bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and Management of Human Trafficking Victims in the Emergency Department
Authors: Hachey Lisa M. , Phillippi Julia C.
Published: January 2020

Health care practitioners serve an important role in identification and assistance of human trafficking victims. Advanced practice registered nurses, including certified nurse midwives, clinical nurse specialists, and nurse practitioners, are in a unique position to interact with persons trafficked and seen in the clinical setting, yet they require knowledge to identify the signs of human trafficking. Lack of training and education has been identified as a barrier for health care professionals to recognize human trafficking victims and implement needed health care services (M. Chisolm-Straker, L. D. Richardson, & T. Cossio, 2012
;
C. Ross et al., 2015). Barriers to identification and management include gap in knowledge about the process to screen for trafficking, to assist victims, and to make referrals. A patient-centered, trauma-informed approach can provide a safe environment to sensitively screen patients for human trafficking. Advanced practice registered nurses should be able to assess for trafficking indicators, collaborate with multidisciplinary service providers, and ensure understanding and availability of federal, state, and local resources to manage the care of victims of trafficking.
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’.
The physics of numerical analysis: a climate modelling case study
Authors: Palmer T. N.
Published: January 2020

The case is made for a much closer synergy between climate science, numerical analysis and computer science.

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’.
Sulfuracidifex tepidarius gen. nov., sp. nov. and transfer of Sulfolobus metallicus Huber and Stetter 1992 to the genus Sulfuracidifex as Sulfuracidifex metallicus comb. nov.
Authors: Itoh Takashi , Miura Tatsuki , Sakai Hiroyuki D. , Kato Shingo , Ohkuma Moriya , Takashina Tomonori
Published: January 2020

Two novel, strictly aerobic, sulfur-dependent, thermoacidophilic strains, IC-006Tand IC-007, were isolated from a solfataric field at Hakone Ohwaku-dani, Kanagawa, Japan. Cells of the two strains were irregular cocci with a diameter of 1.0–1.8 µm. They were strict aerobes and grew in a temperature range between 45 and 69 °C (optimally at 65 °C) and a pH range between 0.4 and 5.5 (optimally at pH 3.5). They required sulfur or a reduced sulfur compound, and sulfur was oxidized to sulfate. They grew autotrophically or mixotrophically utilizing several sugars and complex organic substances as carbon sources. The DNA G+C content was 42.4 mol%. A comparison of the 16S rRNA gene sequences among members of the orderSulfolobalesindicated that they were closely related toSulfolobus metallicus, forming an independent lineage within this order. The two isolates andSulfolobus metallicuswere also diffentiated based on their phenotypic properties from the other members of the orderSulfolobales. Detailed comparisons of the phenotypic properties and DNA–DNA hybridization study illustrated that the two isolates belong to a species different fromSulfolobus metallicus. On the basis of the phylogenetic and phenotypic comparisons, we propose a new genus and species,Sulfuracidifex tepidariusgen. nov., sp. nov. to accommodate strains IC-006Tand IC-007. The type strain ofSulfuracidifex tepidariusis IC-006T(=JCM 16833T=DSM 104736T). In addition,Sulfolobus metallicusshould be transferred to the new genus asSulfuracidifex metallicuscomb. nov.: the type strain is Kra23T(=DSM 6482T=JCM 9184T=NBRC 15436T).
Hypericibacter terrae gen. nov., sp. nov. and Hypericibacter adhaerens sp. nov., two new members of the family Rhodospirillaceae isolated from the rhizosphere of Hypericum perforatum
Authors: Noviana Zahra , Vieira Selma , Pascual Javier , Fobofou Serge Alain Tanemossu , Rohde Manfred , Spröer Cathrin , Bunk Boyke , Overmann Jorg
Published: January 2020

Two strains of the family

Rhodospirillaceae

were isolated from the rhizosphere of the medicinal plant Hypericum perforatum. Cells of both strains were Gram-stain-negative, motile by means of a single polar flagellum, non-spore-forming, non-capsulated, short rods that divided by binary fission. Colonies were small and white. Strains R5913T and R5959T were oxidase-positive, mesophilic, neutrophilic and grew optimally without NaCl. Both grew under aerobic and microaerophilic conditions and on a limited range of substrates with best results on yeast extract. Major fatty acids were C19 : 0 cyclo ω8c and C16 : 0; in addition, C18 : 1ω7c was also found as a predominant fatty acid in strain R5913T. The major respiratory quinone was ubiquinone 10 (Q-10). The DNA G+C contents of strains R5913T and R5959T were 66.0 and 67.4 mol%, respectively. 16S rRNA gene sequence comparison revealed that the closest relatives (<92 % similarity) of the strains are

