bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing nationwide avalanche terrain maps for Norway
Authors: Larsen Håvard T. , Hendrikx Jordy , Slåtten Martine S. , Engeset Rune V.
Published: June 2020

Snow avalanches are a significant natural hazard in Norway. One method to manage the backcountry avalanche hazard is through detailed mapping of avalanche terrain. Avalanche terrain can be mapped using a variety of methods, including using the Avalanche Terrain Exposure Scale (ATES); however, manual classification of terrain using ATES is time consuming. This study has developed and compared a fully automated algorithm to provide ATES mapping for all of Norway. Our new algorithm is based on the technical model for ATES mapping. This model has specific terrain-based thresholds that can be applied for automated terrain-based modeling. Our algorithm expands on prior work by including the potential release area (PRA) model to identify and calculate the likelihood of an avalanche releasing from a start zone. We also use the raster-based TauDEM-model to determine the avalanche runout length. The final product is a 10-m resolution ATES map. We compared this nationwide ATES map with areas that have been manually mapped by avalanche experts, and find that the automated approach yields similar and reliable results. In addition to comparing mapped areas, we also examine manually mapped linear routes and compare these with the automated mapped ATES areas. Our results suggest that for open terrain, the vast majority of the manually classified tracks are predominantly in the same ATES class as our algorithm. For forested areas, we get mixed results, which can be attributed to a lack of suitable vegetation data at an appropriate scale. Despite this limitation, the current ATES algorithm and resulting spatial data are already valuable as a large portion (~ 70%) of the Norwegian backcountry terrain is above tree line. The automated algorithm is also useful to ensure consistent manual classification across different regions in Norway, or globally, and will permit greater reproducibility and easier updating of mapping for the future.
Coping with climatic shocks: local perspectives from Haiti’s rural mountain regions
Authors: Staub Caroline , Gilot Anne , Pierre Molene , Murray Gerald , Koenig Rosalie
Published: June 2020

Haiti’s agrarian society is highly sensitive to changes in weather and climate conditions. Little is known about Haitian farmers’ perceptions of climate-related risks and their ability to cope with hazards, which may reduce the relevance and likelihood of success of proposed adaptation solutions. We discuss the findings from the focus groups held with 104 small-holder farmers from mountain areas. Farmers in the study area regard the impacts of climate hazards on their livelihood as significant but largely prioritize short-term solutions over long-term protective measures, which potentially increase their vulnerability over time. The study provides insights on local decision processes and potential pathways for discussing climate information with farmers. It identifies the types of information perceived as necessary for informed decision-making. The findings, while in some cases distinctive to the study area, have implications for the design of climate change adaptation interventions in other contexts.
Pannexin-1 channel “fuels” by releasing ATP from bone marrow cells a state of sterile inflammation required for optimal mobilization and homing of hematopoietic stem cells
Authors: Cymer Monika , Brzezniakiewicz-Janus Katarzyna , Bujko Kamila , Thapa Arjun , Ratajczak Janina , Anusz Krzysztof , Tracz Michał , Jackowska-Tracz Agnieszka , Ratajczak Mariusz Z. , Adamiak Mateusz
Published: June 2020

An efficient harvest of hematopoietic stem/progenitor cells (HSPCs) after pharmacological mobilization from the bone marrow (BM) into peripheral blood (PB) and subsequent proper homing and engraftment of these cells are crucial for clinical outcomes from hematopoietic transplants. Since extracellular adenosine triphosphate (eATP) plays an important role in both processes as an activator of sterile inflammation in the bone marrow microenvironment, we focused on the role of Pannexin-1 channel in the secretion of ATP to trigger both egress of HSPCs out of BM into PB as well as in reverse process that is their homing to BM niches after transplantation into myeloablated recipient. We employed a specific blocking peptide against Pannexin-1 channel and noticed decreased mobilization efficiency of HSPCs as well as other types of BM-residing stem cells including mesenchymal stroma cells (MSCs), endothelial progenitors (EPCs), and very small embryonic-like stem cells (VSELs). To explain better a role of Pannexin-1, we report that eATP activated Nlrp3 inflammasome in Gr-1+ and CD11b+ cells enriched for granulocytes and monocytes. This led to release of danger-associated molecular pattern molecules (DAMPs) and mitochondrial DNA (miDNA) that activate complement cascade (ComC) required for optimal egress of HSPCs from BM. On the other hand, Pannexin-1 channel blockage in transplant recipient mice leads to a defect in homing and engraftment of HSPCs. Based on this, Pannexin-1 channel as a source of eATP plays an important role in HSPCs trafficking.
Toward automatic C-arm positioning for standard projections in orthopedic surgery
Authors: Kausch Lisa , Thomas Sarina , Kunze Holger , Privalov Maxim , Vetter Sven , Franke Jochen , Mahnken Andreas H. , Maier-Hein Lena , Maier-Hein Klaus
Published: June 2020

Purpose

Guidance and quality control in orthopedic surgery increasingly rely on intra-operative fluoroscopy using a mobile C-arm. The accurate acquisition of standardized and anatomy-specific projections is essential in this process. The corresponding iterative positioning of the C-arm is error prone and involves repeated manual acquisitions or even continuous fluoroscopy. To reduce time and radiation exposure for patients and clinical staff and to avoid errors in fracture reduction or implant placement, we aim at guiding—and in the long-run automating—this procedure.

