bluuebunny/crossref_metadata_2025_split huggingface dataset:
Classification of Coronavirus Images using Shrunken Features
Authors: Ozturk Saban , Ozkaya Umut , Barstugan Mucahid 
Published: April 2020

AbstractNecessary screenings must be performed to control the spread of the Corona Virus (COVID-19) in daily life and to make a preliminary diagnosis of suspicious cases. The long duration of pathological laboratory tests and the wrong test results led the researchers to focus on different fields. Fast and accurate diagnoses are essential for effective interventions with COVID-19. The information obtained by using X-ray and Computed Tomography (CT) images is vital in making clinical diagnoses. Therefore it was aimed to develop a machine learning method for the detection of viral epidemics by analyzing X-ray images. In this study, images belonging to 6 situations, including coronavirus images, are classified. Since the number of images in the dataset is deficient and unbalanced, it is more convenient to analyze these images with hand-crafted feature extraction methods. For this purpose, firstly, all the images in the dataset are extracted with the help of four feature extraction algorithms. These extracted features are combined in raw form. The unbalanced data problem is eliminated by producing feature vectors with the SMOTE algorithm. Finally, the feature vector is reduced in size by using a stacked auto-encoder and principal component analysis to remove interconnected features in the feature vector. According to the obtained results, it is seen that the proposed method has leveraging performance, especially in order to make the diagnosis of COVID-19 in a short time and effectively.
Monitoring Italian COVID-19 spread by an adaptive SEIRD model
Authors: Piccolomini Elena Loli , Zama Fabiana 
Published: April 2020

AbstractDue to the recent diffusion of COVID-19 outbreak, the scientific community is making efforts in analysing models for understanding the present situation and predicting future scenarios. In this paper, we propose a Susceptible-Infected-Exposed-Recovered-Dead (SEIRD) differential model [Weitz J. S. and Dushoff J., Scientific reports, 2015] for the analysis and forecast of the COVID-19 spread in Italian regions, using the data from the Italian Protezione Civile from February 24th 2020. In this study, we investigate an adaptation of SEIRD that takes into account the actual policies of the Italian government, consisting of modelling the infection rate as a time-dependent function (SEIRD(rm)). Preliminary results on Lombardia and Emilia-Romagna regions confirm that SEIRD(rm) fits the data more accurately than the original SEIRD model with constant rate infection parameter. Moreover, the increased flexibility in the choice of the infection rate function makes it possible to better control the predictions due to the lockdown policy.
What does simple power law kinetics tell about our response to coronavirus pandemic?
Authors: Jha Prateek K. 
Published: April 2020

AbstractCoronavirus pandemic of 2019-2020 has already affected over a million people and caused over 50,000 deaths worldwide (as on April 3, 2020). Roughly half of the world population has been asked to work from home and practice social distancing as the search for a vaccine continues. Though government interventions such as lockdown and social distancing are theoretically useful, its debatable whether such interventions are effective in flattening the curve, which is ceasing or reducing the growth of infection in control populations. In this article, I present a simple power law model that enables a comparison of countries in time windows of 14 days since first coronavirus related death is reported in that country. It therefore provides means to access the efficacy of above interventions.
Clinical meanings of rapid serological assay in patients tested for SARS-Co2 RT-PCR
Authors: VirgilioParadiso Angelo , De Summa Simona , Loconsole Daniela , Procacci Vito , Sallustio Anna , Centrone Francesca , Silvestris Nicola , Cafagna Vito , De Palma Giuseppe , Tufaro Antonio , Garrisi Vito , Chironna Maria 
Published: April 2020

