bluuebunny/crossref_metadata_2025_split huggingface dataset:
A gene filter for comparative analysis of single-cell RNA-sequencing trajectory datasets
Authors: Wang Yutong , Thong Tasha , Saligrama Venkatesh , Colacino Justin , Balzano Laura , Scott Clayton 
Published: May 2019

AbstractUnsupervised feature selection, or gene filtering, is a common preprocessing step to reduce the dimensionality of single-cell RNA sequencing (scRNAseq) data sets. Existing gene filters operate on scRNAseq datasets in isolation from other datasets. When jointly analyzing multiple datasets, however, there is a need for gene filters that are tailored to comparative analysis. In this work, we present a method for ranking the relevance of genes for comparing trajectory datasets. Our method is unsupervised, i.e., the cell metadata are not assumed to be known. Using the top-ranking genes significantly improves performance compared to methods not tailored to comparative analysis. We demonstrate the effectiveness of our algorithm on previously published datasets from studies on preimplantation embryo development, neurogenesis and cardiogenesis.
Transcriptional Signatures of the Hierarchical Chronnectome Organization in the Human Brain
Authors: Liu Jin , Xia Mingrui , Wang Xindi , Liao Xuhong , He Yong 
Published: May 2019

AbstractThe chronnectome of the human brain represents the dynamics of functional organization in interacting regions, but its organizational principle and the underlying molecular mechanisms remain unclear. Using task-free fMRI and postmortem gene expression data, we conduct a transcriptome-chronnectome association study to investigate the spatial configurations of dynamic brain networks and their associations with transcriptional signatures. We reveal a spatial layout of network dynamics in the human brain chronnectome that reflects the cortical hierarchy and myelin content spanning from primary to transmodal areas. We further identify the transcriptional signature of this layout, with the top-related genes enriched for the ion channel and mitochondria terms. Moreover, the expression of these genes significantly predicts brain dynamics-behavior coupling. These findings highlight the hierarchical organizing principle and underlying molecular basis of the spatial configurations of dynamic brain networks, thereby contributing to our understanding of the associations among gene expression, network dynamics, and behaviors.
Hip retraction enhances walking stability on a ramp: an equilibrium point hypothesis-based study
Authors: Bahramian Alireza , Shamsi Elham , Towhidkhah Farzad , Jafari Sajad 
Published: May 2019

AbstractHip retraction is a phenomenon observed in human walking. The swing leg rotates backward at the end of the motion. Its positive effect on motion stability was reported in the literature based on some simple models for running or walking. In this study, it is shown that hip retraction angle increases in humans during their ascending and descending walk on a stair. In previous studies, hip retraction was modeled by defining a proper motion for the swing leg. According to the equilibrium point hypothesis, the central nervous system (CNS) defines only the equilibrium point(s) and stiffness(es) for body joint(s) to control the human motion. Human body motion emerges as its natural response as a result of the external forces and the defined equilibrium points of joints. Considering the hip torque as a spring-like model with an equilibrium point and stiffness, this study revealed that the hip retraction can be generated by the natural response of the swing leg. Besides, the stabilizing effect of hip retraction was demonstrated by a model for human’s ascending and descending walking on a ramp with a range of positive and negative angles, respectively. The findings suggest that the CNS needs to define equilibrium point just ahead of the stance leg to take advantage of the hip retraction effect on ascending and descending walks on a ramp.
Bayesian inference of differentially expressed transcripts and their abundance from multi-condition RNA-seq data
Authors: Chen Xi 
Published: May 2019

AbstractDeep sequencing of bulk RNA enables the differential expression analysis at transcript level. We develop a Bayesian approach to directly identify differentially expressed transcripts from RNA-seq data, which features a novel joint model of the sample variability and the differential state of individual transcripts. For each transcript, to minimize the inaccuracy of differential state caused by transcription abundance estimation, we estimate its expression abundance together with the differential state iteratively and enable the differential analysis of weakly expressed transcripts. Simulation analysis demonstrates that the proposed approach has a superior performance over conventional methods (estimating transcription expression first and then identifying differential state), particularly for lowly expressed transcripts. We further apply the proposed approach to a breast cancer RNA-seq data of patients treated by tamoxifen and identified a set of differentially expressed transcripts, providing insights into key signaling pathways associated with breast cancer recurrence.
DNSS2: improvedab initioprotein secondary structure prediction using advanced deep learning architectures
Authors: Hou Jie , Guo Zhiye , Cheng Jianlin 
Published: May 2019