Oceanibaculum pacificum

MCCC 1A02656T,

Dongia mobilis

CGMCC 1.7660T,

Dongia soli

D78T and

Dongia rigui

04SU4-PT. The two novel strains shared 98.6 % sequence similarity and represent different species on the basis of low average nucleotide identity of their genomes (83.8 %). Based on the combined phenotypic, genomic and phylogenetic investigations, the two strains represent two novel species of a new genus in the family

Rhodospirillaceae

, for which the name Hypericibacter gen. nov. is proposed, comprising the type species Hypericibacter terrae sp. nov. (type strain R5913T=DSM 109816T=CECT 9472T) and Hypericibacter adhaerens sp. nov. (type strain R5959T=DSM 109817T=CECT 9620T).
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

CandidaandCryptococcusare 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

To 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

We 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.

SIGNIFICANCE

Most 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

Members 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.

Importance

The 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

SynGAP-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

The 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

SIVmac251-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 summary

Modeling 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

Extensive 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.
Surveying Brain Tumor Heterogeneity by Single-Cell RNA Sequencing of Multi-sector Biopsies
Authors: Yu Kai , Hu Yuqiong , Wu Fan , Guo Qiufang , Qian Zenghui , Hu Waner , Chen Jing , Wang Kuanyu , Fan Xiaoying , Wu Xinglong , Rasko John EJ , Fan Xiaolong , Iavarone Antonio , Jiang Tao , Tang Fuchou , Su Xiao-Dong
Published: January 2020

Brain tumors are among the most challenging human tumors for which the mechanisms driving progression and heterogeneity remain poorly understood. We combined single-cell RNA-seq with multisector biopsies to sample and analyze single-cell expression profiles of gliomas from 13 Chinese patients. After classifying individual cells, we generated a spatial and temporal landscape of glioma that revealed the patterns of invasion between the different sub-regions of gliomas. We also used single-cell inferred CNVs and pseudotime trajectories to inform on the crucial branches that dominate tumor progression. The dynamic cell components of the multi-region biopsy analysis allowed us to spatially deconvolute with unprecedented accuracy the transcriptomic features of the core and those of the periphery of glioma at single cell level. Through this rich and geographically detailed dataset, we were also able to characterize and construct the chemokine and chemokine receptor interactions that exist among different tumor and non-tumor cells. This study provides the first spatial-level analysis of the cellular states that characterize human gliomas. It also presents an initial molecular map of the crosstalks between glioma cells and the surrounding microenvironment with single cell resolution.
Design of a biosensor for direct visualisation of auxin
Authors: Herud-Sikimic Ole , Stiel Andre C. , Ortega-Perez Marina , Shanmugaratnam Sooruban , Höcker Birte , Jürgens Gerd
Published: January 2020

In plants, one of the most important regulative small molecules is indole-3-acetic acid (IAA) known as auxin. Its dynamic redistribution plays an essential role in virtually every aspect of plant life, ranging from cell shape and division to organogenesis and responses to light and gravity1,2. So far, the spatial and temporal distribution of auxin at cellular resolution could not be determined directly. Instead it has been inferred from visualisation of irreversible processes involving the endogenous auxin response machinery3-7. This detection system failed to record transient changes. Here we report on a genetically encoded biosensor for quantitativein vivovisualisation of auxin distributions. The sensor is based on theE. colitryptophan repressor (TrpR)8whose binding pocket was engineered for specific IAA binding and coupled to fluorescent proteins to employ FRET as readout. This sensor, unlike previous systems, enables direct monitoring of the fast uptake and clearance of auxin by individual cells in the plant as well as the graded spatial distribution along the root axis and its perturbation by transport inhibitors. Thus, our auxin sensor enables mapping of auxin concentrations at (sub)cellular resolution and their changes in time and space during plant life.
Human AKTIP interacts with ESCRT proteins and functions at the midbody in cytokinesis
Authors: Merigliano Chiara , Burla Romina , La Torre Mattia , Del Giudice Simona , Teo Hsiang Ling , Liew Chong Wai , Goh Wah Ing , Chojnowski Alexandre , Olmos Yolanda , Chiolo Irene , Carlton Jeremy G. , Raimondo Domenico , Verni Fiammetta , Stewart Colin , Rhodes Daniela , Wright Graham D. , Burke Brian , Saggio Isabella
Published: January 2020

