bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Extended Lower Extremity Cooling Following Zone 3 REBOA in a Porcine Hemorrhage Model
Authors: Kashtan Harris W , Simon Meryl A , Beyer Carl A , Wishy Andrew , Hoareau Guillaume L , Grayson J Kevin , Johnson M Austin
Published: February 2020

Introduction

External cooling of ischemic limbs has been shown to have a significant protective benefit for durations up to 4 hours.

Materials and Methods

It was hypothesized that this benefit could be extended to 8 hours. Six swine were anesthetized and instrumented, then underwent a 25% total blood volume hemorrhage. Animals were randomized to hypothermia or normothermia followed by 8 hours of Zone 3 resuscitative endovascular balloon occlusion of the aorta, then resuscitation with shed blood, warming, and 3 hours of critical care. Physiologic parameters were continuously recorded, and laboratory specimens were obtained at regular intervals.

Results

There were no significant differences between groups at baseline. There were no significant differences between creatine kinase in the hypothermia group when compared to the normothermia group (median [IQR] = 15,206 U/mL [12,476−19,987] vs 23,027 U/mL [18,745−26,843]); P = 0.13) at the end of the study. Similarly, serum myoglobin was also not significantly different in the hypothermia group after 8 hours (7,345 ng/mL [5,082−10,732] vs 5,126 ng/mL [4,720−5,298]; P = 0.28). No histologic differences were observed in hind limb skeletal muscle.

Conclusion

While external cooling during prolonged Zone 3 resuscitative endovascular balloon occlusion of the aorta appears to decrease ischemic muscle injury, this benefit appears to be time dependent. As the ischemic time approaches 8 hours, the benefit from hypothermia decreases.
Hearing Damage Induced by Blast Overpressure at Mild TBI Level in a Chinchilla Model
Authors: Smith Kyle D , Chen Tao , Gan Rong Z
Published: February 2020

Introduction

The peripheral auditory system and various structures within the central auditory system are vulnerable to blast injuries, and even blast overpressure is at relatively mild traumatic brain injury (TBI) level. However, the extent of hearing loss in relation to blast number and time course of post-blast is not well understood. This study reports the progressive hearing damage measured in chinchillas after multiple blast exposures at mild TBI levels (103–138 kPa or 15–20 psi).

Materials and Methods

Sixteen animals (two controls) were exposed to two blasts and three blasts, respectively, in two groups with both ears plugged with foam earplugs to prevent the eardrum from rupturing. Auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) were measured in pre- and post-blasts. Immunohistochemical study of chinchilla brains were performed at the end of experiment.

Results

Results show that the ABR threshold and DPOAE level shifts in 2-blast animals were recovered after 7 days. In 3-blast animals, the ABR and DPOAE shifts remained at 26 and 23 dB, respectively after 14 days. Variation of auditory cortex damage between 2-blast and 3-blast was also observed in immunofluorescence images.

Conclusions

This study demonstrates that the number of blasts causing mild TBI critically affects hearing damage.
Ex-Vivo Normothermic Limb Perfusion With a Hemoglobin-Based Oxygen Carrier Perfusate
Authors: Said Sayf A , Ordeñana Carlos X , Rezaei Majid , Figueroa Brian A , Dasarathy Srinivasan , Brunengraber Henri , Rampazzo Antonio , Gharb Bahar Bassiri
Published: February 2020

Introduction

Ex-vivo normothermic limb perfusion (EVNLP) has been proven to preserve limb viability better than standard cold storage. Perfusates containing packed red blood cells (pRBC) improve outcomes when compared to acellular perfusates. Limitations of pRBC-based perfusion include limited availability, need for cross match, mechanical hemolysis, and activation of pro-inflammatory proteins. Hemoglobin-based oxygen carrier (HBOC)-201 (Hemopure) is a solution of polymerized bovine hemoglobin, characterized by low immunogenicity, no risk of hemolytic reaction, and enhanced convective and diffusive oxygen delivery. This is a preliminary study on the feasibility of EVNLP using HBOC-201 as an oxygen carrier.

Materials and Methods

Three porcine forelimb perfusions were performed using an established EVNLP model and an HBOC-201-based perfusate. The perfusion circuit included a roller pump, oxygenator, heat exchanger, and reservoir. Electrolytes, limb temperature, weight, compartment pressure, nerve conduction, and perfusion indicated by indocyanine green angiography and infra-red thermography were monitored. Histological evaluation was performed with hematoxylin and eosin and electron microscopy.

Results

Three limbs were perfused for 21.3 ± 2.1 hours. Muscle contractility was preserved for 10.6 ± 2.4 hours. Better preservation of the mitochondrial ultrastructure was evident at 12 hours in contrast to crystallization and destruction features in the cold-storage controls.

