bluuebunny/crossref_metadata_2025 huggingface dataset:
ClassiPhages 2.0: Sequence-based classification of phages using Artificial Neural Networks
Authors: Chibani Cynthia Maria , Meinecke Florentin , Farr Anton , Dietrich Sascha , Liesegang Heiko
Published: February 2019

Background/ Motivation

In the era of affordable next generation sequencing technologies we are facing an exploding amount of new phage genome sequences. This requests high throughput phage classification tools that meet the standards of the International Committee on Taxonomy of Viruses (ICTV). However, an accurate prediction of phage taxonomic classification derived from phage sequences still poses a challenge due to the lack of performant taxonomic markers. Since machine learning methods have proved to be efficient for the classification of biological data we investigated how artificial neural networks perform on the task of phage taxonomy.

Results

In this work, 5,920 constructed and refined profile Hidden Markov Models (HMMs), derived from 8,721 phage sequences classified into 12 well known phage families, were used to scan phage proteome datasets. The resulting Phage Family-proteome to Phage-derived-HMMs scoring matrix was used to develop and train an Artificial Neural Network (ANN) to find patterns for phage classification into one of the phage families. Results show that using the 100 fold cross-validation test, the proposed method achieved an overall accuracy of 84.18 %. The ANN was tested on a set of unclassified phages and resulted in a taxonomic prediction. The ANN prediction was benchmarked against the prediction resulting of multi-HMM hits, and showed that the ANN performance is dependent on the quality of the input matrix.

Conclusions

We believe that, as long as some phage families on public databases are underrepresented, multi-HMM hits can be used as a classification method to populate those phage families, which in turn will improve the performance and accuracy of the ANN. We believe that the proposed method is an effective and promising method for phage classification. The good performance of the ANN and HMM based predictor indicates the efficiency of the method for phage classification, where we foresee its improvement with an increasing number of sequenced viral genomes.
Evaluation of computational genotyping of Structural Variations for clinical diagnoses
Authors: Chander Varuna , Gibbs Richard A. , Sedlazeck Fritz J.
Published: February 2019

Background

In recent years, Structural Variation (SV) has been identified as having a pivotal role in causing genetic disease. Nevertheless, the discovery of SVs based on short DNA sequence reads from next-generation DNA sequence methods is still error-prone, suffering from low sensitivity and high false discovery. These shortcomings can be partially overcome with the use of long reads, but the current expense precludes their application for routine clinical diagnostics. Structural Variation genotyping, on the other hand, offers cost-effective application as diagnostic tool in the clinic, with potentially no false positives and low occurrence of false negatives.

Results

We assess five state- of-the- art SV genotyping software methods that test short read sequence data. These methods are characterized based on their ability to genotype certain SV types and size ranges. Furthermore, we analyze their applicability to parse different VCF file sub-formats, or to rely on specific meta information that is not always at hand. We compare the SV genotyping methods across a range of simulated and real data including SVs that were not found with Illumina data alone. We assess their sensitivity and ability to filter out initial false discovery calls to assess their reliability.

Conclusion

Our results indicate that, although SV genotypers have superior performance to SV callers, there are performance limitations that suggest the need for further innovation.
A deconvolution algorithm for multiecho functional MRI: Multiecho Sparse Paradigm Free Mapping
Authors: Caballero-Gaudes César , Moia Stefano , Panwar Puja , Bandettini Peter A. , Gonzalez-Castillo Javier
Published: February 2019

This work introduces a novel algorithm for deconvolution of the BOLD signal in multiecho fMRI data: Multiecho Sparse Paradigm Free Mapping (ME-SPFM). Assuming a linear dependence of the BOLD percent signal change on the echo time (TE) and using sparsity-promoting regularized least squares estimation, ME-SPFM yields voxelwise time-varying estimates of the changes in the transverse relaxationwithout prior knowledge of the timings of individual BOLD events. Our results in multi-echo fMRI data collected during a multi-task event-related paradigm at 3 Tesla demonstrate that the maps ofchanges obtained with ME-SPFM at the times of the stimulus trials show high spatial and temporal concordance with the activation maps and BOLD signals obtained with standard model-based analysis. This method yields estimates ofhaving physiologically plausible values. Owing to its ability to blindly detect events, ME-SPFM also enables us to mapassociated with spontaneous, transient BOLD responses occurring between trials. This framework is a step towards deciphering the dynamic nature of brain activity in naturalistic paradigms, resting-state or experimental paradigms with unknown timing of the BOLD events.
Mechanochemical coupling and junctional forces during collective cell migration
Authors: Bui J. , Conway D. E. , Heise R. L. , Weinberg S.H.
Published: February 2019

