bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine-learning for automatic prediction of flatness deviation considering the wear of the face mill teeth
Authors: Bustillo Andres , Pimenov Danil Yu. , Mia Mozammel , Kapłonek Wojciech
Published: September 2020

The acceptance of the machined surfaces not only depends on roughness parameters but also in the flatness deviation (Δfl). Hence, before reaching the threshold of flatness deviation caused by the wear of the face mill,
the tool inserts need to be changed to avoid the expected product rejection. As current CNC machines have the facility to track, in real-time, the main drive power, the present study utilizes this facility to predict the flatness deviation—with proper consideration to the amount of wear of cutting tool insert’s edge. The prediction of deviation from flatness is evaluated as a regression and a classification problem, while different machine-learning techniques like Multilayer Perceptrons, Radial Basis Functions Networks, Decision Trees and Random Forest ensembles have been examined. Finally, Random Forest ensembles combined with Synthetic Minority Over-sampling Technique (SMOTE) balancing technique showed the highest performance when the flatness levels are discretized taking into account industrial requirements. The SMOTE balancing technique resulted in a very useful strategy to avoid the strong limitations that small experiment datasets produce in the accuracy of machine-learning models.
Convergence of the SQP method for quasilinear parabolic optimal control problems
Authors: Hoppe Fabian , Neitzel Ira
Published: September 2020

Based on the theoretical framework recently proposed by Bonifacius and Neitzel (Math Control Relat Fields 8(1):1–34, 2018. 10.3934/mcrf.2018001) we discuss the sequential quadratic programming (SQP) method for the numerical solution of an optimal control problem governed by a quasilinear parabolic partial differential equation. Following well-known techniques, convergence of the method in appropriate function spaces is proven under some common technical restrictions. Particular attention is payed to how the second order sufficient conditions for the optimal control problem and the resulting $$L^2$$

L
2

-local quadratic growth condition influence the notion of “locality” in the SQP method. Further, a new regularity result for the adjoint state, which is required during the convergence analysis, is proven. Numerical examples illustrate the theoretical results.
Cluster analysis identifies a pathophysiologically distinct subpopulation with increased serum leptin levels and severe obstructive sleep apnea
Authors: Kozu Yutaka , Kurosawa Yusuke , Yamada Shiho , Fukuda Asami , Hikichi Mari , Hiranuma Hisato , Akahoshi Toshiki , Gon Yasuhiro
Published: September 2020

Purpose

To investigate the different pathophysiologies of obstructive sleep apnea (OSA) phenotypes using cluster analysis. Differences between leptin/adiponectin levels in the resulting OSA phenotypes were also examined.

Methods

In total, 1057 OSA patients were selected, and a retrospective survey of clinical records, polysomnography results, and blood gas data was conducted. Patients were grouped into four clusters by their OSA severity, PaCO2, body mass index (BMI), and sleepiness. A k-means cluster analysis was performed, resulting in a division into four subpopulations. The Tukey or Games-Howell tests were used for intergroup comparisons.

Results

Among the 20 clinical OSA items, four common factors (Epworth Sleepiness Scale [ESS], BMI, Apnea-Hypopnea Index [AHI], and PaCO2) were extracted by principal component analysis, and a cluster analysis was performed using the k-means method, resulting in four distinct phenotypes. The Clusters 1 (middle age, symptomatic severe OSA) and 4 (young, obese, symptomatic very severe OSA) exhibited high leptin levels. C-reactive protein levels were also elevated in Cluster 4, indicating a different pathophysiological background. No apparent differences between clusters were observed regarding adiponectin/leptin ratios and adiponectin levels. Classification into groups based on phenotype showed that Epworth Sleepiness Scale [ESS] score and disease severity were not correlated, suggesting that sleepiness is affected by multiple elements.

Conclusions

The existence of multiple clinical phenotypes suggests that different pathophysiological backgrounds exist such as systemic inflammation and metabolic disorder. This classification may be used to determine the efficacy of continuous positive airway pressure treatment that cannot be determined by the AHI.
On predictive entrepreneurial action in uncertain, ill-structured conditions
Authors: Rapp David J. , Olbrich Michael
Published: September 2020

Decision-making is at the heart of entrepreneurship. Unsurprisingly, entrepreneurship research has engaged with processes of entrepreneurial decision-making resulting, most importantly, in the notions of causation, effectuation, and enactment. Nevertheless, the range of processes delineated to date remains somewhat incomplete. Drawing on crucial insights from the analysis of decision problem structures reveals that entrepreneurship theory has lacked a process that both recognizes the ill-structuredness typically surrounding entrepreneurial decisions and places prognoses center stage. While effectuation implicitly addresses structural defects but denies prognoses a central role, causation emphasizes the importance of predictions while being associated with well-structured, risky environments, and thus, unaffected by structural defects. Theorizing about a combination thereof, that is, a process recognizing and considering the ill-structuredness of entrepreneurial environments yet building on predictions of the future is overdue. This paper, therefore, seeks to foster a more comprehensive yet nuanced understanding of entrepreneurial decision-making processes by outlining the intrinsic features of one such process that we termexecutionand relating it to existing processes.
State Responses to the Gold Rush in the Andes (2004–2018): The Politics of State Action (and Inaction)
Authors: Baraybar Hidalgo Viviana , Dargent Eduardo
Published: September 2020

