bluuebunny/crossref_metadata_2025 huggingface dataset:
Whey protein concentrate and skimmed milk powder as encapsulation agents for coffee silverskin extracts processed by spray drying
Authors: Barbosa Letícia Ribeiro , Francisquini Júlia d'Almeida , Cerqueira Ana Flávia Lawall Werneck , Moreira João Paulo , dos Santos Luciana Poty Manso , Scio Elita , Stephani Rodrigo , Perrone Ítalo Tuler , Húngaro Humberto Moreira , Rodarte Mirian Pereira
Published: May 2024

We tested the hypothesis that milk proteins, through microencapsulation, guarantee protection against bioactive substances in coffee silverskin extracts. Therefore, the aim of this study was to carry out technological, nutritional and physicochemical characterisation of a coffee silverskin extract microencapsulated using instant skim milk powder and whey protein concentrate as wall materials. The aqueous extract of coffee silverskin was spray-dried using 10% (w/v) skim milk powder and whey protein concentrate. The samples were characterised by determining the water content, water activity, particle size distribution, colour analysis and total phenolic compound content as well as antioxidant activity using 2,2-diphenyl-radical 1-picrylhydrazyl scavenging methods, nitric oxide radical inhibition and morphological analysis. The product showed water activity within a range that ensured greater stability, and the reduced degradation of the dried coffee silverskin extract with whey protein concentrate resulted in better rehydration ability. The luminosity parameter was higher and the browning index was lower for the encapsulated samples than for the pure coffee silverskin extract. The phenolic compound content (29.23 ± 8.39 and 34.00 ± 8.38 mg gallic acid equivalents/g for the coffee silverskin extract using skimmed milk powder and whey protein concentrate, respectively) and the antioxidant activity of the new product confirmed its potential as a natural source of antioxidant phenolic compounds. We conclude that the dairy matrices associated with spray drying preserved the bioactive and antioxidant activities of coffee silverskin extracts.
Genotypic insights to Panton–Valentine leukocidin positive methicillin-resistant Staphylococcus aureus isolated from cattle mastitis
Authors: Ijaz Muhammad , Ghumman Nauman Zaheer , Javed Muhammad Umar , Ahmed Arslan , Rasheed Hamza , Anwaar Farwa , Sabir Muhammad Jawad , Muzammil Iqra
Published: May 2024

In this research communication we investigate the prevalence and antimicrobial susceptibility of S. aureus harboring virulent genes responsible for mastitis in cattle of Punjab, Pakistan. A total of 690 milk samples were collected from commercial dairy farms for analysis of the prevalence of subclinical and clinical mastitis and isolation of S. aureus. Virulence ability and methicillin resistance in S. aureus (MRSA) was determined by targeting the pvl (the gene for Panton–Valentine leukocidin) and mecA genes, respectively. A total of 175 S. aureus isolates exhibiting prevalence of pvl gene (6.28%) and mecA gene (22.28%) were determined. Antimicrobial susceptibility testing of pvl positive and negative MRSA against different classes of antibiotics revealed 100% resistance against β-lactams while 100% sensitivity towards tylosin and linezolid.
Kinetic stability of Chapman–Enskog plasmas
Authors: Bott Archie F.A. , Cowley S.C. , Schekochihin A.A.
Published: May 2024

In this paper, we investigate the kinetic stability of classical, collisional plasma – that is, plasma in which the mean-free-path

$\lambda$

of constituent particles is short compared with the length scale

$L$

over which fields and bulk motions in the plasma vary macroscopically, and the collision time is short compared with the evolution time. Fluid equations are typically used to describe such plasmas, since their distribution functions are close to being Maxwellian. The small deviations from the Maxwellian distribution are calculated via the Chapman–Enskog (CE) expansion in

$\lambda /L \ll 1$

, and determine macroscopic momentum and heat fluxes in the plasma. Such a calculation is only valid if the underlying CE distribution function is stable at collisionless length scales and/or time scales. We find that at sufficiently high plasma

$\beta$

, the CE distribution function can be subject to numerous microinstabilities across a wide range of scales. For a particular form of the CE distribution function arising in strongly magnetised plasma (viz. plasma in which the Larmor periods of particles are much smaller than collision times), we provide a detailed analytic characterisation of all significant microinstabilities, including peak growth rates and their associated wavenumbers. Of specific note is the discovery of several new microinstabilities, including one at sub-electron-Larmor scales (the ‘whisper instability’) whose growth rate in certain parameter regimes is large compared with other instabilities. Our approach enables us to construct the kinetic stability maps of classical, two-species collisional plasma in terms of

