bluuebunny/crossref_metadata_2025_split huggingface dataset:
Technical note: validation of an automated feeding system for measuring individual animal feed intake in sheep housed in groups
Authors: Muir Stephanie K , Linden Nick P , Kennedy Andrew , Calder Grace , Kearney Gavin , Roberts Richard , Knight Matthew I , Behrendt Ralph 
Published: January 2020

Abstract
The development of feeding systems that can individually measure and control feed intake in a group-housed environment would allow a greater understanding of sheep intake without compromising animal welfare and behavior through the removal of social interactions between sheep. This study validated an automated feeding system for measuring feed intake of individual sheep when housed in groups. Validation of the feeding system was conducted during three separate experiments. The validation sampling involved the activation of four individual “feed events,” whereby four separate samples weighing approximately 50, 100, 200, and 400 g were removed from each feeder, with each feed event being linked to a specific radio frequency identification (RFID) tag. The feeder validation experiments evaluated the ability of the feeding system to 1) create a unique feed event every time a sample of pellets was collected from the feeder, 2) link the feed event to the correct RFID, and 3) accurately record the weight of feed that was manually removed. All feed events were initiated and logged in the feeding system with 100% of the events being linked to the correct test RFID. Concordance correlation coefficients between the feeding system-recorded feed weight and the manually removed weight were 0.99 within all three experiments. There was also no overall and little level-dependent bias between the weights measured by the feeding system and weights measured on the external scales. These results indicate the stability of the feeding system over time and consistency between the feeders within and across the three experiments. In conclusion, the automated feeding system developed for measuring individual animal feed intake was able to detect and record the unique electronic RFID associated with unique feed events and accurately capture the weight of feed removed. Furthermore, there was no change in the accuracy of the system from the start to the end of experimental periods, and the amount of feed removed in the feed event (or meal size) did not impact the accuracy of the results.
Machine learning and big scientific data
Authors: Hey Tony , Butler Keith , Jackson Sam , Thiyagalingam Jeyarajan 
Published: January 2020

This paper reviews some of the challenges posed by the huge growth of experimental data generated by the new generation of large-scale experiments at UK national facilities at the Rutherford Appleton Laboratory (RAL) site at Harwell near Oxford. Such ‘Big Scientific Data’ comes from the Diamond Light Source and Electron Microscopy Facilities, the ISIS Neutron and Muon Facility and the UK's Central Laser Facility. Increasingly, scientists are now required to use advanced machine learning and other AI technologies both to automate parts of the data pipeline and to help find new scientific discoveries in the analysis of their data. For commercially important applications, such as object recognition, natural language processing and automatic translation, deep learning has made dramatic breakthroughs. Google's DeepMind has now used the deep learning technology to develop their AlphaFold tool to make predictions for protein folding. Remarkably, it has been able to achieve some spectacular results for this specific scientific problem. Can deep learning be similarly transformative for other scientific problems? After a brief review of some initial applications of machine learning at the RAL, we focus on challenges and opportunities for AI in advancing materials science. Finally, we discuss the importance of developing some realistic machine learning benchmarks using Big Scientific Data coming from several different scientific domains. We conclude with some initial examples of our ‘scientific machine learning’ benchmark suite and of the research challenges these benchmarks will enable.
This article is part of a discussion meeting issue ‘Numerical algorithms for high-performance computational science’.
Hierarchical algorithms on hierarchical architectures
Authors: Keyes D. E. , Ltaief H. , Turkiyyah G. 
Published: January 2020

A traditional goal of algorithmic optimality, squeezing out flops, has been superseded by evolution in architecture. Flops no longer serve as a reasonable proxy for all aspects of complexity. Instead, algorithms must now squeeze memory, data transfers, and synchronizations, while extra flops on locally cached data represent only small costs in time and energy. Hierarchically low-rank matrices realize a rarely achieved combination of optimal storage complexity and high-computational intensity for a wide class of formally dense linear operators that arise in applications for which exascale computers are being constructed. They may be regarded as algebraic generalizations of the fast multipole method. Methods based on these hierarchical data structures and their simpler cousins, tile low-rank matrices, are well proportioned for early exascale computer architectures, which are provisioned for high processing power relative to memory capacity and memory bandwidth. They are ushering in a renaissance of computational linear algebra. A challenge is that emerging hardware architecture possesses hierarchies of its own that do not generally align with those of the algorithm. We describe modules of a software toolkit, hierarchical computations on manycore architectures, that illustrate these features and are intended as building blocks of applications, such as matrix-free higher-order methods in optimization and large-scale spatial statistics. Some modules of this open-source project have been adopted in the software libraries of major vendors.
This article is part of a discussion meeting issue ‘Numerical algorithms for high-performance computational science’.
High-performance sampling of generic determinantal point processes
Authors: Poulson Jack 
Published: January 2020

