bluuebunny/crossref_metadata_2025 huggingface dataset:
Early dengue outbreak detection modeling based on dengue incidences in Singapore during 2012 to 2017
Authors: Chen Piao , Fu Xiuju , Ma Stefan , Xu Hai‐Yan , Zhang Wanbing , Xiao Gaoxi , Siow Mong Goh Rick , Xu George , Ching Ng Lee
Published: March 2020

Dengue has been as an endemic with year‐round presence in Singapore. In the recent years 2013, 2014, and 2016, there were several severe dengue outbreaks, posing serious threat to the public health. To proactively control and mitigate the disease spread, early warnings of dengue outbreaks, at which there are rapid and large‐scale spread of dengue incidences, are extremely helpful. In this study, a two‐step framework is proposed to predict dengue outbreaks and it is evaluated based on the dengue incidences in Singapore during 2012 to 2017. First, a generalized additive model (GAM) is trained based on the weekly dengue incidence data during 2006 to 2011. The proposed GAM is a one‐week‐ahead forecasting model, and it inherently accounts for the possible correlation among the historical incidence data, making the residuals approximately normally distributed. Then, an exponentially weighted moving average (EWMA) control chart is proposed to sequentially monitor the weekly residuals during 2012 to 2017. Our investigation shows that the proposed two‐step framework is able to give persistent signals at the early stage of the outbreaks in 2013, 2014, and 2016, which provides early alerts of outbreaks and wins time for the early interventions and the preparation of necessary public health resources. In addition, extensive simulations show that the proposed method is comparable to other potential outbreak detection methods and it is robust to the underlying data‐generating mechanisms.
The powerful world of antisense oligonucleotides: From bench to bedside
Authors: Quemener Anaïs M. , Bachelot Laura , Forestier Anne , Donnou‐Fournet Emmanuelle , Gilot David , Galibert Marie‐Dominique
Published: March 2020

Antisense oligonucleotides (ASOs) represent a new and highly promising class of drugs for personalized medicine. In the last decade, major chemical developments and improvements of the backbone structure of ASOs have transformed them into true approved and commercialized drugs. ASOs target both DNA and RNA, including pre‐mRNA, mRNA, and ncRDA, based on sequence complementary. They are designed to be specific for each identified molecular and genetic alteration to restore a normal, physiological situation. Thus, the characterization of the underpinning mechanisms and alterations that sustain pathology is critical for accurate ASO‐design. ASOs can be used to cure both rare and common diseases, such as orphan genetic alterations and cancer. Through pioneering examples, this review shows the versatility of the mechanisms of action that provide ASOs with the potential capacity to achieve custom treatment, revolutionizing personalized medicine.

This article is categorized under:

RNA in Disease and Development > RNA in Disease

RNA Interactions with Proteins and Other Molecules > Small Molecule–RNA Interactions
The cellular basis of organ failure in sepsis—signaling during damage and repair processes
Authors: Bauer M. , Wetzker R.
Published: March 2020

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. This definition, updated in 2016, shifted the conceptual focus from exclusive attention to the systemic inflammatory response toward the multifactorial tissue damage that occurs during the progression of infection to sepsis and shock. Whereas targeting the inflammatory host response to infection did not translate into improved clinical management of sepsis, recent findings might shed new light on the maladaptive host–pathogen interaction in sepsis and pave the way for “theranostic” interventions. In addition to the well-known resistance responses of the immune system that result in pathogen clearance, “disease tolerance” has recently been acknowledged as a coping mechanism of presumably equal importance. We propose that both defense mechanisms, “resistance” and “disease tolerance”, can get out of control in sepsis. Whereas excessive activation of resistance pathways propagates tissue damage via immunopathology, an inappropriate “tolerance” might entail immunoparalysis accompanied by fulminant, recurrent or persisting infection. The review introduces key signaling processes involved in infection-induced “resistance” and “tolerance”. We propose that elaboration of these signaling pathways allows novel insights into sepsis-associated tissue damage and repair processes. Moreover theranostic opportunities for the specific treatment of sepsis-related hyperinflammation or immunoparalysis will be introduced. Agents specifically affecting either hyperinflammation or immunoparalysis in the course of sepsis might add to the therapeutic toolbox of personalized care in the field of organ dysfunction caused by infection. (This article is freely available.)
Backcrossing of a capercaillie × black grouse hybrid male in the wild revealed with molecular markers
Authors: Kleven Oddmund , Brøseth Henrik , Jonassen Kyrre , Pedersen Hans Christian
Published: March 2020

The black grouseLyrurus tetrixand the capercaillieTetrao urogallusare known to produce hybrids in wild populations. In general, these hybrids are regarded as infertile; however, conclusive evidence that F1-hybrids are infertile and unable to backcross in the wild are lacking. Using a molecular approach, we examined the ancestry of a bird assumed to be a male hybrid based on phenotypic characters. The specimen was legally shot during the hunting season in northern Norway in an area where the black grouse is common and the capercaillie is relatively rare. Analysis of the maternally inherited mitochondrial DNA revealed that the mother of the specimen was of capercaillie origin, while a diagnostic sex-chromosome (Z) linked microsatellite marker showed that the father had a black grouse allele. Diagnostic autosomal microsatellite markers revealed that the specimen was a backcross and not a first-generation hybrid. As galliform birds follow Haldane’s rule, i.e., that hybrid sterility is common in the heterogametic sex (female in birds), the hybrid parent of the backcross was, thus, likely a male. Our findings provide molecular evidence that capercaillie × black grouse F1-hybrid males can be fertile and successfully mate and backcross in a wild population.
Theoretical Insights into the Stability of Perovskite Clusters by Studying Magnetization and Magnetocaloric Effect of Nd0.6Sr0.4MnO3 Compound at Room Temperature
Authors: Issaoui F. , Dhahri E. , Hlil E. K.
Published: March 2020