Cell migration, a fundamental physiological process in which cells sense and move through their surrounding physical environment, plays a critical role in development and tissue formation, as well as pathological processes, such as cancer metastasis and wound healing. During cell migration, dynamics are governed by the bidirectional interplay between cell-generated mechanical forces and the activity of Rho GTPases, a family of small GTP-binding proteins that regulate actin cytoskeleton assembly and cellular contractility. These interactions are inherently more complex during the collective migration of mechanically coupled cells, due to the additional regulation of cell-cell junctional forces. In this study, we present a minimal modeling framework to simulate the interactions between mechanochemical signaling in individual cells and interactions with cell-cell junctional forces during collective cell migration. We find that migration of individual cells depends on the feedback between mechanical tension and Rho GTPase activity in a biphasic manner. During collective cell migration, waves of Rho GTPase activity mediate mechanical contraction/extension and thus synchronization throughout the tissue. Further, cell-cell junctional forces exhibit distinct spatial patterns during collective cell migration, with larger forces near the leading edge. Larger junctional force magnitudes are associated with faster collective cell migration and larger tissue size. Simulations of heterogeneous tissue migration exhibit a complex dependence on the properties of both leading and trailing cells. Computational predictions demonstrate that collective cell migration depends on both the emergent dynamics and interactions between cellular-level Rho GTPase activity and contractility, and multicellular-level junctional forces.
Precision-weighting of superior frontal cortex unsigned prediction error signals benefits learning, is mediated by dopamine, and is impaired in psychosis
Authors: Haarsma J. , Fletcher P.C. , Griffin J.D. , Taverne H.J. , Ziauddeen H. , Spencer T.J. , Goodyer I. , Diederen K.M.J. , Murray G.K
Published: February 2019

Recent theories of cortical function construe the brain as performing hierarchical Bayesian inference. According to these theories, the precision of cortical unsigned prediction error (i.e., surprise) signals plays a key role in learning and decision-making, to be controlled by dopamine, and to contribute to the pathogenesis of psychosis. To test these hypotheses, we studied learning with variable outcome-precision in healthy individuals after dopaminergic modulation and in patients with early psychosis. Behavioural computational modelling indicated that precision-weighting of unsigned prediction errors benefits learning in health, and is impaired in psychosis. FMRI revealed coding of unsigned prediction errors relative to their precision in bilateral superior frontal gyri and dorsal anterior cingulate, which was perturbed by dopaminergic modulation, impaired in psychosis, and associated with task performance and schizotypy. We conclude that precision-weighting of cortical prediction error signals is a key mechanism through which dopamine modulates inference and contributes to the pathogenesis of psychosis.
A SMAD1/5-YAP signaling module drives radial glia self-amplification and growth of the developing cerebral cortex
Authors: Najas Sonia , Pijuan Isabel , Esteve-Codina Anna , Usieto Susana , Martinez Juan D. , Zwijsen An , Arbonés Maria L. , Martí Elisa , Le Dréau Gwenvael
Published: February 2019

The growth and evolutionary expansion of the cerebral cortex are defined by the spatial-temporal production of neurons, which itself depends on the decision of radial glial cells (RGCs) to self-amplify or to switch to neurogenic divisions. The mechanisms regulating these RGC fate decisions are still incompletely understood. Here we describe a novel and evolutionarily conserved role of the canonical BMP transcription factors SMAD1/5 in controlling neurogenesis and growth during corticogenesis. Reducing the expression of both SMAD1 and SMAD5 in neural progenitors at early mouse cortical development caused microcephaly and an increased production of early-born cortical neurons at the expense of late-born ones, which correlated with the premature differentiation and depletion of the pool of cortical progenitors. Gain- and loss-of-function experiments performed during early cortical neurogenesis in the chick revealed that SMAD1/5 activity supports self-amplifying RGC divisions and restrain the neurogenic ones. Furthermore, we demonstrate that SMAD1/5 stimulate RGC self-amplification through the positive post-transcriptional regulation of the Hippo signaling effector YAP. We anticipate this SMAD1/5-YAP signaling module to be fundamental in controlling growth and evolution of the amniote cerebral cortex.
Cellular heterogeneity results from indirect effects under metabolic tradeoffs
Authors: Ollé-Vila Aina , Solé Ricard
Published: February 2019

The emergence of multicellularity requires the coexistence of diverse cellular populations displaying cooperative relationships. This enables long-term persistence of cellular consortia, particularly under environmental constraints that challenge cell survival. Toxic environments are known to trigger the formation of multicellular consortia capable of dealing with waste while promoting cell diversity as a way to overcome selection barriers. In this context, recent theoretical studies suggest that an environment containing both resources and toxic waste can promote the emergence of complex, spatially distributedproto-organismsexhibiting division of labor and higher-scale features beyond the cell-cell pairwise interactions. Some previous non-spatial models suggest that the presence of a growth inhibitor can trigger the coexistence of competitive species in an antibiotic-resistance context. In this paper we further explore this idea using both mathematical and computational models taking the most fundamental features of theproto-organismsinteractions. It is shown that this resource-waste environmental context, in which both species are lethally affected by the toxic waste and metabolic tradeoffs are present, favours the maintenance of diverse populations. A spatial, stochastic extension confirms our basic results. The evolutionary and ecological implications of these results are outlined.
Complete assembly ofEscherichia coliST131 genomes using long reads demonstrates antibiotic resistance gene variation within diverse plasmid and chromosomal contexts
Authors: Decano Arun , Ludden Catherine , Feltwell Theresa , Judge Kim , Parkhill Julian , Downing Tim
Published: February 2019