Conclusions

An HBOC-201-EVNLP produced outcomes similar to RBC-EVNLP with preservation of muscle contractility and mitochondrial structure.
Chemokine Receptor Antagonists in Combination with Morphine as a Novel Strategy for Opioid Dose Reduction in Pain Management
Authors: Eisenstein Toby K , Chen Xiaohong , Inan Saadet , Meissler Joseph J , Tallarida Christopher S , Geller Ellen B , Rawls Scott M , Cowan Alan , Adler Martin W
Published: February 2020

Introduction

Although opioids are widely prescribed for pain, in many circumstances, they have only modest efficacy. Preclinical studies have shown that chemokines, immune mediators released during tissue injury and inflammation, can desensitize opioid receptors and block opioid analgesia by a process termed “heterologous desensitization.” The present studies tested the hypothesis that in evoked pain, certain chemokine receptor antagonists (CRAs), given with a submaximal dose of morphine, would result in enhanced morphine potency.

Methods

Three rodent pain assays were used: incisional pain in rats, the cold-water tail flick test in rats, and the formalin test in mice. The FDA-approved, commercially available CRAs, maraviroc and AMD3100, were used. They block the chemokine receptors and ligands, CCR5/CCL5 (RANTES) and CXCR4/CXCL4 (SDF-1α), respectively.

Results

In the incisional pain assay, it was found that the combination of a single CRA, or of both CRAs, with morphine significantly shifted the morphine dose-response curve to the left, as much as 3.3-fold. In the cold-water tail flick and formalin tests, significant increases of the antinociceptive effects of morphine were also observed when combined with CRAs.

Conclusions

These results support the potential of a new “opioid-sparing” approach for pain treatment, which combines CRAs with reduced doses of morphine.
The role of extracellular vesicles and PD-L1 in glioblastoma-mediated immunosuppressive monocyte induction
Authors: Himes Benjamin T , Peterson Timothy E , de Mooij Tristan , Garcia Luz M Cumba , Jung Mi-Yeon , Uhm Sarah , Yan David , Tyson Jasmine , Jin-Lee Helen J , Parney Daniel , Abukhadra Yasmina , Gustafson Michael P , Dietz Allan B , Johnson Aaron J , Dong Haidong , Maus Rachel L , Markovic Svetomir , Lucien Fabrice , Parney Ian F
Published: February 2020

Background

Immunosuppression in glioblastoma (GBM) is an obstacle to effective immunotherapy. GBM-derived immunosuppressive monocytes are central to this. Programmed cell death ligand 1 (PD-L1) is an immune checkpoint molecule, expressed by GBM cells and GBM extracellular vesicles (EVs). We sought to determine the role of EV-associated PD-L1 in the formation of immunosuppressive monocytes.

Methods

Monocytes collected from healthy donors were conditioned with GBM-derived EVs to induce the formation of immunosuppressive monocytes, which were quantified via flow cytometry. Donor-matched T cells were subsequently co-cultured with EV-conditioned monocytes in order to assess effects on T-cell proliferation. PD-L1 constitutive overexpression or short hairpin RNA–mediated knockdown was used to determined the role of altered PD-L1 expression.

Results

GBM EVs interact with both T cells and monocytes but do not directly inhibit T-cell activation. However, GBM EVs induce immunosuppressive monocytes, including myeloid-derived suppressor cells (MDSCs) and nonclassical monocytes (NCMs). MDSCs and NCMs inhibit T-cell proliferation in vitro and are found within GBM in situ. EV PD-L1 expression induces NCMs but not MDSCs, and does not affect EV-conditioned monocytes T-cell inhibition.

Conclusion

These findings indicate that GBM EV-mediated immunosuppression occurs through induction of immunosuppressive monocytes rather than direct T-cell inhibition and that, while PD-L1 expression is important for the induction of specific immunosuppressive monocyte populations, immunosuppressive signaling mechanisms through EVs are complex and not limited to PD-L1.
Neurosurgical Randomized Trials in Low- and Middle-Income Countries
Authors: Griswold Dylan P , Khan Ahsan A , Chao Tiffany E , Clark David J , Budohoski Karol , Devi B Indira , Azad Tej D , Grant Gerald A , Trivedi Rikin A , Rubiano Andres M , Johnson Walter D , Park Kee B , Broekman Marike , Servadei Franco , Hutchinson Peter J , Kolias Angelos G
Published: February 2020

BACKGROUND

The setting of a randomized trial can determine whether its findings are generalizable and can therefore apply to different settings. The contribution of low- and middle-income countries (LMICs) to neurosurgical randomized trials has not been systematically described before.

OBJECTIVE

To perform a systematic analysis of design characteristics and methodology, funding source, and interventions studied between trials led by and/or conducted in high-income countries (HICs) vs LMICs.

METHODS

From January 2003 to July 2016, English-language trials with >5 patients assessing any one neurosurgical procedure against another procedure, nonsurgical treatment, or no treatment were retrieved from MEDLINE, Scopus, and Cochrane Library. Income classification for each country was assessed using the World Bank Atlas method.

RESULTS

A total of 73.3% of the 397 studies that met inclusion criteria were led by HICs, whereas 26.7% were led by LMICs. Of the 106 LMIC-led studies, 71 were led by China. If China is excluded, only 8.8% were led by LMICs. HIC-led trials enrolled a median of 92 patients vs a median of 65 patients in LMIC-led trials. HIC-led trials enrolled from 7.6 sites vs 1.8 sites in LMIC-led studies. Over half of LMIC-led trials were institutionally funded (54.7%). The majority of both HIC- and LMIC-led trials evaluated spinal neurosurgery, 68% and 71.7%, respectively.