Despite many similarities, the gold rush that hit the Andean countries in 2004 elicited different state responses in Bolivia, Colombia, and Peru. Initially, there was a lack of enforcement of regulations towards informal mining, but eventually Colombia (2009) and later Peru (2011) enforced regulations with mixed results. Bolivia, on the other hand, has not enforced such regulations. At first, this may appear to be a matter of state capacity; however, a closer look uncovers different motivations behind these state actions (and inaction). We propose that the nature of social actors (or the lack of social actors) who profited from the gold boom, along with international and domestic pressures, are a crucial determinant of these different government responses. We explore this proposal through an analysis of the cases before and during the gold rush using a mix of archival research and interviews with key government actors. These findings allow us to distinguish empirically between forms of state inaction—standoff and forbearance—with distinct political consequences.
The Role of Eating Behaviours in Genetic Susceptibility to Obesity
Authors: Herle Moritz , Smith Andrea D. , Kininmonth Alice , Llewellyn Clare
Published: September 2020

Purpose of Review

Eating behaviours are hypothesised to be the behavioural expression of genetic risk of obesity. In this review, we summarise findings from behavioural genetic research on the association between genetic risk for obesity and validated psychometrics measures of eating behaviours in children and adults (published in the past 10 years).

Recent Findings

Twin studies have produced some evidence for a shared genetic aetiology underlying body mass index and eating behaviours. Studies using measured genetic susceptibility to obesity have suggested that increased genetic liability for obesity is associated with variation in obesogenic eating behaviours such as emotional and uncontrolled eating.

More research on this topic is needed. Especially longitudinal studies using genetically sensitive designs to investigate the direction of genetic pathways between genetic liability of eating behaviours to weight and vice versa, as well as the potential subsequent link to eating disorders.
Cellbow: a robust customizable cell segmentation program
Authors: Ren Huixia , Zhao Mengdi , Liu Bo , Yao Ruixiao , Liu Qi , Ren Zhipeng , Wu Zirui , Gao Zongmao , Yang Xiaojing , Tang Chao
Published: September 2020

Background

Time‐lapse live cell imaging of a growing cell population is routine in many biological investigations. A major challenge in imaging analysis is accurate segmentation, a process to define the boundaries of cells based on raw image data. Current segmentation methods relying on single boundary features have problems in robustness when dealing with inhomogeneous foci which invariably happens in cell population imaging.

Methods

Combined with a multi‐layer training set strategy, we developed a neural‐network‐based algorithm — Cellbow.

Results

Cellbow can achieve accurate and robust segmentation of cells in broad and general settings. It can also facilitate long‐term tracking of cell growth and division. To facilitate the application of Cellbow, we provide a website on which one can online test the software, as well as an ImageJ plugin for the user to visualize the performance before software installation.

Conclusion

Cellbow is customizable and generalizable. It is broadly applicable to segmenting fluorescent images of diverse cell types with no further training needed. For bright‐field images, only a small set of sample images of the specific cell type from the user may be needed for training.
The Dynamic Potential of European Union Health Law
Authors: HERVEY Tamara , DE RUIJTER Anniek
Published: September 2020

Some understandings of European Union health law are based on a presumption of law as a static and closed system. This approach to the Union as a legal entity has important ramifications. The Union is a political system created by and subject to the rule of law. Its successes (and failures) are attributable to the legalisation of solving externalities and ensuring Member State solidarity to gain benefits from integration. Member States, which create and sustain the Union by repeated acts of sovereign choice, choose to subject themselves to the rule of (Union) law. This protects both the Member States and the Union institutions (imperfectly, but nonetheless) from charges of illegitimacy. While recognising the benefits of such an approach to European Union integration and law-making, we take the view that law also has an important dynamic potential. That dynamic potential is inherent in all law, for law is embodied in text, and always open to interpretation, as the external contexts that give legal text meaning in the real-world change through time. We trace the dynamic potential of Union health law by looking at its legal basis to its foundational Treaties, and we plot its trajectory going forward.
Flooding and diameter in general weighted random graphs
Authors: Mountford Thomas , Saliba Jacques
Published: September 2020

In this paper we study first passage percolation on a random graph model, the configuration model. We first introduce the notions of weighted diameter, which is the maximum of the weighted lengths of all optimal paths between any two vertices in the graph, and the flooding time, which represents the time (weighted length) needed to reach all the vertices in the graph starting from a uniformly chosen vertex. Our result consists in describing the asymptotic behavior of the diameter and the flooding time, as the number of vertices n tends to infinity, in the case where the weight distribution G has an exponential tail behavior, and proving that this category of distributions is the largest possible for which the asymptotic behavior holds.
Trees grown under young-age preferential attachment
Authors: Lyon Merritt R. , Mahmoud Hosam M.
Published: September 2020

We introduce a class of non-uniform random recursive trees grown with an attachment preference for young age. Via the Chen–Stein method of Poisson approximation, we find that the outdegree of a node is characterized in the limit by ‘perturbed’ Poisson laws, and the perturbation diminishes as the node index increases. As the perturbation is attenuated, a pure Poisson limit ultimately emerges in later phases. Moreover, we derive asymptotics for the proportion of leaves and show that the limiting fraction is less than one half. Finally, we study the insertion depth in a random tree in this class. For the insertion depth, we find the exact probability distribution, involving Stirling numbers, and consequently we find the exact and asymptotic mean and variance. Under appropriate normalization, we derive a concentration law and a limiting normal distribution. Some of these results contrast with their counterparts in the uniform attachment model, and some are similar.
Consumption of ultra-processed foods and non-communicable disease-related nutrient profile in Portuguese adults and elderly (2015–2016): the UPPER project
Authors: Costa de Miranda Renata , Rauber Fernanda , de Moraes Milena Miranda , Afonso Cláudia , Santos Cristina , Rodrigues Sara , Levy Renata Bertazzi
Published: September 2020