The Nd0.6Sr0.4MnO3sample has been synthesized by the solid-state reaction. In this research paper, structural, morphological, magnetic and magnetocaloric properties are reported. The refinement by Fullprof has revealed the coexistence of both Pnma orthorhombic and R-3c rhombohedral phases. The obtained magnetic results show a paramagnetic–ferromagnetic transition atTC = 245 K. The magnetocaloric effect was estimated from the magnetic isotherms. We can estimate that the magnetic entropy change (ΔS) values by the Hamad theory are very close to those obtained using the classical Maxwell relation. Under an applied field 5 T, the maximum of the magnetic entropy change (ΔS) max and the relative cooling power is found to be 3.68 J/kg K and 216.03 J/kg, respectively. The obtained values are compared with those of some other reported manganite and show that our compound could be a promising candidate for magnetic refrigeration. Finally, the construction of the universal curve of the magnetic entropy change confirmed the studied manganite undergoes a second-order magnetic phase transition.
Executive compensation in Germany
Authors: Beck Daniel , Friedl Gunther , Schäfer Peter
Published: March 2020

Understanding executive compensation and its effects helps design better organizations. Research on this area is thus of paramount importance. For large US companies, the ExecuComp database offers access to standardized and comprehensive executive compensation data. Hence, research on executive compensation has strongly focused on US companies. It is not clear that research results based on US data apply to other countries due to differences in corporate governance and culture. We have built up a database that is similar to ExecuComp for Germany, which is by far the largest economy in Europe. This database includes companies from the two largest German stock indices DAX and MDAX. We make these data available for academic research. We describe the data and we provide important results to outline the opportunities that our database offers. We find that only some of the empirical results for US companies such as the association between company size and pay level generalize to German companies while others such as compensation structure and the vertical pay inequality provide opportunities for further investigation.
Supercritical methane adsorption and storage in pores in shales and isolated kerogens
Authors: Rexer Thomas F. , Mathia Eliza J. , Aplin Andrew C. , Thomas K. Mark
Published: March 2020

Shale gas is an important hydrocarbon resource in a global context. It has had a significant impact on energy resources in the US, but the worldwide development of this methane resource requires further research to increase the understanding of the relationship of shale structural characteristics to methane storage capacity. In this study a range of gas adsorption, microscopic, mercury injection capillary pressure porosimetry and pycnometry techniques were used to characterize the full range of porosity in a series of shales of different thermal maturity. Supercritical methane adsorption methods for shale under conditions which simulate geological conditions (up to 473 K and 15 MPa) were developed. These methods were used to measure the methane adsorption isotherms of Posidonia shales where the kerogen maturity ranged from immature, through oil window, to gas window. Subcritical methane and carbon dioxide adsorption studies were used for determining pore structure characteristics of the shales. Mercury injection capillary pressure porosimetry was used to characterize the meso and macro porosity of shales. The sum of the CO2sorption pore volume at 195 K and mercury injection capillary pressure pore volumes (1093–5.6 nm) were equal to the corresponding total pore volume (< 1093 nm) thereby giving an equation accounting for virtually all the available shale porosity. These measurements allowed quantification of all the available porosity in shales and were used for estimating the contributions of methane stored as ‘free’ compressed gas and as adsorbed gas to overall methane storage capacity of shales. Both the mineral and kerogen components of shale were studied by comparing shale and the corresponding isolated kerogens so that the relative contributions of these components could be assessed. The results show that the methane adsorption characteristics were much higher for the kerogens and represented 35–60% of the total adsorption capacity for the shales used in this study, which had total organic contents in range 5.8–10.9 wt%. Microscopy studies revealed that the pore systems in clay-rich, organic-rich and microfossil-rich parts of shale are very different, and also the importance of the inter-granular organic-mineral interface.
Innovative Nanotechnological Formulations to Reach the Hepatic Stellate Cell
Authors: Poelstra Klaas
Published: March 2020

Purpose of Review

Treatment of liver fibrosis benefits from hepatic stellate cell (HSC)-specific delivery. Since the description of first carrier to HSC, many developments have taken place in this area. The purpose is to give an overview of the different carriers and homing moieties that are available for HSC targeting and illustrate the opportunities and hurdles they provide.

Recent Findings

There is a growing number of homing devices to deliver drugs to HSC, and options to deliver siRNA to HSC have emerged. Other developments include controlling corona formation, development of linker technology, and design of theranostic approaches. We are on the eve of reaching the clinic with innovative HSC-specific compounds.