To complete mitosis, the intercellular bridge that links daughter cells needs to be cleaved. This abscission step is carried out by the sequential recruitment of ESCRT proteins at the midbody. We report here that a new factor, named AKTIP, works in association with ESCRTs. We find that AKTIP binds to the ESCRT I subunit VPS28, and show by high resolution microscopy that AKTIP forms a ring in the dark zone of the intercellular bridge. This ring is positioned in between the circular structures formed by ESCRTs type III. Functionally, we observe that the reduction of AKTIP impinges on the recruitment of the ESCRT III member IST1 at the midbody and causes abscission defects. Taken together, these data indicate that AKTIP is a new factor that contributes to the formation of the ESCRT complex at the midbody and is implicated in the performance of the ESCRT machinery during cytokinetic abscission.
Computational estimates of mechanical constraints on cell migration through the extracellular matrix
Authors: Maxian Ondrej , Mogilner Alex , Strychalski Wanda
Published: January 2020

Cell migration through a three-dimensional (3D) extracellular matrix (ECM) underlies important physiological phenomena and is based on a variety of mechanical strategies depending on the cell type and the properties of the ECM. By using computer simulations, we investigate two such migration mechanisms – ‘push-pull’ (forming a finger-like protrusion, adhering to an ECM node, and pulling the cell body forward) and ‘rear-squeezing’ (pushing the cell body through the ECM by contracting the cell cortex and ECM at the cell rear). We present a computational model that accounts for both elastic deformation and forces of the ECM, an active cell cortex and nucleus, and for hydrodynamic forces and flow of the extracellular fluid, cytoplasm and nucleoplasm. We find that relations between three mechanical parameters – the cortex’s contractile force, nuclear elasticity and ECM rigidity – determine the effectiveness of cell migration through the dense ECM. The cell can migrate persistently even if its cortical contraction cannot deform a near-rigid ECM, but then the contraction of the cortex has to be able to sufficiently deform the nucleus. The cell can also migrate even if it fails to deform a stiff nucleus, but then it has to be able to sufficiently deform the ECM. Simulation results show that nuclear stiffness limits the cell migration more than the ECM rigidity. Simulations of the rear-squeezing mechanism of motility results in more robust migration with larger cell displacements than those with the push-pull mechanism over a range of parameter values.

Author summary

Computational simulations of models representing two different mechanisms of 3D cell migration in an extracellular matrix are presented. One mechanism represents a mesenchymal mode, characterized by finger-like actin protrusions, while the second mode is more amoeboid in that rear contraction of the cortex propels the cell forward. In both mechanisms, the cell generates a thin actin protrusion on the cortex that attaches to an ECM node. The cell is then either pulled (mesenchymal) or pushed (amoeboid) forward. Results show both mechanisms result in successful migration over a range of simulated parameter values as long as the contractile tension of the cortex exceeds either the nuclear stiffness or ECM stiffness, but not necessarily both. However, the distance traveled by the amoeboid migration mode is more robust to changes in parameter values, and is larger than in simulations of the mesenchymal mode. Additionally cells experience a favorable fluid pressure gradient when migrating in the amoeboid mode, and an adverse fluid pressure gradient in the mesenchymal mode.
Super-Beacons: open-source probes with spontaneous tuneable blinking compatible with live-cell super-resolution microscopy
Authors: Pereira Pedro M. , Gustafsson Nils , Marsh Mark , Mhlanga Musa M. , Henriques Ricardo
Published: January 2020

Localization based super-resolution microscopy relies on the detection of individual molecules cycling between fluorescent and non-fluorescent states. These transitions are commonly regulated by high-intensity illumination, imposing constrains to imaging hardware and producing sample photodamage. Here, we propose single-molecule self-quenching as a mechanism to generate spontaneous photoswitching independent of illumination. To demonstrate this principle, we developed a new class of DNA-based open-source Super-Resolution probes named Super-Beacons, with photoswitching kinetics that can be tuned structurally, thermally and chemically. The potential of these probes for live-cell friendly Super-Resolution Microscopy without high-illumination or toxic imaging buffers is revealed by imaging Interferon Inducible Transmembrane proteins (IFITMs) at sub-100nm resolutions.
Automated screening by 3D light-sheet microscopy with high spatial and temporal resolution reveals mitotic phenotypes
Authors: Eismann Björn , Krieger Teresa G , Beneke Jürgen , Bulkescher Ruben , Adam Lukas , Erfle Holger , Herrmann Carl , Eils Roland , Conrad Christian
Published: January 2020