Methods

In contrast to the state of the art, we tackle this inherently ill-posed problem without requiring patient-individual prior information like preoperative computed tomography (CT) scans, without the need of registration and without requiring additional technical equipment besides the projection images themselves. We propose learning the necessary anatomical hints for efficient C-arm positioning fromin silicosimulations, leveraging masses of 3D CTs. Specifically, we propose a convolutional neural network regression model that predicts 5 degrees of freedom pose updates directly from a first X-ray image. The method is generalizable to different anatomical regions and standard projections.

Results

Quantitative and qualitative validation was performed for two clinical applications involving two highly dissimilar anatomies, namely the lumbar spine and the proximal femur. Starting from one initial projection, the mean absolute pose error to the desired standard pose is iteratively reduced across different anatomy-specific standard projections. Acquisitions of both hip joints on 4 cadavers allowed for an evaluation on clinical data, demonstrating that the approach generalizes without retraining.

Conclusion

Overall, the results suggest the feasibility of an efficient deep learning-based automated positioning procedure, which is trained on simulations. Our proposed 2-stage approach for C-arm positioning significantly improves accuracy on synthetic images. In addition, we demonstrated that learning based on simulations translates to acceptable performance on real X-rays.
A perturbation view of level-set methods for convex optimization
Authors: Estrin Ron , Friedlander Michael P.
Published: June 2020

Level-set methods for convex optimization are predicated on the idea that certain problems can be parameterized so that their solutions can be recovered as the limiting process of a root-finding procedure. This idea emerges time and again across a range of algorithms for convex problems. Here we demonstrate that strong duality is a necessary condition for the level-set approach to succeed. In the absence of strong duality, the level-set method identifies $$\epsilon $$
ϵ
-infeasible points that do not converge to a feasible point as $$\epsilon $$
ϵ
tends to zero. The level-set approach is also used as a proof technique for establishing sufficient conditions for strong duality that are different from Slater’s constraint qualification.
The psychometric properties of the Hungarian version of the Personality Inventory for DSM-5 in a clinical and a community sample
Authors: Labancz Eszter , Balázs Katalin , Kuritárné Szabó Ildikó
Published: June 2020

The alternative dimensional model for personality disorders characterizes the individual on pathological personality traits, which can be measured by the Personality Inventory for DSM-5 (PID-5). Our study focused on the psychometric properties of the Hungarian version of PID-5 in 239 psychiatric patients and 226 non-clinical participants. The distribution of gender, age, and educational level were the same in the two samples. In the clinical sample, we examined the assumed unidimensionality of the 25 facets. The results of the exploratory factor analysis for five factors indicated the supposed five-factor structure. The convergent validity was studied by correlations with Big Five Inventory. The PID-5 domains showed moderate or strong correlation with the domains of Big Five except for Psychoticism. The comparison of the clinical and non-clinical samples revealed that psychiatric patients had a higher score on all pathological facets and domains, except for the domain of Antagonism with all its related facets, and the facet of Risk Taking. As a whole, we recommend the use of the Hungarian version of the PID-5 in research and clinical practice.
The new concept of power transmission to the entomopter wings
Authors: Sochacki Wojciech , Cekus Dawid
Published: June 2020

The aim of this study is to discuss the design of the mechanism used for power transmission to the entomopter wings in order to perform a flapping motion and control the angle of attack of the wings. The study presents a kinematic diagram and a simulation model obtained in SolidWorks for the proposed mechanism, which includes a slotted link mechanism and a slider mechanism (with bilateral slider) that actuates the rocking lever of the wing. The simulation model allowed for observation of the system work and verification of the adopted kinematic assumptions. The comparative analysis showed that trajectories obtained from the both models are very similar. The correct operation of the proposed solution has been demonstrated by building a prototype of the mechanism and conducting experimental research. In the case of the application of the solution presented for the real object it is sufficient to choose the system parameters in order to properly reflect the living organism. The proposed mechanism is characterized by simplicity and offers opportunity for miniaturization while ensuring reliable work at reduced demand for power to drive the mechanism. A technological advantage of the presented solution is the use of only one component in order to perform flapping wing motion and change the angle of attack of the entomopter.
Ritual practices and social organisation at the Middle Yayoi culture settlement site of Maenakanishi, eastern Japan
Authors: Leipe Christian , Kuramochi Shunsuke , Wagner Mayke , Tarasov Pavel E.
Published: June 2020

Combined archaeobotanical and archaeological data from Middle Yayoi (fourth century bce–first century ce) cultural layers of the Maenakanishi site (36°08′55″ N, 139°24′08″ E) in northern Saitama Prefecture indicate that rice was less significant as everyday food, but played an important role in ritual practices and in strengthening social stratification at the studied settlement site. The results further suggest that the crop was used in feasting performed in context of pillared buildings that were often large and occupied a spatially separated central location within a settlement. We propose that these pillared buildings were residences of political/religious leaders, who directed these rituals related to agricultural production and worship of elite ancestors. Such ritual practices were likely introduced to Japan from continental East Asia as part of the ‘Yayoi package’ and conducted for empowerment and labour mobilisation.
Evacuating a First Nation Due to Wildfire Smoke: The Case of Dene Tha’ First Nation
Authors: Mottershead Kyla D. , McGee Tara K. , Christianson Amy
Published: June 2020