AbstractMotivationAccurate prediction of protein secondary structure (alpha-helix, beta-strand and coil) is a crucial step for protein inter-residue contact prediction andab initiotertiary structure prediction. In a previous study, we developed a deep belief network-based protein secondary structure method (DNSS1) and successfully advanced the prediction accuracy beyond 80%. In this work, we developed multiple advanced deep learning architectures (DNSS2) to further improve secondary structure prediction.ResultsThe major improvements over the DNSS1 method include (i) designing and integrating six advanced one-dimensional deep convolutional/recurrent/residual/memory/fractal/inception networks to predict secondary structure, and (ii) using more sensitive profile features inferred from Hidden Markov model (HMM) and multiple sequence alignment (MSA). Most of the deep learning architectures are novel for protein secondary structure prediction. DNSS2 was systematically benchmarked on two independent test datasets with eight state-of-art tools and consistently ranked as one of the best methods. Particularly, DNSS2 was tested on the 82 protein targets of 2018 CASP13 experiment and achieved the best Q3 score of 83.74% and SOV score of 72.46%. DNSS2 is freely available at:https://github.com/multicom-toolbox/DNSS2.
A Novel L-Serine Exporter and Its Positive Regulator in Corynebacterium glutamicum
Authors: Zhang Xiaomei , Gao Yujie , Chen Ziwei , Xu Guoqiang , Zhang Xiaojuan , Li Hui , Shi Jinsong , Koffas Mattheos , Xu Zhenghong 
Published: May 2019

ABSTRACTExporters play an essential role in the fermentative production of amino acids. In Corynebacterium glutamicum, ThrE, which can export L-threonine and L-serine, is the only identified L-serine exporter so far. In this study, a novel L-serine exporter NCgl0580 was identified and characterized in C. glutamicum ΔSSAAI (SSAAI), and named as SerE (encoded by serE). Deletion of serE in SSAAI led to a 56.5% decrease in L-serine titer, whereas overexpression of serE compensated for the lack of serE with respect to L-serine titer. A fusion protein with SerE and enhanced green fluorescent protein (EGFP) was constructed to confirm that SerE localized at the plasma membrane. The function of SerE was studied by peptide feeding approaches, and the results showed that SerE is a novel exporter for L-serine and L-threonine in C. glutamicum. Subsequently, the interaction of a known L-serine exporter ThrE and SerE was studied, and the results suggested that SerE is more important than ThrE in L-serine export in SSAAI. Probe plasmid and electrophoretic mobility shift assays (EMSA) revealed NCgl0581 as the transcriptional regulator of SerE. Comparative transcriptomics between SSAAI and the NCgl0581 deletion strain showed that NCgl0581 regulated the transcription of 115 genes in C. glutamicum, among which the transcriptional level of NCgl0580 decreased 280-fold in a NCgl0581 deletion strain, indicating that NCgl0581 is a positive regulator of SerE. Thus, this study provides a novel target for L-serine and L-threonine export engineering as well as a novel global transcriptional regulator NCgl0581 in C. glutamicum.ImportanceExporters are gaining increasing attention for improving industrial production of amino acids. This study identified a novel exporter NCgl0580 for L-serine and L-threonine in C. glutamicum, and its positive regulator (NCgl0581), which was shown to be a novel global transcriptional regulator in C. glutamicum. This study provides a new target for engineering efflux of L-serine and L-threonine, expands the exporter and transcriptional regulator family, and enriches our understanding of amino acid transport system in C. glutamicum.
Dynamic Changes of G-CSF etc. Nine Cytokines in Mouse Bloodstream Infection Models of Staphylococcus aureus and Klebsiella pneumoniae and their Clinical Performances
Authors: He Shang , Yang Ming , Li Xinjun , Chen Chen , Yating Ma , Wang Chi , Yang Jiyong , Wang Chengbin 
Published: May 2019