$\lambda$

, the electron inertial scale

$d_e$

and the plasma

$\beta$

. This work is of general consequence in emphasising the fact that high-

$\beta$

collisional plasmas can be kinetically unstable; for strongly magnetised CE plasmas, the condition for instability is

$\beta \gtrsim L/\lambda$

. In this situation, the determination of transport coefficients via the standard CE approach is not valid.
Direct, simple and efficient computation of all components of the virtual-casing magnetic field in axisymmetric geometries with Kapur–Rokhlin quadrature
Authors: Toler Evan , Cerfon A.J. , Malhotra D.
Published: May 2024

In a recent publication (Toler et al., J. Plasma Phys., vol. 89, issue 2, 2023, p. 905890210), we demonstrated that for axisymmetric geometries, the Kapur–Rokhlin quadrature rule provided an efficient and high-order accurate method for computing the normal component, on the plasma surface, of the magnetic field due to the toroidal current flowing in the plasma, via the virtual-casing principle. The calculation was indirect, as it required the prior computation of the magnetic vector potential from the virtual-casing principle, followed by the computation of its tangential derivative by Fourier differentiation, to obtain the normal component of the magnetic field. Our approach did not provide the other components of the virtual-casing magnetic field. In this letter, we show that a more direct and more general approach is available for the computation of the virtual-casing magnetic field. The Kapur–Rokhlin quadrature rule accurately calculates the principal value integrals in the expression for all the components of the magnetic field on the plasma boundary, and the numerical error converges at a rate nearly as high as the indirect method we presented previously.
The future is just another past
Authors: Kessler Oliver , Leira Halvard
Published: May 2024

Before International Studies can confront the future, it needs to get a better grip on its past and present. The discipline lacks agreement on both its own name and the name of its object of study. More importantly, key concepts used to describe phenomena have changed continuously: no concept emerging in the 19th century has remained untouched, no envisioned future of the past could have prepared us for the present. Old concepts have been discarded, new ones adopted, and existing ones modified. This implies that any exercise in ‘futurology’ must necessarily come with an openness towards conceptual change, and that a key challenge for International Studies going forward will consist in matching our conceptual toolbox to an ever-changing world. The importance of conceptual change has until recently been neglected in the study of global politics. Thus, in this paper we start by presenting the empirical case for incorporating conceptual change by laying out key past and present conceptual changes in the international realm. We then move on to a presentation of conceptual history and the tools it provides us for grasping conceptual change, before discussing how to tackle conceptual developments when thinking about the future of global politics.
The terrestrial trap: International Relations beyond Earth
Authors: van Wingerden Enrike , Vigneswaran Darshan
Published: May 2024

Human capacity to explore and shape outer space will increase substantially over the next 50 years. Yet, International Relations (IR) theory still treats outer space as an isolated, unique, or inconsequential realm of political life. This paper moves IR beyond its ‘terrestrial trap’ by theorising planetary politics as inherently embedded in relations with environments and actors that are located beyond Earth. To face the momentous and often alarming political developments taking place in outer space, from space militarisation to space colonisation, we challenge two of IR’s terrestrial biases. First, we confront the assumption that developments in international relations take place only or primarily on Earth. We show how the historically constituted ideologies and political economies of colonisation and domination are extended to – but also transformed within – outer space exploration and settlement. Second, we challenge the notion that developments in outer space form a logical extension of politics as it has emerged on the habitable surface of our planet. We move beyond zones of human habitation and explore how the material conditions of space intersect with situated histories of political governance and control. By analysing politics beyond Earth, we retool IR theory to confront an extraterrestrial political future.
Development and testing of two tools to assess point-of-sale food and beverage marketing to children in restaurants
Authors: Minaker Leia M , Menko Patrycia , Olona David
Published: May 2024

Objective:

To describe the development and testing of two assessment tools designed to assess exterior (including drive-thru) and interior food and beverage marketing in restaurants with a focus on marketing to children and teens.