Almost every year, First Nations are evacuated in Canada because of wildfire proximity and smoke. Dynamics of wildfires, and remote locations, unique sociocultural characteristics, and limited emergency management resources present challenges for evacuation organizers and residents. This study explores how Dene Tha’ First Nation evacuated their Taché community in July 2012 due to wildfire smoke and how the evacuation process affected evacuees. Interviews were completed with 31 evacuation organizers and residents to examine the factors that helped and hindered the evacuation process. Lack of information about the nearby wildfire, smoke, and evacuation of the nearby small community of Zama City, combined with a generic evacuation plan, delayed and posed challenges during the evacuation of this Dene Tha’ community. Strong leadership and its role in community organizing, keeping families together, providing the social support they needed, and using familiar host communities, demonstrated and contributed to the community’s resilience during the evacuation. Measures to improve evacuations and emergency management in the community and other First Nations in Canada are identified and discussed.
On the BACB’s Ethics Requirements: A Response to Rosenberg and Schwartz (2019)
Authors: Sellers Tyra P. , Carr James E. , Nosik Melissa R.
Published: June 2020

Rosenberg and Schwartz (Behavior Analysis in Practice, 12, 473–482, 2019) criticize a number of aspects of the Behavior Analyst Certification Board’s Professional and Ethical Compliance Code for Behavior Analysts and propose, as an alternative, a decision-making process for evaluating the ethicality of behavior under a particular set of circumstances. We respond to the authors’ main criticisms and discuss the broader professional and legal context of any profession’s ethics code and enforcement activity.
The Ocean's Impact on Slow Slip Events
Authors: Gomberg J. , Baxter P. , Smith E. , Ariyoshi K. , Chiswell S. M.
Published: June 2020

We test the hypothesis that ocean seafloor pressures impart stresses that alter the initiation or termination of transient slow slip events (SSEs) on shallow submarine and near‐coastal faults, using simulated seafloor pressures and a new catalog of SSEs in the Hikurangi subduction zone. We show that seafloor pressures may be represented by an average time history over the ~100‐km dimensions of the study area. We account for SSE uncertainties and the multiplicity of processes that affect SSEs statistically by estimating the probabilities of rejecting the null hypothesis that SSE initiation or termination pressures are those to be expected by chance sampling of known (modeled) seafloor pressures, with low probabilities indicating some causal connection. No impact of ocean pressure changes on SSE initiation is detectable, but a correlation with their terminations is suggested. SSE slip that weakens the fault and makes it more sensitive to small stress changes may explain results.
Modulation of Tropical Cyclone Genesis in the Bay of Bengal by the Central Indian Ocean Mode
Authors: Li Baosheng , Zhou Lei , Wang Chunzai , Gao Cong , Qin Jianhuang , Meng Ze
Published: June 2020

Tropical cyclones (TCs) can be modified by various processes in the multiscale weather and climate system. In this study, the TC genesis locations are found to shift northward in the Bay of Bengal (BoB) due to the intraseasonal central Indian Ocean (CIO) mode. During the positive phase of the CIO mode, convection center moves from the equator to the BoB. Correspondingly, over the BoB, the updraft transports moisture to the mid‐troposphere, and the associated convergence and cyclonic vorticity in the lower troposphere are favorable for TC genesis. The diagnoses on eddy kinetic energy budget indicate that the barotropic energy gain from intraseasonal variabilities nourishes TC genesis over the BoB, which is mainly attributable to the horizontal gradient of zonal winds associated with the enhanced low‐level convergence and vorticity during the positive CIO mode. During the negative CIO mode, convection is around the equator. The TC genesis locations shift southward, but the modifications are not significant. The impacts of the CIO mode on TC genesis over the BoB are different from the influences of Madden‐Julian Oscillation. Hence, the results are expected to contribute to a comprehensive understanding of the relations between TCs and intraseasonal variabilities over the Indian Ocean.
Inhibition of miR-450b-5p ameliorates hepatic ischemia/reperfusion injury via targeting CRYAB
Authors: Huang Zuotian , Mou Tong , Luo Yunhai , Pu Xingyu , Pu Junliang , Wan Lei , Gong Junhua , Yang Hang , Liu Yanyao , Li Zhongtang , Shen Ai , Wu Zhongjun
Published: June 2020

Hepatic ischemia/reperfusion injury (IRI) is an unavoidable course in liver transplantation, during which the immune response of inflammation plays a leading part. MicroRNA-450b-5p (miR-450b-5p), which has been reported to participate in several inflammatory diseases, was investigated in this study. The purpose of this study is to identify the potential function of miR-450b-5p toward remission of hepatic IRI and elucidate the specific mechanism. Herein we found that expression of miR-450b-5p, interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), and IL-6 was stimulated in hepatic IRI. Inhibition of miR-450b-5p could remarkably alleviate mouse hepatic IRI and improve liver function measured by hematoxylin–eosin (HE) staining, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL), and enzyme-linked immunosorbent assay (ELISA). We further assessed protein expression undergoing Western blot and immunofluorescence, and discovered that miR-450b-5p suppressed alpha B-crystallin (CRYAB), thus restraining the inhibitory κB kinase (IKK) β-mediated canonical nuclear factor-κB (NF-κB) signaling, instead of the noncanonical path guided by IKKα in hepatic IRI. In addition, we demonstrated CRYAB as an activator of M2 polarization through protein kinase B (Akt) 1/mammalian target of rapamycin (mTOR), thus resulting in relief of liver IRI. Combination treatment containing both paths revealed a better antidamage efficacy than adjusting either path alone, suggesting that the joint therapy might be a promising solution in hepatic IRI.
Lentiviral gene therapy rescues p47phox chronic granulomatous disease and the ability to fight Salmonella infection in mice
Authors: Schejtman Andrea , Aragão-Filho Walmir Cutrim , Clare Simon , Zinicola Marta , Weisser Maren , Burns Siobhan O. , Booth Claire , Gaspar Hubert B. , Thomas David C. , Condino-Neto Antonio , Thrasher Adrian J. , Santilli Giorgia
Published: June 2020