The incidence of infections caused by extraintestinalEscherichia coli(ExPEC) is rising globally, which is a major public health concern. ExPEC strains that are resistant to antimicrobials have been associated with excess mortality, prolonged hospital stays and higher healthcare costs.E. coliST131 is a major ExPEC clonal group worldwide with variable plasmid composition, and has an array of genes enabling antimicrobial resistance (AMR). ST131 isolates frequently encode the AMR genesblaCTX-M-14/15/27, which are often rearranged, amplified and translocated by mobile genetic elements (MGEs). Short DNA reads do not fully resolve the architecture of repetitive elements on plasmids to allow MGE structures encodingblaCTX-Mgenes to be fully determined. Here, we performed long read sequencing to decipher the genome structures of sixE. coliST131 isolated from six patients. Most long read assemblies generated entire chromosomes and plasmids as single contigs, contrasting with more fragmented assemblies created with short reads alone. The long read assemblies highlighted diverse accessory genomes withblaCTX-M-15,blaCTX-M-14andblaCTX-M-27genes identified in three, one and one isolates, respectively. One sample had noblaCTX-Mgene. Two samples had chromosomalblaCTX-M-14andblaCTX-M-15genes, and the latter was at three distinct locations, likely transposed by the adjacent MGEs: ISEcp1, IS903Band Tn2. This study showed that AMR genes exist in multiple different chromosomal and plasmid contexts even between closely-related isolates within a clonal group such asE. coliST131.

Importance

Drug-resistant bacteria are a major cause of illness worldwide and a specific subtype calledEscherichia coliST131 cause a significant amount of these infections. ST131 become resistant to treatment by modifying their DNA and by transferring genes among one another via large packages of genes called plasmids, like a game of pass-the-parcel. Tackling infections more effectively requires a better understanding of what plasmids are being exchanged and their exact contents. To achieve this, we applied new high-resolution DNA sequencing technology to six ST131 samples from infected patients and compared the output to an existing approach. A combination of methods shows that drug-resistance genes on plasmids are highly mobile because they can jump into ST131’s chromosomes. We found that the plasmids are very elastic and undergo extensive rearrangements even in closely related samples. This application of DNA sequencing technologies illustrates at a new level the highly dynamic nature of ST131 genomes.
Necrotizing enterocolitis is preceded by increased gut bacterial replication, Klebsiella, and fimbriae-encoding bacteria that may stimulate TLR4 receptors
Authors: Olm Matthew R. , Bhattacharya Nicholas , Crits-Christoph Alexander , Firek Brian A. , Baker Robyn , Song Yun S. , Morowitz Michael J. , Banfield Jillian F.
Published: February 2019

Necrotizing enterocolitis (NEC) is a devastating intestinal disease that occurs primarily in premature infants. We performed genome-resolved metagenomic analysis of 1,163 fecal samples from premature infants to identify microbial features predictive of NEC. Features considered include genes, bacterial strain types, eukaryotes, bacteriophages, plasmids and growth rates. A machine learning classifier found that samples collected prior to NEC diagnosis harbored significantly more Klebsiella, bacteria encoding fimbriae, and bacteria encoding secondary metabolite gene clusters related to quorum sensing and bacteriocin production. Notably, replication rates of all bacteria, especially Enterobacteriaceae, were significantly higher two days before NEC diagnosis. The findings uncover biomarkers that could lead to early detection of NEC and targets for microbiome-based therapeutics.
Programmable DNA cleavage by Ago nucleases from mesophilic bacteria Clostridium butyricum and Limnothrix rosea
Authors: Kuzmenko Anton , Yudin Denis , Ryazansky Sergei , Kulbachinskiy Andrey , Aravin Alexei A.
Published: February 2019

Argonaute (Ago) proteins are the key players in RNA interference in eukaryotes, where they function as RNA-guided RNA endonucleases. Prokaryotic Argonautes (pAgos) are much more diverse than their eukaryotic counterparts but their cellular functions and mechanisms of action remain largely unknown. Some pAgos were shown to use small DNA guides for endonucleolytic cleave of complementary DNA in vitro. However, previously studied pAgos from thermophilic prokaryotes function at elevated temperatures which limits their potential use as a tool in genomic applications. Here, we describe two pAgos from mesophilic bacteria, Clostridium butyricum (CbAgo) and Limnothrix rosea (LrAgo), that act as DNA-guided DNA nucleases at physiological temperatures. In contrast to previously studied pAgos, CbAgo and LrAgo can use not only 5’-phosphorylated but also 5’-hydroxyl DNA guides, with diminished precision of target cleavage. Both LrAgo and CbAgo can tolerate guide/target mismatches in the seed region, but are sensitive to mismatches in the 3’-guide region. CbAgo is highly active under a wide range of conditions and can be used for programmable endonucleolytic cleavage of both single-stranded and double-stranded DNA substrates at moderate temperatures. The biochemical characterization of mesophilic pAgo proteins paths the way for their use for DNA manipulations both in vitro and in vivo.
YAP is involved in replenishment of granule cell progenitors following injury to the neonatal cerebellum
Authors: Yang Zhaohui , Joyner Alexandra L.
Published: February 2019