CONCLUSION

We have established that there is a substantial disparity between HICs and LMICs in the number of published neurosurgical trials. A concerted effort to invest in research capacity building in LMICs is an essential step towards ensuring context- and resource-specific high-quality evidence is generated.
Inoculation Period and Citrus Host Effect Establishment of New Infections of ‘Candidatus Liberibacter asiaticus’ Transmitted via Vegetative Grafting
Authors: Hilf Mark E. , Luo Weiqi
Published: February 2020

Vegetative grafting is a common method of transmitting and propagating ‘Candidatus Liberibacter asiaticus’, the bacterial species accepted as the causal agent of the citrus disease huanglongbing (HLB). Generally, infected tissue that is grafted to a receptor tree remains in place indefinitely to ensure transmission. In this study, individual HLB-symptomatic leaves were grafted as ‘Ca. L. asiaticus’ inoculum sources to receptor trees of six citrus types and removed after an inoculation period (IP) of 21, 51, or 81 days. The goal was to assess the effect of varying IPs on transmission of bacteria to the receptor tree and on the successful establishment of a new infection. Survival analysis of data from three trials showed a significantly reduced proportion of infected trees with an IP of 21 days compared with IPs of 51 and 81 days but that there was no significant difference in the proportion of infected trees between IPs of 51 and 81 days. In addition, the time to first detection of pathogen DNA in an infected tree was delayed significantly for the 21-day IP when compared with the 51- and 81-day IPs. Survival analysis showed that the probability of infection of sweet orange trees was significantly higher than for trees of five other citrus types throughout the experiment. There was no significant difference between the infection probabilities of these latter five citrus types. The data from this study show that successful infection by grafting is dependent upon the time of exposure to the inoculum, that shorter IPs increase the time needed to establish a systemic infection, and that citrus types vary in their overall susceptibility to infection by ‘Ca. L. asiaticus’.
Eosinophilic gastroenteritis: epidemiology, diagnosis, and treatment
Authors: Kinoshita Yoshikazu , Ishihara Shunji
Published: February 2020

Purpose of review

Although several reviews concerning diagnosis and treatment of eosinophilic esophagitis (EoE) have been presented, there are few in regard to eosinophilic gastroenteritis (EGE). Fortunately, findings related to epidemiology, as well as diagnosis and treatment of this disease have recently been increasing.

Recent findings

The rates of incidence of both EoE and EGE have been reported to be increasing. For accurate diagnosis, plasma concentrations of thymic stromal lymphopoietin and IL-33 may be useful as biomarkers, though consensus has not been reached, while increased eosinophil infiltration in gastrointestinal tissue remains a critical factor. Topical glucocorticoid administration, an elimination diet, and molecular target therapy with neutralizing antibodies are potentially effective therapies that have recently been evaluated.

As seen with other allergic diseases, EGE seems to be increasing. Several research projects regarding diagnosis and treatment of the disease are currently in progress.
Limitations of the UNAIDS 90-90-90 metrics: a simulation-based comparison of cross-sectional and longitudinal metrics for the HIV care continuum
Authors: Haber Noah A. , Lesko Catherine R. , Fox Matthew P. , Powers Kimberly A. , Harling Guy , Edwards Jessie K. , Salomon Joshua A. , Lippman Sheri A. , Bor Jacob , Chang Angela Y. , Anglemyer Andrew , Pettifor Audrey
Published: February 2020

Objectives:

The Joint United Nations Programme on HIV/AIDS (UNAIDS) 90–90–90 and other cross-sectional metrics can lead to potentially counterintuitive conclusions when used to evaluate health systems’ performance. This study demonstrates how time and population dynamics impact UNAIDS 90–90–90 metrics in comparison with a longitudinal analogue.

Design:

A simplified simulation representing a hypothetical population was used to estimate and compare inference from UNAIDS 90–90–90 metrics and longitudinal metrics based on Kaplan–Meier-estimated 2-year probability of transition between stages.

Methods:

We simulated a large cohort over 15 years. Everyone started out at risk for HIV, and then transitioned through the HIV care continuum based on fixed daily probabilities of acquiring HIV, learning status, entering care, initiating antiretroviral therapy (ART), and becoming virally suppressed, or dying. We varied the probability of ART initiation over three five-year periods (low, high, and low). We repeated the simulation with an increased probability of death.

Results:

The cross-sectional probability of being on ART among persons who were diagnosed responded relatively slowly to changes in the rate of ART initiation. Increases in ART initiation rates caused apparent declines in the cross-sectional probability of being virally suppressed among persons who had initiated ART, despite no changes in the rate of viral suppression. In some cases, higher mortality resulted in the cross-sectional metrics implying improved healthcare system performance. The longitudinal continuum was robust to these issues.