This study aims to investigate the dietary share of ultra-processed foods and its association with the non-communicable disease (NCD)-related nutrient profile of adult and elderly populations in Portugal. Cross-sectional data from the National Food, Nutrition and Physical Activity Survey (2015–2016) of the Portuguese population were analysed. Dietary intake was assessed by two non-consecutive 24-h recalls, and food items were classified according to the NOVA system. We estimated the percentage of dietary energy provided by each of the NOVA food groups and assessed the NCD-related nutrient profile of the overall diet across quintiles of ultra-processed food consumption. Weightedttests, besides crude and adjusted linear and Poisson regressions, were performed. Ultra-processed foods contributed to around 24 and 16 % of daily energy intake for adults and elderly, respectively. In both groups, as the consumption of ultra-processed foods increased, the dietary content of free sugars, total fats and saturated fats increased, while the dietary content of protein decreased. In adults, total energy intake, dietary energy density and content of carbohydrates also increased as the consumption of ultra-processed foods increased, while the dietary content of fibre, Na and K decreased. The prevalence of those exceeding the upper limits recommended for free sugars and saturated fats increased by 544 and 153 % in adults and 619 and 60 % in elderly, when comparing the lowest with the highest quintile of ultra-processed food consumption. Such a scenario demands for effective strategies addressing food processing in the Portuguese population to improve their diet quality and prevention against diet-related NCD.
Instanton sheaves and representations of quivers
Authors: Jardim M. , Silva D. D.
Published: September 2020

We study the moduli space of rank 2 instanton sheaves on ℙ3 in terms of representations of a quiver consisting of three vertices and four arrows between two pairs of vertices. Aiming at an alternative compactification for the moduli space of instanton sheaves, we show that for each rank 2 instanton sheaf, there is a stability parameter θ for which the corresponding quiver representation is θ-stable (in the sense of King), and that the space of stability parameters has a non-trivial wall-and-chamber decomposition. Looking more closely at instantons of low charge, we prove that there are stability parameters with respect to which every representation corresponding to a rank 2 instanton sheaf of charge 2 is stable and provide a complete description of the wall-and-chamber decomposition for representation corresponding to a rank 2 instanton sheaf of charge 1.
Neural effects of a short-term virtual reality self-training program to reduce social anxiety
Authors: Kim Min-Kyeong , Eom Hyojung , Kwon Jun Hee , Kyeong Sunghyon , Kim Jae-Jin
Published: September 2020

Background

Social anxiety disorder (SAD) is characterized by anxiety regarding social situations, avoidance of external social stimuli, and negative self-beliefs. Virtual reality self-training (VRS) at home may be a good interim modality for reducing social fears before formal treatment. This study aimed to find neurobiological evidence for the therapeutic effect of VRS.

Methods

Fifty-two patients with SAD were randomly assigned to a VRS or waiting list (WL) group. The VRS group received an eight-session VRS program for 2 weeks, whereas the WL group received no intervention. Clinical assessments and functional magnetic resonance imaging scanning with the distress and speech evaluation tasks were repeatedly performed at baseline and after 3 weeks.

Results

The post-VRS assessment showed significantly decreased anxiety and avoidance scores, distress index, and negative evaluation index for ‘self’, but no change in the negative evaluation index for ‘other’. Patients showed significant responses to the distress task in various regions, including both sides of the prefrontal regions, occipital regions, insula, and thalamus, and to the speech evaluation task in the bilateral anterior cingulate cortex. Among these, significant neuronal changes after VRS were observed only in the right lingual gyrus and left thalamus.

Conclusions

VRS-induced improvements in the ability to pay attention to social stimuli without avoidance and even positively modulate emotional cues are based on functional changes in the visual cortices and thalamus. Based on these short-term neuronal changes, VRS can be a first intervention option for individuals with SAD who avoid society or are reluctant to receive formal treatment.
Retrospective analysis of clinical features in 134 coronavirus disease 2019 cases
Authors: Zhang Lin , Huang Bin , Xia Hongzhen , Fan Hua , Zhu Muxin , Zhu Liping , Zhang Huan , Tao Xiaogen , Cheng Shaohui , Chen Jian
Published: September 2020

We aimed to describe the clinical features in coronavirus disease 2019 (COVID-19) cases. We studied 134 critically ill COVID-19 cases from 30 December 2019 to 20 February 2020 in an intensive care unit (ICU) at Wuhan Jinyintan Hospital. Demographics, underlying diseases, therapy strategies and test results were collected and analysed from patients on admission, admission to the ICU and 48 h before death. The non-survivors were older (65.46 (s.d. 9.74) vs. 46.45 (s.d. 11.09)) and were more likely to have underlying diseases. The blood group distribution of the COVID-19 cases differed from that of the Han population in Wuhan, with type A being 43.85%; type B, 26.92%; type AB, 10% and type O, 19.23%. Non-survivors tend to develop more severe lymphopaenia, with higher C-reactive protein, interleukin-6, procalcitonin, D-dimer levels and gradually increased with time. The clinical manifestations were non-specific. Compared with survivors, non-survivors more likely to have organ function injury, and to receive mechanical ventilation, either invasively or noninvasively. Multiple organ failure and secondary bacterial infection in the later period is worthy of attention.
FROM LAVAPIÉS TO STOCKHOLM: EIGHTEENTH-CENTURY VIOLIN FANDANGOS AND THE SHAPING OF MUSICAL ‘SPANISHNESS’
Authors: LOMBARDÍA ANA
Published: September 2020