The cerebellum (CB) undergoes major rapid growth during the third trimester and early neonatal stage in humans, making it vulnerable to injuries in pre-term babies. Experiments in mice have revealed a remarkable ability of the neonatal CB to recover from injuries around birth. In particular, recovery following irradiation-induced ablation of granule cell precursors (GCPs) involves adaptive reprogramming of Nestin-expressing glial progenitors (NEPs). Sonic hedgehog signaling is required for the initial step in NEP reprogramming; however, the full spectrum of developmental signaling pathways that promote NEP-driven regeneration is not known. Since the growth regulatory Hippo pathway has been implicated in the repair of several tissue types, we tested whether Hippo signaling is involved in regeneration of the CB. Using mouse models, we found that the Hippo pathway transcriptional co-activator YAP (Yes-associated protein) but not TAZ (transcriptional coactivator with PDZ binding motif) is required in NEPs for full recovery of the CB following irradiation one day after birth. The size of the adult CB, and in particular the internal granule cell layer produced by GCPs, is significantly reduced in mutants, and the organization of Purkinje cells and Bergmann glial fibers is disrupted. Surprisingly, the initial proliferative response ofYapmutant NEPs to irradiation is normal and the cells migrate to the GCP niche, but then undergo increased cell death. Loss ofYapin NEPs or GCPs during normal development leads to only mild defects in differentiation. Moreover, loss ofTazdoes not abrogate regeneration of GCPs byYapmutant NEPs or alter development of the cerebellum. Our study provides new insights into the molecular signaling underlying postnatal cerebellar development and regeneration.
Analysis of synapse-level neuronal morphology in human post-mortem brain tissue
Authors: Das Sujan C. , Chen Danli , Callor W. Brandon , Christensen Eric , Coon Hilary , Williams Megan E.
Published: February 2019

Many cognitive and psychiatric disorders are thought to be disorders of the synapse, yet the precise synapse defects underlying these disorders remain unknown. Because synapses are highly specialized anatomical structures, defects in synapse formation and function can often be observed as changes in micro-scale neuroanatomy. Unfortunately, few methods are available for accurate analysis of synapses in human post-mortem tissues. Here, we present a new methodological pipeline for assessing synapse-level neuron morphology in human post-mortem tissue that is accurate, rapid, and relatively inexpensive. Our method uses small tissue blocks from postmortem human brains, immersion fixation, single cell resolution by dye labeling, and confocal microscopy. As proof of principle, we analyzed pre-and postsynaptic structures from hippocampi of 13 individuals aged 4 months to 71 years. Our results suggest that postsynaptic CA1 dendritic spine shape and density are stable across ages, while presynaptic DG mossy fiber boutons undergo significant structural rearrangements with normal aging. This suggests that mossy fiber synapses, which play a major role in learning and memory, remain dynamic throughout life. Importantly, we find no effect of postmortem intervals up to 28 hours on neuron morphology. Thus, the ease of our new protocol should facilitate higher powered studies of human synapse structure in healthy and diseased states.
Differential functional roles of fibroblasts and pericytes in the formation of tissue-engineered microvascular networks in vitro
Authors: Kosyakova Natalia , Kao Derek D. , López-Giráldez Francesc , Spindler Susann , Graham Morven , James Kevin J. , Shin Jee Won , Liu Xinran , Tietjen Gregory T. , Pober Jordan S. , Chang William G.
Published: February 2019

Aims

Formation of a perfusable microvascular network (μVN) is critical for tissue engineering of solid organs. Stromal cells can support endothelial cell (EC) self-assembly into a μVN, but distinct stromal cell populations may play different roles in this process. Here we investigated the effects that two widely used stromal cells populations, fibroblasts (FBs) and pericytes (PCs), have on μVN formation.

Methods and results

We examined the effects of adding defined stromal cell populations on the self-assembly of ECs derived from human endothelial colony forming cells (ECFCs) into perfusable μVNs in fibrin gels cast within a microfluidics chamber. ECs alone fail to fully assemble a perfusable μVN. Human lung FBs stimulate the formation of EC lined μVNs within microfluidic devices. RNA-seq analysis suggested that FBs produce high levels of hepatocyte growth factor (HGF), and addition of recombinant HGF improved μVN formation within devices. Human placental PCs could not substitute for FBs, but in the presence of FBs, PCs closely associated with ECs, formed a common basement membrane, extended microfilaments intercellularly, and reduced microvessel diameters.

Conclusions

Different stromal cell types provide different functions in microvessel assembly by ECs. FBs support μVN formation by providing paracrine growth factors whereas PCs directly interact with ECs to modify microvascular morphology.

Statement of Contribution

Natalia Kosyakova, Derek Kao, William G. Chang were primarily responsible for the conception, design, interpretation of experiments, and drafting of the manuscript. Francesc López-Giráldez carried out analysis of RNA-seq data. Susann Spindler and Gregory Tietjen assisted with microvessel analysis software. Morven Graham and Xinran Liu assisted with the electron microscopy. Kevin J. James and Jee Won Shin assisted with data collection. Jordan Pober assisted with a critical review of manuscript and experimental design.
CHETAH: a selective, hierarchical cell type identification method for single-cell RNA sequencing
Authors: de Kanter Jurrian K. , Lijnzaad Philip , Candelli Tito , Margaritis Thanasis , Holstege Frank C.P.
Published: February 2019