Conclusion:

The UNAIDS 90–90–90 care continuum may lead to incorrect inference when used to evaluate health systems performance. We recommend that evaluation of HIV care delivery include longitudinal care continuum metrics wherever possible.
HIV influences microtubule associated protein-2: potential marker of HIV-associated neurocognitive disorders
Authors: Avdoshina Valeria , Mahoney Matthew , Gilmore Sean F. , Wenzel Erin D. , Anderson Albert , Letendre Scott L. , Imamichi Tomozumi , Fischer Nicholas O. , Mocchetti Italo
Published: February 2020

Objective:

Postmortem brains of patients diagnosed with HIV-1-associated neurocognitive disorders (HAND) exhibit loss of dendrites. However, the mechanisms by which synapses are damaged are not fully understood.

Design:

Dendrite length and remodeling occurs via microtubules, the dynamics of which are regulated by microtubule-binding proteins, including microtubule-associated protein 2 (MAP2). The HIV protein gp120 is neurotoxic and interferes with neuronal microtubules. We measured MAP2 concentrations in human cerebrospinal fluid (CSF) and MAP2 immunoreactivity in rat cortical neurons exposed to HIV and gp120.

Methods:

First, we examined whether HIV affects MAP2 levels by analyzing the CSF of 27 persons living with HIV (PLH) whose neurocognitive performance had been characterized. We then used rat cortical neurons to study the mechanisms of HIV-mediated dendritic loss.

Results:

PLH who had HAND had greater MAP2 concentrations within the CSF than cognitive normal PLH. In cortical neurons, the deleterious effect of HIV on MAP2-positive dendrites occurred through a gp120-mediated mechanism. The neurotoxic effect of HIV was blocked by a CCR5 antagonist and prevented by Helix-A, a peptide that displaces gp120 from binding to microtubules, conjugated to a nanolipoprotein particle delivery platform.

Conclusion:

Our findings support that HIV at least partially effects its neurotoxicity via neuronal cytoskeleton modifications and provide evidence of a new therapeutic compound that could be used to prevent the HIV-associated neuropathology.
Stochastic fluctuations in apoptotic threshold of tumour cells can enhance apoptosis and combat fractional killing
Authors: Qiu Baohua , Zhou Tianshou , Zhang Jiajun
Published: February 2020

Fractional killing, which is a significant impediment to successful chemotherapy, is observed even in a population of genetically identical cancer cells exposed to apoptosis-inducing agents. This phenomenon arises not from genetic mutation but from cell-to-cell variation in the activation timing and level of the proteins that regulates apoptosis. To understand the mechanism behind the phenomenon, we formulate complex fractional killing processes as a first-passage time (FPT) problem with a stochastically fluctuating boundary. Analytical calculations are performed for the FPT distribution in a toy model of stochastic p53 gene expression, where the cancer cell is killed only when the p53 expression level crosses an active apoptotic threshold. Counterintuitively, we find that threshold fluctuations can effectively enhance cellular killing by significantly decreasing the mean time that the p53 protein reaches the threshold level for the first time. Moreover, faster fluctuations lead to the killing of more cells. These qualitative results imply that fluctuations in threshold are a non-negligible stochastic source, and can be taken as a strategy for combating fractional killing of cancer cells.
In situ
analysis of shear bands and boundary layer formation in metals
Authors: Yadav Shwetabh , Sagapuram Dinakar
Published: February 2020

Shear banding is a plastic instability in large deformation of solids where the flow becomes concentrated in narrow layers, with broad implications in materials processing applications and dynamic failure of metals. Given the extremely small length and time scales involved, several challenges persist in studying the development of shear bands. Here, we present a new approach to study shear bands at low speeds using low melting point alloys. We use
in situ
imaging to directly capture the essential features of shear banding, including transition from homogeneous to shear banded flow, band nucleation and propagation dynamics, and temporal evolution of the flow around a developing band. High-resolution, time-resolved measurements of the local displacement and velocity profiles during shear band growth are presented. The experiments are complemented by an analysis of the shear band growth as a Bingham fluid flow. It is shown that shear banding occurs only beyond a critical shear stress and is accompanied by a sharp drop in the viscosity by several orders of magnitude, analogous to the yielding transition in yield-stress fluids. Likewise, the displacement field around a nucleated band evolves in a manner that resembles boundary layer formation, with the band thickness scaling with time as a power law.
Integrable two-component systems of difference equations
Authors: Kassotakis Pavlos , Nieszporski Maciej , Papageorgiou Vassilios , Tongas Anastasios
Published: February 2020

We present two lists of two-component systems of integrable difference equations defined on the edges of the

Z

2

graph. The integrability of these systems is manifested by their Lax formulation which is a consequence of the multi-dimensional compatibility of these systems. Imposing constraints consistent with the systems of difference equations, we recover known integrable quad-equations including the discrete version of the Krichever–Novikov equation. The systems of difference equations give us in turn quadrirational Yang–Baxter maps.
Coral species composition drives key ecosystem function on coral reefs
Authors: Richardson Laura E. , Graham Nicholas A. J. , Hoey Andrew S.
Published: February 2020