Design:

A scoping review on restaurant marketing to children was undertaken, followed by expert and government consultations to produce a draft assessment tool. The draft tool was mounted online and further refined into two separate tools: the Canadian Marketing Assessment Tool for Restaurants (CMAT-R) and the CMAT-Photo Coding Tool (CMAT-PCT). The tools were tested to assess inter-rater reliability using Cohen’s Kappa and per cent agreement for dichotomous variables, and intra-class correlation coefficients (ICCs) for continuous or rank-order variables.

Setting:

Waterloo, Ontario, Canada.

Participants:

Restaurants of all types were assessed using the CMAT-R (n 57), and thirty randomly selected photos were coded using the CMAT-PCT.

Results:

The CMAT-R collected data on general promotions and restaurant features, drive-thru features, the children’s menu and the dollar/value menu. The CMAT-PCT collected data on advertisement features, features considered appealing to children and teens, and characters. The inter-rater reliability of the CMAT-R tool was strong (mean per cent agreement was 92·4 %, mean Cohen’s κ = 0·82 for all dichotomous variables and mean ICC = 0·961 for continuous/count variables). The mean per cent agreement for the CMAT-PCT across items was 97·3 %, and mean Cohen’s κ across items was 0·91, indicating very strong inter-rater reliability.

Conclusions:

The tools assess restaurant food and beverage marketing. Both showed high inter-rater reliability and can be adapted to better suit other contexts.
Albträume austricksen
Authors: Frisch Janos , Wolf Jeannine
Published: May 2024

Gemeinsam stark gegen Albträume:
Super Tricks von Albas Freund*innen

Alba, die Bärin, hat jede Nacht ganz schlimme Albträume. Aber sie hat eine super Idee! So macht sie sich auf den Weg zu ihren besten Freund*innen aus dem Wald, die alle einen hilfreichen Trick gegen Albträume kennen. Gemeinsam werden sie die fiesen Alb­träume austricksen!

Wenn du auch schlecht träumst, dann bist du hier richtig. Das ist nämlich ein Mitmachbuch! Du kannst jeden Trick selbst ausprobieren und deine eigenen Albträume austricksen. Und das klappt wirklich und macht tierisch Spaß! Bärentatze drauf!

Für die Erwachsenen gibt es im Eltern- und Fachkräfteteil hilfreiche Tipps zu den wissenschaftlich fundierten Tricks aus dem Kinderteil. Sie erfahren, wie sie das Kind bei Albträumen gut unterstützen können, warum es zu Albträumen kommt und wie man sie von anderen Schlafstörungen unterscheiden kann.

Der erste Teil des Bilderbuchs richtet sich an die Kinder selbst. Es handelt sich um einen Praxisleitfaden, in dem diverse psychologische Methoden, sogenannte Tricks, gegen Albträume angewendet werden. Durch die verschiedenen Ansätze werden unterschiedliche Wirkfaktoren zur Bewältigung von kindlichen Albträumen eingesetzt. Der motivierende, interaktive und spaßige Charakter dieses Teils lädt die Kinder zum Mitmachen ein. Sie werden angeleitet, die Tricks direkt anzuwenden und deren Effekt selbst auszuprobieren und zu erleben.

Der zweite Teil informiert Eltern, Bezugspersonen oder Fachkräfte in Form eines Ratgebers sachlich, wissenschaftlich fundiert und einfach verständlich über das Wesen kindlicher Albträume. Zudem enthält dieser Teil zusätzliche Erklärungen, Theorien und praktische Tipps zu Albträumen bei Kindern.
Cumulative Exposures to Environmental and Socioeconomic Risk Factors in Milwaukee County, Wisconsin
Authors: Kodros John K. , Carter Ellison , Oke Oluwatobi , Wilson Ander , Jathar Shantanu H. , Magzamen Sheryl
Published: May 2024