Chronic granulomatous disease (CGD) is an inherited primary immunodeficiency disorder characterised by recurrent and often life-threatening infections and hyperinflammation. It is caused by defects of the phagocytic NADPH oxidase, a multicomponent enzyme system responsible for effective pathogen killing. A phase I/II clinical trial of lentiviral gene therapy is underway for the most common form of CGD, X-linked, caused by mutations in the gp91phoxsubunit of the NADPH oxidase. We propose to use a similar strategy to tackle p47phox-deficient CGD, caused by mutations inNCF1, which encodes the p47phoxcytosolic component of the enzymatic complex. We generated a pCCLCHIM-p47phoxlentiviral vector, containing the chimericCathepsin G/FESmyeloid promoter and a codon-optimised version of the humanNCF1cDNA. Here we show that transduction with the pCCLCHIM-p47phoxvector efficiently restores p47phoxexpression and biochemical NADPH oxidase function in p47phox-deficient human and murine cells. We also tested the ability of our gene therapy approach to control infection by challenging p47phox-null mice withSalmonellaTyphimurium, a leading cause of sepsis in CGD patients, and found that mice reconstituted with lentivirus-transduced hematopoietic stem cells had a reduced bacterial load compared with untreated mice. Overall, our results potentially support the clinical development of a gene therapy approach using the pCCLCHIM-p47phoxvector.
The acute effects of adjuvant radiation and chemotherapy on peripheral blood epigenetic age in early stage breast cancer patients
Authors: Sehl Mary E. , Carroll Judith E. , Horvath Steve , Bower Julienne E.
Published: June 2020

Survival has increased in early stage breast cancer (BC), and the late effects of treatment persist for decades. Molecular mechanisms underlying the acceleration of age-related diseases after chemotherapy and radiotherapy are poorly understood. We examined epigenetic changes in peripheral whole blood cells in early stage BC patients undergoing surgery followed by adjuvant radiotherapy, or surgery followed by adjuvant chemotherapy and radiotherapy. DNA methylation experiments were performed on whole blood samples collected before and after adjuvant therapy. Methylation profiles were used to estimate four measures of epigenetic age acceleration—intrinsic, extrinsic, phenotypic, and Grim—and cell counts. We found significant increases in extrinsic, phenotypic, and Grim epigenetic age acceleration and in estimated proportions of senescent T lymphocytes from pre- to post-treatment. When examining differential effects by treatment category, most of these increases were significant only in women undergoing radiation alone. Further studies are needed to examine whether these effects are related to the risk of cognitive and functional decline in BC survivors.
Prevalence of disease-causing genes in Japanese patients with BRCA1/2-wildtype hereditary breast and ovarian cancer syndrome
Authors: Kaneyasu Tomoko , Mori Seiichi , Yamauchi Hideko , Ohsumi Shozo , Ohno Shinji , Aoki Daisuke , Baba Shinichi , Kawano Junko , Miki Yoshio , Matsumoto Naomichi , Nagasaki Masao , Yoshida Reiko , Akashi-Tanaka Sadako , Iwase Takuji , Kitagawa Dai , Masuda Kenta , Hirasawa Akira , Arai Masami , Takei Junko , Ide Yoshimi , Gotoh Osamu , Yaguchi Noriko , Nishi Mitsuyo , Kaneko Keika , Matsuyama Yumi , Okawa Megumi , Suzuki Misato , Nezu Aya , Yokoyama Shiro , Amino Sayuri , Inuzuka Mayuko , Noda Tetsuo , Nakamura Seigo
Published: June 2020

Panel sequencing of susceptibility genes for hereditary breast and ovarian cancer (HBOC) syndrome has uncovered numerous germline variants; however, their pathogenic relevance and ethnic diversity remain unclear. Here, we examined the prevalence of germline variants among 568 Japanese patients with BRCA1/2-wildtype HBOC syndrome and a strong family history. Pathogenic or likely pathogenic variants were identified on 12 causal genes for 37 cases (6.5%), with recurrence for 4 SNVs/indels and 1 CNV. Comparisons with non-cancer east-Asian populations and European familial breast cancer cohorts revealed significant enrichment of PALB2, BARD1, and BLM mutations. Younger onset was associated with but not predictive of these mutations. Significant somatic loss-of-function alterations were confirmed on the wildtype alleles of genes with germline mutations, including PALB2 additional somatic truncations. This study highlights Japanese-associated germline mutations among patients with BRCA1/2 wildtype HBOC syndrome and a strong family history, and provides evidence for the medical care of this high-risk population.
Field-free spin–orbit torque perpendicular magnetization switching in ultrathin nanostructures
Authors: Dai Minyi , Hu Jia-Mian
Published: June 2020