Rapid and unprecedented ecological change threatens the functioning and stability of ecosystems. On coral reefs, global climate change and local stressors are reducing and reorganizing habitat-forming corals and associated species, with largely unknown implications for critical ecosystem functions such as herbivory. Herbivory mediates coral–algal competition, thereby facilitating ecosystem recovery following disturbance such as coral bleaching events or large storms. However, relationships between coral species composition, the distribution of herbivorous fishes and the delivery of their functional impact are not well understood. Here, we investigate how herbivorous fish assemblages and delivery of two distinct herbivory processes, grazing and browsing, differ among three taxonomically distinct, replicated coral habitats. While grazing on algal turf assemblages was insensitive to different coral configurations, browsing on the macroalga
Laurencia
cf.
obtusa
varied considerably among habitats, suggesting that different mechanisms may shape these processes. Variation in browsing among habitats was best predicted by the composition and structural complexity of benthic assemblages (in particular the cover and composition of corals, but not macroalgal cover), and was poorly reflected by visual estimates of browser biomass. Surprisingly, the lowest browsing rates were recorded in the most structurally complex habitat, with the greatest cover of coral (branching
Porites
habitat). While the mechanism for the variation in browsing is not clear, it may be related to scale-dependent effects of habitat structure on visual occlusion inhibiting foraging activity by browsing fishes, or the relative availability of alternate dietary resources. Our results suggest that maintained functionality may vary among distinct and emerging coral reef configurations due to ecological interactions between reef fishes and their environment determining habitat selection.
Microbial and volatile profiling of soils suppressive to
Fusarium culmorum
of wheat
Authors: Ossowicki Adam , Tracanna Vittorio , Petrus Marloes L. C. , van Wezel Gilles , Raaijmakers Jos M. , Medema Marnix H. , Garbeva Paolina
Published: February 2020

In disease-suppressive soils, microbiota protect plants from root infections. Bacterial members of this microbiota have been shown to produce specific molecules that mediate this phenotype. To date, however, studies have focused on individual suppressive soils and the degree of natural variability of soil suppressiveness remains unclear. Here, we screened a large collection of field soils for suppressiveness to
Fusarium culmorum
using wheat (
Triticum aestivum
) as a model host plant. A high variation of disease suppressiveness was observed, with 14% showing a clear suppressive phenotype. The microbiological basis of suppressiveness to
F. culmorum
was confirmed by gamma sterilization and soil transplantation. Amplicon sequencing revealed diverse bacterial taxonomic compositions and no specific taxa were found exclusively enriched in all suppressive soils. Nonetheless, co-occurrence network analysis revealed that two suppressive soils shared an overrepresented bacterial guild dominated by various Acidobacteria. In addition, our study revealed that volatile emission may contribute to suppression, but not for all suppressive soils. Our study raises new questions regarding the possible mechanistic variability of disease-suppressive phenotypes across physico-chemically different soils. Accordingly, we anticipate that larger-scale soil profiling, along with functional studies, will enable a deeper understanding of disease-suppressive microbiomes.
How do predators generalize warning signals in simple and complex prey communities? Insights from a videogame
Authors: Arias Mónica , Davey John W. , Martin Simon , Jiggins Chris , Nadeau Nicola , Joron Mathieu , Llaurens Violaine
Published: February 2020

The persistence of distinct warning signals within and between sympatric mimetic communities is a puzzling evolutionary question because selection favours convergence of colour patterns among toxic species. Such convergence is partly shaped by predators' reaction to similar but not identical stimulus (i.e. generalization behaviour), and generalization by predators is likely to be shaped by the diversity of local prey. However, studying generalization behaviour is generally limited to simple variations of prey colour patterns. Here, we used a computer game played by humans as surrogate predators to investigate generalization behaviours in simple (4 morphs) and complex (10 morphs) communities of unprofitable (associated with a penalty) and profitable butterflies. Colour patterns used in the game are observed in the natural populations of unprofitable butterfly species such asHeliconius numata. Analyses of 449 game participants' behaviours show that players avoided unprofitable prey more readily in simple than in complex communities. However, generalization was observed only in players that faced complex communities, enhancing the protection of profitable prey that looked similar to at least one unprofitable morph. Additionally, similarity among unprofitable prey also reduced attack rates only in complex communities. These results are consistent with previous studies using avian predators but artificial colour patterns and suggest that mimicry is more likely to evolve in complex communities where increases in similarity are more likely to be advantageous.
Structural modeling of 2019-novel coronavirus (nCoV) spike protein reveals a proteolytically-sensitive activation loop as a distinguishing feature compared to SARS-CoV and related SARS-like coronaviruses
Authors: Jaimes Javier A. , André Nicole M. , Millet Jean K. , Whittaker Gary R.
Published: February 2020