Since the mid-eighteenth century the fandango has been regarded as the epitome of Spanish cultural identity. It became increasingly popular in instrumental chamber music, as well-known examples by Domenico Scarlatti, Antonio Soler and Luigi Boccherini show. To date, published musicological scholarship has not considered the role of solo violin music in the dissemination of the fandango or the shaping of a ‘Spanish’ musical identity. Now, eight rediscovered pieces – which can be dated to the period 1730–1775 – show that the violin was frequently used to perform fandangos, including stylized chamber-music versions. In addition to offering evidence of the violin's role in the genre, these pieces reveal the hybridization of the fandango with foreign musical traditions, such as the Italian violin sonata and French courtly dances, demonstrating hitherto overlooked negotiations between elite and popular culture in mid-eighteenth-century Spain. Analysis of these works’ musical features challenges traditional discourses on the ‘Spanishness’ of the fandango and, more broadly, on the opposition between ‘native’ and ‘foreign’ music in eighteenth-century Spain.
Bidirectional Loading of the Subduction Interface: Evidence From the Kinematics of Slow Slip Events
Authors: McKenzie K. A. , Furlong K. P. , Herman M. W.
Published: September 2020

Subduction zones host some of Earth's most damaging natural hazards, including megathrust earthquakes and earthquake‐induced tsunamis. A major control on the initiation and rupture characteristics of subduction megathrust earthquakes is how the coupled zone along the subduction interface accumulates elastic strain between events. We present results from observations of slow slip events (SSEs) in Cascadia occurring during the interseismic period downdip of the fully coupled zone, which imply that the orientation of strain accumulation within the coupled zone can vary with depth. Interseismic GPS motions suggest that forces derived from relative plate motions across a shallow, offshore locked plate interface dominate over decadal timescales. Deeper on the plate interface, below the locked (seismogenic) patch, slip during SSEs dominantly occurs in the updip direction, reflecting a dip‐parallel force acting on the slab, such as slab pull. This implies that in subduction zones with obliquely convergent plate motions, the seismogenic zone of the megathrust is loaded by forces acting in two discrete directions, leading to a depth‐varying orientation of strain accumulation on the plate interface.
Unsteady Ekman‐Stokes Dynamics: Implications for Surface Wave‐Induced Drift of Floating Marine Litter
Authors: Higgins C. , Vanneste J. , van den Bremer T. S.
Published: September 2020

We examine Stokes drift and wave‐induced transport of floating marine litter on the surface of a rotating ocean with a turbulent mixed layer. Due to Coriolis‐Stokes forcing and surface wave stress, a second‐order Eulerian‐mean flow forms, which must be added to the Stokes drift to obtain the correct wave‐induced Lagrangian velocity. We show that this wave‐driven Eulerian‐mean flow can be expressed as a convolution between the unsteady Stokes drift and an “Ekman‐Stokes kernel.” Using this convolution, we calculate the unsteady wave‐driven contribution to particle transport. We report significant differences in both direction and magnitude of transport when the Eulerian‐mean Ekman‐Stokes velocity is included.
The 2018 MW 7.5 Papua New Guinea Earthquake: A Dissipative and Cascading Rupture Process
Authors: Zhang Xu , Feng Wanpeng , Du Hailin , Li Lu , Wang Shuai , Yi Lei , Wang Yongzhe
Published: September 2020

The 2018 MW 7.5 Papua New Guinea earthquake is the largest earthquake instrumentally recorded in the Papuan Fold Belt since 1900. Based on a combined analysis of backprojection imaging and finite‐fault joint inversion, we determined a complex spatiotemporal rupture model of the mainshock. During the rupture process, three major asperities were ruptured successively with relatively low rupture velocities ranging from 1.9 to 2.3 km/s. The spatiotemporal evolution of the imparted Coulomb stress indicates that the rupture of the preceding asperity played an important role in triggering the delayed rupture of the adjacent asperity. Based on our rupture model, the upper bound of the radiation efficiency of this event is estimated to be 9.7–12.3%, a relatively low value, indicating that this earthquake is extremely dissipative. The high energy dissipation implies that the 2018 MW 7.5 Papua New Guinea earthquake may be controlled by the immature seismogenic environment.
Climatology of Nighttime Upper Thermospheric Winds From Fabry‐Perot Interferometer 2011–2019 Measurements Over Kelan (38.7°N, 111.6°E), China: Local Time, Seasonal, Solar Cycle, and Geomagnetic Activity Dependence
Authors: Yang Changjun , Zhao Biqiang , Jin Yuyan , Huang Cong , Yao Xin , Wan Weixing
Published: September 2020