AbstractBackgroundRT-PCR test for identification of viral nucleic acid is the current standard diagnostic method for the diagnosis of COVID-19 disease but technical reasons limit the utilization of this assay onlarge scalescreenings.MethodWe verified in a consecutive series of 191 symptomatic patients the clinical information that new rapid serological colorimetric test qualitatively analyzing IgM/IgG expression can provide with respect to standard assay and with respect to clinical outcome of patients.ResultsRapid serological test showed a sensitivity of 30% and a specificity of 89% with respect to the standard assay but, interestingly, these performances improve after 8 days of symptoms appearance. After 10 days of symptoms the predictive value of rapid serological test is higher than that of standardassay. When the behaviour of the two immunoglobulins was evaluated with respect to time length of symptoms appaerance, no significant difference in immunoglobulins behaviour was shown.ConclusionsThe rapid serological test analyzed in the present study is candidate to provide information on immunoreaction of the subject to COVID-19 exposure.
Computational Recipe for Designing Antibodies against the Ebola Virus
Authors: Farimani Amir Barati , Aluru Narayana R. , Tajkhorshid Emad , Jakobsson Eric 
Published: April 2020

AbstractA conceptual basis for antiviral therapy is to deliver a synthetic antibody that binds to a viral surface protein, and thus prevents the virus from deploying its cell-entry mechanism. The fast and untraceable virus mutations take lives of thousands of people before the immune system can produce the inhibitory antibody. In this paper, we devised a computational recipe to predict both the viral escape mutations and the possible inhibitory synthetic antibodies. We combined bioinformatics, structural biology, and molecular dynamics (MD) simulations to explore the most likely viral mutations and the candidate antibodies that can inhibit those escape mutations. Specifically, using the crystal structures of the Sudan and Zaire Ebola viral GPs in complex to their respective antibodies (ABs), we have performed an extensive set of MD simulations, both on the wild-type structures and on a large array of additional complexes designed and generated through combinatorial mutations. We discovered that our methods enabled the successful redesign of antibody sequences to essentially all likely glycoprotein mutations. Our findings and the computational methodology developed here for general antibody design can facilitate therapy of current and possibly next generations of viruses.Significance of the ManuscriptThis manuscript has high significance both methodologically and in potential biomedical application. In methodology, the manuscript combines molecular dynamics, Monte Carlo calculations, and bioinformatics in a novel way to simulate the evolutionary arms race between an evolving viral coat protein and a counter-evolving antibody against the virus. This simulation is shown to provide a method for designing a synthetic antibody against the newly emerging viral strains. This work is done in the context of ongoing work in other laboratories in which cells can be induced to produce synthetic antibodies and those synthetic antibodies can be edited (via, for example, CRISPR) to have an arbitrary sequence in the region that binds the viral coat protein. Putting those experimental methods together with the computational methods we present in this paper has the potential to provide a important approach to produce antibodies-on-demand against evolving viruses.
Genome-wide circadian rhythm detection methods: systematic evaluations and practical guidelines
Authors: Mei Wenwen , Jiang Zhiwen , Chen Yang , Chen Li , Sancar Aziz , Jiang Yuchao 
Published: April 2020

ABSTRACTCircadian rhythms are oscillations of behavior, physiology, and metabolism in many organisms. Recent advancements in omics technology make it possible for genome-wide profiling of circadian rhythms. Here, we conducted a comprehensive analysis of seven existing algorithms commonly used for circadian rhythm detection. Using gold-standard circadian and non-circadian genes, we systematically evaluated the accuracy and reproducibility of the algorithms on empirical datasets generated from various omics platforms under different experimental designs. We also carried out extensive simulation studies to test each algorithm’s robustness to key variables, including sampling patterns, replicates, waveforms, signal-to-noise ratios, uneven samplings, and missing values. Furthermore, we examined the distributions of the nominal p-values under the null and raised issues with multiple testing corrections using traditional approaches. With our assessment, we provide method selection guidelines for circadian rhythm detection, which are applicable to different types of high-throughput omics data.Key pointsVarious methods have been developed for circadian rhythm detection on a genome-wide scale using omics technologies, yet there has not been a comprehensive summary and evaluation of all existing methods to date.Using gold-standard circadian and non-circadian genes, we systematically evaluated the accuracy and reproducibility of seven existing algorithms for circadian rhythm detection on empirical datasets generated from various omics platforms.We carried out extensive simulation studies to test each algorithm’s robustness to key variables, including sampling patterns, replicates, waveforms, signal-to-noise ratios, uneven samplings, and missing values.We examined the distributions of the nominal p-values under the null and raised issues with multiple testing corrections using the Benjamini-Hochberg procedure due to gene-gene correlation and testing being overly conservative.We provide method selection guidelines for circadian rhythm detection, which are applicable to different types of high-throughput omics data.
Post-synaptic morphology of mouse neuromuscular junctions is linked to muscle fibre type
Authors: Mech Aleksandra M. , Brown Anna-Leigh , Schiavo Giampietro , Sleigh James N. 
Published: April 2020