An overview of different core molecules is presented together with an overview of targeting strategies toward different receptors on HSC, providing a versatile toolbox. Many therapeutics, ranging from small chemical entities and proteins to RNA- or DNA-modulating substances, have already been incorporated in these constructs in the recent years.
Associating State of Water and Sanitation with Childhood diarrhoea: Anomalies and Contradictions
Authors: Vijayan Bevin , Mishra Udaya
Published: March 2020

Information on safe water, sanitation and hand washing obtained in large scale surveys are used to validate its responsiveness to childhood ailments. Definition of these variables are uniform to enable comparison within and across countries and devoid of the context and circumstance. Associating these variables with prevalence of diarrhoea overlooking the context seem to distort the relationship and lead to spurious results. An empirical verification of such an association in an Indian context based on the most recently conducted NFHS-4 data set brings to the fore apparent contradictions that cautions on the use of these variables as they are obtained. It calls for a redefinition of these variables prior to verifying their responsiveness to childhood diarrhoea as illustrated here.
The growth of the longitudinal beam–plasma instability in the presence of an inhomogeneous background
Authors: Shalaby Mohamad , Broderick Avery E. , Chang Philip , Pfrommer Christoph , Puchwein Ewald , Lamberts Astrid
Published: March 2020

We study the longitudinal stability of beam–plasma systems in the presence of a density inhomogeneity in the background plasma. Previous works have focused on the non-relativistic regime where hydrodynamical models are used to evolve pre-existing Langmuir waves within inhomogeneous background plasmas. Here, for the first time we study the problem with kinetic equations in a fully relativistic way. We do not assume the existence of Langmuir waves, and we focus on the rate and the mechanism by which waves are excited in such systems from an initial perturbation. We derive the structure of the unstable modes and compute an analytical approximation for their growth rates. Our computation is limited to dilute and cold beams, and shows an excellent agreement with particle-in-cell simulations performed using the SHARP code. We show that, due to such an inhomogeneity, the virulent beam–plasma instabilities in the intergalactic medium are not suppressed but their counterparts in the solar wind can be suppressed as evidenced by propagating type-III solar radio bursts.
Dynamic Houses and Communities at Çatalhöyük: A Building Biography Approach to Prehistoric Social Structure
Authors: Kay Kevin
Published: March 2020

Houses are rich resources for understanding prehistoric social structure. However, conventional working methods often handle houses as stable entities that reflect the nature of households and other social units. Social groups may be inadvertently rendered static in the process. A biographical understanding, in which the on-going transformation of built space is part of different kinds of human collaboration, allows us to explore the dynamic qualities of past communities. I examine detailed life-histories of four contemporary houses at Çatalhöyük in Central Turkey, using the site's fine stratigraphy to interrogate how furnishings, elaborations and rhythms of burial varied through each building's use-life. These trace shifting practice and performance in relation to built space. Çatalhöyük buildings’ social roles changed dramatically over their lives. The spatial dynamics observed suggest that commensal groups were less stable and less bound to specific houses than in more conventional views of the site, and interacted in unpredictable ways with larger forms of social collaboration. Ultimately, this suggests a more dynamic approach to both houses and social units in the Near East and the archaeology of houses generally.
The Suicide Prevention for College Student Gatekeepers Program
Authors: Ross Sarah G. , DeHay Tamara , Deiling Megan
Published: March 2020

Abstract. Background: American college students are presenting with increasingly lower levels of mental health and higher levels of anxiety and depression. Close to 30% of college students report having seriously considered suicide in their lifetime. It is critical to train peer gatekeepers to recognize and react to mental health emergency scenarios on college campuses. Aims: The Suicide Prevention for College Student Gatekeepers training program was designed to provide college students with information about the warning signs of suicide, as well as how to intervene when indicated. The program incorporates research specific to college students and suicide risk, utilizes a college student co-leader alongside a licensed psychologist, and maximizes discussion and role-play to support student learning and engagement. Method: The program was piloted with 65 undergraduate students and the results of the program are discussed. Results: Students who participated in the program reported increased feelings of suicide prevention competence both immediately after the training and at a 12-week follow-up. Additionally, students demonstrated increased knowledge about suicide and decreased stigma. Finally, students indicated high levels of acceptability of the program. Limitations: The lack of diversity and small sample size within this pilot should be addressed in future studies. Conclusion: This pilot study offers promising results for an efficient, college-student focused suicide prevention gatekeeper training program.
Assessing the Quality of Systematic Reviews in Healthcare Using AMSTAR and AMSTAR2
Authors: De Santis Karina Karolina , Kaplan Ilkay
Published: March 2020

Abstract. The current study assessed the consistency between A Measurement Tool to Assess Systematic Reviews (AMSTAR) and its updated version (AMSTAR2) applied to the same systematic reviews in healthcare. Data from k = 10 systematic reviews were coded by two raters using AMSTAR and AMSTAR2. AMSTAR and AMSTAR2 perfectly agreed on a subset of nine individual items and strongly correlated based on the total scores (percentage scores: ρ = .84, p = .002, k = 10; absolute scores: Spearman ρ = .83, p = .003, k = 10). The overall review quality was medium to high on AMSTAR, while the overall confidence in the results was low to critically low on AMSTAR2 for the same systematic reviews. AMSTAR2 can identify the sources of strengths, weaknesses, and biases in systematic reviews. However, the interpretation of the overall confidence in results of systematic reviews requires additional guidelines for users.
The Solidus and Melt Productivity of Nominally Anhydrous Martian Mantle Constrained by New High Pressure‐Temperature Experiments—Implications for Crustal Production and Mantle Source Evolution
Authors: Ding Shuo , Dasgupta Rajdeep , Tsuno Kyusei
Published: March 2020