For the first time, we develop a local time and day of year dependent climatological model in different geomagnetic activity based on 630.0 nm Fabry‐Perot Interferometer (FPI) measurements over Kelan (38.7°N, 111.6°E) during 2011–2019. With this model, we analyze the regional climatological characteristics of nighttime thermospheric neutral winds, and a comparison is made with two recent versions of the Horizontal Wind Model series (HWMs), HWM07 and HWM14. Due to the location of Kelan far from the northern magnetic pole longitude at middle latitude, the statistical characterizations of meridional and zonal winds show some unique local time, seasonal, solar cycle and geomagnetic activity dependence. There are predominantly annual variations of horizontal winds characterized by rapid transitions from eastward December winds to westward or less eastward June winds and largest equatorward meridional winds during summer months. To some degree, the wind patterns show casual solar activity dependence especially for the zonal component. The maximum southward winds show negative relationship with increasing solar activity in summer months, while the maximum eastward winds present negative trend in winter months. The Kp dependencies are characterized by larger westward perturbation winds for all night and enhanced northward winds in the premidnight sector and equatorward surges in the postmidnight sector during strongly active conditions. With increasing solar flux, the westward perturbation winds become weaker at nights. Results also reveal that HWM14 predictions are in better agreement with Kelan FPI winds in the shape and magnitude than HWM07, and the consistency improves with increasing Kp.
Variability in the Energetic Electron Bombardment of Ganymede
Authors: Liuzzo Lucas , Poppe Andrew R. , Paranicas Christopher , Nénon Quentin , Fatemi Shahab , Simon Sven
Published: September 2020

This study examines the bombardment of energetic magnetospheric electrons onto Ganymede as a function of Jovian magnetic latitude. We use the output from a three‐dimensional, hybrid model to constrain features of the electromagnetic environment during the G1, G8, and G28 Galileo encounters when Ganymede was located far above, within, or far below Jupiter's magnetospheric current sheet, respectively. To quantify electron fluxes, we use a test‐particle model and trace relativistic electrons at discrete energies between 4.5 keV ≤E ≤ 100 MeV while exposed to these fields. For each location with respect to Jupiter's current sheet, electrons of all energies bombard Ganymede's poles with average number and energy fluxes of 1 · 108 cm−2 s−1 and 3 · 109 keV cm−2 s−1, respectively. However, bombardment is locally inhomogeneous: poleward of the open‐closed field line boundary, fluxes are enhanced in the trailing hemisphere but reduced in the leading hemisphere. When embedded within the Jovian current sheet, closed field lines of Ganymede's minimagnetosphere shield electrons below 40 MeV from accessing the equator. Above these energies, equatorial fluxes are longitudinally inhomogeneous between the sub‐Jovian and anti‐Jovian hemispheres, but the averaged number flux (4 · 103 cm−2 s−1) is comparable to the flux deposited here by each of the dominant energetic ion species near Ganymede. When located outside of the Jovian current sheet, electrons below 100 keV enter Ganymede's minimagnetosphere via the downstream reconnection region and bombard the leading apex, while electrons of all energies are shielded from the trailing apex. Averaged over a full synodic rotation period of Jupiter, the energetic electron flux pattern agrees well with brightness features observed across Ganymede's polar and equatorial surface.
A New Full 3‐D Model of Cosmogenic Tritium 3H Production in the Atmosphere (CRAC:3H)
Authors: Poluianov S. V. , Kovaltsov G. A. , Usoskin I. G.
Published: September 2020

A new model of cosmogenic tritium (3H) production in the atmosphere is presented. The model belongs to the CRAC (Cosmic Ray Atmospheric Cascade) family and is named as CRAC:3H. It is based on a full Monte Carlo simulation of the cosmic ray induced atmospheric cascade using the Geant4 toolkit. The CRAC:3H model is able, for the first time, to compute tritium production at any location and time, for any given energy spectrum of the primary incident cosmic ray particles, explicitly treating, also for the first time, particles heavier than protons. This model provides a useful tool for the use of 3H as a tracer of atmospheric and hydrological circulation. A numerical recipe for practical use of the model is appended.
Ad26 vaccine protects against SARS-CoV-2 severe clinical disease in hamsters
Authors: Tostanoski Lisa H. , Wegmann Frank , Martinot Amanda J. , Loos Carolin , McMahan Katherine , Mercado Noe B. , Yu Jingyou , Chan Chi N. , Bondoc Stephen , Starke Carly E. , Nekorchuk Michael , Busman-Sahay Kathleen , Piedra-Mora Cesar , Wrijil Linda M. , Ducat Sarah , Custers Jerome , Atyeo Caroline , Fischinger Stephanie , Burke John S. , Feldman Jared , Hauser Blake M. , Caradonna Timothy M. , Bondzie Esther A. , Dagotto Gabriel , Gebre Makda S. , Jacob-Dolan Catherine , Lin Zijin , Mahrokhian Shant H. , Nampanya Felix , Nityanandam Ramya , Pessaint Laurent , Porto Maciel , Ali Vaneesha , Benetiene Dalia , Tevi Komlan , Andersen Hanne , Lewis Mark G. , Schmidt Aaron G. , Lauffenburger Douglas A. , Alter Galit , Estes Jacob D. , Schuitemaker Hanneke , Zahn Roland , Barouch Dan H.
Published: September 2020

