bluuebunny/crossref_metadata_2025 huggingface dataset:
Microneedle Mediated Iontophoretic Delivery of Tofacitinib Citrate
Authors: Dandekar Amruta A. , Garimella Harsha T. , German Carrie L. , Banga Ajay K.
Published: February 2022

Purpose

To investigate in vitro transdermal delivery of tofacitinib citrate across human skin using microporation by microneedles and iontophoresis alone and in combination.

Methods

In vitro permeation studies were conducted using vertical Franz diffusion cells. Microneedles composed of polyvinyl alcohol and carboxymethyl cellulose were fabricated and successfully characterized using scanning electron microscopy. The microchannels created were further characterized using histology, dye binding study, scanning electron microscopy, and confocal microscopy studies. The effect of microporation on delivery of tofacitinib citrate was evaluated alone and in combination with iontophoresis. In addition, the effect of current density on iontophoretic delivery was also investigated.

Results

Total delivery of tofacitinib citrate via passive permeation was found out to be 11.04 ± 1 μg/sq.cm. Microporation with microneedles resulted in significant enhancement where a 28-fold increase in delivery of tofacitinib citrate was observed with a total delivery of 314.7±33.32 μg/sq.cm. The characterization studies confirmed the formation of microchannels in the skin where successful disruption of stratum corneum was observed after applying microneedles. Anodal iontophoresis at 0.1 and 0.5 mA/sq.cm showed a total delivery of 18.56 μg/sq.cm and 62.07 μg/sq.cm, respectively. A combination of microneedle and iontophoresis at 0.5 mA/sq.cm showed the highest total delivery of 566.59 μg/sq.cm demonstrating a synergistic effect. A sharp increase in transdermal flux was observed for a combination of microneedles and iontophoresis.

Conclusion

This study demonstrates the use of microneedles and iontophoresis to deliver a therapeutic dose of tofacitinib citrate via transdermal route.
How Meaningful is the Elite Quality Index Ranking?
Authors: Diebold Céline
Published: February 2022

The Elite Quality Index (EQx) attempts to measure the propensity of elites—on aggregate—to create value, rather than to rent seek. The index has attracted worldwide media and press attention. In their articles, journalists have based their analyses primarily on their own countries’ position in the EQx ranking. But how meaningful is the EQx ranking? How do the uncertainties underlying some of the assumptions made in the index propagate to the country rankings? We conduct a global uncertainty and sensitivity analysis (UA and SA) of the EQx and compute Sobol’ first and total order sensitivity indices using state of the art estimators, in order to scrutinise the implications of index assumptions and assess the reliability of the EQx ranking. The UA suggests that the EQx ranking of 2021 (EQx2021) is largely stable for the top 50 countries, but exhibits considerable uncertainties especially for middle and lower performing countries. The SA highlights the handling of missing data, the normalisation process and the weighting scheme as most important methodological choices, while the largest potential for improvement is observed in how raw missing indicator data is handled.
Insect “Bee&Bees” and pollinator penthouses: teaching students about pollinators and their services in an urban environment
Authors: Hane Elizabeth N. , Korfmacher Karl F.
Published: February 2022

Pollination services are a frequently overlooked component of urban ecosystems. As cities look to become more sustainable and incorporate more urban green spaces, these pollinator services are coming to the forefront, and educating the public about the habitat and foraging needs of urban pollinators is becoming more important. Increasingly popular features in urban gardens are “bug hotels”, which are artificial structures that humans can install to create habitat or shelter for urban insect pollinators. In a college-level Urban Ecology class, we use a structured classroom activity to teach students about pollinator needs, but also place the activity in a larger context of a discussion about the value of urban landscapes, as well as the importance of evaluating sources of information. Here we describe the steps of a research activity that students undertake to design a “bug hotel”, as well as suggestions for how to extend the activity beyond the classroom.
Psychodramatische-Selbsterfahrung im Gruppen- und Einzelsetting
Authors: Kern Sabine
Published: February 2022

Dieser Artikel der Zeitschrift Psychodrama und Soziometrie beschäftigt sich mit psychodramatischen Arrangements, die im Einzel- und Gruppensetting für das Vorankommen im Selbsterfahrungsprozess hilfreich sein können. Zu Beginn wird auf Unterschiede zwischen Selbsterfahrung und Psychotherapie eingegangen. Die Voraussetzungen für eine gewinnbringende und sichere Reise zum Selbst, wie etwa eine gute therapeutische Beziehung, Gruppenkohäsion und klare Gruppenregeln, werden angeführt. Danach werden Arrangements vorgestellt, die zum besseren Verständnis der Beziehung zum Selbst beitragen sollen und psychodramatische Aufgabenstellungen präsentiert, die unterstützen, mögliche belastende Erfahrungen aus der Kindheit oder Jugend aufzuspüren. Ebenso wird auf psychodramatische Übungen eingegangen, die rigide Beziehungsmuster unter die Lupe nehmen. Zuletzt wird erörtert, welche wichtige Funktion Rollenspiele in der Selbsterfahrung einnehmen. Ein Resümee schließt den Artikel ab.
Analysing the mathematical activity in a modelling process from the cognitive and onto-semiotic perspectives
Authors: Ledezma Carlos , Font Vicenç , Sala Gemma
Published: February 2022