Magnetic-field-free current-controlled switching of perpendicular magnetization via spin–orbit torque (SOT) is necessary for developing a fast, long data retention, and high-density SOT magnetoresistive random access memory (MRAM). Here, we use both micromagnetic simulations and atomistic spin dynamics (ASD) simulations to demonstrate an approach to field-free SOT perpendicular magnetization switching without requiring any changes in the architecture of a standard SOT-MRAM cell. We show that this field-free switching is enabled by a synergistic effect of lateral geometrical confinement, interfacial Dyzaloshinskii–Moriya interaction (DMI), and current-induced SOT. Both micromagnetic and atomistic understanding of the nucleation and growth kinetics of the reversed domain are established. Notably, atomically resolved spin dynamics at the early stage of nucleation is revealed using ASD simulations. A machine learning model is trained based on ~1000 groups of benchmarked micromagnetic simulation data. This machine learning model can be used to rapidly and accurately identify the nanomagnet size, interfacial DMI strength, and the magnitude of current density required for the field-free switching.
Adaptive characterization of spatially inhomogeneous fields and errors in qubit registers
Authors: Gupta Riddhi Swaroop , Edmunds Claire L. , Milne Alistair R. , Hempel Cornelius , Biercuk Michael J.
Published: June 2020

New quantum computing architectures consider integrating qubits as sensors to provide actionable information useful for calibration or decoherence mitigation on neighboring data qubits, but little work has addressed how such schemes may be efficiently implemented in order to maximize information utilization. Techniques from classical estimation and dynamic control, suitably adapted to the strictures of quantum measurement, provide an opportunity to extract augmented hardware performance through automation of low-level characterization and control. In this work, we present an adaptive learning framework, Noise Mapping for Quantum Architectures (NMQA), for scheduling of sensor–qubit measurements and efficient spatial noise mapping (prior to actuation) across device architectures. Via a two-layer particle filter, NMQA receives binary measurements and determines regions within the architecture that share common noise processes; an adaptive controller then schedules future measurements to reduce map uncertainty. Numerical analysis and experiments on an array of trapped ytterbium ions demonstrate that NMQA outperforms brute-force mapping by up to 20× (3×) in simulations (experiments), calculated as a reduction in the number of measurements required to map a spatially inhomogeneous magnetic field with a target error metric. As an early adaptation of robotic control to quantum devices, this work opens up exciting new avenues in quantum computer science.
GDNF promotes hair formation and cutaneous wound healing by targeting bulge stem cells
Authors: Lisse Thomas S. , Sharma Manju , Vishlaghi Neda , Pullagura Sri Ramulu , Braun Robert E.
Published: June 2020

Glial-cell-derived neurotrophic factor (GDNF) is a well-studied neuroregenerative factor; however, the degree to which it supports hair formation and skin wound repair is not known. By using a Gfra1 (GDNF family receptor alpha 1) knock-in reporter mouse line, GDNF signaling was found to occur within hair bulge stem cells (BSCs) during the initiation of the hair cycle and early stages of hair formation after depilation. Both recombinant and transgene overexpression of GDNF promoted BSC colony growth, hair formation, and skin repair after wounding through enhanced self-renewal of BSCs and commitment of BSC-derived progenitors into becoming epidermal cells at the injury site. Conditional ablation of Gfra1 among BSCs impaired the onset of the hair cycle, while conditional ablation of the GDNF family member signal transducer, Ret, within BSCs prevented the onset of the hair cycle and depilation-induced anagen development of hair follicles. Our findings reveal that GDNF promotes hair formation and wound repair and that bulge stem cells are critical mediators of both.
Advice from a systems-biology model of the corona epidemics
Authors: Westerhoff Hans V. , Kolodkin Alexey N.
Published: June 2020

Using standard systems biology methodologies a 14-compartment dynamic model was developed for the Corona virus epidemic. The model predicts that: (i) it will be impossible to limit lockdown intensity such that sufficient herd immunity develops for this epidemic to die down, (ii) the death toll from the SARS-CoV-2 virus decreases very strongly with increasing intensity of the lockdown, but (iii) the duration of the epidemic increases at first with that intensity and then decreases again, such that (iv) it may be best to begin with selecting a lockdown intensity beyond the intensity that leads to the maximum duration, (v) an intermittent lockdown strategy should also work and might be more acceptable socially and economically, (vi) an initially intensive but adaptive lockdown strategy should be most efficient, both in terms of its low number of casualties and shorter duration, (vii) such an adaptive lockdown strategy offers the advantage of being robust to unexpected imports of the virus, e.g. due to international travel, (viii) the eradication strategy may still be superior as it leads to even fewer deaths and a shorter period of economic downturn, but should have the adaptive strategy as backup in case of unexpected infection imports, (ix) earlier detection of infections is the most effective way in which the epidemic can be controlled, whilst waiting for vaccines.
Author Correction: Identifying inhibitors of epithelial–mesenchymal plasticity using a network topology-based approach
Authors: Hari Kishore , Sabuwala Burhanuddin , Subramani Balaram Vishnu , La Porta Caterina A. M. , Zapperi Stefano , Font-Clos Francesc , Jolly Mohit Kumar
Published: June 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Effects of biochar and crop straws on the bioavailability of cadmium in contaminated soil
Authors: Chen Xuan , He Hong-Zhi , Chen Gui-Kui , Li Hua-Shou
Published: June 2020