3D cell cultures enable thein vitrostudy of dynamic biological processes such as the cell cycle, but their use in high-throughput screens remains impractical with conventional fluorescent microscopy. Here, we present a screening workflow for the automated evaluation of mitotic phenotypes in 3D cell cultures by light-sheet microscopy. After sample preparation by a liquid handling robot, three-dimensional cell spheroids are imaged for 24 hoursin totowith a dual inverted selective plane illumination (diSPIM) microscope with a much improved signal-to-noise ratio, higher imaging speed, isotropic resolution and reduced light exposure compared to a spinning disc confocal microscope. A dedicated high-content image processing pipeline implements convolutional neural network based phenotype classification. We illustrate the potential of our approach by siRNA knock-down and epigenetic modification of 28 mitotic target genes for assessing their phenotypic role in mitosis. By rendering light-sheet microscopy operational for high-throughput screening applications, this workflow enables target gene characterization or drug candidate evaluation in tissue-like 3D cell culture models.
Impact of the Basel III bank regulation on US agricultural lending
Authors: Kim Kevin Nooree , Katchova Ani L.
Published: January 2020

Purpose

Following the recent global financial crisis, US regulatory agencies issued laws to implement the Basel III accords to ensure the resiliency of the US banking sector. Theories predict that enhanced regulations may alter credit issuance of the regulated banks due to increased capital requirements, but the direction of changes might not be straightforward especially with respect to the agricultural loans. A decrease in credit availability from banks might pose a serious problem for farmers who rely on bank credit especially during economic recessions. The paper aims to discuss these issues.

Design/methodology/approach

In this study, the impact of Basel III regulatory framework implementation on agricultural lending in the USA is examined. Using panel data of FDIC-insured banks from 2008 to 2017, the agricultural loan volume and growth rates are examined for agricultural banks and all US banks.

Findings

The results show that agricultural loan growth rates have slowed down, but the amount of agricultural loan volume issuance still remained positive. More detailed examination finds that regulated agricultural banks have decreased both the agricultural loan volume and their loan exposure to the agricultural sector, showing a possible sign of credit crunch.

Originality/value

This study examines whether the implementation of the Basel III regulation has resulted in changes in agricultural loan issuance by US banks as predicted by the lending channel theory.
Sustainable construction
Authors: Khan Muhammad Waseem , Ali Yousaf
Published: January 2020

Purpose

The change in climate and depletion of natural resources because of the harmful emissions from different materials becomes a main issue for the globe. Some of the developed and developing countries have focused on this issue and performed research to provide a solution. The purpose of this study is to identify the best types of concrete based on its impact on the environment and economy.

Design/methodology/approach

The life cycle assessment and life cycle cost analysis of six concrete mixtures that include construction and demolition wastes (CDW), marble sludge, rice husk and bagasse ash as a partial replacement of cement, are performed. These types of concrete are compared with each other and with ordinary concrete to select the best possible concrete type for a developing country, like Pakistan.

Findings

The results show that, although for an agricultural country like Pakistan, the agriculture wastes such as rice husk and bagasse ash are preferable to be used, if the emissions of CO2 and CO from rice husk and NOx and SO2 from bagasse ash are properly controlled. However, based on the results, it is recommended to use the CDW in concrete because of the small amount of air emissions and affordable prices.

Originality/value

Through this study, a path has been provided to construction companies and relative government organizations of Pakistan, which leads to sustainable practices in the construction industry. Moreover, the base is provided for future researchers who want to work in this area, as for Pakistan, there is no database available that helps to identify the impact of different concrete on the environment.
Connecting theory and practice: reviewing six learning theories to inform online instruction
Authors: Brieger Earl , Arghode Vishal , McLean Gary
Published: January 2020

Purpose

The purpose of this paper is to analyze six learning theories, beyond those presented in an earlier article by the authors, and discuss their relevance and application in online instruction.

Design/methodology/approach

The following databases were used to review the literature on adult learning theories: Academic Search Premier, ERIC and ProQuest. The following key search terms were used in the search process: online instruction, cognitivism, connectivism, heutagogy, social learning theory, transformative learning theory and Vygotsky’s zone of proximal development. The titles of the identified articles were first reviewed for relevance, followed by the abstract, before any further review for suitability for inclusion in this article.

Findings

The theory comparison revealed that it is critical to ascertain which learning theory best matches an instructional situation and the background of the learners. The selected learning theories differ in several parameters. The theories were critiqued for their contributions to identified elements in promoting learning. The discussed theories suggest ways to improve online learning environments.