The aim of this article is to carry out a work of networking theories which combines two perspectives on the mathematical activity involved in a modelling process, in order to answer the following question: To what extent does the application of the onto-semiotic tools complement the analysis from a cognitive perspective of a mathematical modelling process? To this end, we considered two theoretical frameworks: on the one hand, the onto-semiotic approach, which provides tools for the analysis of any mathematical activity and which here we applied to the activity of modelling; on the other hand, the modelling cycle from a cognitive perspective, which is a reflection on the specific mathematical activity of modelling. Then, we took a modelling problem that we applied to prospective mathematics teachers (at undergraduate and postgraduate level), and we analysed it from the perspective of both frameworks, in order to identify concordances and complementarities between these two ways of analysing the mathematical activity involved in the modelling process. The main conclusion is that both frameworks complement each other for a more detailed analysis of the mathematical activity that underlies the modelling process. Specifically, the analysis with the tools provided by the onto-semiotic approach reveals the phases or transitions of the modelling cycle as a conglomerate of mathematical practices, processes, and the primary objects activated in these practices.
A Practical Decision Tool to Evaluate and Rank Potential Solutions for Expected Downhole Drilling Problems During the Well-planning Phase
Authors: Elmgerbi Asad , Les Borna , Ashena Rahman , Atkin Timothy
Published: February 2022

Currently, the main objective of oil operating companies is to increase drilling efficiency and minimize drilling costs; this can be achieved in several ways. One of them is the curtailment of downhole events associated with trouble time by obtaining the key factors that drive the best proactive solutions in terms of cost and effectiveness. From this perspective, the core focus of this paper is to present a detailed description to develop an integrated decision tool that will assist well planner engineers in evaluating multiple solutions considered to address a downhole problem anticipated during the well construction process. The tool presented here provides the means of assessing a particular solution's cost and anticipated effectiveness by generating an evaluation matrix based on two intercorrelated decision-driving indices, technical and monetary. To theoretically validate the concept, an artificial case study was created to find the best solution in mitigating a bit balling problem. The results of the case study reveal that: the concept is indeed theoretically applicable. However, a real life case study must be performed to prove the concept practically.
Potassium intake is associated with nutritional quality and actual diet cost: a study at formulating a low sodium high potassium (LSHP) healthy diet
Authors: Farapti Farapti , Buanasita Annas , Atmaka Dominikus R. , Setyaningtyas Stefania W. , Adriani Merryana , Rejeki Purwo S. , Yamaoka Yoshio , Miftahussurur Muhammad
Published: February 2022

Increasing potassium and reducing sodium intake have been identified as a priority intervention to reduce non-communicable diseases. A low sodium high potassium (LSHP) healthy diet can be a predictor of overall dietary quality and is associated with higher diet costs. The present study was a randomised controlled-feeding trial, formulating menus of low sodium and potassium-rich healthy diet and comparing with usual diet (a control diet based on typical Indonesian diet) to assess the association of potassium intake in the menus with other nutritional contents and diet cost. Totally seventy menus, which consisted of LSHP diets and the usual diets for a 7-d cycle, were composed from the analysis of the Indonesian food composition database. The correlation coefficient of the potassium content of all menus with nutritional quality and diet cost was analysed using the Pearson test. Multiple linear regression analysis was performed to determine the most important nutrient in determining diet cost. A comparison of nutrition quality and diet cost from the two menus was analysed using the independent t-test. LSHP diet had significantly higher carbohydrate, protein, fibre, magnesium, calcium, vitamin C, potassium density and diet cost but lower total fat, saturated fat and energy density than the usual diet (P < 0⋅05). Furthermore, there was a strong positive correlation between fibre, potassium and diet cost (coefficient correlation of >0⋅8). Potassium is a nutrient that is closely related to diet quality although the cost of the diet often may inhibit its intake. A targeted and effective strategy is required to provide affordable food for achieving a sustainable nutrient-rich diet.
Key toHeterodermia(Physciaceae,Teloschistales) in Brazil, with 15 new species
Authors: Fernanda de Souza Maria , Aptroot André , Spielmann Adriano Afonso
Published: February 2022

The species ofHeterodermiain Brazil have been revised based on literature reports, public databases and examination of 500 recent specimens from 15 states. So far, 43 species have been reported in the literature, two of which are not accepted here. We report 10 additional species from Brazil and describe 15 new to science, mostly from the Atlantic rainforest biome, raising the total number to 68, including two still undescribed species from Santa Catarina State. A key to all accepted species is given, keying out more species than represented in any previously published key of the genus. Based on new phylogenetic work, we do not accept the split genera that were recently proposed. We do informally recognize an additional group, theH. dactyliza-group. The following species are described as new:Heterodermia amphilacinulataM. F. N. Martins & M. P. Marcelli,H. caneziaeM. F. Souza & Aptroot,H. delicatulaM. P. Marcelli & M. F. N. Martins,H. dissecticodiademataM. F. Souza & Aptroot,H. dissecticoflabellataM. F. Souza & Aptroot,H. flavodactylizaM. F. Souza & Aptroot,H. flavuliferaM. F. Souza & Aptroot,H. labiataM. P. Marcelli & M. F. N. Martins,H. macrosoraliataM. P. Marcelli & M. F. N. Martins,H. minorM. F. Souza & Aptroot,H. neocroceaM. F. Souza & Aptroot,H. nigromarginataM. F. Souza & Aptroot,H. phyllalbicansM. F. Souza & Aptroot,H. spielmanniiM. F. Souza & Aptroot andH. sublinearisM. P. Marcelli & M. F. N. Martins. The following new combinations are also proposed:Heterodermia africana(Kurok.) M. F. Souza & Aptroot andH. borphyllidiata(Kalb & Meesim) M. F. Souza & Aptroot. Dissectic acid was found in species belonging to three different groups and was not restricted to (and characteristic of) one subgroup, as previously reported.
Optimal call center forecasting and staffing
Authors: Ding Sihan , Koole Ger
Published: February 2022