Numerous studies have been investigated the potential of biochar (BC) derived from various materials and crop straw (CS) to decrease the bioavailability of heavy metals in soil contaminated with cadmium (Cd), and thereby reduce their potential risk to human health and the ecological environment. However, little attention has been given to the comparison of heavy metal remediation efficiency using BC and CS such as peanut vine (PV) and rice straw (RS), especially in soil contaminated with Cd. Here, we explore if Cd bioavailability is affected in contaminated soil by BC and CS. Peanuts were grown in plastic pots, which contained BC or CS at 5% (dry weight, w/w) in controlled environment mesocosms. The bioavailability of Cd in contaminated soil was measured by Cd concentration in the plant and the concentrations of various forms of Cd in the soil. At the same plant age, growth with BC (compared with PV and RS) led to 13.56% and 8.28% lower rates of Cd content in the aboveground parts, 40.65% and 35.67% lower rates of Cd content in the seeds, yet 9.08% and 7.09% lower rates of Cd content in the roots, yet 35.80% and 28.48% lower rates of exchangeable Cd content in the soil. Moreover, BC amendment enhanced the biomass of peanut and physiological quality. Thus, BC had a greater impact on immobilizing Cd in the soil. The results imply that BC was more significantly (P < 0.05) remarkable in decreasing the Cd bioavailability and improving the biomass of peanut. BC has greater potential for enhancing soil quality and promoting peanut growth. In conclusion, this research demonstrates an understanding of employing BC as a promising inexpensive and eco-friendly amendment to remediate soil contaminated with Cd.
A LAMP assay for the detection of Bactrocera tryoni Queensland fruit fly (Diptera: Tephritidae)
Authors: Blacket Mark J. , Agarwal Arati , Zheng Linda , Cunningham J. Paul , Britton David , Schneider Isarena , Rodoni Brendan C.
Published: June 2020

LAMP assays are targeted molecular tests for the rapid detection of species in the laboratory and field. We developed a LAMP assay for an economically important fruit fly species, Queensland fruit fly, Bactrocera tryoni. This assay was assessed against a broad panel of target and non-target species and found to be specific, only amplifying the target species and closest relatives, in a portable real-time fluorometer (Genie III) in under 15 minutes with an anneal derivative temperature of 82.5 oC. The assay is sensitive to low levels of target DNA (>0.016 ng/µl), performing equally to the existing qPCR test. To enable retention of a physical voucher specimen, for potential morphological confirmation of LAMP results, a novel whole-specimen non-destructive DNA extraction method was developed, suitable for LAMP in the field. The stability of DNA extraction and LAMP reagents was tested under simulated and actual field conditions and shown to be robust. Our new assay now provides a portable molecular tool for the detection of this significant tephritid fruit fly pest species of biosecurity/quarantine concern. This has already proven invaluable for in-field diagnostics, providing real-time support influencing immediate actions, with negative results allowing the release of fruit produce, and positive results initiating fruit fly control measures.
Understanding the effect of temperature and time on protein degree of hydrolysis and lipid oxidation during ensilaging of herring (Clupea harengus) filleting co-products
Authors: Sajib Mursalin , Albers Eva , Langeland Markus , Undeland Ingrid
Published: June 2020

The aims of this study were to investigate the effect of temperature, time and stirring on changes in protein degree of hydrolysis (DH), free amino acids (FAA), lipid oxidation and total volatile basic nitrogen (TVB-N) during ensilaging of herring (Clupea harengus) filleting co-products. Results showed that temperature and time, and in some cases the interaction effect between these two factors, significantly influenced all the studied responses. Increasing ensilaging temperature and time from 17 to 37 °C and 3 to 7 days, respectively, increased DH, FAA, and TVB-N content from 44.41 to 77.28%, 25.31 to 51.04 mg/g, and 4.73 to 26.25 mg/100 g, respectively. The lipid oxidation marker 2-thiobarbituric acid reactive substances (TBARS) did not increase with time at temperatures above 22 °C, while 2-pentylfuran increased up to 37 °C. Based on the process parameters and responses investigated in this study, and considering energy requirements, it was suggested to perform ensilaging at ambient temperatures (i.e. around 20 °C) with continuous stirring at 10 rpm for 1-3 days; the exact length being determined by the desired DH.
Antigen Discovery, Bioinformatics and Biological Characterization of Novel Immunodominant Babesia microti Antigens
Authors: Verma Nitin , Puri Ankit , Essuman Edward , Skelton Richard , Anantharaman Vivek , Zheng Hong , White Siera , Gunalan Karthigayan , Takeda Kazuyo , Bajpai Surabhi , Lepore Timothy J. , Krause Peter J. , Aravind L. , Kumar Sanjai
Published: June 2020