AbstractBlood culture has been considered as the gold standard to diagnose the bacterial bloodstream infection, but its long turnaround time gravely obstructed the clinical medication by physicians. Cytokines play an important role in bacterial infection. The purpose of this study was to monitor the kinetic changes of nine cytokines in mouse infection models and to infer their diagnostic value in early infection.MethodsThe mouse bloodstream infection model of Staphylococcus aureus and the other model of Staphylococcus aureus and Klebsiella pneumoniae were constructed respectively, and the dynamic changes of nine cytokines were monitored within 48 hours after infected with 1/2 LD50 bacterial concentration. Cytokines with significant differences between the two groups and PBS control group from 0 to 6 hours after infection were selected for theoretical proof in patient sera that were clearly diagnosed as bloodstream infection. Receiver operating characteristic (ROC) curve analysis was conducted to determine the clinical differentiation of different cytokines.ResultsTwo models of S.aureus and K. pneumoniae bloodstream infection in mice were constructed successfully. In the two mouse models, six of the nine cytokines monitored were different (P<0.05) in each experimental group. In the 121 patient sera samples, three cytokines, IL-6, IL-12p70 and G-CSF in the infection groups and control group had showed differences. In particular, AUC of G-CSF was 0.9051, the accuracy is better than IL-6 for diagnosing the infection. In addition, only G-CSF was significantly different between the two infection groups and in the analysis of ROC curve, AUC is equal to 0.735.ConclusionsG-CSF can not only judge the bacterial infection and non-infection, but also distinguish the infection of S.aureus from K. pneumoniae.
DNA writing at a single genomic site enables lineage tracing and analog recording in mammalian cells
Authors: Loveless Theresa B. , Grotts Joseph H. , Schechter Mason W. , Forouzmand Elmira , Carlson Courtney K. , Agahi Bijan S. , Liang Guohao , Ficht Michelle , Liu Beide , Xie Xiaohui , Liu Chang C. 
Published: May 2019

SummaryThe study of intricate cellular and developmental processes in the context of complex multicellular organisms is difficult because it can require the non-destructive observation of thousands, millions, or even billions of cells deep within an animal. To address this difficulty, several groups have recently reported CRISPR-based DNA recorders that convert transient cellular experiences and processes into changes in the genome, which can then be read by sequencing in high-throughput. However, existing DNA recorders act primarily byerasingDNA: they use the random accumulation of CRISPR-induced deletions to record information. This is problematic because in the limit of progressive deletion, no record remains. Here, we present a new type of DNA recorder that acts primarily bywritingnew DNA. Our system, called CHYRON (Cell HistorY Recording by Ordered iNsertion), inserts random nucleotides at a single locus in temporal orderin vivoand can be applied as an evolving lineage tracer as well as a recorder of user-selected cellular stimuli. As a lineage tracer, CHYRON allowed us to perfectly reconstruct the population lineage relationships among 16 groups of human cells descended from four starting groups that were subject to a series of splitting steps. In this experiment, CHYRON progressively wrote and retained base insertions in 20% percent of cells where the average amount written was 8.4 bp (~14.5 bits), reflecting high information content and density. As a stimulus recorder, we showed that when the CHYRON machinery was placed under the control of a stress-responsive promoter, the frequency and length of writing reflected the dose and duration of the stress. We believe CHYRON represents a conceptual advance in DNA recording technologies where writing rather than erasing becomes the primary mode of information accumulation. With further engineering of CHYRON’s components to increase writing efficiency, CHYRON should lead to single-cell-resolution recording of lineage and other information through long periods of time in complex animals or tumors, advancing the pursuit of a full picture of mammalian development.
The fitness cost of mismatch repair mutators inSaccharomyces cerevisiae: partitioning the mutational load
Authors: Galeota-Sprung Benjamin , Guindon Breanna , Sniegowski Paul 
Published: May 2019