In this paper, we consider a two-stage call center staffing model. In the first stage, the interval staffing levels are set under arrival rate uncertainty. In the second stage, these initial staffing levels are corrected to the right value based on more precise arrival rate information. We show that this problem is of newsvendor type, where the costs are the initial staffing costs plus the second stage adaptation costs. We show that we should initially staff according to a quantile of the distributional forecast, rather than the mean. It is also shown that the errors in staffing are approximately linear in the forecasting errors. This leads to the conclusion that the weighted sum of errors should be the error measurement in call center forecasting, since minimizing, it minimizes the total staffing costs. In special cases where the costs are symmetric for over- and understaffing, this is equivalent to minimizing the weighted absolute percentage error.
Revised cardiac score index is a predictor of long-term outcomes	after carotid endarterectomy
Authors: Jácome Filipa , Nóbrega Leandro , Pereira-Neves António , Duarte-Gamas Luís , Mourão Joana , Videira-Reis Pedro , Dias-Neto Marina , Rocha-Neves João
Published: February 2022

Summary: Background: Cardiac complications represent the main cause of mortality after non-cardiac surgery and the Revised Cardiac Risk Index (RCRI) was created to estimate the perioperative risk of these events. It considers history of ischaemic heart disease, congestive heart failure, diabetes requiring preoperative insulin, stroke or transient ischaemic attack and renal impairment. We aim to describe the accuracy of the RCRI for predicting perioperative major adverse cardiovascular events (MACE) - a composite of heart failure, ischemic events and all-cause death. Also, the authors aimed to review the score for better prediction of cardiovascular outcomes. Patients and methods: From January 2012 to January 2020, patients who underwent Carotid endarterectomy (CEA) with regional anaesthesia (RA) were selected. RCRI was calculated for each case. Estimated and reported cardiovascular complications were compared using multivariate logistic regression and cox proportional hazards. An alternative and optimized carotid-RCRI (CtRCRI) was obtained. Overall predictive accuracy was assessed and compared by measuring model discrimination. Adjustments for overfitting and evaluation of the new model were performed by bootstrap. Results: 186 patients were selected, of which 80% were male with a mean age of 70.0±9.05 years old. The median follow-up was 50 months, interquartile range 21–69 months. None of the scores were able to predict MACE in the perioperative period. Both were associated with 30-day Clavien-Dindo ≥2 (p=0.022 and p=0.041, respectively). Regarding long-term prognosis, both were able to predict MACE (RCRI: hazard ratio (HR) 3.54 (95% confidence interval [CI] 1.04–11.48) vs. CtRCRI: HR 2.08 (95%CI 1.08–3.98) and all-cause mortality (RCRI: HR 3.33, 95%CI 0.99–11.11 vs. CtRCRI: HR 1.57, 95%CI 1.14–7.04). Conclusions: RCRI and CtRCRI did not predict MACE in the perioperative period but are good predictors of 30-day complications (Clavien-Dindo ≥2). Both RCRI and CtRCRI have good prognostic value as predictors of long-term cardiovascular events.
Climate Sensitivities of Carbon Turnover Times in Soil and Vegetation: Understanding Their Effects on Forest Carbon Sequestration
Authors: Ge Rong , He Honglin , Zhang Li , Ren Xiaoli , Williams Mathew , Yu Guirui , Luke Smallman T. , Zhou Tao , Li Pan , Xie Zongqiang , Wang Silong , Wang Huimin , Zhou Guoyi , Zhang Qibin , Wang Anzhi , Fan Zexin , Zhang Yiping , Shen Weijun , Yin Huajun , Lin Luxiang
Published: February 2022

The high uncertainty associated with the response of terrestrial carbon (C) cycle to climate is dominated by ecosystem C turnover time (τeco). Although the relationship between τeco and climate has been extensively studied, significant knowledge gaps remain regarding the differential climate sensitivities of turnover time in major biomass (τveg) and soil (τsoil) pools, and their effects on vegetation and soil C sequestration under climate change are poorly understood. Here, we collected multiple time series observations on soil and vegetation C from permanent plots in 10 Chinese forests and used model‐data fusion to retrieve key C cycle process parameters that regulate τsoil and τveg. Our analysis showed that τveg and τsoil both decreased with increasing temperature and precipitation, and τsoil was more than twice as sensitive (1.27 years/°C, 1.70 years/100 mm) than τveg (0.53 years/°C, 0.40 years/100 mm). The higher climate sensitivity of τsoil caused a more rapid decrease in τsoil than in τveg with increasing temperature and precipitation, thereby significantly reducing the difference between τsoil and τveg (τdiff) under warm and humid conditions. τdiff, an indicator of the balance between the soil C input and exit rate, was strongly responsible for the variation (more than 50%) in soil C sequestration. Therefore, a smaller τdiff under warm and humid conditions suggests a relatively lower contribution from soil C sequestration. This information has strong implications for understanding forest C‐climate feedback, predicting forest C sink distributions in soil and vegetation under climate change, and implementing C mitigation policies in forest plantations or soil conservation.
Van Allen Probes Observations of Oxygen Ion Cyclotron Harmonic Waves: Statistical Study
Authors: Wang Yan , Liu Kaijun , Min Kyungguk , Yao Fei , Xiong Ying , Cheng Kun , Liu Yuqi , Zheng Xianming , Zhou Jingyi
Published: February 2022