The environmental justice literature demonstrates consistently that low‐income and minority communities are disproportionately exposed to environmental hazards. In this case study, we examined cumulative multipollutant, multidomain, and multimatrix environmental exposures in Milwaukee County, Wisconsin for the year 2015. We identified spatial hot spots in Milwaukee County both individually (using local Moran's I) and through clusters (using K‐means clustering) across a profile of environmental pollutants that span regulatory domains and matrices of exposure, as well as socioeconomic indicators. The cluster with the highest exposures within the urban area was largely characterized by low socioeconomic status and an overrepresentation of the Non‐Hispanic Black population relative to the county as a whole. In this cluster, average pollutant concentrations were equivalent to the 78th percentile in county‐level blood lead levels, 67th percentile in county‐level NO2, 79th percentile in county‐level CO, and 78th percentile in county‐level air toxics. Simultaneously, this cluster had an average equivalent to the 62nd percentile in county‐level unemployment, 70th percentile in county‐level population rate lacking a high school diploma, 73rd percentile in county‐level poverty rate, and 28th percentile in county‐level median household income. The spatial patterns of pollutant exposure and SES indicators suggested that these disparities were not random but were instead structured by socioeconomic and racial factors. Our case study, which combines environmental pollutant exposures, sociodemographic data, and clustering analysis, provides a roadmap to identify and target overburdened communities for interventions that reduce environmental exposures and consequently improve public health.
Near‐Inertial Wave Propagation in the Deep Canadian Basin: Turning Depths and the Homogeneous Deep Layer
Authors: Bracamontes‐Ramírez Joel , Walter Maren , Losch Martin
Published: May 2024

The internal wave climate in the deep Arctic Ocean, away from the shelves, is quiet because the ice cover shields the ocean from wind energy input, and tidal amplitudes are small. Hence, mixing due to internal wave breaking is small. The shrinking Arctic sea ice cover, however, exposes more open ocean areas to energy transfer by wind. Consequently, more energetic near‐inertial internal waves (NIWs) may carry energy to the bottom, potentially enhancing deep mixing. In the deep Canadian Basin, weakly stratified layers with local buoyancy frequencies smaller than the wave frequency may prevent NIW propagation to the seafloor. We estimate the distribution of these near‐inertial turning depths from temperature and salinity data of the years 2005–2014. Near‐inertial turning depths are ubiquitous in the deep Canadian Basin at ∼2,750 m depth, between 100 and 1,200 m above the bottom. A deep homogeneous layer below 3,300 m is characterized by small squared buoyancy frequencies N2 ∼ 0 with locally unstable layers (N2 < 0). The turning depths reflect NIWs and hence limit their contribution to deep mixing, but the waves create an evanescent perturbation with exponentially decreasing amplitude that can interact with the bathymetry, especially above slopes and ridges where the height of the turning depths above the seafloor is small. After reflection, the main part of the wave energy is trapped between turning depths and the surface, so that a potential increase of wave energy input mainly affects mixing of mid‐depth water masses like the Atlantic Water.
62°S Witnesses the Transition of Boundary Layer Marine Aerosol Pattern Over the Southern Ocean (50°S–68°S, 63°E–150°E) During the Spring and Summer: Results From MARCUS (I)
Authors: Niu Qing , McFarquhar Greg M. , Marchand Roger , Theisen Adam , Cavallo Steven M. , Flynn Connor , DeMott Paul J. , McCluskey Christina S. , Humphries Ruhi S. , Hill Thomas C. J.
Published: May 2024

The Atmospheric Radiation Measurement Mobile Facility‐2 was installed onboard the research vessel Aurora Australis to measure aerosol properties during the 2017–2018 Measurement of Aerosols, Radiation, and CloUds over the pristine Southern ocean (MARCUS) Experiment, providing unique data on aerosols latitudinal and seasonal variation, including south of 60°S where previous observations are scarce. Data from a Cloud Condensation Nuclei (CCN) counter and Ultra‐High‐Sensitivity Aerosol Spectrometer show that both the number concentration (NCCN) and size distribution of CCN‐active aerosols, with diameters (D) between 60 nm < D < 1,000 nm are different over the North Southern Ocean (NSO) (50°S–60°S) and the South Southern Ocean (SSO) (62°S–68°S). The average NSO NCCN at 0.2% and 0.5% supersaturation were 28% and 49% less than that over the SSO. This increase of CCN over the SSO is caused by the increase of aerosols with 60 nm < D < 200 nm, consistent with calculations of Aerosol Scattering Angstrom Exponents derived from a nephelometer. Aerosol hygroscopicity growth factor measured by the Hygroscopic Tandem Differential Mobility Analyzer stayed close to 1.41 for aerosols with 50 nm < D < 250 nm over the SSO, but increased from 1.30 to 1.67 over the NSO, indicating different chemical compositions. Both CCN and Ice Nucleating Particles (INPs) showed a stronger variation with season than with latitude. The variation of heat‐labile and presumably proteinacous INPs suggests an increase of ice nucleating‐active microbes in summer.
Impact of Anthropogenic Aerosol Transport on Cloud Condensation Nuclei Activity During Summertime in Qilian Mountain, in the Northern Tibetan Plateau
Authors: Xu J. Z. , Mei F. , Zhang X. H. , Zhao W. H. , Zhai L. X. , Zhong M. , Hou S. G.
Published: May 2024