AbstractMutational load is the depression in a population’s mean fitness that results from the continual influx of deleterious mutations. Here, we directly estimate the mutational load in a population of haploidSaccharomyces cerevisiaethat are deficient for mismatch repair. We partition the load in haploids into two components. To estimate the load due to nonlethal mutations, we measure the competitive fitness of hundreds of randomly selected clones from both mismatch repair-deficient and - proficient populations. Computation of the mean clone fitness for the mismatch repair-deficient strain permits an estimation of the nonlethal load, and the histogram of fitness provides an interesting visualization of a loaded population. In a separate experiment, in order to estimate the load due to lethal mutations (i.e. the lethal mutation rate), we manipulate thousands of individual pairs of mother and daughter cells and track their fates. These two approaches yield point estimates for the two contributors to load, and the addition of these estimates is nearly equal to the separately measured short-term competitive fitness deficit for the mismatch repair-deficient strain. This correspondence suggests that there is no need to invoke direct fitness effects to explain the fitness difference between mismatch repair-deficient and - proficient strains. Assays in diploids are consistent with deleterious mutations in diploids tending towards recessivity. These results enhance our understanding of mutational load, a central population genetics concept, and we discuss their implications for the evolution of mutation rates.
Distinct antagonist-bound inactive states underlie the divergence in the structures of the dopamine D2 and D3 receptors
Authors: Lane J. Robert , Abramyan Ara M. , Verma Ravi Kumar , Lim Herman D. , Javitch Jonathan A. , Shi Lei 
Published: May 2019

ABSTRACTUnderstanding how crystal structures reflect the range of possible G protein-coupled receptor (GPCR) states is critical for rational drug discovery (RDD). Combining computational simulations with mutagenesis and binding studies, we find that the structure of the dopamine D2 receptor (D2R)/risperidone complex captures an inactive receptor conformation that accommodates some but not all antagonist scaffolds. Indeed, we find that eticlopride binds D2R in a configuration very similar to that seen in the D3R structure, in a pose that is incompatible with the D2R/risperidone structure. Moreover, our simulations reveal that extracellular loops 1 and 2 (EL1 and EL2) are highly dynamic, with spontaneous transitions of EL2 from the helical conformation in the D2R/risperidone structure to an extended conformation similar to that in the D3R/eticlopride structure. Our results highlight previously unappreciated conformational diversity and dynamics in the inactive state of a GPCR with potential functional implications. These findings are also of paramount importance for RDD as limiting a virtual screen to one state will miss relevant ligands.
Modeling tissue growth with the Stokes equation
Authors: Häkkinen Teemu J. , Jernvall Jukka , Hannukainen Antti 
Published: May 2019

AbstractWe present a cell-free continuum model for simulating generalized bulk tissue growth in 3D. We assume that the tissue behaves mechanically as viscous fluid so that its behavior can be described with the Stokes equation with mass sources. The growth is directed by a diffusing morphogen produced by specialized signaling centers, whose positions are established through a reaction-diffusion system coupled with differentiation. We further assume that the tissue interface may be stiff (modeled as surface tension), and that tissue adhesion can vary (modeled as variable viscosity). The numerical validity of the implementation is investigated using test cases with known solutions, and the model dynamics are demonstrated in simulations of idealized tissue growth. The combination of Stokes equation and diffusing morphogens allow the integration of patterning and growth as in real organs systems such as limbs and teeth. We propose that the presented techniques could be useful for simulating and exploring mechanistic principles of tissue growth in various developing organs.
Poor consumers’ preferences for nutritionally enhanced foods
Authors: Wanyama Rosina , Gödecke Theda , Jager Matthias , Qaim Matin 
Published: May 2019