Determinantal point processes (DPPs) were introduced by Macchi (Macchi 1975Adv. Appl. Probab.7, 83–122) as a model for repulsive (fermionic) particle distributions. But their recent popularization is largely due to their usefulness for encouraging diversity in the final stage of a recommender system (Kulesza & Taskar 2012Found. Trends Mach. Learn.5, 123–286). The standard sampling scheme for finite DPPs is a spectral decomposition followed by an equivalent of a randomly diagonally pivoted Cholesky factorization of an orthogonal projection, which is only applicable to Hermitian kernels and has an expensive set-up cost. Researchers Launayet al.2018 (http://arxiv.org/abs/1802.08429); Chen & Zhang 2018NeurIPS(https://papers.nips.cc/paper/7805-fast-greedy-map-inference-for-determinantal-point-process-to-improve-recommendation-diversity.pdf) have begun to connect DPP sampling toLDLHfactorizations as a means of avoiding the initial spectral decomposition, but existing approaches have only outperformed the spectral decomposition approach in special circumstances, where the number of kept modes is a small percentage of the ground set size. This article proves that trivial modifications ofLUandLDLHfactorizations yield efficient direct sampling schemes for non-Hermitian and Hermitian DPP kernels, respectively. Furthermore, it is experimentally shown that even dynamically scheduled, shared-memory parallelizations of high-performance dense and sparse-direct factorizations can be trivially modified to yield DPP sampling schemes with essentially identical performance. The software developed as part of this research, Catamari (hodgestar.com/catamari) is released under the Mozilla Public License v.2.0. It contains header-only, C++14 plus OpenMP 4.0 implementations of dense and sparse-direct, Hermitian and non-Hermitian DPP samplers.This article is part of a discussion meeting issue ‘Numerical algorithms for high-performance computational science’.
Big telescope, big data: towards exascale with the Square Kilometre Array
Authors: Scaife A. M. M. 
Published: January 2020

Unlike optical telescopes, radio interferometers do not image the sky directly but require specialized image formation algorithms. For the Square Kilometre Array (SKA), the computational requirements of this image formation are extremely demanding due to the huge data rates produced by the telescope. This processing will be performed by the SKA Science Data Processor facilities and a network of SKA Regional Centres, which must not only deal with SKA-scale data volumes but also with stringent science-driven image fidelity requirements.
This article is part of a discussion meeting issue ‘Numerical algorithms for high-performance computational science’.
In vitroactivities of the tetrazole SHR8008 compared to itraconazole and fluconazole againstCandidaandCryptococcusspecies
Authors: Wang Lili , Zhang Min , Guo Jian , Guo Wenzheng , Zhong Ni , Shen Hui , Wu Wenjuan 
Published: January 2020

AbstractCandidaandCryptococcusare the main pathogens of clinical fungal infection associated with high morbidity and mortality. SHR8008 (in fact, this is the only official name in China and it is called VT-1161 by FDA) is a novel tetrazole agent that selectively inhibits fungal CYP51A compared to mammalian cytochrome P450 enzymes to achieve a better antifungal effect. Thein vitroactivities of SHR8008 and its comparators itraconazole and fluconazole were determined in 127Candidaand 50Cryptococcusstrains isolated from Chinese patients in the last 2 years by Invasive Fungal Infection Group. The MICs of SHR8008 and other triazoles were measured by the Clinical and Laboratory Standards Institute guidelines M27-E4. ForCandidaspp., SHR8008 (geometric mean MIC=0.078 μg/mL) was 6.5-fold and 11.2-fold more potent than itraconazole and fluconazole, respectively. There is a good correlation of MICs between SHR8008 and itraconazole/fluconazole. The MIC values of SHR8008 againstCandida glabrataandCandida tropicaliswere significantly lower than those of fluconazole, while forCandida albicansandCandida parapsilosis, the differences between SHR8008 and fluconazole were not statistically significant, either. ForCryptococcusspp., SHR8008 (geometric mean MIC=0.024 μg/mL) was 21.7-fold and 104.5-fold more potent than itraconazole and fluconazole, respectively. Against the sevenCryptococcus neoformansisolates with elevated fluconazole MICs (≥8μg/mL based on the MIC90 value for this azole), SHR8008 maintained potent activity, with MICs ranging between 0.031 and 0.5 μg/mL. The results showed that tetrazole SHR8008 was more promising in the treatment ofCandidaandCryptococcusinfection than itraconazole and fluconazole.
Transient Commensal Clonal Interactions Can Drive Tumor Metastasis
Authors: Amara Suha Naffar-Abu , Kuiken Hendrik J. , Selfors Laura M. , Butler Timothy , Leung Marco L. , Leung Cheuk T. , Kuhn Elaine P. , Kolarova Teodora , Hage Carina , Ganesh Kripa , Foster Rosemary , Rueda Bo R. , Aktipis Athena , Spellman Paul , Ince Tan , Navin Nicholas , Mills Gordon B. , Bronson Rodrick T. , Brugge Joan S. 
Published: January 2020