We report the first statistical survey of the oxygen ion cyclotron harmonic waves observed by Van Allen Probes throughout the mission. Our statistical study shows that the waves occurred over 2 < L < 6 and across all magnetic local time. More than 50% of the events were observed just outside the plasmapause, and the typical wave amplitude is between ∼0.1 and several nT. The frequency spacing between two consecutive wave harmonics decreases with increasing L but stabilizes when L > 5. The frequency spacing is larger than the local oxygen ion gyrofrequency for many events, especially those observed at larger L, suggesting that these waves propagated there from lower L shell regions. The waves are mainly on the dayside at L > 4 under quiet geomagnetic conditions, but can occur at lower L shells with a more uniform MLT distribution under more active geomagnetic conditions.
Dynamic Rupture Modeling of Coseismic Interactions on Orthogonal Strike‐Slip Faults
Authors: Lozos J. C.
Published: February 2022

Intersecting orthogonal strike‐slip faults with opposite senses of slip pose the question of what allows rupture to propagate through the junction and through both faults versus confining rupture to a single fault. I conduct dynamic rupture simulations on simplified orthogonal strike‐slip fault systems, to determine which conditions produce rupture on both component faults. In models with uniform initial tractions on both faults, slip on the first fault must reduce normal stress on the second fault for it to rupture. If the first fault ends at the cross fault, a stopping phase causes the cross fault to rupture. In models where I resolve a uniform regional stress field on the faults, only a narrow range of stress orientations allow multifault ruptures. These results will be helpful for evaluating hazard near orthogonal strike‐slip faults.
Improved High‐Resolution 3D Vs Model of Long Beach, CA: Inversion of Multimodal Dispersion Curves From Ambient Noise of a Dense Array
Authors: Fu Lei , Pan Lei , Li Zhengbo , Dong Sheng , Ma Qingbo , Chen Xiaofei
Published: February 2022

Ambient noise recorded by a dense seismic array provides an opportunity to resolve detailed 3D shear wave velocity (Vs) structures. We utilize the frequency‐Bessel transform (F‐J) method to compute the dispersion spectrogram for ambient noise recorded by the Long Beach seismic array, extract multimodal dispersion curves with a deep learning approach, and invert multimodal dispersion curves with a gradient algorithm. The addition of higher‐mode dispersion curves reduces nonuniqueness and provides an improved high‐resolution 3D Vs model that shows good correlations with the known stratigraphic sequence and geologic features in the study area. Furthermore, the Richard fault between the Pacific Coast Highway and Newport‐Inglewood faults, which have never been discussed in previous studies, is resolved. Our study demonstrates the potential of using the F‐J method to extract multimodal dispersion curves and consequently retrieve an improved high‐resolution 3D Vs model from a dense seismic array.
Foamquake: A Novel Analog Model Mimicking Megathrust Seismic Cycles
Authors: Mastella G. , Corbi F. , Funiciello F. , Rosenau M.
Published: February 2022

In the last decades, seismotectonic analog models have been developed to better understand many aspects of the seismic cycle. Differently from other lab‐quake experiments, seismotectonic models mimic the first order characteristics of the seismic cycle in a scaled fashion. Here we introduce Foamquake: A novel seismotectonic model with a granular frictional interface that as a whole behaves elastoplastically. The model experiences cycles of elastic loading and release via spontaneous nucleation of frictional instabilities at the base of an elastic foam wedge, hereafter called foamquakes. These analog earthquakes show source parameters (i.e., moment‐duration and moment‐rupture area) scaling as great interplate earthquakes and a coseismic displacement of few tens of meters when scaled to nature. Models with two asperities separated by a barrier can be performed with Foamquake given the 3D nature of the setup. Such model configuration generates sequences of full and partial ruptures with different recurrence intervals as well as rupture cascades. By tuning the normal load acting on individual asperities, Foamquake reproduces superimposed cycles rupture patterns such as those observed along natural megathrusts. The physical properties of asperities and barriers affect model seismic behavior. Asperities with similar properties and low yield strength fail preferentially in a simultaneous manner. The combination of all those characteristics suggests that Foamquake is a valuable tool for investigating megathrust seismicity and seismic processes that depend on the 3D nature of the subduction environment.
From the Top of Martian Olympus to Deep Craters and Beneath: Mars Radiation Environment Under Different Atmospheric and Regolith Depths
Authors: Zhang Jian , Guo Jingnan , Dobynde Mikhail I. , Wang Yuming , Wimmer‐Schweingruber Robert F.
Published: February 2022