Coronavirus disease 2019 (COVID-19) in humans is often a clinically mild illness, but some individuals develop severe pneumonia, respiratory failure and death1–4. Studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in hamsters5–7 and nonhuman primates8–10 have generally reported mild clinical disease, and preclinical SARS-CoV-2 vaccine studies have demonstrated reduction of viral replication in the upper and lower respiratory tracts in nonhuman primates11–13. Here we show that high-dose intranasal SARS-CoV-2 infection in hamsters results in severe clinical disease, including high levels of virus replication in tissues, extensive pneumonia, weight loss and mortality in a subset of animals. A single immunization with an adenovirus serotype 26 vector-based vaccine expressing a stabilized SARS-CoV-2 spike protein elicited binding and neutralizing antibody responses and protected against SARS-CoV-2-induced weight loss, pneumonia and mortality. These data demonstrate vaccine protection against SARS-CoV-2 clinical disease. This model should prove useful for preclinical studies of SARS-CoV-2 vaccines, therapeutics and pathogenesis.
Telomere-to-telomere assembled and centromere annotated genomes of the two main subspecies of the button mushroom Agaricus bisporus reveal especially polymorphic chromosome ends
Authors: Sonnenberg Anton S. M. , Sedaghat-Telgerd Narges , Lavrijssen Brian , Ohm Robin A. , Hendrickx Patrick M. , Scholtmeijer Karin , Baars Johan J. P. , van Peer A.
Published: September 2020

Agaricus bisporus, the most cultivated edible mushroom worldwide, is represented mainly by the subspecies var. bisporus and var. burnettii. var. bisporus has a secondarily homothallic life cycle with recombination restricted to chromosome ends, while var. burnettii is heterothallic with recombination seemingly equally distributed over the chromosomes. To better understand the relationship between genomic make-up and different lifestyles, we have de novo sequenced a burnettii homokaryon and synchronised gene annotations with updated versions of the published genomes of var. bisporus. The genomes were assembled into telomere-to-telomere chromosomes and a consistent set of gene predictions was generated. The genomes of both subspecies were largely co-linear, and especially the chromosome ends differed in gene model content between the two subspecies. A single large cluster of repeats was found on each chromosome at the same respective position in all strains, harbouring nearly 50% of all repeats and likely representing centromeres. Repeats were all heavily methylated. Finally, a mapping population of var. burnettii confirmed an even distribution of crossovers in meiosis, contrasting the recombination landscape of var. bisporus. The new findings using the exceptionally complete and well annotated genomes of this basidiomycete demonstrate the importance for unravelling genetic components underlying the different life cycles.
Human plasma protein corona decreases the toxicity of pillar-layer metal organic framework
Authors: Jafari Samira , Izadi Zhila , Alaei Loghman , Jaymand Mehdi , Samadian Hadi , Kashani Vali ollah , Derakhshankhah Hossein , Hayati Payam , Noori Foad , Mansouri Kamran , Moakedi Faezeh , Janczak Jan , Soltanian Fard Mohammad Jaafar , Fayaz bakhsh Nozar
Published: September 2020

This scenario was designed to investigate the protein corona pattern on the pillar-layer surface of a Cu-based metal–organic framework (MOF) in human plasma. The [Cu(L)(L/)].1.3DMA (MOF-1) {L = 4, 4/-bipyridine and L/ = 5-aminoisophthalic acid}, was synthesized through the sonochemical irradiation approach as well as characterized by various techniques like scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray powder diffraction and single-crystal X-ray diffraction. The space group was determined to be an orthorhombic space group (Pbam) by single-crystal X-ray diffraction. Single-crystal X-ray analyses on MOF-1 showed that Cu+2 ion was 6-coordinated. Besides, to study and clarify interactions between MOFs and biological milieu, human whole blood plasma was selected as a model. Fluorescence spectroscopy and SDS-PAGE techniques were employed to explore quantitative and qualitative in situ characterization of protein corona as well. Furthermore, cell viability in a cancerous cell lines was evaluated by MTT assay in the presence and absence of the corona. The results from SDS-PAGE illustrated that the most adsorbed quantity among plasma proteins belongs to fibrinogen (α, β and γ chains), and this protein showed the maximum frequency on the MOF-1s surface, so the possible interactions of MOF-1s with fibrinogen also studied using fluorescence spectroscopy and corresponding data were plotted. According to the obtained data from MTT assay, these structures have concentration-dependent toxicity. In brief, based on the obtained data in the current study, the designed MOF can be introduced as a new desirable carrier for drug/gen delivery after further prerequisite assessments.
Association of TDP-43 proteinopathy, cerebral amyloid angiopathy, and Lewy bodies with cognitive impairment in individuals with or without Alzheimer’s disease neuropathology
Authors: Thomas David X. , Bajaj Sumali , McRae-McKee Kevin , Hadjichrysanthou Christoforos , Anderson Roy M. , Collinge John
Published: September 2020