Babesia microti is an intraerythrocytic parasite and the primary causative agent of human babesiosis. It is transmitted by Ixodes ticks, transfusion of blood and blood products, organ donation, and perinatally. Despite its global public health impact, limited progress has been made to identify and characterize immunodominant B. microti antigens for diagnostic and vaccine use. Using genome-wide immunoscreening, we identified 56 B. microti antigens, including some previously uncharacterized antigens. Thirty of the most immunodominant B. microti antigens were expressed as recombinant proteins in E. coli. Among these, the combined use of two novel antigens and one previously described antigen provided 96% sensitivity and 100% specificity in identifying B. microti antibody containing sera in an ELISA. Using extensive computational sequence and bioinformatics analyses and cellular localization studies, we have clarified the domain architectures, potential biological functions, and evolutionary relationships of the most immunodominant B. microti antigens. Notably, we found that the BMN-family antigens are not monophyletic as currently annotated, but rather can be categorized into two evolutionary unrelated groups of BMN proteins respectively defined by two structurally distinct classes of extracellular domains. Our studies have enhanced the repertoire of immunodominant B. microti antigens, and assigned potential biological function to these antigens, which can be evaluated to develop novel assays and candidate vaccines.
Graphene oxide integrated silicon photonics for detection of vapour phase volatile organic compounds
Authors: Leo Tsui H. C. , Alsalman Osamah , Mao Boyang , Alodhayb Abdullah , Albrithen Hamad , Knights Andrew P. , Halsall Matthew P. , Crowe Iain F.
Published: June 2020

The optical response of a graphene oxide integrated silicon micro-ring resonator (GOMRR) to a range of vapour phase Volatile Organic Compounds (VOCs) is reported. The response of the GOMRR to all but one (hexane) of the VOCs tested is significantly higher than that of the uncoated (control) silicon MRR, for the same vapour flow rate. An iterative Finite Difference Eigenmode (FDE) simulation reveals that the sensitivity of the GO integrated device (in terms of RIU/nm) is enhanced by a factor of ~2, which is coupled with a lower limit of detection. Critically, the simulations reveal that the strength of the optical response is determined by molecular specific changes in the local refractive index probed by the evanescent field of the guided optical mode in the device. Analytical modelling of the experimental data, based on Hill-Langmuir adsorption characteristics, suggests that these changes in the local refractive index are determined by the degree of molecular cooperativity, which is enhanced for molecules with a polarity that is high, relative to their kinetic diameter. We believe this reflects a molecular dependent capillary condensation within the graphene oxide interlayers, which, when combined with highly sensitive optical detection, provides a potential route for discriminating between different vapour phase VOCs.
Systematic Evaluation of PKH Labelling on Extracellular Vesicle Size by Nanoparticle Tracking Analysis
Authors: Dehghani Mehdi , Gulvin Shannon M. , Flax Jonathan , Gaborski Thomas R.
Published: June 2020

Extracellular vesicles (EVs) are membrane vesicles secreted by cells and can modulate biological activities by transferring their content following uptake into recipient cells. Labelling of EVs is a commonly used technique for understanding their cellular targeting and biodistribution. A reliable fluorescent technique needs to preserve the size of EVs since changes in size may alter their uptake and biodistribution. Lipophilic fluorescent dye molecules such as the PKH family have been widely used for EV labelling. Here, the effect of PKH labelling on the size of EVs was systematically evaluated using nanoparticle tracking analysis (NTA), which is a widely used technique for determining the size and concentration of nanoparticles. NTA analysis showed a size increase in all the PKH labelling conditions tested. As opposed to lipophilic dye molecules, no significant shift in the size of labelled EVs was detected with luminal binding dye molecules such as 5-(and-6)-carboxyfluorescein diacetate succinimidyl ester (CFDA-SE, hereinafter CFSE). This finding suggests that PKH labelling may not be a reliable technique for the tracking of EVs.
Splice-specific deficiency of the PTSD-associated gene PAC1 leads to a paradoxical age-dependent stress behavior
Authors: Biran Jakob , Gliksberg Michael , Shirat Ido , Swaminathan Amrutha , Levitas-Djerbi Talia , Appelbaum Lior , Levkowitz Gil
Published: June 2020

The pituitary adenylate cyclase-activating polypeptide receptor (PAC1, also known as ADCYAP1R1) is associated with post-traumatic stress disorder and modulation of stress response in general. Alternative splicing of PAC1 results in multiple gene products, which differ in their mode of signalling and tissue distribution. However, the roles of distinct splice variants in the regulation of stress behavior is poorly understood. Alternative splicing of a short exon, which is known as the “hop cassette”, occurs during brain development and in response to stressful challenges. To examine the function of this variant, we generated a splice-specific zebrafish mutant lacking the hop cassette, which we designated ‘hopless’. We show that hopless mutant larvae display increased anxiety-like behavior, including reduced dark exploration and impaired habituation to dark exposure. Conversely, adult hopless mutants displayed superior ability to rebound from an acute stressor, as they exhibited reduced anxiety-like responses to an ensuing novelty stress. We propose that the developmental loss of a specific PAC1 splice variant mimics prolonged mild stress exposure, which in the long term, predisposes the organism’s stress response towards a resilient phenotype. Our study presents a unique genetic model demonstrating how early-life state of anxiety paradoxically correlates with reduced stress susceptibility in adulthood.
The tumor immune microenvironmental analysis of 2,033 transcriptomes across 7 cancer types
Authors: Kim Sungjae , Kim Ahreum , Shin Jong-Yeon , Seo Jeong-Sun
Published: June 2020