AbstractThe neuromuscular junction (NMJ) is the highly specialised peripheral synapse formed between lower motor neuron terminals and muscle fibres. Post-synaptic acetylcholine receptors (AChRs), which are found in high density in the muscle membrane, bind to acetylcholine released into the synaptic cleft of the NMJ, ultimately facilitating the conversion of motor action potentials to muscle contractions. NMJs have been studied for many years as a general model for synapse formation, development and function, and are known to be early sites of pathological changes in many neuromuscular diseases. However, information is limited on the diversity of NMJs in different muscles, whether muscle fibre type impacts NMJ morphology and growth, and the relevance of these parameters to neuropathology. Here, this crucial gap was addressed using a robust and standardised semi-automated workflow called NMJ-morph to quantify features of pre- and post-synaptic NMJ architecture in an unbiased manner. Five wholemount muscles from wild-type mice were dissected and compared at immature (post-natal day, P7) and early adult (P31-32) timepoints. Post-synaptic AChR morphology was found to be more variable between muscles than that of the motor neuron terminal and there were greater differences in the developing NMJ than at the mature synapse. Post-synaptic architecture, but not neuronal morphology or post-natal synapse growth, correlates with fibre type and is largely independent of muscle fibre diameter. Counter to previous observations, this study indicates that smaller NMJs tend to innervate muscles with higher proportions of fast twitch fibres and that NMJ growth rate is not conserved across all muscles. Furthermore, healthy pre- and post-synaptic NMJ morphological parameters were collected for five anatomically and functionally distinct mouse muscles, generating reference data that will be useful for the future assessment of neuromuscular disease models.Graphical Abstract
Structure of intact human MCU supercomplex with the auxiliary MICU subunits
Authors: Zhuo Wei , Zhou Heng , Guo Runyu , Yi Jingbo , Yu Lei , Sui Yinqiang , Zhang Laixing , Zeng Wenwen , Wang Peiyi , Yang Maojun 
Published: April 2020

AbstractThe mitochondrial Ca2+uniporter (MCU) supercomplex is essential for mitochondrial Ca2+uptake. Here, we present high-resolution cryo-EM structures of human MCU-EMRE supercomplex (MES, 3.41 Å) and MCU-EMRE-MICU1-MICU2 supercomplex (MEMMS, 3.64 Å). MES adopts a V-shaped dimer architecture comprising two hetero-octamers, and a pair of MICU1-MICU2 hetero-dimers form a bridge across the two halves of MES to constitute an O-shaped architecture of MEMMS. The MES and MEMMS pore profiles are almost identical, with Ca2+in the selectivity filters and no obstructions, indicating both channels are conductive. Contrary to the current model in which MICUs block the MCU pore, MICU1-MICU2 dimers are located on the periphery of the MCU pores and do not occlude them. However, MICU1-MICU2 dimers may modulate MCU gating by affecting the matrix gate through the EMRE lever.
EngineeringYarrowia lipolyticaas a chassis forde novosynthesis of five aromatic-derived natural products and chemicals
Authors: Gu Yang , Ma Jingbo , Zhu Yonglian , Ding Xinyu , Xu Peng 
Published: April 2020