We constrained the solidus of a model Martian composition with low bulk Mg# (molar MgO/(MgO + FeOT) × 100 ~75) and high total alkali (Na2O + K2O = 1.09 wt.%) concentration at 2 to 5 GPa by experiments. Based on the new solidus brackets, we provide a new parameterization of the solidus temperature as a function of pressure of Martian mantle: Ts(°C) =  − 5P (GPa)2 + 107P(GPa) + 1,068. The newly constrained solidus of the Lodders and Fegley (1997; https://doi.org/10.1006/icar.1996.5653) model Martian composition (LF composition) is 20 to 90 °C lower than the previous solidus of model Martian mantle with lower total alkali (~0.54 wt.%). The supersolidus experiments yield an average isobaric melt productivity, dF/dT, of 20 ± 6 wt.%/100 °C. We also bracketed the solidi of model Martian mantle compositions with low Mg# (~75) and low alkali (~0.54 wt.%), and with high Mg# (~80) and low alkali (~0.54 wt.%) at a constant pressure of 3 GPa. We find that bulk Mg# enhances the solidus temperature and bulk total alkalis suppress it. A parameterization that estimates the effect of bulk Mg# and total alkalis on peridotite solidus, including Mars and Earth, at 3 GPa can be described as: Ts(°C) = 4.23Mg #  − 85(Na2O(wt. %) + K2O(wt. %)) + 1,120. Based on the new solidus parameterizations, 10–40 km more Martian crust would be produced by columnar decompression melting for LF model composition compared to the low Mg#‐low alkali model composition. The quantitative constraints on the solidus shift with Mg# and total alkalis from this study can be used to assess the Martian mantle solidus change through melting and melt extraction over time and the role of mantle heterogeneity in crustal production.
The Penetration of Solar Radiation Into Granular Carbon Dioxide and Water Ices of Varying Grain Sizes on Mars
Authors: Chinnery H. E. , Hagermann A. , Kaufmann E. , Lewis S. R.
Published: March 2020

The penetration depth of broad spectrum solar irradiation over the wavelength range 300–1,100 nm has been experimentally measured for water and carbon dioxide ices of different grain size ranges. Both of these ice compositions are found on the surface of Mars and have been observed as surface frosts, snow deposits, and ice sheets. The e‐folding scale of snow and slab ice has been previously measured, but understanding the behavior between these end‐member states is important for modeling the thermal behavior and surface processes associated with ice deposits on Mars, such as grain growth and slab formation via sintering, and carbon dioxide jetting leading to the formation of araneiforms. We find the penetration depth increases in a predictable way with grain size, and an empirical model is given to fit these data, varying with both ice composition and grain size.
Reliability and validity of a General Nutrition Knowledge Questionnaire for adults in a Romanian population
Authors: Putnoky Salomeia , Banu Ancuța Mioara , Moleriu Lavinia Cristina , Putnoky Sandra , Șerban Denis Mihai , Niculescu Mihai Dinu , Șerban Costela Lăcrimioara
Published: March 2020

Background

Nutritional knowledge assessment is an important component in nutrition research, and a prerequisite for the implementation of many policies and programs aimed at improving eating behavior. In order to generate objective results, validated tools for a given population must be employed. The aim of this study was to determine the validity and reliability of a nutrition knowledge questionnaire for Romanian adults.

Methods

Kleimann’s version of a General Nutrition Knowledge Questionnaire, was translated and adapted to Romanian language, culture, and cuisine. The final format was developed in several steps and used four components: internal and external reliability were assessed in a general population sample (n1 = 412), respectively in a subgroup (n2 = 46) from Component 1; Component 3 assessed construct validity (n3 = 96) using the “known-groups” method; Component 4 (convergent validity, n4 = 508) tested the association between socio-demographic characteristics and nutrition knowledge.

Results

The overall internal reliability was 0.878 and the external reliability was >0.880 in all sections, and overall. Specialists had higher scores than nonspecialists, with a very large effect size. In the general population, females scored higher than males, and middle-aged and older adults scored higher than young adults. Higher scores were associated with higher levels of education. The characteristics of individuals prone to giving wrong answers were: males (beta = 0.170), high school or less (beta = 0.167), and no training in nutrition (beta = 0.154).