Alzheimer’s disease patients typically present with multiple co-morbid neuropathologies at autopsy, but the impact of these pathologies on cognitive impairment during life is poorly understood. In this study, we developed cognitive trajectories for patients with common co-pathologies in the presence and absence of Alzheimer’s disease neuropathology. Cognitive trajectories were modelled in a Bayesian hierarchical regression framework to estimate the effects of each neuropathology on cognitive decline as assessed by the mini-mental state examination and the clinical dementia rating scale sum of boxes scores. We show that both TDP-43 proteinopathy and cerebral amyloid angiopathy associate with cognitive impairment of similar magnitude to that associated with Alzheimer’s disease neuropathology. Within our study population, 63% of individuals given the ‘gold-standard’ neuropathological diagnosis of Alzheimer’s disease in fact possessed either TDP-43 proteinopathy or cerebral amyloid angiopathy of sufficient severity to independently explain the majority of their cognitive impairment. This suggests that many individuals diagnosed with Alzheimer’s disease may actually suffer from a mixed dementia, and therapeutics targeting only Alzheimer’s disease-related processes may have severely limited efficacy in these co-morbid populations.
Micromorphological details and identification of chitinous wall structures in Rapana venosa (Gastropoda, Mollusca) egg capsules
Authors: Schröder Verginica , Rău Ileana , Dobrin Nicolae , Stefanov Constanţa , Mihali Ciprian-Valentin , Pădureţu Carla-Cezarina , Apetroaei Manuela Rossemary
Published: September 2020

The present study evaluated the structural and ultrastructural characteristics of Rapana venosa egg capsules, starting from observations of their antifouling activity and mechanical resistance to water currents in mid-shore habitats. Optical microscopy, epifluorescence, and electron microscopy were used to evaluate the surface and structure of the R. venosa egg capsules. These measurements revealed an internal multilamellar structure of the capsule wall with in-plane distributions of layers with various orientations. It was found that the walls contained vacuolar structures in the median layer, which provided the particular characteristics. Mechanical, viscoelastic and swelling measurements were also carried out. This study revealed the presence and distribution of chitosan in the capsule of R. venosa. Chitosan identification in the egg capsule wall structure was carried out through SEM–EDX measurements, colorimetric assays, FT-IR spectra and physical–chemical tests. The biopolymer presence in the capsule walls may explain the properties of their surfaces as well as the mechanical resistance of the capsule and its resistance to chemical variations in the living environment.
miRNALoc: predicting miRNA subcellular localizations based on principal component scores of physico-chemical properties and pseudo compositions of di-nucleotides
Authors: Meher Prabina Kumar , Satpathy Subhrajit , Rao Atmakuri Ramakrishna
Published: September 2020

MicroRNAs (miRNAs) are one kind of non-coding RNA, play vital role in regulating several physiological and developmental processes. Subcellular localization of miRNAs and their abundance in the native cell are central for maintaining physiological homeostasis. Besides, RNA silencing activity of miRNAs is also influenced by their localization and stability. Thus, development of computational method for subcellular localization prediction of miRNAs is desired. In this work, we have proposed a computational method for predicting subcellular localizations of miRNAs based on principal component scores of thermodynamic, structural properties and pseudo compositions of di-nucleotides. Prediction accuracy was analyzed following fivefold cross validation, where ~ 63–71% of AUC-ROC and ~ 69–76% of AUC-PR were observed. While evaluated with independent test set, > 50% localizations were found to be correctly predicted. Besides, the developed computational model achieved higher accuracy than the existing methods. A user-friendly prediction server “miRNALoc” is freely accessible athttp://cabgrid.res.in:8080/mirnaloc/, by which the user can predict localizations of miRNAs.
Deciphering the secretome of leukocyte-platelet rich fibrin: towards a better understanding of its wound healing properties
Authors: Hermida-Nogueira Lidia , Barrachina María N. , Morán Luis A. , Bravo Susana , Diz Pedro , García Ángel , Blanco Juan
Published: September 2020

Leukocyte-platelet rich fibrin (L-PRF) is extensively used in the dentistry field and other clinical scenarios due to its regeneration properties. The goal of the present study was to depict the L-PRF secretome and how it changes over time. We obtained L-PRF membranes and cultured them in DMEM. The secretome was collected at days 3, 7 and 21. The secretome at day 3 was analysed by LC–MS/MS and differences over time were analysed by Sequential Window Acquisition of all Theoretical Mass Spectra (SWATH). Overall, 705 proteins were identified in the secretome of L-PRF membranes after 3 days of culture, including growth factors (EGF, PDGFA) and proteins related to platelet and neutrophil degranulation. A total of 202 differentially secreted proteins were quantified by SWATH when comparing secretomes at days 3, 7 and 21. Most of them were enriched at day 3 such as MMP9, TSP1 and CO3. On the contrary, fibrinogen and CATS were found down-regulated at day 3. Growth factor and western blotting analysis corroborated the proteomic results. This is the most detailed proteome analysis of the L-PRF secretome to date. Proteins and growth factors identified, and their kinetics, provide novel information to further understand the wound healing properties of L-PRF.
Differences between young and older adults in physiological and subjective responses to emotion induction using films
Authors: Fernández-Aguilar Luz , Latorre José M. , Martínez-Rodrigo Arturo , Moncho-Bogani José V. , Ros Laura , Latorre Pablo , Ricarte Jorge J. , Fernández-Caballero Antonio
Published: September 2020