The 2019 novel coronavirus (2019-nCoV) is currently causing a widespread outbreak centered on Hubei province, China and is a major public health concern. Taxonomically 2019-nCoV is closely related to SARS-CoV and SARS-related bat coronaviruses, and it appears to share a common receptor with SARS-CoV (ACE-2). Here, we perform structural modeling of the 2019-nCoV spike glycoprotein. Our data provide support for the similar receptor utilization between 2019-nCoV and SARS-CoV, despite a relatively low amino acid similarity in the receptor binding module. Compared to SARS-CoV, we identify an extended structural loop containing basic amino acids at the interface of the receptor binding (S1) and fusion (S2) domains, which we predict to be proteolytically-sensitive. We suggest this loop confers fusion activation and entry properties more in line with MERS-CoV and other coronaviruses, and that the presence of this structural loop in 2019-nCoV may affect virus stability and transmission.
Model Reduction Tools For Phenomenological Modeling of Input-Controlled Biological Circuits
Authors: Pandey Ayush , Murray Richard M.
Published: February 2020

We present a Python-based software package to automatically obtain phenomenological models of input-controlled synthetic biological circuits from descriptive models. From the parts and mechanism description of a synthetic biological circuit, it is easy to obtain a chemical reaction model of the circuit under the assumptions of mass-action kinetics using various existing tools. However, using these models to guide design decisions during an experiment is difficult due to a large number of reaction rate parameters and species in the model. Hence, phenomenological models are often developed that describe the effective relationships among the circuit inputs, outputs, and only the key states and parameters. In this paper, we present an algorithm to obtain these phenomenological models in an automated manner using a Python package for circuits with inputs that control the desired outputs. This model reduction approach combines the common assumptions of time-scale separation, conservation laws, and species’ abundance to obtain the reduced models that can be used for design of synthetic biological circuits. We consider an example of a simple gene expression circuit and another example of a layered genetic feedback control circuit to demonstrate the use of the model reduction procedure.
Epidemic analysis of COVID-19 in China by dynamical modeling
Authors: Peng Liangrong , Yang Wuyue , Zhang Dongyan , Zhuge Changjing , Hong Liu
Published: February 2020

The outbreak of novel coronavirus-caused pneumonia (COVID-19) in Wuhan has attracted worldwide attention. Here, we propose a generalized SEIR model to analyze this epidemic. Based on the public data of National Health Commission of China from Jan. 20th to Feb. 9th, 2020, we reliably estimate key epidemic parameters and make predictions on the inflection point and possible ending time for 5 different regions. According to optimistic estimation, the epidemics in Beijing and Shanghai will end soon within two weeks, while for most part of China, including the majority of cities in Hubei province, the success of anti-epidemic will be no later than the middle of March. The situation in Wuhan is still very severe, at least based on public data until Feb. 15th. We expect it will end up at the beginning of April. Moreover, by inverse inference, we find the outbreak of COVID-19 in Mainland, Hubei province and Wuhan all can be dated back to the end of December 2019, and the doubling time is around two days at the early stage.
The effects of microcystin-LR inOryza sativaroot cells: F-actin as a new target of cyanobacterial toxicity
Authors: Pappas D. , Gkelis S. , Panteris E.
Published: February 2020

Microcystins are toxins produced by cyanobacteria, notorious for negatively affecting a wide range of living organisms, among which several plant species. Although microtubules are a well-established target of microcystin toxicity, its effect on filamentous actin (F-actin) in plant cells has not been studied yet.

The effects of microcystin-LR (MC-LR) and the extract of a microcystin-producing freshwater cyanobacterial strain (Microcystis flos-aquaeTAU-MAC 1510) on the cytoskeleton (F-actin and microtubules) ofOryza sativa(rice) root cells, were studied by light, confocal, and transmission electron microscopy. Considering the role of F-actin in endomembrane system distribution, the endoplasmic reticulum and the Golgi apparatus in extract-treated cells were also examined.

F-actin in both MC-LR- and extract-treated meristematic and differentiating root cells exhibited time-dependent alterations, ranging from disorientation and bundling to the formation of ring-like structures, eventually resulting to a collapse of the F-actin network at longer treatments. Disorganization and eventual depolymerization of microtubules, as well as abnormal chromatin condensation were observed following treatment with the extract, effects which could be attributed to microcystins and other bioactive compounds. Moreover, cell cycle progression was inhibited in extract-treated roots, specifically affecting the mitotic events. As a consequence of F-actin network disorganization, endoplasmic reticulum elements appeared stacked and diminished, while Golgi dictyosomes appeared aggregated.

These results support that F-actin is a prominent target of MC-LR, both in pure form and as an extract ingredient. Endomembrane system alterations can also be attributed to the effects of cyanobacterial bioactive compounds (including microcystins) on F-actin cytoskeleton.
Learning polygenic scores for human blood cell traits
Authors: Xu Yu , Vuckovic Dragana , Ritchie Scott C , Akbari Parsa , Jiang Tao , Grealey Jason , Butterworth Adam S. , Ouwehand Willem H , Roberts David J , Di Angelantonio Emanuele , Danesh John , Soranzo Nicole , Inouye Michael
Published: February 2020