Conclusions

The Romanian version of the General Nutrition Knowledge Questionnaire is a reliable and valid tool for measuring nutrition knowledge in adults.
Narcea—an unknown, ancient cultivated rose variety from northern Spain
Authors: Martínez María-Carmen , Santiago José-Luis , Boso Susana , Gago Pilar , Álvarez-Acero Inmaculada , De Vega María-Estela , Martínez-Bartolomé Miguel , Álvarez-Nogal Rafael , Molíst Pilar , Caser Matteo , Scariot Valentina , Gómez-García Daniel
Published: March 2020

The present work reports the discovery and the complete characterisation of an ancient cultivated rose variety found growing in a private garden in the southwest of the Principality of Asturias (northern Spain). The variety is here given the name Narcea. The majority of roses currently cultivated belong to the so-called group of ‘Modern Roses’, all of which were obtained after 1867 via artificial crosses and improvement programmes. All are destined for ornamental use. Until the 19th century, the great majority of the many ancient cultivated roses in Europe were used in perfumery and cosmetics, or had medicinal uses.Rosa damascenaandRosa centifolliaare still grown and used by the French and Bulgarian perfume industries. The Asturian Massif of the Cantabrian Mountain Range provides a natural habitat for some 75% of the wild members of the genusRosa, but until now there was no evidence that this area was home to ancient cultivated roses. A complete botanical description is here provided for a discovered ancient rose. It is also characterised according to a series of sequence tagged microsatellite sites, and its agronomic features are reported. In addition, a histological description (optical and scanning electronic microscope studies) of the petals is offered, along with an analysis of the volatile compounds present in these organs as determined by solid phase microextraction and gas chromatography-mass spectroscopy. The results reveal the uniqueness of this ancient type of rose and suggest it may be of interest to the perfume industry.
The chromosome-scale assembly of the willow genome provides insight into Salicaceae genome evolution
Authors: Wei Suyun , Yang Yonghua , Yin Tongming
Published: March 2020

Salix suchowensis is an early-flowering shrub willow that provides a desirable system for studies on the basic biology of woody plants. The current reference genome of S. suchowensis was assembled with 454 sequencing reads. Here, we report a chromosome-scale assembly of S. suchowensis generated by combining PacBio sequencing with Hi-C technologies. The obtained genome assemblies covered a total length of 356 Mb. The contig N50 of these assemblies was 263,908 bp, which was ~65-fold higher than that reported previously. The contiguity and completeness of the genome were significantly improved. By applying Hi-C data, 339.67 Mb (95.29%) of the assembled sequences were allocated to the 19 chromosomes of haploid willow. With the chromosome-scale assembly, we revealed a series of major chromosomal fissions and fusions that explain the genome divergence between the sister genera of Salix and Populus. The more complete and accurate willow reference genome obtained in this study provides a fundamental resource for studying many genetic and genomic characteristics of woody plants.
Turbocharging introgression breeding of perennial fruit crops: a case study on apple
Authors: Kumar Satish , Hilario Elena , Deng Cecilia H. , Molloy Claire
Published: March 2020

The allelic diversity of primitive germplasm of fruit crops provides a useful resource for introgressing novel genes to meet consumer preferences and environmental challenges. Pre-breeding facilitates the identification of novel genetic variation in the primitive germplasm and expedite its utilisation in cultivar breeding programmes. Several generations of pre-breeding could be required to minimise linkage drag from the donor parent and to maximise the genomic content of the recipient parent. In this study we investigated the potential of genomic selection (GS) as a tool for rapid background selection of parents for the successive generation. A diverse set of 274 accessions was genotyped using random-tag genotyping-by-sequencing, and phenotyped for eight fruit quality traits. The relationship between ‘own phenotypes’ of 274 accessions and their general combining ability (GCA) was also examined. Trait heritability influenced the strength of correspondence between own phenotype and the GCA. The average (across eight traits) accuracy of predicting own phenotype was 0.70, and the correlations between genomic-predicted own phenotype and GCA were similar to the observed correlations. Our results suggest that genome-assisted parental selection (GAPS) is a credible alternative to phenotypic parental selection, so could help reduce the generation interval to allow faster accumulation of favourable alleles from donor and recipient parents.
Spatial heterogeneity of flesh-cell osmotic potential in sweet cherry affects partitioning of absorbed water
Authors: Grimm Eckhard , Pflugfelder Daniel , Hahn Jan , Schmidt Moritz Jonathan , Dieckmann Hendrik , Knoche Moritz
Published: March 2020

A fleshy fruit is commonly assumed to resemble a thin-walled pressure vessel containing a homogenous carbohydrate solution. Using sweet cherry (Prunus avium L.) as a model system, we investigate how local differences in cell water potential affect H2O and D2O (heavy water) partitioning. The partitioning of H2O and D2O was mapped non-destructively using magnetic resonance imaging (MRI). The change in size of mesocarp cells due to water movement was monitored by optical coherence tomography (OCT, non-destructive). Osmotic potential was mapped using micro-osmometry (destructive). Virtual sections through the fruit revealed that the H2O distribution followed a net pattern in the outer mesocarp and a radial pattern in the inner mesocarp. These patterns align with the disposition of the vascular bundles. D2O uptake through the skin paralleled the acropetal gradient in cell osmotic potential gradient (from less negative to more negative). Cells in the vicinity of a vascular bundle were of more negative osmotic potential than cells more distant from a vascular bundle. OCT revealed net H2O uptake was the result of some cells loosing volume and other cells increasing volume. H2O and D2O partitioning following uptake is non-uniform and related to the spatial heterogeneity in the osmotic potential of mesocarp cells.
Petermann-factor sensitivity limit near an exceptional point in a Brillouin ring laser gyroscope
Authors: Wang Heming , Lai Yu-Hung , Yuan Zhiquan , Suh Myoung-Gyun , Vahala Kerry
Published: March 2020