In this study, we conducted field campaigns at two mountain‐top observatories on the Qilian Mountains (QLM) in the northeastern Tibetan Plateau of China, which plays a vital role in sustaining water resources for the downstream arid and semi‐arid regions. The two observatories, Waliguan Baseline Observatory (WLG) and Laohugou station (LHG), are situated on the eastern and western edge of the QLM, respectively. The objectives of this study were to examine the properties of atmospheric aerosols, CCN concentrations (NCCN) at varying supersaturation levels (SS = 0.2%–1.0%), and the hygroscopic nature of aerosols in the QLM, especially during the formation of orographic cloud. Notably, the average aerosol concentration and NCCN was approximately 2–3 factors higher at WLG compared to LHG. The chemical compositions of aerosols were primarily dominated by sulfate and organic aerosol (OA) at these two sites. A very high hygroscopicity parameter of aerosol calculated using chemical composition was observed at these two sites (0.37 ± 0.03 at LHG vs. 0.30 ± 0.04 at WLG). Enhanced aerosol loading episodes impacted by anthropogenic emission were observed at these two sites. Exploration on high‐loading cases at each site, we found that the CCN activity was dominated by aerosol size, but the chemical processes of aerosol during the formation of orographic cloud could also be important in CCN activity, especially for low SS conditions. These findings collectively underscore the significant impact of anthropogenic air plumes on CCN concentrations in the QLM and their potential influence on precipitation patterns.
A Hybrid, Non‐Stationary Stochastic Watershed Model (SWM) for Uncertain Hydrologic Simulations Under Climate Change
Authors: Brodeur Zach , Wi Sungwook , Shabestanipour Ghazal , Lamontagne Jon , Steinschneider Scott
Published: May 2024

Stochastic Watershed Models (SWMs) are emerging tools in hydrologic modeling used to propagate uncertainty into model predictions by adding samples of model error to deterministic simulations. One of the most promising uses of SWMs is uncertainty propagation for hydrologic simulations under climate change. However, a core challenge is that the historical predictive uncertainty may not correctly characterize the error distribution under future climate. For example, the frequency of physical processes (e.g., snow accumulation and melt) may change under climate change, and so too may the frequency of errors associated with those processes. In this work, we explore for the first time non‐stationarity in hydrologic model errors under climate change in an idealized experimental design. We fit one hydrologic model to historical observations, and then fit a second model to the simulations of the first, treating the first model as the true hydrologic system. We then force both models with climate change impacted meteorology and investigate changes to the error distribution between the models. We develop a hybrid machine learning method that maps model state variables to predictive errors, allowing for non‐stationary error distributions based on changes in the frequency of model states. We find that this procedure provides an internally consistent methodology to overcome stationarity assumptions in error modeling and offers an important advance for implementing SWMs under climate change. We test this method on three hydrologically distinct watersheds in California (Feather River, Sacramento River, Calaveras River), finding that the hybrid model performs best in larger and less flashy basins.
2D and 3D Computational Modeling of Surface Flooding in Urbanized Floodplains: Modeling Performance for Various Building Layouts
Authors: Li Xuefang , Dellinger Guilhem , Erpicum Sébastien , Chen Lihua , Yu Shuyue , Guiot Léo , Archambeau Pierre , Pirotton Michel , Dewals Benjamin
Published: May 2024