Polygenic scores (PGSs) for blood cell traits can be constructed using summary statistics from genome-wide association studies. As the selection of variants and the modelling of their interactions in PGSs may be limited by univariate analysis, therefore, such a conventional method may yield sub-optional performance. This study evaluated the relative effectiveness of four machine learning and deep learning methods, as well as a univariate method, in the construction of PGSs for 26 blood cell traits, using data from UK Biobank (n=~400,000) and INTERVAL (n=~40,000). Our results showed that learning methods can improve PGSs construction for nearly every blood cell trait considered, with this superiority explained by the ability of machine learning methods to capture interactions among variants. This study also demonstrated that populations can be well stratified by the PGSs of these blood cell traits, even for traits that exhibit large differences between ages and sexes, suggesting potential for disease prevention. As our study found genetic correlations between the PGSs for blood cell traits and PGSs for several common human diseases (recapitulating well-known associations between the blood cell traits themselves and certain diseases), it suggests that blood cell traits may be indicators or/and mediators for a variety of common disorders via shared genetic variants and functional pathways.
Understanding the mechanical limitations of the performance of soft X-ray monochromators at MAX IV laboratory
Authors: Sjöblom Peter , Todorescu Gabriela , Urpelainen Samuli
Published: February 2020

MAX IV is a fourth-generation, or diffraction-limited, synchrotron light source with a number of state-of-the-art beamlines. The performance of a beamline is, to a high degree, set by the energy resolution it can achieve, which in turn is governed to a large extent by the monochromator. During the design phase of a monochromator, the mechanical requirements must be fully understood and met with margin. During commissioning, the performance must be verified and optimized. In this paper, six soft X-ray monochromators at MAX IV beamlines (Bloch, Veritas, HIPPIE, SPECIES, FinEstBeAMS and SoftiMAX) are examined with a focus on their resolving power, energy range and the time required to change measurement range, as those parameters are dependent on each other. The monochromators have a modern commercial design, planned and developed in close collaboration with the vendors. This paper aims to present the current status of the commissioning at MAX IV with emphasis on elucidating the mechanical limitations on the performance of the monochromators. It contains analysis of the outcome and our approach to achieve fast and high-resolution monochromators.
When foreign brands appear local, and local brands appear foreign
Authors: Chen Bo
Published: February 2020

Purpose

Both foreign and local companies frequently name their brands in foreign language on the market of developing countries, and some of them choose to disclose the brands' country of origin to consumers. The purpose of this research is to investigate the joint effects between the practices of disclosing the actual country of origin of the brands and the language of the brand names on consumers' purchase intention for foreign brands and local brands in developing countries.

Design/methodology/approach

The proposed hypotheses were tested in two studies, namely an experiment and a field experimental survey, with stimuli from two product categories.

Findings

The results of the two empirical studies with Chinese participants consistently demonstrate that revealing the actual country of origin of the brands undermines consumers' purchase intention for local brands that use foreign brand names, but does not impact consumers' purchase intention for foreign brands that use local brand names.

Originality/value

This research first investigates the effects of adapting the brand names into local language of developing countries for brands from developed countries on consumers' purchase intention, which provides new insight into the literature on foreign branding and country of origin effects as well as practical implications for brand managers.
High-performance work system and organizational citizenship behaviour at the shop floor
Authors: Singh Jitendra Pratap , Chand Pawan Kumar , Mittal Amit , Aggarwal Arun
Published: February 2020

Purpose

The manufacturing industry is presently experiencing technological disruption on a global scale. Consequently, to tackle such disruption, firms are identifying a volatile, uncertain, complex and ambiguous (VUCA) scenario and seeking ways to counter it. Accordingly, this paper aims to investigate the employee performance through assessing organizational citizenship behaviour (OCB) among the shop floor employees of the fast-moving consumer goods (FMCG) industry where a high-performance work system (HPWS) has been implemented.

Design/methodology/approach

A descriptive research design was used in the study, and 395 shop floor employees working in leading multinational firms, with a minimum global turnover of US$1bn, were interviewed. These manufacturing firms were located in three industrial clusters in the northern part of India.

Findings

The results indicate that HPWS influences OCB. Most of the dimensions of HPWS and OCB were found to be positively associated. The findings also disprove the labour process theory in the context of the study.

Practical implications

The findings report a broad view of the relationship between HPWS and OCB in the Indian manufacturing context. The study offers the practical insights that HPWS is a universally accepted framework and that organizations should focus on the effective implementation of HPWS in a VUCA scenario, which is in line with past studies. The study also provides future directions for research.

Originality/value

This paper has established the relationship between HPWS and OCB in the manufacturing sector, especially for shop floor employees.
IFRS adoption, corporate governance and management earnings forecasts
Authors: Hlel Khawla , Kahloul Ines , Bouzgarrou Houssam
Published: February 2020

Purpose

This paper aims to examine whether International Financial Reporting Standards (IFRS) adoption and corporate governance attributes increase the management earnings forecasts’ accuracy disclosed in prospectuses for French Initial Public Offerings (IPOs).

Design/methodology/approach

The analysis is based on cross-sectional regression explaining the absolute forecast errors by using 45 French firms that made IPOs between 2005 and 2016 in two French financial markets: Euronext and Alternext.

Findings

In agreement with the agency theory and the signaling theory, the authors find that the IFRS adoption and the effective corporate governance, proxied by the board characteristics, increase the accuracy of management forecasts. As a result, this latter gives a credible signal in constructing and sustaining shareholders’ trust on the transparency and the reliability of such financial information.