Exceptional points are singularities of open systems, and among their many remarkable properties, they provide a way to enhance the responsivity of sensors. Here we show that the improved responsivity of a laser gyroscope caused by operation near an exceptional point is precisely compensated by increasing laser noise. The noise, of fundamental origin, is enhanced because the laser mode spectrum loses the oft-assumed property of orthogonality. This occurs as system eigenvectors coalesce near the exceptional point and a bi-orthogonal analysis confirms experimental observations. While the results do not preclude other possible advantages of the exceptional-point-enhanced responsivity, they do show that the fundamental sensitivity limit of the gyroscope is not improved through this form of operation. Besides being important to the physics of microcavities and non-Hermitian photonics, these results help clarify fundamental sensitivity limits in a specific class of exceptional-point sensor.
Publisher Correction: A CRISPR-Cas9-based reporter system for single-cell detection of extracellular vesicle-mediated functional transfer of RNA
Authors: de Jong Olivier G. , Murphy Daniel E. , Mäger Imre , Willms Eduard , Garcia-Guerra Antonio , Gitz-Francois Jerney J. , Lefferts Juliet , Gupta Dhanu , Steenbeek Sander C. , van Rheenen Jacco , El Andaloussi Samir , Schiffelers Raymond M. , Wood Matthew J. A. , Vader Pieter
Published: March 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Hierarchically-structured metalloprotein composite coatings biofabricated from co-existing condensed liquid phases
Authors: Jehle Franziska , Macías-Sánchez Elena , Sviben Sanja , Fratzl Peter , Bertinetti Luca , Harrington Matthew J.
Published: March 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Estimated discharge of antibiotic-resistant bacteria from combined sewer overflows of urban sewage system
Authors: Honda Ryo , Tachi Chihiro , Yasuda Keisuke , Hirata Tatsuki , Noguchi Mana , Hara-Yamamura Hiroe , Yamamoto-Ikemoto Ryoko , Watanabe Toru
Published: March 2020

Yearly discharge of antibiotic-resistant bacteria (ARB) from combined sewer overflow (CSO) was estimated. The volume of CSO was estimated from operating data of the pumping station. In the target sewer catchment, 23% of the total of the volume of combined sewage was discharged untreated as CSO. Combined sewage contained 3-log larger E. coli than secondary treatment effluent although the abundance of antibiotic-resistant E. coli was not significantly different. In the target-combined sewer catchment, a yearly total of 4.8 × 1016 CFU of E. coli was discharged from 6.1 × 106 m3 of CSO, while 1.3 × 1012 CFU of E. coli from 2.1 × 107 m3 of effluent from the wastewater treatment plant (WWTP). This E. coli discharge was equivalent to 7.9 × 109 CFU/m3 from CSO, and 6.2 × 104 CFU/m3 from WWTP effluent. Consequently, a yearly total discharge of antibiotic-resistant E. coli from CSO was 3.7-log larger than the WWTP effluent. The small-flow CSO events, which had hourly flow rate smaller than five times of the average dry-weather flow, accounted for 43% of the total CSO volume, but 79% of the total discharge of antibiotic-resistant E. coli due to a small dilution factor with stormwater and frequent discharge. Reduction of small-flow CSO events would be important for effective reduction of ARB discharge from CSO.
Diurnal activity in cane toads (Rhinella marina) is geographically widespread
Authors: Pettit Lachlan , Ducatez Simon , DeVore Jayna L. , Ward-Fear Georgia , Shine Richard
Published: March 2020

Although adult cane toads (Rhinella marina) are generally active only at night, a recent study reported that individuals of this species switched to diurnal activity in response to encountering a novel habitat type (deeply shaded gorges) in the course of their Australian invasion. Our sampling over a broader geographic scale challenges the idea that this behaviour is novel; we documented diurnal behaviour both in the species’ native range and in several sites within the invaded range, in multiple habitat types. Diurnal activity was most common in the tropics and in areas where toads attain high population densities and are in poor body condition, suggesting that the expansion of activity times may be induced by intraspecific competition for food.
Multi-resolution convolutional neural networks for inverse problems
Authors: Wang Feng , Eljarrat Alberto , Müller Johannes , Henninen Trond R. , Erni Rolf , Koch Christoph T.
Published: March 2020

Inverse problems in image processing, phase imaging, and computer vision often share the same structure of mapping input image(s) to output image(s) but are usually solved by different application-specific algorithms. Deep convolutional neural networks have shown great potential for highly variable tasks across many image-based domains, but sometimes can be challenging to train due to their internal non-linearity. We propose a novel, fast-converging neural network architecture capable of solving generic image(s)-to-image(s) inverse problems relevant to a diverse set of domains. We show this approach is useful in recovering wavefronts from direct intensity measurements, imaging objects from diffusely reflected images, and denoising scanning transmission electron microscopy images, just by using different training datasets. These successful applications demonstrate the proposed network to be an ideal candidate solving general inverse problems falling into the category of image(s)-to-image(s) translation.
The Extracellular Domain of Two-component System Sensor Kinase VanS from Streptomyces coelicolor Binds Vancomycin at a Newly Identified Binding Site
Authors: Lockey Christine , Edwards Richard J. , Roper David I. , Dixon Ann M.
Published: March 2020