Research limitations/implications

Many adult perspectives about learning, while called theories, are largely lacking in evidence leading to them becoming theories. Thus, there remains a need for empirical evidence of these theories and their roles in online instruction. Comparisons of the application of these theories for adult learners in online instruction would also be useful in establishing the effectiveness of the various learning theories in different adult learning situations.

Practical implications

This paper provides a theoretical lens for adult instructors and instructional designers in incorporating these adult learning theories appropriately in improving online instruction.

Originality/value

This literature review uniquely critiques and compares common adult theories as they apply to adult online instruction.
Research on project risk response strategy selection based on grey K-shell algorithm
Authors: Chu Yanfeng , Wang Zhongren
Published: January 2020

Purpose

There are a large number of interdependent risk factors in complex project. Risk response strategy without considering risk correlation cannot achieve good risk response. Therefore, the purpose of this paper is to propose a risk response strategy selection model considering risk correlation based on the grey K-shell algorithm.

Design/methodology/approach

This paper mainly focuses on the measurement of two aspects of risk factors. One is the ability of the risk factors to influence other risk factors, another is the degree affected by other risk factors. Both of the above are measured by the grey K-shell algorithm improved in this paper, and the weights of these are used for the constructing of risk response strategy selection model.

Findings

The risk response strategy considering risk relevance is more effective than the risk response strategy without considering risk relevance. Also, results indicate that as the risk response budget increases the risk response effect also increases, and the increasing trend is weakens. The relative gap between the effect of response strategies considering risk relevance and the strategy without considering risk relevance increases first and, then, decreases with the increase of budget.

Originality/value

The results of this paper demonstrate that the risk response strategy considering risk relevance is more effective than not considering risk relevance. The approach presented in this paper can guide project managers’ risk decisions and may also help to find the best risk response budget.
Analyzing the usage of character groups and keyboard patterns in password creation
Authors: Kävrestad Joakim , Zaxmy Johan , Nohlberg Marcus
Published: January 2020

Purpose

Using passwords to keep account and data safe is very common in modern computing. The purpose of this paper is to look into methods for cracking passwords as a means of increasing security, a practice commonly used in penetration testing. Further, in the discipline of digital forensics, password cracking is often an essential part of a computer examination as data has to be decrypted to be analyzed. This paper seeks to look into how users that actively encrypt data construct their passwords to benefit the forensics community.

Design/methodology/approach

The study began with an automated analysis of over one billion passwords in 22 different password databases that leaked to the internet. The study validated the result with an experiment were passwords created on a local website was analyzed during account creation. Further a survey was used to gather data that was used to identify differences in password behavior between user that actively encrypt their data and other users.

Findings

The result of this study suggests that American lowercase letters and numbers are present in almost every password and that users seem to avoid using special characters if they can. Further, the study suggests that users that actively encrypt their data are more prone to use keyboard patterns as passwords than other users.

Originality/value

This paper contributes to the existing body of knowledge around password behavior and suggests that password-guessing attacks should focus on American letters and numbers. Further, the paper suggests that forensics experts should consider testing patterns-based passwords when performing password-guessing attacks against encrypted data.
Impact of female executives’ fraudulent behaviour on other women employees
Authors: Agnihotri Arpita , Bhattacharya Saurabh
Published: January 2020

Purpose

The purpose of this paper is to discuss the adverse impact of a female executive’s fraudulent behaviour on other female employees working in the same organisation.

Design/methodology/approach

This developmental study uses a comprehensive literature review and a set of propositions to identify the consequences of a female’s fraudulent activity on other female employees working in the focal organisation. It develops a conceptual framework for the same. Propositions are further supported by five focus group interviews.

Findings

Leveraging stigma-by-association theory, the paper asserts that fraud committed by one female executive in an organisation enhances discriminatory practices against other female employees in the organisation. The level of adverse impact is contingent on the seniority of the female executive committing the fraud, severity of the fraud, gender of the other female employees’ managers and diversity in culture in the organisation.

Research limitations/implications

This paper extends the stigma-by-association theory. In its original spirit, the theory describes how individuals who keep company with stigmatised individuals are also stigmatised. This study asserts that for this effect to take place, especially under fraudulent conditions, mere group affiliation, such as working in the same organisation, may cause an adverse effect on other women.

Originality/value

The paper is based on a rich conceptual and theoretical discussion that identifies the key consequences of a female executive’s fraudulent activity in an organisation. The study also conceptually establishes the moderating relationship between a female executive’s fraudulent activity and several key organisation-level variables.