In preparation for future human habitats on Mars, it is important to understand the Martian radiation environment. Mars does not have an intrinsic magnetic field and Galactic cosmic ray (GCR) particles may directly propagate through and interact with its atmosphere before reaching the surface and subsurface of Mars. However, Mars has many high mountains and low‐altitude craters where the atmospheric thickness can be more than 10 times different from one another. We thus consider the influence of the atmospheric depths on the Martian radiation levels including the absorbed dose, dose equivalent and body effective dose rates induced by GCRs at varying heights above and below the Martian surface. The state‐of‐the‐art Atmospheric Radiation Interaction Simulator based on GEometry And Tracking Monte Carlo method has been employed for simulating particle interactions with the Martian atmosphere and terrain. We find that higher surface pressures can effectively reduce the heavy ion contribution to the radiation, especially the biologically weighted radiation quantity. However, enhanced shielding (both by the atmosphere and the subsurface material) can considerably enhance the production of secondary neutrons which contribute significantly to the effective dose. In fact, both neutron flux and effective dose peak at around 30 cm below the surface. This is a critical concern when using the Martian surface material to mitigate radiation risks. Based on the calculated effective dose, we finally estimate some optimized shielding depths, under different surface pressures (corresponding to different altitudes) and various heliospheric modulation conditions. This may serve for designing future Martian habitats.
More Realistic Intermediate Depth Dry Firn Densification in the Energy Exascale Earth System Model (E3SM)
Authors: Schneider Adam M. , Zender Charles S. , Price Stephen F.
Published: February 2022

Earth system models account for seasonal snow cover, but many do not accommodate the deeper snowpack on ice sheets (aka firn) that slowly transforms to ice under accumulating snowfall. To accommodate and resolve firn depths of up to 60 m in the Energy Exascale Earth System Model's land surface model (ELM), we add 11 layers to its snowpack and evaluate three dry snow compaction equations in multi‐century simulations. After comparing results from ELM simulations (forced with atmospheric reanalysis) with empirical data, we find that implementing into ELM a two‐stage firn densification model produces more accurate dry firn densities at intermediate depths of 20–60 m. Compared to modeling firn using the equations in the (12 layer) Community Land Model (version 5), switching to the two‐stage firn densification model (with 16 layers) significantly decreases root‐mean‐square errors in upper 60 m dry firn densities by an average of 41 kg m−3 (31%). Simulations with three different firn density parameterizations show that the two‐stage firn densification model should be used for applications that prioritize accurate upper 60 m firn air content (FAC) in regions where the mean annual surface temperature is greater than roughly −31°C. Because snow metamorphism, firn density, and FAC are major components in modeling ice sheet surface albedo, melt water retention, and climatic mass balance, these developments advance broader efforts to simulate the response of land ice to atmospheric forcing in Earth system models.
Fiber-Optic Cables Can Produce High-Resolution Underground Maps
Authors: Lee Jack
Published: February 2022

Telecom fiber repurposed as distributed acoustic sensing arrays can image near-surface structure and potentially improve seismic hazard mapping in urban areas.
Acute-stress-induced change in salience network coupling prospectively predicts post-trauma symptom development
Authors: Zhang Wei , Kaldewaij Reinoud , Hashemi Mahur M. , Koch Saskia B. J. , Smit Annika , van Ast Vanessa A. , Beckmann Christian F. , Klumpers Floris , Roelofs Karin
Published: February 2022

Substantial individual differences exist in how acute stress affects large-scale neurocognitive networks, including salience (SN), default mode (DMN), and central executive networks (CEN). Changes in the connectivity strength of these networks upon acute stress may predict vulnerability to long-term stress effects, which can only be tested in prospective longitudinal studies. Using such longitudinal design, we investigated whether the magnitude of acute-stress-induced functional connectivity changes (delta-FC) predicts the development of post-traumatic stress-disorder (PTSD) symptoms in a relatively resilient group of young police students that are known to be at high risk for trauma exposure. Using resting-state fMRI, we measured acute-stress-induced delta-FC in 190 police recruits before (baseline) and after trauma exposure during repeated emergency-aid services (16-month follow-up). Delta-FC was then linked to the changes in perceived stress levels (PSS) and post-traumatic stress symptoms (PCL and CAPS). Weakened connectivity between the SN and DMN core regions upon acute-stress induction at baseline predicted longitudinal increases in perceived-stress level but not of post-traumatic stress symptoms, whereas increased coupling between the overall SN and anterior cerebellum was observed in participants with higher clinician-rated PTSD symptoms, particularly intrusion levels. All the effects remained significant when controlling for trauma-exposure levels and cortisol-stress reactivity. Neither hormonal nor subjective measures exerted similar predictive or acquired effects. The reconfiguration of large-scale neural networks upon acute-stress induction is relevant for assessing and detecting risk and resilience factors for PTSD. This study highlights the SN connectivity-changes as a potential marker for trauma-related symptom development, which is sensitive even in a relatively resilient sample.
No long-term effects of antenatal synthetic glucocorticoid exposure on epigenetic regulation of stress-related genes
Authors: Müller Svenja , Moser Dirk , Frach Leonard , Wimberger Pauline , Nitzsche Katharina , Li Shu-Chen , Kirschbaum Clemens , Alexander Nina
Published: February 2022