AbstractTo interrogate functional heterogeneity and crosstalk between tumor cells, we generated clonal populations from a patient-derived ovarian clear cell carcinoma model which forms malignant ascites and solid peritoneal tumors upon intraperitoneal transplantation in mice. The clonal populations were engineered with secretedGaussialuciferase to monitor tumor growth dynamics and tagged with a unique DNA barcode to track their fate in multiclonal mixtures during tumor progression. Only one clone, CL31, grew robustly, generating exclusively malignant ascites. However, multiclonal mixtures formed large solid peritoneal metastases, populated almost entirely by CL31, suggesting that transient cooperative interclonal interactions were sufficient to promote metastasis of CL31. CL31 uniquely harboredERBB2amplification, and its acquired metastatic trait was dependent on transient exposure to amphiregulin, which was exclusively secreted by non-tumorigenic clones. Amphiregulin enhanced CL31 mesothelial clearance, a prerequisite for metastasis. These findings demonstrate that transient, ostensibly innocuous tumor subpopulations can promote metastases via “hit- and-run” commensal interactions.
New plasmon-polariton model of the saltatory conduction
Authors: Jacak W. A. 
Published: January 2020

ABSTRACTWe propose a new model of the saltatory conduction in myelinated axons. This conduction of the action potential in myelinated axons does not agree with the conventional cable theory, though the latter has satisfactorily explained the electrosignaling in dendrites and in unmyelinated axons. By the development of the wave-type concept of ionic plasmon-polariton kinetics in axon cytosol we have achieved an agreement of the model with observed properties of the saltatory conduction. Some resulting consequences of the different electricity model in the white and the gray matter for nervous system organization have been also outlined.SIGNIFICANCEMost of axons in peripheral nervous system and in white matter of brain and spinal cord are myelinated with the action potential kinetics speed two orders greater than in dendrites and in unmyelinated axons. A decrease of the saltatory conduction velocity by only 10% ceases body functioning. Conventional cable theory, useful for dendrites and unmyelinated axon, does not explain the saltatory conduction (discrepancy between the speed assessed and the observed one is of one order of the magnitude). We propose a new nonlocal collective mechanism of ion density oscillations synchronized in the chain of myelinated segments of plasmon-polariton type, which is consistent with observations. This model explains the role of the myelin in other way than was previously thought.
T cell responses induced by attenuated flavivirus vaccination are specific and show limited cross-reactivity with other flavivirus species
Authors: Grifoni Alba , Voic Hannah , Dhanda Sandeep Kumar , Kidd Conner K. , Brien James D , Buus Søren , Stryhn Anette , Durbin Anna P , Whitehead Stephen , Diehl Sean A. , De Silva Aruna D. , Balmaseda Angel , Harris Eva , Weiskopf Daniela , Sette Alessandro 
Published: January 2020