Cell type identification is essential for single-cell RNA sequencing (scRNA-seq) studies that are currently transforming the life sciences. CHETAH (CHaracterization of cEll Types Aided by Hierarchical clustering) is an accurate cell type identification algorithm that is rapid and selective, including the possibility of intermediate or unassigned categories. Evidence for assignment is based on a classification tree of previously available scRNA-seq reference data and includes a confidence score based on the variance in gene expression per cell type. For cell types represented in the reference data, CHETAH’s accuracy is as good as existing methods. Its specificity is superior when cells of an unknown type are encountered, such as malignant cells in tumor samples which it pinpoints as intermediate or unassigned. Although designed for tumor samples in particular, the use of unassigned and intermediate types is also valuable in other exploratory studies. This is exemplified in pancreas datasets where CHETAH highlights cell populations not well represented in the reference dataset, including cells with profiles that lie on a continuum between that of acinar and ductal cell types. Having the possibility of unassigned and intermediate cell types is pivotal for preventing misclassification and can yield important biological information for previously unexplored tissues.
Human genetic disease is greatly influenced by the underlying fragility of evolutionarily ancient genes
Authors: Martin-Geary Alexandra , Reardon Mark , Keith Benjamin , Tassabehji May , Robertson David L.
Published: February 2019

The ability to predict disease association in human genes is enhanced by an evolutionary understanding. Importantly genes linked with heritable disease, particularly dominant disorders, tend to have undergone duplication in our early vertebrate ancestors, with a strong asymmetric relationship between disease-association within duplicate/paralog pairs. Using a novel phylogenetic approach, alongside a whole-genome comparative analysis, we show that contrary to the accepted compensatory model of disease evolution, the majority of disease-associations reside with the more evolutionary constrained gene, inferred to most closely resemble the progenitor. This indicates that the strong association between paralogs, specifically ohnologs, and dominant disorders is often a consequence of a mechanism through which pre-existing dosage sensitive/haploinsufficient genes are successfully duplicated and retained. Heritable disease is thus as much a consequence of the fragility of evolutionarily more ancient genes as compensatory mechanisms. From these findings, we demonstrate the utility of a new model with which to predict disease associated genes in the human genome.
Transient developmental increase of prefrontal activity alters network maturation and causes cognitive dysfunction in adult mice
Authors: Bitzenhofer Sebastian H. , Pöpplau Jastyn A. , Chini Mattia , Marquardt Annette , Hanganu-Opatz Ileana L.
Published: February 2019

Disturbed neuronal activity in neuropsychiatric pathologies emerges during development and might cause multifold neuronal dysfunction by interfering with apoptosis, dendritic growth and synapse formation. However, how altered electrical activity early in life impacts neuronal function and behavior of adults is unknown. Here, we address this question by transiently increasing the coordinated activity of layer 2/3 pyramidal neurons in the medial prefrontal cortex of neonatal mice and monitoring long-term functional and behavioral consequences. We show that increased activity during early development causes premature maturation of pyramidal neurons and alters interneuron density. Consequently, reduced inhibitory feedback by fast-spiking interneurons and excitation/inhibition imbalance in prefrontal circuits of young adults result in weaker evoked synchronization in gamma frequency. These structural and functional changes ultimately lead to poorer mnemonic and social abilities. Thus, prefrontal activity during early development actively controls the cognitive performance of adults and might be critical for cognitive symptoms of neuropsychiatric diseases.
Temporal dynamics of inhalation-linked activity across defined subpopulations of mouse olfactory bulb neurons imaged in vivo
Authors: Short Shaina M. , Wachowiak Matt
Published: February 2019

In mammalian olfaction, inhalation drives the temporal patterning of neural activity that underlies early olfactory processing, and a single inhalation of odorant is sufficient for odor perception. However, how the neural circuits that process incoming olfactory information are activated in the context of inhalation-linked dynamics remains poorly understood. To better understand early olfactory processing in vivo, we used an artificial inhalation paradigm combined with two-photon calcium imaging to compare the dynamics of activity evoked by odorant inhalation across major cell types of the mouse olfactory bulb. Transgenic models and cell-type specific genetic tools were used to express GCaMP6f or jRGECO1a in mitral and tufted cell subpopulations, olfactory sensory neurons and two major juxtaglomerular interneuron classes, and responses to a single inhalation of odorant were compared. Activity in all cell types was strongly linked to inhalation, and all cell types showed some variance in the latency, rise-times and durations of their inhalation-linked response patterns. The dynamics of juxtaglomerular interneuron activity closely matched that of sensory neuron inputs, while mitral and tufted cells showed the highest diversity in dynamics, with a range of latencies and durations that could not be accounted for by heterogeneity in the dynamics of sensory input. Surprisingly, temporal response patterns of mitral and superficial tufted cells were highly overlapping such that these two subpopulations could not be distinguished on the basis of their inhalation-linked dynamics, with the exception of a subpopulation of superficial tufted cells expressing the peptide transmitter cholecystokinin. Overall, these results support a model in which diversity in inhalation-linked patterning of OB output arises first at the level of OSN inputs to the OB and is enhanced by feedforward inhibition from juxtaglomerular interneurons which differentially impacts different subpopulations of OB output neurons.
Individual alpha frequency increases during a task but is unchanged by alpha-band flicker
Authors: Gray Michael J. , Emmanouil Tatiana A.
Published: February 2019