Antenatal synthetic glucocorticoid (sGC) treatment is a potent modifier of the hypothalamic-pituitary-adrenal (HPA) axis. In this context, epigenetic modifications are discussed as potential regulators explaining how prenatal exposure to GCs might translate into persistent changes of HPA axis “functioning”. The purpose of this study was to investigate whether DNA methylation and gene expression profiles of stress-associated genes (NR3C1; FKBP5; SLC6A4)may mediate the persistent effects of sGC on cortisol stress reactivity that have been previously observed. In addition, hair cortisol concentrations (hairC) were investigated as a valid biomarker of long-term HPA axis activity. This cross-sectional study comprised 108 term-born children and adolescents, including individuals with antenatal GC treatment and controls. From whole blood, DNA methylation was analyzed by targeted deep bisulfite sequencing. Relative mRNA expression was determined by RT-qPCR experiments and qBase analysis. Acute stress reactivity was assessed by the Trier Social Stress Test (TSST) measuring salivary cortisol by ELISA and hairC concentrations were determined from hair samples by liquid chromatography coupled with tandem mass spectrometry. First, no differences in DNA methylation and mRNA expression levels of the stress-associated genes between individuals treated with antenatal sGC compared to controls were found. Second, DNA methylation and mRNA expression levels were neither associated with cortisol stress reactivity nor with hairC. These findings do not corroborate the belief that DNA methylation and mRNA expression profiles of stress-associated genes (NR3C1; FKBP5; SLC6A4)play a key mediating role of the persistent effects of sGC on HPA axis functioning.
Polygenic association with severity and long-term outcome in eating disorder cases
Authors: Johansson Therese , Birgegård Andreas , Zhang Ruyue , Bergen Sarah E. , Landén Mikael , Petersen Liselotte V. , Bulik Cynthia M. , Hübel Christopher
Published: February 2022

About 20% of individuals with anorexia nervosa (AN) remain chronically ill. Therefore, early identification of poor outcome could improve care. Genetic research has identified regions of the genome associated with AN. Patients with anorexia nervosa were identified via the Swedish eating disorder quality registers Stepwise and Riksät and invited to participate in the Anorexia Nervosa Genetics Initiative. First, we associated genetic information longitudinally with eating disorder severity indexed by scores on the Clinical Impairment Assessment (CIA) in 2843 patients with lifetime AN with or without diagnostic migration to other forms of eating disorders followed for up to 16 years (mean = 5.3 years). Second, we indexed the development of a severe and enduring eating disorder (SEED) by a high CIA score plus a follow-up time ≥5 years. We associated individual polygenic scores (PGSs) indexing polygenic liability for AN, schizophrenia, and body mass index (BMI) with severity and SEED. After multiple testing correction, only the BMI PGS when calculated with traditional clumping andpvalue thresholding was robustly associated with disorder severity (βPGS = 1.30; 95% CI: 0.72, 1.88;p = 1.2 × 10–5) across allpvalue thresholds at which we generated the PGS. However, using the alternative PGS calculation method PRS-CS yielded inconsistent results for all PGS. The positive association stands in contrast to the negative genetic correlation between BMI and AN. Larger discovery GWASs to calculate PGS will increase power, and it is essential to increase sample sizes of the AN GWASs to generate clinically meaningful PGS as adjunct risk prediction variables. Nevertheless, this study provides the first evidence of potential clinical utility of PGSs for eating disorders.
Structural and functional insights into ABHD5, a ligand-regulated lipase co-activator
Authors: Tseng Yan Yuan , Sanders Matthew A. , Zhang Huamei , Zhou Li , Chou Chia-Yi , Granneman James G.
Published: February 2022

Alpha/beta hydrolase domain-containing protein 5 (ABHD5) is a highly conserved protein that regulates various lipid metabolic pathways via interactions with members of the perilipin (PLIN) and Patatin-like phospholipase domain-containing protein (PNPLA) protein families. Loss of function mutations in ABHD5 result in Chanarin–Dorfman Syndrome (CDS), characterized by ectopic lipid accumulation in numerous cell types and severe ichthyosis. Recent data demonstrates that ABHD5 is the target of synthetic and endogenous ligands that might be therapeutic beneficial for treating metabolic diseases and cancers. However, the structural basis of ABHD5 functional activities, such as protein–protein interactions and ligand binding is presently unknown. To address this gap, we constructed theoretical structural models of ABHD5 by comparative modeling and topological shape analysis to assess the spatial patterns of ABHD5 conformations computed in protein dynamics. We identified functionally important residues on ABHD5 surface for lipolysis activation by PNPLA2, lipid droplet targeting and PLIN-binding. We validated the computational model by examining the effects of mutating key residues in ABHD5 on an array of functional assays. Our integrated computational and experimental findings provide new insights into the structural basis of the diverse functions of ABHD5 as well as pathological mutations that result in CDS.
Achieving 9.6% efficiency in 304 nm p-AlGaN UVB LED via increasing the holes injection and light reflectance
Authors: Khan M. Ajmal , Maeda Noritoshi , Yun Joosun , Jo Masafumi , Yamada Yoichi , Hirayama Hideki
Published: February 2022