Research limitations/implications

It is plausible that the limited size of the sample represents a limitation of this study. Another limitation is that no other corporate governance attributes such as board meeting frequency, audit committee measures and ownership structure are used.

Practical implications

Shareholders can take benefit from management forecasts accuracy to structure their investment portfolios efficiently to allocate their funds more effectively and mitigate the costs of adverse selection that they have to face. Furthermore, the authors expect the findings to be interesting to IPO firms, as this study highlights the efficiency of larger and independent boards in decreasing managerial discretion, increasing disclosure quality and supervising management. The results could encourage GAAP-adopters countries to move toward IFRS, as this research reinforces the role of IFRS in enhancing the quality of financial disclosure by offering the required information for shareholders.

Originality/value

This study is important because the potential investors should assess management earnings forecasts accuracy before they consider it when evaluating IPO firms. Also, this paper has some implications for the financial market. It is recommended that future investors pay more attention, when assessing the accuracy of management earnings forecasts, to the accounting regulations of the financial reporting along with the corporate governance mechanisms. Moreover, this study could incite French regulators to revise the AFEP-MEDEF code. Under this code, it could insist that larger and independent boards are more effective in performing their governing roles than smaller boards.
Leading with moral courage: The interplay of guilt and courage on perceived ethical leadership and group organizational citizenship behaviors
Authors: Mansur Juliana , Sobral Filipe , Islam Gazi
Published: February 2020

This study uses a moderated mediation model to investigate the role of leaders’ moral courage and guilt in promoting group‐level organizational citizenship behavior (OCB). Based on the idea that leaders model ethical behavior among followers, we examine whether leaders’ display of morally laden emotions weaken follower perceptions of ethical leadership, thus disrupting the influence of moral courage on followers. Two independent studies examined the proposed model. Study 1 used an experimental design to examine leaders’ moral displays, testing the interactive effects of leader moral courage, and guilt on follower perceptions of ethical leadership. Study 2 used a multisource field study with 100 leaders and 336 subordinates to explore how a leader displays of courage and guilt influenced group‐level OCB, mediated by ethical leadership. Consistent with our theoretical model, we find an indirect positive relationship between a leader’s moral courage and group OCB. However, we also find that this effect is weakened by displays of guilt by the leader.
Unpleasant Bodily Odour in a Psychoanalytic Treatment: Bridge or Drawbridge to a Troubled Past?
Authors: Hilty Raffaella
Published: February 2020

In this paper, I explore the topic of primitive bodily communications and countertransference enactments, with a particular focus on the part played by bodily odour. To explore this topic, I discuss a two‐year treatment with a patient who presented with a mix of borderline and narcissistic diagnostic features. I describe meaningful aspects of the difficulties faced in countertransference work when receiving and making sense of the patient's use of primitive defences and I highlight their expression through a very uncomfortable symptom: an extremely unpleasant bodily smell. My thesis is that the smell communicated preverbal and unsymbolized experiences of early physical and emotional neglect, as well as evacuating the toxicity of those experiences. In this way the smell acted both as a bridge, which could help me reconstruct my patient's early traumatic past, and as a drawbridge, to keep me at distance and maintain his past dissociated. The invasive and aversive nature of the smell can also be seen as representing the approach‐avoidance dilemma typical of a disorganized attachment state of mind, acting both as a bridge and as a drawbridge to attachment and relating.
The natural rate of interest: An estimate for the United Kingdom
Authors: Evans Anthony J
Published: February 2020

The natural rate of interest, also known as R*, is a central concept for many monetary economists. Although policymakers and commentators make judgements based on an implicit belief regarding its value, attempts to measure it are quite rare. This article uses productivity data to estimate the natural rate for the UK economy during 1998–2018. It finds that the median real natural rate up to and including 2008:2 was 2.11 per cent and has been 1.9 per cent since then. This supports the view that the natural rate can change over time and has fallen in recent years. Policymakers who use the natural rate as a benchmark should therefore monitor this more closely.
Bipartite Network Projections of Multi‐Locational Corporations: Realising the Potential
Authors: Derudder Ben
Published: February 2020

In this commentary, I evaluate the potential of bipartite network projections of multilocational corporations in quantitative structural analyses of world/global cities. My starting point is that the Geographical Analysis paper by Pazitka, Wójcik, and Knight (2019) paper provides a number of useful critical observations in this regard, but their analysis is also incomplete and at points potentially misleading. I make three points. First, in this literature the notion of “construct validity” is vague because there is no such thing as a comprehensive world city network: we are dealing with abstractions of a complex and multilayered reality at best, and bipartite network projections are no more than generic tools that can help capturing the multiple globalizations of specific sets of cities. Second, there is no reason to assume that a spatial interaction‐based benchmark model can be used to assess the “structural validity” of these bipartite network projections. And third, rather than replacing bipartite network projections of multilocational corporations with bipartite network projections of project ecologies, this literature could above all benefit from geographers no longer borrowing projections from the social networks literature. Instead, we should try and come up with bipartite network projections that more adequately capture the geographical nature of how multilocational corporations/projects operate/unfold.