Visual perception fluctuates in-synch with ongoing neural oscillations in the delta, theta, and alpha frequency bands of the human EEG. Supporting the relationship between alpha and perceptual sampling, recent work has demonstrated that variations in individual alpha frequency (IAF) correlate with the ability to discriminate one from two stimuli presented briefly in the same location. Other studies have found that after being presented with a flickering stimulus at alpha frequencies, perception of near-threshold stimuli fluctuates for a short time at the same frequency. Motivated by previous work, we were interested in whether this alpha entrainment involves shifts in IAF. While recording EEG, we tested whether two-flash discrimination (a behavioral correlate of IAF) can be influenced by ∼1s of rhythmic visual stimulation at two different alpha frequencies (8.3hz and 12.5hz). Speaking against the bottom-up malleability of IAF, we found no change in IAF during stimulation and no change in two-flash discrimination immediately afterwards. We also found synchronous activity that persisted after 12.5hz stimulation, which suggests that a separate source of alpha was entrained. Importantly, we replicated the correlation between IAF and two-flash discrimination in a no-stimulation condition, demonstrating the sensitivity of our behavioral measure. We additionally found that IAF increased during the task compared to rest, which demonstrates that IAF is influenced by top-down factors but is not involved in entrainment. In the framework of existing findings, we suggest that visual entrainment may involve ongoing perceptually-relevant oscillations from the delta to alpha frequency bands, serving to maintain rhythmic temporal expectations.
Vibrational Properties of a Hemispherical Shell With Its Inner Fluid Pressure: An Inverse Method for Noninvasive Intracranial Pressure Monitoring
Authors: Eslaminejad Ashkan , Ziejewski Mariusz , Karami Ghodrat
Published: February 2019

Vibration due to a hammer impact on an aluminum hemisphere fully filled with water is determined to study the frequency response of the structure at different inner fluid pressures. Modal analysis techniques are utilized on the frequency response function (FRF) to extract the modal frequencies and the damping ratios at each pressure level. As fluid pressure increases, changes to the peaks of frequency response are observed. Due to this, modal frequencies will also undergo some shifts with changes in the repeated poles of frequency response. Changes can also be observed in singular bending wave modes. An inverse analysis of such changes due to inner pressure in modal frequencies of the structure can make a possible method for using vibrational stimulus and response in a noninvasive intracranial pressure (ICP) monitoring system.
Combining Pole Placement and Online Empirical Mode Decomposition Methods to Adaptive Active Control of Structural Vibration
Authors: Massouleh S. H. Momeni , Kordkheili S. A. Hosseini , Navazi H. Mohammad , Bahai H.
Published: February 2019

Using a combination of the pole placement and online empirical mode decomposition (EMD) methods, a new algorithm is proposed for adaptive active control of structural vibration. The EMD method is a time-frequency domain analysis method that can be used for nonstationary and nonlinear problems. Combining the EMD method and Hilbert transform, which is called Hilbert–Huang transform, achieves a method that can be implemented to extract instantaneous properties of signals such as structural response dominant instantaneous frequencies. In the proposed algorithm, these estimated instantaneous properties are utilized to improve the pole-placement method as an adaptive active control technique. The required active control gains are obtained using a genetic algorithm scheme, and optimal gains are calculated corresponding to preselected excitation frequencies. An algorithm is also introduced to choose excitation frequencies based on online EMD method resolution. In order to investigate the efficiency of the proposed method, some case studies that include a discrete model, continuous samples of beam and plate structures, and experimental cantilevered beam are carried out, and the results of the proposed method are compared with the preset (nonadaptive) optimal gains conditions.
Effect of Surface Wave on Development of Turbulent Boundary Layer Over a Train of Rib Roughness
Authors: Singh Santosh Kumar , Raushan Pankaj Kumar , Debnath Koustuv , Mazumder B. S.
Published: February 2019

In this paper, detailed experimental results are reported to study the effect of the surface wave of different frequencies on unidirectional current over the bed-mounted train of rib roughness. The model roughness used in this study is transverse square ribs that lengthened across the entire width of the recirculating wave channel. The center-to-center rib pitch (P) was constant during the experiments, thus generating a broad range of near-bed flow patterns for each of the three different surface wave frequencies studied here. The relative submergence associated with the roughness height (k) was 8, which fall in the category of large roughness. Velocity measurements were conducted using acoustic Doppler velocimeter (ADV), and a surface wave of different frequencies was generated using the plunger-type wavemaker. The measured velocity data were analyzed to determine the relative importance of mean flow over the train of rib roughness. Mean velocity profiles illustrate the well-known downward shift from the flat surface data of the semi-logarithmic portion of the law of the wall. The width of the turbulent boundary layer increases with the superposition of surface wave compared to that of the current-only flow. The results also show that the mean reattachment length decreases due to the superposition of surface wave on unidirectional current.
Finite Element Analysis of Flexible Pipes Under Compression: Influence of the Friction Coefficient
Authors: Malta Eduardo Ribeiro , Martins Clóvis de Arruda
Published: February 2019