Understanding the tumor microenvironment is important to efficiently identify appropriate patients for immunotherapies in a variety of cancers. Here, we presented the tumor microenvironmental analysis of 2,033 cancer samples across 7 cancer types: colon adenocarcinoma, skin cutaneous melanoma, kidney renal papillary cell carcinoma, sarcoma, pancreatic adenocarcinoma, glioblastoma multiforme, and pheochromocytoma / paraganglioma from The Cancer Genome Atlas cohort. Unsupervised hierarchical clustering based on the gene expression profiles separated the cancer samples into two distinct clusters, and characterized those into immune-competent and immune-deficient subtypes using the estimated abundances of infiltrated immune and stromal cells. We demonstrated differential tumor microenvironmental characteristics of immune-competent subtypes across 7 cancer types, particularly immunosuppressive tumor microenvironment features in kidney renal papillary cell carcinoma with significant poorer survival rates and immune-supportive features in sarcoma and skin cutaneous melanoma. Additionally, differential genomic instability patterns between the subtypes were found across the cancer types, and discovered that immune-competent subtypes in most of cancer types had significantly higher immune checkpoint gene expressions. Overall, this study suggests that our subtyping approach based on transcriptomic data could contribute to precise prediction of immune checkpoint inhibitor responses in a wide range of cancer types.
Crepidtumines A and B, Two Novel Indolizidine Alkaloids from Dendrobium crepidatum
Authors: Xu Xiaolin , Chen Xingyue , Yang Runmei , Li Zesheng , Zhou Houguang , Bai Yanbing , Yu Meng , Li Biao , Ding Gang
Published: June 2020

Two new indolizidine alkaloids crepidatumines A (1) and B (2) together with the stereoisomer of dendrocrepidine B (3) and known analog dendrocrepine (4) were isolated from D. crepidatum. Their structures were determined by HR-ESI-MS, NMR, and Electronic Circular Dichroism (ECD) experiments together with comparison of analogues. Compound (1) possess a (5/6/6/5) tetra-hetero-cyclic ring, whereas compound (2) contains a tricyclic system with an unusual bridged ring, which are the first report in Nature. The biological evaluation revealed that dendrocrepine (4) displayed a potent hypoglycemic effect in vitro.
Genome-wide analysis of the U-box E3 ubiquitin ligase enzyme gene family in tomato
Authors: Sharma Bhaskar , Taganna Joemar
Published: June 2020

E3 ubiquitin ligases are a central modifier of plant signaling pathways that act through targeting proteins to the degradation pathway. U-box E3 ubiquitin ligases are a distinct class of E3 ligases that utilize intramolecular interactions for its scaffold stabilization. U-box E3 ubiquitin ligases are prevalent in plants in comparison to animals. However, the evolutionary aspects, genetic organizations, and functional fate of the U-box E3 gene family in plant development, especially in tomato is not well understood. In the present study, we have performed in-silico genome-wide analysis of the U-box E3 ubiquitin ligase gene family in Solanum lycopersicum. We have identified 62 U-box genes with U-box/Ub Fusion Degradation 2 (UFD2) domain. The chromosomal localization, phylogenetic analysis, gene structure, motifs, gene duplication, syntenic regions, promoter, physicochemical properties, and ontology were investigated. The U-box gene family showed significant conservation of the U-box domain throughout the gene family. Duplicated genes discerned noticeable functional transitions among duplicated genes. The gene expression profiles of U-box E3 family members show involvement in abiotic and biotic stress signaling as well as hormonal pathways. We found remarkable participation of the U-box gene family in the vegetative and reproductive tissue development. It is predicted to be actively regulating flowering time and endosperm formation. Our study provides a comprehensive picture of distribution, structural features, promoter elements, evolutionary relationship, and gene expression of the U-box gene family in the tomato. We predict the crucial participation of the U-box gene family in tomato plant development and stress responses.
Effects of a high fat diet on gut microbiome dysbiosis in a mouse model of Gulf War Illness
Authors: Angoa-Pérez Mariana , Zagorac Branislava , Francescutti Dina M. , Winters Andrew D. , Greenberg Jonathan M. , Ahmad Madison M. , Manning Shannon D. , Gulbransen Brian D. , Theis Kevin R. , Kuhn Donald M.
Published: June 2020

Gulf War Illness (GWI) is a chronic health condition that appeared in Veterans after returning home from the Gulf War. The primary symptoms linked to deployment are posttraumatic stress disorder, mood disorders, GI problems and chronic fatigue. At first glance, these symptoms are difficult to ascribe to a single pathological mechanism. However, it is now clear that each symptom can be linked individually to alterations in the gut microbiome. The primary objective of the present study was to determine if gut microbiome dysbiosis was evident in a mouse model of GWl. Because the majority of Gulf War Veterans are overweight, a second objective was to determine if a high fat diet (HF) would alter GWI outcomes. We found that the taxonomic structure of the gut microbiome was significantly altered in the GWI model and after HF exposure. Their combined effects were significantly different from either treatment alone. Most treatment-induced changes occurred at the level of phylum in Firmicutes and Bacteroidetes. If mice fed HF were returned to a normal diet, the gut microbiome recovered toward normal levels in both controls and GWI agent-treated mice. These results add support to the hypotheses that dysbiosis in the gut microbiome plays a role in GWI and that life-style risk factors such as an unhealthy diet can accentuate the effects of GWI by impacting the gut microbiome. The reversibility of the effect of HF on the gut microbiome suggests new avenues for treating GWI through dietary intervention.