PurposeMicronutrient malnutrition is a public health problem in many developing countries, especially in the poorest population segments. Fortification and other food-based approaches, such as using more nutritious ingredients in processing, could help to address this problem, but little is known about poor consumers’ attitudes toward nutritionally enhanced foods. The purpose of this paper is to analyze whether poor consumers in Africa would purchase foods with more nutritious ingredients and the related willingness and ability to pay.Design/methodology/approachA survey and choice experiment were conducted with 600 randomly selected households in the poorest neighborhoods of Nairobi (Kenya) and Kampala (Uganda). Participants were asked to choose between various alternatives of porridge flour with different types of nutritional attributes. The data were analyzed with mixed logit models. Porridge flour is widely consumed among the urban poor, so that the example can also provide interesting broader lessons.FindingsPoor consumers welcome foods that are micronutrient-fortified or include new types of nutritious ingredients. However, willingness to pay for nutritional attributes is small. New ingredients that are perceived to have little effect on taste and appearance are seen more positively than ingredients that may change food products more notably.Practical implicationsNew nutritionally enhanced foods have good potential in markets for the poor, if they build on local consumption habits and are not associated with significant price increases.Originality/valueThis is among the first studies to explicitly analyze poor consumers’ preferences for nutritionally enhanced foods.
The moderating effect of temporal distance on partitioned vs combined pricing
Authors: Choi Jungsil , Bolton Dorcia E. , Grishin Marija 
Published: May 2019

Purpose
This paper aims to explore how temporal distance influences the evaluation of partitioned pricing.

Design/methodology/approach
The effect of temporal distance on the effectiveness of partitioned pricing is tested using data collected through experiments in the USA.

Findings
Study 1 reveals that people perceive partitioned pricing as more attractive than combined pricing, but only for a distant event. Study 2 reveals that individuals predisposed to global information processing perceive partitioned pricing as more attractive than combined pricing. However, for individuals who commonly engage in local processing, combined pricing was equally attractive as partitioned pricing. In Study 3, the authors examine a boundary condition and find that the joint effect of temporal distance and partitioned pricing is attenuated when the purchase is made for a gift in which consumers are assumed to pay less attention to a surcharge. In Study 4, the authors examine how partitioned pricing influences a consumer’s choice in terms of temporal distance.

Practical implications
The findings provide practical guidelines to business leaders looking for practical guidelines for pricing policy decisions.

Originality/value
Previous research shows that partitioned pricing is more effective in increasing consumers’ purchase intention and demand than combined pricing. In the present research, the authors introduce temporal distance as an important moderator that affects the effectiveness of partitioned pricing.
Antecedents and consequences of staff-related fraud in the Ghanaian banking industry
Authors: Asmah Alexander Ekow , Atuilik Williams Abayaawien , Ofori Dominic 
Published: May 2019

PurposeThe purpose of this paper is to investigate the antecedents and consequences of employee fraud, focusing on the banking industry in Ghana.Design/methodology/approachA major bank was selected for the case study analysis. The researchers used qualitative data analysis for the study. Content analysis of investigation reports and interviews of employees from different functional areas were used as the main data collection tools.FindingsThis study found that loans contracted by bank employees with huge repayment amounts put financial pressure on them to commit fraud. The study also found that inadequate controls in some areas of the bank can fuel the commission of fraud. In addition, aggrieved employees have a high propensity of committing fraud. Huge punitive consequences were noted to exist for employees who perpetrate fraud, and shareholders are also affected by the fraudulent behaviour of employees.Research limitations/implicationsFindings shown in the study confirm the hypotheses of the fraud triangle theory on the causes of fraud despite its criticisms. The findings are also consistent with extant studies on the antecedents and consequences of fraud. The use of one bank for the case study analysis as well as the three-year analysis period impose a limitation on the study. Future studies can explore fraud using other different theoretical lenses. Gathering data from more than one bank and for a longer period of analysis may provide more accurate results.Practical implicationsThis study provides some recommendations for fraud prevention in the banking industry in Ghana. The major one is the need for the central bank to collaborate with financial institutions to set up an effective creditworthiness system that will aid the monitoring of activities of the banks. Banks should also ensure that systems of controls are reviewed regularly to identify and deal with fraud.Originality/valueThis study is original, as it focuses on an industry that is highly susceptible to fraud due to issues of confidentiality with data and with scanty literature on fraud.