AbstractMembers of the flavivirus genus share a high level of sequence similarity and often circulate in the same geographical regions. However, whether T cells induced by one viral species cross-react with other related flaviviruses has not been globally addressed. Here, we tested pools of epitopes derived from dengue (DENV), zika (ZIKV), Japanese Encephalitis (JEV), West Nile (WNV), and yellow fever (YFV) viruses by Intracellular Cytokine Staining (ICS) using PBMCs of individuals naturally exposed to DENV or immunized with DENV (TV005) or YF17D vaccines. CD8 T cell responses recognized epitopes from multiple flaviviruses, however, the magnitude of cross-reactive responses was consistently several-fold lower than those to the autologous epitope pools, and associated with lower expression of activation markers such as CD40L, CD69, and CD137. Next, we characterized the antigen sensitivity of short-term T cell lines (TCL) representing twenty-nine different individual epitope/donor combinations. TCL derived from DENV monovalent vaccinees induced CD8 and CD4 T cells that cross-reacted within the DENV serocomplex but were consistently associated with more than 100-fold lower antigen sensitivity for most other flaviviruses, with no cross-recognition of YFV derived peptides. CD8 and CD4 TCL from YF17D vaccinees were associated with very limited cross-reactivity with any other flaviviruses, and in five out of eight cases more than 1000-fold lower antigen sensitivity. Overall, our data suggest limited cross-reactivity for both CD4 and CD8 T cell responses between flaviviruses and has implications for understanding immunity elicited by natural infection, and strategies to develop live attenuated vaccines against flaviviral species.ImportanceThe envelope (E) protein is the dominant target of neutralizing antibodies for dengue virus (DENV) and yellow fever virus (YFV). Accordingly, several DENV vaccine constructs use the E protein in a live attenuated vaccine format, utilizing a backbone derived from a heterologous flavivirus (such as YF) as a delivery vector. This backbone comprises the non-structural (NS) and capsid (C) antigens which are dominant targets of T cell responses. Here, we demonstrate that cross-reactivity at the level of T cell responses amongst different flaviviruses is very limited, despite high levels of sequence homology. Thus, the use of heterologous flavivirus species as a live attenuated vaccine vector is not likely to generate optimal T cell responses, and might thus impair vaccine performance.
Splicing of the SynGAP Carboxyl-Terminus Enables Isoform-Specific Tuning of NMDA Receptor Signaling Linked to Cognitive Function
Authors: Kilinc Murat , Creson Thomas K. , Rojas Camilo , Maity Sabyasachi , Le Aliza A. , Lauterborn Julie , Wilkinson Brent , Hartel Nicolas , Graham Nicholas , Reich Adrian , Gou Gemma , Araki Yoichi , Bayés Àlex , Coba Marcelo P. , Lynch Gary , Miller Courtney A. , Rumbaugh Gavin 
Published: January 2020

SummarySynGAP-α1 is a splice variant of the neurodevelopmental disorder risk gene,SYNGAP1/Syngap1. α1 encodes the C-terminal PDZ binding motif (PBM) that promotes liquid-liquid phase separation, a candidate process for postsynaptic density organization within excitatory synapses. However, it remains unknown how the endogenous SynGAP PBM regulates synapse properties and related cognitive functions. We found that a major PBM function in mice is to limit the mobility of SynGAP-α1 in response to NMDA receptor activation. Genetic disruption of the PBM increased SynGAP-α1 mobility to levels consistent with other non-PBM-containing C-terminal isoforms. This resulted in a lowering of the threshold for NMDA receptor-dependent signaling required for plasticity, leading to aberrant strengthening of excitatory synapses in spontaneously active neurons. PBM-deficient animals also exhibited a lower seizure threshold, disrupted LTP, and impaired cognition. Thus, the PBM enables isoform-specific SynGAP gating of NMDA receptor function, a mechanism linking synaptic signaling dynamics to network excitability and cognition.
The Requirement For US28 During Cytomegalovirus Latency Is Independent Of US27 And US29 Gene Expression
Authors: Krishna Benjamin A. , Wass Amanda B. , Sridharan Rajashri , O’Connor Christine M. 
Published: January 2020