In order to study the compressive behavior of flexible pipes, a nonlinear finite element model was developed. This fully tridimensional model recreates a five-layer flexible pipe with two tensile armor layers, an external polymeric sheath, an orthotropic high strength tape, and a rigid inner nucleus. The friction coefficient is known as a key parameter in determining the instability response of flexible pipes’ tensile armor. Since the featured model includes all nonlinear frictional contacts between the layers, it has been used to conduct several experiments in order to investigate its influence on the response. This article includes a description of the finite element model itself and a case study where the friction between the layers of the pipe is changed. The procedure of this analysis is described here, along with the results.
Rapid Information Transfer in Swarms Under Update-Rate-Bounds Using Delayed Self-Reinforcement
Authors: Devasia Santosh
Published: February 2019

The effectiveness of a network's response to external stimuli depends on rapid distortion-free information transfer across the network. However, the rate of information transfer, when each agent aligns with information from its network neighbors, is limited by the update rate at which each individual can sense and process information. Moreover, such neighbor-based, diffusion-type information transfer does not predict the superfluid-like information transfer during swarming maneuvers observed in nature. The main contribution of this paper is to propose a novel model that uses self-reinforcement, where each individual augments its neighbor-averaged information update using its previous update to (i) increase the information-transfer rate without requiring an increased, individual update-rate and (ii) enable superfluid-like information transfer. Simulations results of example systems show substantial improvement, more than an order of magnitude increase, in the information transfer rate, without the need to increase the update rate. Moreover, the results show that the delayed self-reinforcement (DSR) approach's ability to enable superfluid-like, distortion-free information transfer results in maneuvers with smaller turn radius and improved cohesiveness. Such faster response rate with limited individual update rate can enable better understanding of cohesiveness of flocking in nature, as well as improve the performance of engineered swarms such as unmanned mobile systems.
Toughening stretchable fibers via serial fracturing of a metallic core
Authors: Cooper Christopher B. , Joshipura Ishan D. , Parekh Dishit P. , Norkett Justin , Mailen Russell , Miller Victoria M. , Genzer Jan , Dickey Michael D.
Published: February 2019

Stretchable fibers dissipate energy via the sequential fracturing of a metallic core held together by an elastomeric shell.
Observation of enhanced thermopower due to spin fluctuation in weak itinerant ferromagnet
Authors: Tsujii Naohito , Nishide Akinori , Hayakawa Jun , Mori Takao
Published: February 2019

Thermopower, which generates electricity from heat, can be greatly enhanced in weak ferromagnets even above room temperature.
Nano-bio-computing lipid nanotablet
Authors: Seo Jinyoung , Kim Sungi , Park Ha H. , Choi Da Yeon , Nam Jwa-Min
Published: February 2019

A supported lipid bilayer is used as a chemical circuit board to carry out molecular computation with a network of nanoparticles.
Supramolecular architectures of molecularly thin yet robust free-standing layers
Authors: Moradi Mina , Opara Nadia L. , Tulli Ludovico G. , Wäckerlin Christian , Dalgarno Scott J. , Teat Simon J. , Baljozovic Milos , Popova Olha , van Genderen Eric , Kleibert Armin , Stahlberg Henning , Abrahams Jan Pieter , Padeste Celestino , Corvini Philippe F.-X. , Jung Thomas A. , Shahgaldian Patrick
Published: February 2019

Synergistically acting weak molecular interactions create robust free-standing monolayers via self-assembly.
Optimal therapeutic activity of monoclonal antibodies against chikungunya virus requires Fc-FcγR interaction on monocytes
Authors: Fox Julie M. , Roy Vicky , Gunn Bronwyn M. , Huang Ling , Edeling Melissa A. , Mack Matthias , Fremont Daved H. , Doranz Benjamin J. , Johnson Syd , Alter Galit , Diamond Michael S.
Published: February 2019

Anti–chikungunya virus antibodies require FcγR engagement but not complement activation for protection and viral clearance.
Pathways to inequalities in child health
Authors: Pearce Anna , Dundas Ruth , Whitehead Margaret , Taylor-Robinson David
Published: February 2019

From birth, children living in disadvantaged socioeconomic circumstances (SECs) suffer from worse health than their more advantaged peers. The pathways through which SECs influence children’s health are complex and inter-related, but in general are driven by differences in the distribution of power and resources that determine the economic, material and psychosocial conditions in which children grow up. A better understanding of why children from more disadvantaged backgrounds have worse health and how interventions work, for whom and in what contexts, will help to reduce these unfair differences. Macro-level change is also required, including the reduction of child poverty through improved social security systems and employment opportunities, and continued investment in high-quality and accessible services (eg, childcare, key workers, children’s centres and healthy school environments). Child health professionals can play a crucial role by being mindful of the social determinants of health in their daily practice, and through advocating for more equitable and child-focussed resource allocation.
Liver haematoma as a presentation of peliosis hepatis
Authors: Dave Yatee A , Gupta Alisha , Shah Mihir M , Carpizo Darren
Published: February 2019

Peliosis hepatis (PH) is an uncommon, benign hepatic vascular condition involving liver lesions consisting of dilated sinusoidal spaces that ultimately lead to numerous blood-filled cavities within the liver parenchyma. We detail the case of a 62-year-old woman who presented with a large hepatic haematoma resulting from intracystic haemorrhage. She was subsequently diagnosed with PH via arteriogram. Her symptoms were successfully treated surgically with open fenestration. Patient’s postoperative course was unremarkable, with no recurrence of symptoms to date.
Transient sinus arrest due to sinus node artery thrombus after revascularisation of the left circumflex artery
Authors: Saad Shaukat Muhammad Hamza , Tatusov Alexey , Nappi Anthony , Yager Neil
Published: February 2019