Crystal growth of eco-friendly, ultrawide bandgap aluminium gallium nitride (AlGaN) semiconductor-based ultraviolet-B (UVB) light-emitting diodes (LEDs) hold the potential to replace toxic mercury-based ultraviolet lamps. One of the major drawbacks in the utilisation of AlGaN-based UVB LEDs is their low efficiency of about 6.5%. The study investigates the influence of Al-graded p-type multi-quantum-barrier electron-blocking-layer (Al-grad p-MQB EBL) and Al-graded p-AlGaN hole source layer (HSL) on the generation and injection of 3D holes in the active region. Using the new UVB LED design, a significant improvement in the experimental efficiency and light output power of about 8.2% and 36 mW is noticed. This is accomplished by the transparent nature of Al-graded Mg-doped p-AlGaN HSL for 3D holes generation and p-MQB EBL structure for holes transport toward multi-quantum-wells via intra-band tunnelling. Based on both the numerical and experimental studies, the influence of sub-nanometre scale Ni film deposited underneath the 200 nm-thick Al-film p-electrode on the optical reflectance in UVB LED is investigated. A remarkable improvement in the efficiency of up to 9.6% and light output power of 40 mW, even in the absence of standard package, flip-chip, and resin-like lenses, is achieved on bare-wafer under continuous-wave operation at room temperature. The enhanced performance is attributed to the use of Al-graded p-MQB EBL coupled with softly polarised p-AlGaN HSL and the highly reflective 0.4 nm-thick Ni and 200 nm-thick Al p-electrode in the UVB LED. This research study provides a new avenue to improve the performance of high-power p-AlGaN-based UVB LEDs and other optoelectronic devices in III–V semiconductors.
Long noncoding RNA ADAMTS9-AS1 represses ferroptosis of endometrial stromal cells by regulating the miR-6516-5p/GPX4 axis in endometriosis
Authors: Wan Yiting , Gu Cancan , Kong Jueying , Sui Jin , Zuo Ling , Song Yanhua , Chen Jing
Published: February 2022

Endometriosis (EMs) is one of the most frequent diseases of reproductive-age women and is characterized by the growth of endometrial tissues beyond the uterus. The enhanced proliferative and migratory potential of endometrial stromal cells (ESCs) plays an important role in the progression of EMs. Mounting studies have demonstrated that long noncoding RNAs (lncRNAs) exert an important role in regulating the development and progression of EMs. Given the aberrant expression of lncRNA ADAMTS9-AS1 in ectopic endometrium (ecEM), we investigated the biological effect of ADAMTS9-AS1 on ESC proliferation and migration and explored the underlying mechanism. The current data showed that ADAMTS9-AS1 expression was significantly upregulated in ecEM compared with eutopic endometrium (euEM) in patients with EMs and in a murine model of EMs. Functionally, ADAMTS9-AS1 knockdown in ectopic ESCs (EESCs) decreased cell viability and migration, whereas ADAMTS9-AS1 overexpression in normal ESCs (NESCs) enhanced cell viability and migration. More importantly, the effect of ADAMTS9-AS1 inhibition on decreasing ESC viability was significantly blocked by ferrostatin-1 (Fer-1, a ferroptosis inhibitor), and ADAMTS9-AS1 overexpression repressed erastin (a ferroptosis activator)-induced cell death. Furthermore, the regulatory role of ADAMTS9-AS1 in ferroptosis was defined and evidenced by increased reactive oxygen species (ROS) levels and malonyl dialdehyde (MDA) content and decreased expression of glutathione peroxidase 4 (GPX4) after ADAMTS9-AS1 inhibition. Mechanistically, ADAMTS9-AS1 functioned as a competing endogenous RNA (ceRNA) by sponging miR-6516-5p to derepress the expression of GPX4, the critical repressor of ferroptosis. Taken together, these results demonstrate that upregulated ADAMTS9-AS1 accelerates ESC proliferation and migration by regulating miR-6516-5p/GPX4-dependent ferroptosis and may be a potential target for the treatment of EMs.
Individual differences in vocal size exaggeration
Authors: Belyk Michel , Waters Sheena , Kanber Elise , Miquel Marc E , McGettigan Carolyn
Published: February 2022

The human voice carries socially relevant information such as how authoritative, dominant, and attractive the speaker sounds. However, some speakers may be able to manipulate listeners by modulating the shape and size of their vocal tract to exaggerate certain characteristics of their voice. We analysed the veridical size of speakers’ vocal tracts using real-time magnetic resonance imaging as they volitionally modulated their voice to sound larger or smaller, corresponding changes to the size implied by the acoustics of their voice, and their influence over the perceptions of listeners. Individual differences in this ability were marked, spanning from nearly incapable to nearly perfect vocal modulation, and was consistent across modalities of measurement. Further research is needed to determine whether speakers who are effective at vocal size exaggeration are better able to manipulate their social environment, and whether this variation is an inherited quality of the individual, or the result of life experiences such as vocal training.
Driver drowsiness estimation using EEG signals with a dynamical encoder–decoder modeling framework
Authors: Arefnezhad Sadegh , Hamet James , Eichberger Arno , Frühwirth Matthias , Ischebeck Anja , Koglbauer Ioana Victoria , Moser Maximilian , Yousefi Ali
Published: February 2022