AbstractThe ability to establish a latent infection with periodic reactivation events ensures herpesviruses, like human cytomegalovirus (HCMV), lifelong infection and serial passage. The host-pathogen relationship throughout HCMV latency is complex, though both cellular and viral factors influence the equilibrium between latent and lytic infection. We and others have shown one of the viral-encoded G protein-coupled receptors, US28, is required for HCMV latency. US28 potentiates signals both constitutively and in response to ligand binding, and we previously showed deletion of the ligand binding domain or mutation of the G protein-coupling domain results in the failure to maintain latency similar to deletion of the entire US28 open reading frame (ORF). Interestingly, a recent publication detailed an altered phenotype from that previously reported, showing US28 is required for viral reactivation rather than latency, suggesting the US28 ORF deletion impacts transcription of the surrounding genes. Here, we show an independently generated US28-stop mutant, like the US28 ORF deletion mutant, fails to maintain latency in hematopoietic cells. Further, we foundUS27andUS29transcription in each of these mutants was comparable to their expression during wild type infection, suggesting neither US28 mutant alters mRNA levels of the surrounding genes. Finally, infection with a US28 ORF deletion virus expressed US27 protein comparable to its expression following wild type infection. In sum, our new data strongly support previous findings from our lab and others, detailing a requirement for US28 during HCMV latent infection.
Modeling SIV kinetics supports that cytotoxic response drives natural control and unravels heterogeneous populations of infected cells
Authors: Madelain V. , Passaes C. , Millet A. , Avettand-Fenoel V. , Djidjou-Demasse R. , Dereuddre-Bosquet N. , Le Grand R. , Rouzioux C. , Vaslin B. , Saez-Cirion A. , Guedj J. 
Published: January 2020

AbstractSIVmac251-infected Mauritius cynomolgus macaques presenting a M6 MHC haplotype or challenged with a low inoculum dose by mucosal route are models for natural HIV control. Here we characterized by modeling the dynamics of plasma SIV-RNA and of SIV-DNA in blood cells of 16 macaques of the ANRS SIC study.SIV-RNA kinetics was best fitted using a model where the cytotoxic immune response progressively mounted up and reduced actively infected cells half-life (t1/2) from 5.5 days early on to about 0.3 days. The model predicted that the control was achieved in animals able to mount an effective immune response within three months, and this was corroborated by the longitudinal analysis of the CD8+T-cell antiviral activity measuredex vivo. The control of SIV-RNA was accompanied in parallel by a slow and biphasic decline of SIV-DNA. This unravels the presence of at least two compartments of non-actively infected cells that are not rapidly eliminated by the immune system, one with a rapid turnover rate (t1/2=5.1 days) and predominant as long as SIV-RNA levels are still large, and one with a slow turnover (t1/2=118 days) consistent with the half-life of memory T-cells, and only visible when control is achieved,.In summary, our analysis suggests that the establishment of an efficient CD8+T-cell response in the first three months of the infection, and that progressively increases overtime is key to achieve SIV-RNA control in this model. Frequent SIV-DNA quantifications allowed identifying that most cells infected after viral peak have a short t1/2but do not contribute significantly to viral production.One sentence summaryModeling viral dynamics in SIV natural controller macaques predicts that viral control is primarily driven by the capability to establish an efficient cytotoxic response and the viral decline during control unravels distinct compartments of infected cells.
On the origin and evolution of RNA editing in metazoans
Authors: Li Qiye , Zhang Pei , Li Ji , Yu Hao , Zhan Xiaoyu , Zhu Yuanzhen , Guo Qunfei , Tan Huishuang , Lundholm Nina , Garcia Lydia , Martin Michael D. , Subirats Meritxell Antó , Su Yi-Hsien , Ruiz-Trillo Iñaki , Martindale Mark Q. , Yu Jr-Kai , Gilbert M. Thomas P. , Zhang Guojie 
Published: January 2020

AbstractExtensive adenosine-to-inosine (A-to-I) editing of nuclear-transcribed RNAs is the hallmark of metazoan transcriptional regulation, and is fundamental to numerous biochemical processes. Here we explore the origin and evolution of this regulatory innovation, by quantifying its prevalence in 22 species that represent all major transitions in metazoan evolution. We provide substantial evidence that extensive RNA editing emerged in the common ancestor of extant metazoans. We find the frequency of RNA editing varies across taxa in a manner independent of metazoan complexity. Nevertheless, cis-acting features that guide A-to-I editing are under strong constraint across all metazoans. RNA editing seems to preserve an ancient mechanism for suppressing the more recently evolved repetitive elements, and is generally nonadaptive in protein-coding regions across metazoans, except forDrosophilaand cephalopods. Interestingly, RNA editing preferentially target genes involved in neurotransmission, cellular communication and cytoskeleton, and recodes identical amino acid positions in several conserved genes across diverse taxa, emphasizing broad roles of RNA editing in cellular functions during metazoan evolution that have been previously underappreciated.