Emotional response in aging is typically studied using the dimensional or the discrete models of emotion. Moreover, it is typically studied using subjective or physiological variables but not using both perspectives simultaneously. Additionally, tenderness is neglected in emotion induction procedures with older adults, with the present work being the first to include the study of physiological tenderness using film clips. This study integrated two separate approaches to emotion research, comparing 68 younger and 39 older adults and using a popular set of film clips to induce tenderness, amusement, anger, fear, sadness and disgust emotions. The direction of subjective emotional patterns was evaluated with self-reports and that of physiological emotional patterns was evaluated with a wearable emotion detection system. The findings suggest a dual-process framework between subjective and physiological responses, manifested differently in young and older adults. In terms of arousal, the older adults exhibited higher levels of subjective arousal in negative emotions and tenderness while young adults showed higher levels of physiological arousal in these emotions. These findings yield information on the multidirectionality of positive and negative emotions, corroborating that emotional changes in the adult lifespan appear to be subject to the relevance of the emotion elicitor to each age group.
Benefits of tunnel handling persist after repeated restraint, injection and anaesthesia
Authors: Henderson Lindsay J. , Dani Bridgette , Serrano Esme M. N. , Smulders Tom V. , Roughan Johnny V.
Published: September 2020

Millions of mice are used every year for scientific research, representing the majority of scientific procedures conducted on animals. The standard method used to pick up laboratory mice for general husbandry and experimental procedures is known as tail handling and involves the capture, elevation and restraint of mice via their tails. There is growing evidence that, compared to non-aversive handling methods (i.e. tunnel and cup), tail handling increases behavioural signs of anxiety and induces anhedonia. Hence tail handling has a negative impact on mouse welfare. Here, we investigated whether repeated scruff restraint, intraperitoneal (IP) injections and anaesthesia negated the reduction in anxiety-related behaviour in tunnel compared with tail handled BALB/c mice. We found that mice which experienced repeated restraint spent less time interacting with a handler compared to mice that were handled only. However, after repeated restraint, tunnel handled mice showed increased willingness to interact with a handler, and reduced anxiety in standard behavioural tests compared with tail handled mice. The type of procedure experienced (IP injection or anaesthesia), and the duration after which behaviour was measured after a procedure affected the willingness of mice to interact with a handler. Despite this, compared with tail handling, tunnel handling reduced anxiety in standard behavioural tests and increased willingness to interact with a handler within hours after procedures. This suggests that the welfare benefits of tunnel handling are widely applicable and not diminished by the use of other putatively more invasive procedures that are frequently used in the laboratory. Therefore, the simple refinement of replacing tail with tunnel handling for routine husbandry and procedures will deliver a substantial improvement for mouse welfare and has the potential for improving scientific outcomes.
Keratin 17-positive Civatte bodies in oral lichen planus—distribution variety, diagnostic significance and histopathogenesis
Authors: Abé Tatsuya , Kitagawa Norio , Yoshimoto Shohei , Maruyama Satoshi , Yamazaki Manabu , Inai Tetsuichiro , Hashimoto Shuichi , Saku Takashi
Published: September 2020

Although emergence of keratin 17 (K17) and reciprocal loss of K13 are immunohistochemical hallmarks for oral mucosal malignancy, we report here findings of K17-positive (+) speckles, possibly equivalent to Civatte bodies, in benign oral lichen planus. Sixty-two biopsy samples from oral lichen planus cases were subjected to immunohistochemical examinations to analyze the distribution as well as histopathogenesis of Civatte bodies. K17 was irregularly positive among oral lichen planus-affected epithelial cells, and K17-positive (+) filamentous structures were irregularly distributed within the cytoplasm in confocal images. K17+ speckles were identified as Civatte bodies, and they were mainly distributed in the interface between epithelial cells and lymphocytic infiltrates (type A, 52.8%), followed by distribution within the epithelial layer (type B, 24.7%) or within the lamina propria with lymphocytic infiltration (type C, 22.5%). Apoptotic figures were often engulfed by macrophages and clearly distinguished from Civatte bodies by the presence TUNEL signals. These results indicate that K17 is a sensitive immunohistochemical marker for Civatte bodies and useful for differential diagnosis of oral lichen planus from other oral mucosal lesions. Civatte bodies are generated from denucleation of K17+ epithelial cells during the process of cell death via dyskeratosis, which is possibly related to blood capillary collapse.
Untargeted lipidomics reveals progression of early Alzheimer’s disease in APP/PS1 transgenic mice
Authors: Zhang Xueju , Liu Weiwei , Zan Jie , Wu Chuanbin , Tan Wen
Published: September 2020

Alzheimer’s Disease (AD) is closely connected to aberrant lipid metabolism. However, how early AD-like pathology synchronously influences brain and plasma lipidome in AD mice remains unclear. The study of dynamic change of lipidome in early-stage AD mice could be of great interest for the discovery of lipid biomarkers for diagnosis and monitoring of early-stage AD. For the purpose, an untargeted lipidomic strategy was developed for the characterization of lipids (≤ 1,200 Da) perturbation occurring in plasma and brain in early-stage AD mice (2, 3 and 7 months) by ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry. Significant changes were detected in the levels of several lipid species including lysophospholipids, phosphatidylcholines (PCs), phosphatidylethanolamines (PEs) and Ceramides (Cers), as well as other related lipid compounds such as fatty acids (FAs), diacylglycerols (DGs) and triacylglycerols (TGs) in AD mice. In this sense, disorders of lipid metabolism appear to involve in multiple factors including overactivation of phospholipases and diacylglycerol lipases, decreased anabolism of lysophospholipids in plasma and PEs in plasma and brain, and imbalances in the levels of PCs, FAs and glycerides at different ages. We revealed the changing panels of potential lipid biomarkers with the development of early AD. The study raises the possibility of developing lipid biomarkers for diagnosis of early-stage AD.