Drowsiness is a leading cause of accidents on the road as it negatively affects the driver’s ability to safely operate a vehicle. Neural activity recorded by EEG electrodes is a widely used physiological correlate of driver drowsiness. This paper presents a novel dynamical modeling solution to estimate the instantaneous level of the driver drowsiness using EEG signals, where the PERcentage of eyelid CLOSure (PERCLOS) is employed as the ground truth of driver drowsiness. Applying our proposed modeling framework, we find neural features present in EEG data that encode PERCLOS. In the decoding phase, we use a Bayesian filtering solution to estimate the PERCLOS level over time. A data set that comprises 18 driving tests, conducted by 13 drivers, has been used to investigate the performance of the proposed framework. The modeling performance in estimation of PERCLOS provides robust and repeatable results in tests with manual and automated driving modes by an average RMSE of 0.117 (at a PERCLOS range of 0 to 1) and average High Probability Density percentage of 62.5%. We further hypothesized that there are biomarkers that encode the PERCLOS across different driving tests and participants. Using this solution, we identified possible biomarkers such as Theta and Delta powers. Results show that about 73% and 66% of the Theta and Delta powers which are selected as biomarkers are increasing as PERCLOS grows during the driving test. We argue that the proposed method is a robust and reliable solution to estimate drowsiness in real-time which opens the door in utilizing EEG-based measures in driver drowsiness detection systems.
A genome-wide association study in a large community-based cohort identifies multiple loci associated with susceptibility to bacterial and viral infections
Authors: Tängdén Thomas , Gustafsson Stefan , Rao Abhiram S. , Ingelsson Erik
Published: February 2022

There is limited data on host-specific genetic determinants of susceptibility to bacterial and viral infections. Genome-wide association studies using large population cohorts can be a first step towards identifying patients prone to infectious diseases and targets for new therapies. Genetic variants associated with clinically relevant entities of bacterial and viral infections (e.g., abdominal infections, respiratory infections, and sepsis) in 337,484 participants of the UK Biobank cohort were explored by genome-wide association analyses. Cases (n = 81,179) were identified based on ICD-10 diagnosis codes of hospital inpatient and death registries. Functional annotation was performed using gene expression (eQTL) data. Fifty-seven unique genome-wide significant loci were found, many of which are novel in the context of infectious diseases. Some of the detected genetic variants were previously reported associated with infectious, inflammatory, autoimmune, and malignant diseases or key components of the immune system (e.g., white blood cells, cytokines). Fine mapping of the HLA region revealed significant associations with HLA-DQA1, HLA-DRB1, and HLA-DRB4 locus alleles. PPP1R14A showed strong colocalization with abdominal infections and gene expression in sigmoid and transverse colon, suggesting causality. Shared significant loci across infections and non-infectious phenotypes in the UK Biobank cohort were found, suggesting associations for example between SNPs identified for abdominal infections and CRP, rheumatoid arthritis, and diabetes mellitus. We report multiple loci associated with bacterial and viral infections. A better understanding of the genetic determinants of bacterial and viral infections can be useful to identify patients at risk and in the development of new drugs.
Robustness of large-area suspended graphene under interaction with intense laser
Authors: Kuramitsu Y. , Minami T. , Hihara T. , Sakai K. , Nishimoto T. , Isayama S. , Liao Y. T. , Wu K. T. , Woon W. Y. , Chen S. H. , Liu Y. L. , He S. M. , Su C. Y. , Ota M. , Egashira S. , Morace A. , Sakawa Y. , Abe Y. , Habara H. , Kodama R. , Döhl L. N. K. , Woolsey N. , Koenig M. , Kumar H. S. , Ohnishi N. , Kanasaki M. , Asai T. , Yamauchi T. , Oda K. , Kondo Ko. , Kiriyama H. , Fukuda Y.
Published: February 2022

Graphene is known as an atomically thin, transparent, highly electrically and thermally conductive, light-weight, and the strongest 2D material. We investigate disruptive application of graphene as a target of laser-driven ion acceleration. We develop large-area suspended graphene (LSG) and by transferring graphene layer by layer we control the thickness with precision down to a single atomic layer. Direct irradiations of the LSG targets generate MeV protons and carbons from sub-relativistic to relativistic laser intensities from low contrast to high contrast conditions without plasma mirror, evidently showing the durability of graphene.
Contagion dynamics in self-organized systems of self-propelled agents
Authors: Zhao Yinong , Huepe Cristián , Romanczuk Pawel
Published: February 2022

We investigate the susceptible–infectious–recovered contagion dynamics in a system of self-propelled particles with polar alignment. Using agent-based simulations, we analyze the outbreak process for different combinations of the spatial parameters (alignment strength and Peclet number) and epidemic parameters (infection-lifetime transmissibility and duration of the individual infectious period). We show that the emerging spatial features strongly affect the contagion process. The ordered homogeneous states greatly disfavor infection spreading, due to their limited mixing, only achieving large outbreaks for high values of the individual infectious duration. The disordered homogeneous states also present low contagion capabilities, requiring relatively high values of both epidemic parameters to reach significant spreading. Instead, the inhomogeneous ordered states display high outbreak levels for a broad range of parameters. The formation of bands and clusters in these states favor infection propagation through a combination of processes that develop inside and outside of these structures. Our results highlight the importance of self-organized spatiotemporal features in a variety of contagion processes that can describe epidemics or other propagation dynamics, thus suggesting new approaches for understanding, predicting, and controlling their spreading in a variety of self-organized biological systems, ranging from bacterial swarms to animal groups and human crowds.