AbstractsYarrowia lipolyticais a novel microbial chassis to upgrade renewable low-cost carbon feedstocks to high-value commodity chemicals and natural products. In this work, we systematically characterized and removed the rate-limiting steps of the shikimate pathway and achievedde novosynthesis of five aromatic chemicals inY. lipolytica. We determined that eliminating amino acids formation and engineering feedback-insensitive DAHP synthases are critical steps to mitigate precursor competition and relieve the feedback regulation of shikimate pathway. Further overexpression of heterologous phosphoketolase and deletion of pyruvate kinase provided a sustained metabolic driving force that channels E4P (erythrose 4-phosphate) and PEP (phosphoenolpyruvate) precursors through the shikimate pathway. Precursor competing pathways and byproduct formation pathways were also blocked by inactivating chromosomal genes. To demonstrate the utility of our engineered chassis strain, three natural products, 2-phenylethanol (2-PE),p-coumaric acid and violacein, which were derived from phenylalanine, tyrosine and tryptophan, respectively, were chosen to test the chassis performance. We obtained 2426.22 ± 48.33 mg/L of 2-PE, 593.53 ± 28.75 mg/L ofp-coumaric acid, 12.67 ± 2.23 mg/L of resveratrol, 366.30 ± 28.99 mg/L of violacein and 55.12 ± 2.81 mg/L of deoxyviolacein from glucose in shake flask. The 2-PE production represents a 286-fold increase over the initial strain (8.48 ± 0.50 mg/L). Specifically, we obtained the highest 2-PE, violacein and deoxyviolacein titer ever reported from thede novoshikimate pathway in yeast. These results set up a new stage of engineeringY. lipolyticaas a sustainable biorefinery chassis strain forde novosynthesis of aromatic compounds with economic values.
Action-based organization and function of cerebellar cortical microcircuits
Authors: Cerminara Nadia L , Garwicz Martin , Darch Henry , Houghton Conor , Marple-Horvat Dilwyn E , Apps Richard 
Published: April 2020

AbstractThe cerebellum is the largest sensorimotor structure in the brain, but its mode of operation is not well understood. However, a fundamental organizational feature of the cerebellar cortex is division into elongated zones, defined by their inputs from specific parts of the inferior olive and Purkinje cell output to cerebellar and vestibular nuclei. Little is known about how the pattern of neuronal activity in zones, and their functional microcircuit subdivisions, microzones, is related to behaviour in awake animals. Here, we studied the organization of microzones within the C3 zone and their activity during a skilled forelimb reaching task in cats. Neurons in different parts of the C3 zone, functionally determined by receptive field characteristics, differed in their patterns of activity during movement. Our results suggest that the cerebellar C3 zone is organized and operates within an action-based frame of reference, with different microcircuits within the zone controlling specific muscle synergies.
Monocyte recruitment to the inflamed central nervous system: migration pathways and distinct functional polarization
Authors: Ivan Daniela C. , Walthert Sabrina , Locatelli Giuseppe 
Published: April 2020