We present a case of sinus arrest and junctional escape rhythm from sinus node artery (SNA) thrombus in a 55-year-old man after revascularisation of right coronary and proximal circumflex arteries for infero-posterior wall ST-segement elevation myocardial infarction (STEMI). Sinus arrest from occlusion of the SNA is uncommon. The ensuing bradycardia may have haemodynamic consequences requiring temporary pacing but is almost always self-limited.
Transient iatrogenic Horner’s syndrome following carotid endarterectomy
Authors: Hidayat Hena , Medani Mekki , Kavanagh Eamon
Published: February 2019

We present a case of a 72-year-old man who developed a transient Horner’s syndrome in the immediate postoperative period after right carotid endarterectomy which resolved within 3 months. Although Horner’s syndrome has been reported with several disorders of the carotid artery, our case documents a rare iatrogenic oculosympathetic paresis after elective carotid endarterectomy.
Revised criteria of International Workshop on Ocular Sarcoidosis (IWOS) for the diagnosis of ocular sarcoidosis
Authors: Mochizuki Manabu , Smith Justine R , Takase Hiroshi , Kaburaki Toshikatsu , Acharya Nisha R , Rao Narsing A
Published: February 2019

Aims

International criteria for the diagnosis of ocular sarcoidosis (OS) was established by the first International Workshop on Ocular Sarcoidosis (IWOS) and validations studies revealed certain limitations of the criteria. To overcome the limitations, revised IWOS criteria was established in an international meeting. This manuscript was aimed at reporting the revised IWOS criteria.

Methods

A consensus workshop was carried out to discuss and revise the IWOS criteria. The workshop was held on 27 April 2017, in Nusa Dua, Bali, Indonesia. Prior to the workshop, a questionnaire proposing revised criteria and consisting of one item for differential diagnosis, seven items for ocular clinical signs, 10 items for systemic investigations and three categories of diagnostic criteria was circulated to 30 uveitis specialists. Questionnaire items with over 75% support were taken as consensus agreement; items with below 50% support were taken as consensus disagreement and items with 50%–75% support were discussed at the workshop. Of the latter items, those supported by two-thirds majority in the workshop were taken as consensus agreement.

Results

The survey and subsequent workshop reached consensus agreements of the revised criteria for the diagnosis of OS as follows: (1) other causes of granulomatous uveitis must be ruled out; (2) seven intraocular clinical signs suggestive of OS; (3) eight results of systemic investigations in suspected OS and (4) three categories of diagnostic criteria depending on biopsy results and combination of intraocular signs and results of systemic investigations.

Conclusions

Revised IWOS criteria were proposed by a consensus workshop.
Comparison between manual trephination versus femtosecond laser-assisted deep anterior lamellar keratoplasty for keratoconus
Authors: Salouti Ramin , Zamani Mohammad , Ghoreyshi Maryam , Dapena Isabel , Melles Gerrit R.J. , Nowroozzadeh Mohammad Hossein
Published: February 2019

Background/aims

To compare the outcomes of femtosecond laser-assisted deep anterior lamellar keratoplasty (F-DALK) versus manual trephination DALK (M-DALK) in patients with keratoconus.

Methods

In this retrospective, comparative, clinical study, medical charts of 860 patients with keratoconus who underwent F-DALK (n=391) or M-DALK (n=469) with the Melles’s technique, and had at least a 12-month follow-up record were reviewed. The main outcome measures comprised best spectacle-corrected visual acuity (BSCVA), manifest refraction and keratometric indices. The postsurgical measurements were recorded for all patients at 12 months (suture-in condition), and a subset of patients with complete data at 24 months (suture-out condition; 111 F-DALK and 282 M-DALK cases).

Results

Both procedures had comparable mean (±SD) logMAR BSCVA at 12 months (0.18±0.12 for M-DALK and 0.17±0.12 for F-DALK; p=0.224) and 24 months (0.11±0.10 vs 0.09±0.09, respectively; p=0.166) examinations. M-DALK was associated with a significant more residual myopia at 12 months (−3.85±3.27 vs -1.94±2.86 D; p<0.001), and a milder similar trend at 24 months follow-up (−2.94±2.72 vs −2.38±2.65 D, p=0.064). The mean keratometry (12 months: 46.15±1.88 vs 44.39±1.72, p<0.001; 24 months: 45.33±2.37 vs 44.14±1.68, p<0.001) and apical keratometry values (12 months: 50.92±5.00 vs 47.13±2.38, p<0.001; 24 months: 50.29±4.25 vs 48.12±3.81) were significantly greater for M-DALK than F-DALK, while the keratometric astigmatism was similar (12 months: 2.62±1.58 vs 2.53±1.33, p=0.364; 24 months: 3.21±1.83 vs 3.34±1.88, p=0.529).

Conclusions

F-DALK for advanced keratoconus performs as well as M-DALK in terms of BSCVA and keratometric astigmatism in both suture-in (12 months) and suture-out (24 months) conditions. It might have advantages over M-DALK for residual myopia and restoring corneal anatomy.