 
Published: June 2018

Purpose
The purpose of this paper is to investigate the role of trust in enhancing customer loyalty, and to test the mediation role of commitment and customer intimacy in the relationship between trust and customer loyalty.

Design/methodology/approach
A total of 500 questionnaires were distributed and 200 were returned (40 percent response rate), and a structural equation modeling technique was used to test the hypotheses.

Findings
The results of this study show that trust has a significant relationship with commitment and customer intimacy but no significant relationship was found with customer loyalty. Commitment and customer intimacy have a significant relationship with customer loyalty. The mediation analysis reveals that commitment and customer intimacy play a mediation role in the relationship between trust and customer loyalty.

Practical implications
This study indicates that commitment and customer intimacy affect customer loyalty. The role of commitment and customer intimacy as a mediator between trust and customer loyalty indicates that customers are committed to continuing and maintaining the relationships with Islamic banks.

Originality/value
This study provides empirical evidence on interrelationships between trust, commitment, customer intimacy and customer loyalty in banking relationships.