ABSTRACTThe central nervous system (CNS) parenchyma is enclosed by anatomical interfaces including multilayered meninges, the blood-brain barrier (BBB), the choroid plexuses within ventricles and the glia limitans. These border areas hold distinct functional specializations which control the trafficking of monocyte-derived cells toward the CNS parenchyma, altogether maintaining CNS homeostasis. By crossing activated endothelial, epithelial and glial borders, circulating leukocytes gain however access to the CNS parenchyma in several inflammatory diseases including multiple sclerosis.Studies in animal models of neuroinflammation have helped describing the phenotypic specifications of these invading monocyte-derived cells, able to exert detrimental or beneficial functions depending on the local environment. In this context,in vivovisualization of iNOS+pro-inflammatory and arginase-1+anti-inflammatory macrophages has recently revealed that these distinct cell phenotypes are highly compartmentalized by CNS borders. While arginase-1+macrophages densely populate the leptomeninges, iNOS+macrophages rather accumulate in perivascular spaces and at the pia mater-CNS parenchymal interface.How and where these macrophages acquire their functional commitment, and whether differentially-activated monocyte-derived cells infiltrate the CNS through distinct gateways, remains however unclear.In this study, we have investigated the interaction of monocyte-derived macrophages with endothelial (BBB) and epithelial (choroid plexus) barriers of the CNS, bothin vitroandin vivo. By using primary mouse brain microvascular endothelial cells asin vitromodel of the BBB, we observed that, compared to unpolarized primary macrophages, adhesion of functionally-committed macrophages to endothelial cells was drastically reduced, literally abrogating their diapedesis across the BBB. Conversely, when interacting with an activated choroid plexus epithelium, both pro- and anti-inflammatory macrophages displayed substantial adhesive and migratory properties. Accordingly,in vivoanalysis of choroid plexuses revealed increased macrophage trafficking and a scattered presence of polarized cells upon induction of anti-CNS inflammation.Altogether, we show that acquisition of distinct macrophage polarizations significantly alters the adhesive and migratory properties of these cells in a barrier-specific fashion. While monocytes trafficking at the level of the BBB seem to acquire their signature phenotype only following diapedesis, other anatomical interfaces can be the entry site for functionally activated monocyte-derived cells. Our study highlights the choroid plexus as a key access gateway for macrophages during neuroinflammation, and its stroma as a potential priming site for their functional polarization.
Reward impacts visual statistical learning
Authors: Park Su Hyoun , Rogers Leeland L. , Johnson Matthew R. , Vickery Timothy J. 
Published: April 2020

AbstractHumans automatically detect and remember regularities in the visual environment—a type of learning termed visual statistical learning (VSL). Many aspects of learning from reward resemble statistical learning in respects, yet whether and how reward learning impacts VSL is largely unexamined. In two studies, we found that reward contingencies affect VSL, with high-value associated with stronger behavioral and neural signatures of such learning than low-value images. In Experiment 1, participants learned values (high or low) of images through a trial-and-error risky choice task. Unbeknownst to them, images were paired as four types—High-High, High-Low, Low-High, and Low-Low. In subsequent recognition and reward memory tests, participants chose the more familiar of two pairs (a target and a foil) and recalled the value of images. We found better recognition when the first images of pairs have high-values, with High-High pairs showing the highest recognition rate. In Experiment 2, we provided evidence that brain responses were affected by both value and statistical contingencies. When we compared responses between the high-value first image and the low-value first image, greater activation in regions that included inferior frontal gyrus, anterior cingulate gyrus, hippocampus, among other regions were found. These findings were driven by the interaction between statistically structured information and reward—the same value contrast yielded no regions for second-image contrasts and for singletons. Our results suggested that the powerful allocation of attention in response to the high-value first image potentially enables better memory for statistically learned pairs and reward information than low-value first image.
Mental geometry of perceiving 3D size in pictures
Authors: Maruya Akihito , Zaidi Qasim 
Published: April 2020

AbstractWe show that the classical problem of 3D size perception in obliquely viewed pictures can be understood by comparing human performance to the optimal geometric solution. A photograph seen from the camera position, forms the same retinal projection as the physical 3D scene, but retinal projections of sizes and shapes are distorted in oblique viewing. For real scenes, we previously showed that size and shape inconstancy result despite observers using the correct geometric back-transform, because some retinal images evoke misestimates of viewing elevation. Now, we examine how observers estimate 3D sizes in oblique views of pictures of objects in different poses on the ground. Compared to the camera position estimates, sizes in oblique views were seriously underestimated for objects at fronto-parallel poses, but there was almost no change for objects perceived as pointing towards the viewer. The inverse of the function relating projected length to pose, camera elevation and viewing azimuth, gives the optimal correction factor for inferring correct 3D lengths if the elevation and azimuth are estimated accurately. Empirical correction functions had similar shapes to optimal, but lower amplitude. Measurements revealed that observers systematically underestimated viewing azimuth, similar to the fronto-parallel bias for object pose perception. A model that adds underestimation of viewing azimuth to the geometrical back-transform, provided good fits to estimated 3D lengths from oblique views. These results add to accumulating evidence that observers use internalized projective geometry to perceive sizes, shapes and poses in 3D scenes and their pictures.