The glycopeptide antibiotic vancomycin has been widely used to treat infections of Gram-positive bacteria including Clostridium difficile and methicillin-resistant Staphylococcus aureus. However, since its introduction, high level vancomycin resistance has emerged. The genes responsible require the action of the two-component regulatory system VanSR to induce expression of resistance genes. The mechanism of detection of vancomycin by this two-component system has yet to be elucidated. Diverging evidence in the literature supports activation models in which the VanS protein binds either vancomycin, or Lipid II, to induce resistance. Here we investigated the interaction between vancomycin and VanS from Streptomyces coelicolor (VanSSC), a model Actinomycete. We demonstrate a direct interaction between vancomycin and purified VanSSC, and traced these interactions to the extracellular region of the protein, which we reveal adopts a predominantly α-helical conformation. The VanSSC-binding epitope within vancomycin was mapped to the N-terminus of the peptide chain, distinct from the binding site for Lipid II. In targeting a separate site on vancomycin, the effective VanS ligand concentration includes both free and lipid-bound molecules, facilitating VanS activation. This is the first molecular description of the VanS binding site within vancomycin, and could direct engineering of future therapeutics.
Engineered cartilage utilizing fetal cartilage-derived progenitor cells for cartilage repair
Authors: Park Do Young , Min Byoung-Hyun , Park So Ra , Oh Hyun Ju , Truong Minh-Dung , Kim Mijin , Choi Ja-Young , Park In-Su , Choi Byung Hyune
Published: March 2020

The aim of this study was to develop a fetal cartilage-derived progenitor cell (FCPC) based cartilage gel through self-assembly for cartilage repair surgery, with clinically useful properties including adhesiveness, plasticity, and continued chondrogenic remodeling after transplantation. Characterization of the gels according to in vitro self-assembly period resulted in increased chondrogenic features over time. Adhesion strength of the cartilage gels were significantly higher compared to alginate gel, with the 2-wk group showing a near 20-fold higher strength (1.8 ± 0.15 kPa vs. 0.09 ± 0.01 kPa, p < 0.001). The in vivo remodeling process analysis of the 2 wk cultured gels showed increased cartilage repair characteristics and stiffness over time, with higher integration-failure stress compared to osteochondral autograft controls at 4 weeks (p < 0.01). In the nonhuman primate investigation, cartilage repair scores were significantly better in the gel group compared to defects alone after 24 weeks (p < 0.001). Cell distribution analysis at 24 weeks showed that human cells remained within the transplanted defects only. A self-assembled, FCPC-based cartilage gel showed chondrogenic repair potential as well as adhesive properties, beneficial for cartilage repair.
Instabilities of Thin Films on a Compliant Substrate: Direct Numerical Simulations from Surface Wrinkling to Global Buckling
Authors: Nikravesh Siavash , Ryu Donghyeon , Shen Yu-Lin
Published: March 2020

For structures consisting of a thin film bonded to a compliant substrate, wrinkling of the thin film is commonly observed as a result of mechanical instability. Although this surface undulation may be an undesirable feature, the development of new functional devices has begun to take advantage of wrinkled surfaces. The wrinkled structure also serves to improve mechanical resilience of flexible devices by suppressing crack formation upon stretching and bending. If the substrate has a reduced thickness, buckling of the entire structure may also occur. It is important to develop numerical design tools for predicting both wrinkle and buckle formations. In this paper we report a comprehensive finite element-based study utilizing embedded imperfections to directly simulate instabilities. The technique overcomes current computational challenges. The temporal evolution of the wrinkling features including wavelength and amplitude, as well as the critical strains to trigger the surface undulation and overall structural buckling, can all be predicted in a straightforward manner. The effects of model dimensions, substrate thickness, boundary condition, and composite film layers are systematically analyzed. In addition to the separate wrinkling and buckling instabilities developed under their respective geometric conditions, we illustrate that concurrent wrinkling and buckling can actually occur and be directly simulated. The correlation between specimen geometry and instability modes, as well as how the deformation increment size can influence the simulation result, are also discussed.
Coronary Plaque Characteristics and Cut-Off Stenosis for Developing Spasm in Patients with Vasospastic Angina
Authors: Jo Sang-Ho , Sim Ju Ho , Baek Sang Hong
Published: March 2020

Coronary plaque distribution, frequency and cut-off value of percent stenosis for developing vasospasm are uncertain in patients with vasospastic angina (VA). We enrolled 2960 patients who received coronary angiography (CAG) and ergonovine provocation test prospectively in 11 university hospitals in Korea. A total of 1836 patients with VA and 867 without VA were included. Plaque and % stenosis were defined as ≥1% luminal narrowing and mean of each segmental stenosis. Overall frequency of plaque and % diameter stenosis was compared among VA-patients with index coronary spasm positive, those with index arterial spasm negative/other arterial spasm positive (INOP) and non-VA patients. Diameter stenosis associated with the spasm positivity was investigated. Overall plaque frequency and % stenosis were higher in VA patients than non-VA patients. Plaque frequency was 27.6% (243/881) in spasm positive at LAD, 16.4% (157/955) in LAD INOP and 12.6% (109/867) in non-VA with statistic difference (P < 0.001). Same trend for higher rate was observed in LCx and RCA. For % stenosis, 36.6 vs 32.4% (p = 0.010) in LAD, 36.1 vs. 28% (p < 0.001) in LCx and 35.3 vs.30.0% (p = 0.047) in RCA, respectively. Diameter stenosis of LAD with spasm positive vs. LAD INOP vs. non-VA were 38.3%, 34.0%, 32% (P = 0.002) with similar pattern in LCx and RCA. By multivariate logistic regression analysis, coronary stenosis of LAD ≥ 35% or LCx ≥35% or RCA ≥ 40% were independent predictor of developing spasm (OR 2.019, 95% CI 1.315–3.100, P = 0.001). In conclusions, spastic coronary artery had more plaque frequency, higher % stenosis than in non-spastic coronary in VA patients. The spasm related and unrelated coronary in VA patients had more plaque than in matched and unmatched coronary arteries in non-VA patients. Coronary stenosis ≥35% in LAD and LCx was an independent predictor of developing spasm.
The rubber hand illusion in hypnosis provides new insights into the sense of body ownership
Authors: Fiorio Mirta , Modenese Michele , Cesari Paola
Published: March 2020

Body ownership can be experimentally investigated with the rubber hand illusion (RHI), in which watching a rubber hand stroked synchronously with one’s own hidden hand induces a feeling of ownership over the rubber hand. The aim of this study was to investigate response to the RHI in high (N = 21) and low (N = 19) hypnotizable individuals in normal waking state and in hypnosis. Response to the RHI was measured via a question on the illusory feeling of ownership and with proprioceptive drift. The Highs expressed an overall feeling of more ownership over the rubber hand in both the normal waking state and hypnosis, although both groups gave higher ownership scores after synchronous than after asynchronous stroking and the difference between conditions was similar across groups. Conversely, the proprioceptive drift appeared to be differentially modulated by hypnosis and hypnotic suggestibility: it was increased in the Highs and decreased in the Lows after hypnosis induction. These findings hint at an interplay between hypnotic suggestibility and hypnosis in modulating response to the RHI. The selective breakdown of proprioceptive drift among the Lows suggests resistance to recalibrate one’s own limb in hypnosis.
Anti-inflammatory Effect of Curcuma longa and Allium hookeri Co-treatment via NF-κB and COX-2 Pathways
Authors: Lee Soon-Young , Cho Seung-Sik , Li YongChun , Bae Chun-Sik , Park Kyung Mok , Park Dae-Hun
Published: March 2020

Although inflammation is a host defense mechanism, chronic inflammation mediates several diseases, including cancer, allergy, asthma, and autoimmune diseases, and reportedly, it is associated with a 60% mortality rate. There are several reports on the anti-inflammatory effects of Curcuma longa and Allium hookeri. However, although they can be used as culinary materials and have biological effects, they are not effective anti-inflammatory agents. In this study, we evaluated the synergic effect of C. longa and A. hookeri in order to confirm the possibility of a new anti-inflammatory agent. Based on cell viability and cytokine analyses, the appropriate ratio of C. longa and A. hookeri was confirmed using an air pouch animal model. Then, the anti-inflammatory effect of C. longa and A. hookeri co-treatment was evaluated by measuring the immune cell count and cytokines in the exudate and by comparing the morphological changes and cytokines in inflamed skin samples. Additionally, we evaluated the NF-κB/COX-2 pathway and iNOS levels. The active constituents detected in C. longa were demethoxycurcumin and bisdemethoxycurcumin, and that detected in A. hookeri was methylsulfonylmethane. An in vitro assessment determined the appropriate drug ratio as 3:7. In a carrageenan-induced inflammatory model, co-treatment effectively suppressed inflammatory cytokines, including IFN-γ, IL-1β, IL-6, IL-13, and IL-17, and recovered inflammation-related morphological changes in the skin. The anti-inflammatory effect of the co-treatment was mediated through the NF-κB/COX-2 pathway and iNOS inhibition. We concluded that co-treatment with C. longa and A. hookeri synergistically inhibited inflammation via the NF-κB/COX-2/iNOS pathway.
Iridophoroma associated with the Lemon Frost colour morph of the leopard gecko (Eublepharis macularius)
Authors: Szydłowski Paweł , Madej Jan Paweł , Duda Magdalena , Madej Janusz A. , Sikorska-Kopyłowicz Agnieszka , Chełmońska-Soyta Anna , Ilnicka Lucyna , Duda Przemysław
Published: March 2020

The Lemon Frost is a new colour morph of the leopard gecko, which emerged in ca. 2015 as a result of selective breeding and spontaneous mutation. According to multiple breeders observation of Lemon Frost inbreeding with wild-type leopard geckos, Lemon Frost seems to be a codominant trait. Additionally breeders observed another, presumably associated trait - tumour-like skin lesions. Three private-owned Lemon Frost morph leopard geckos with tumour-like skin lesions were admitted to our clinic for examination, which included histopathology, X-ray and ultrasonography. The histopathological investigation of the biopsies indicated malignant iridophoroma; however, no changes were observed in diagnostic imaging. This research is the first report of clinical and histopathological findings of iridophoroma in leopard geckos.