Understanding the strengths and limitations of the modeling capacity of surface flooding in urbanized floodplains is of utmost importance as such events are becoming increasingly frequent and extreme. In this study, we assess two computational models against laboratory observations of surface urban flooding in a reduced‐scale physical model of idealized urban districts. Four urban layouts were considered, involving each three inlets and three outlets as well as a combination of three‐ and four‐branch crossroads together with open spaces. The first model (2D) solves the shallow‐water equations while the second one (3D) solves the Reynolds‐averaged Navier‐Stokes equations. Both models accurately predict the flow depths in the inlet branches. For the discharge partition between the outlets, deviations between the computations and laboratory observations remain close to the experimental uncertainties (maximum 2.5 percent‐points). The velocity fields computed in 3D generally match the measured surface velocity fields. In urban layouts involving mostly a network of streets, the depth‐averaged velocity fields computed by the 2D model agree remarkably well with those of the 3D model, with differences not exceeding 10%, despite the presence of helicoidal flow (revealed by the 3D computations). In configurations with large open areas, the 3D model captures generally well the trajectory and velocity distribution of main surface flow jet and recirculations; but the 2D model does not perform as well as it does in relatively channelized flow regions. Visual inspection of the jet trajectories computed by the 2D model in large open areas reveals that they substantially deviate from the observations.
A Hydrodynamic‐Based Physical Unified Modeling for Simulating Shallow Landslide Local Failures, Mass Release and Debris Flow Run‐Out Extent Behavior
Authors: Hu Xiaobo , Jiang Yuanjun , Ning Po , Liang Heng , Fan Xiaoyi , Liu Wei , Xia Xin , Zhu Yuanjia
Published: May 2024

Accurate prediction of shallow landslide occurrence and the subsequent motion range after transformation into debris flows is crucial for reducing disaster‐induced losses. The use of Cellular Automata‐based (CA) hydrodynamic models has seen increasing application in predicting landslides, debris flows, and other related hazards. However, previous CA‐based models have primarily focused on the motion and evolution process of debris flows, lacking detailed description about the dynamic instability associated with shallow landslides. In this study, we propose a comprehensive CA‐based model that is based on existing theories and improved models for simulating hydrological processes, sliding surface identification algorithms, threshold‐based mechanical interactions, material entrainment, and deposition. The model was applied to the Yindongzi (YDZ) landslides in Sichuan, China. The accuracy of the model was validated through comparisons with field investigation results and calculations based on shallow water equations. This model enables efficient and rapid prediction of shallow landslide occurrence time, volume, spatial distribution, and runout distance. Evaluation of the model’s predictive performance reveals an error range of −23.12% to +44.26% for YDZ landslides. Moreover, the influence of different shallow landslide failure patterns on the deposition and erosion of debris flows was analyzed. The results indicate that the failure patterns of shallow landslides significantly affect the deposition and entrainment capacity of debris flows. This study provides a novel approach for predicting the occurrence of shallow landslides and the subsequent motion, entrainment, and deposition after transformation into debris flows.
Assessing the effect of metastasis-directed therapy in oligometastatic disease using the restricted mean survival time
Authors: Averbuch Itamar , Moore Assaf , Ludmir Ethan B. , Markel Gal , Meirson Tomer
Published: May 2024

Background

Metastasis-directed therapy (MDT) with stereotactic body radiotherapy (SBRT) is emerging as an effective therapeutic option for oligometastatic disease (OMD). However, a lack of phase III data, consensus guidelines, and toxicity concerns limit its widespread use. Randomized controlled trials (RCTs) routinely report hazard ratios (HRs) and medians that lack clear clinical and robust interpretation. Restricted-mean survival time (RMST) is the duration of time a patient is expected to survive over the follow-up period, providing a robust and interpretable alternative. We analyzed the efficacy of SBRT using RMST.

Methods

All registered RCTs of ablative radiotherapy in OMD in ClinicalTrials.gov through 2022 were identified. Data were reconstructed from Kaplan–Meier curves, and the HRs and RMST differences were estimated for surrogate endpoints (SEs) and overall survival (OS).

Results

Six studies comprising 426 patients met the inclusion criteria. The RMST differences for SEs ranged from 4.6 months in a study by Iyengar et al. to 11.1 months in SABR-COMET. The RMST differences for OS in SABR-COMET, Gomez et al., and SINDAS studies were 12.6, 15 and 7.9 months, respectively.

Conclusion

RMST demonstrates the efficacy of local treatment in OMD. Representing the expected survival time, this method effectively communicates outcomes to patients and clinicians.
TNF-α/TNFR1 activated astrocytes exacerbate depression-like behavior in CUMS mice
Authors: Gao Mengjiao , Song Yu , Liu Yaqi , Miao Yuqing , Guo Yanwu , Chai Huihui
Published: May 2024

Neuroinflammation is considered to be a significant mechanism contributing to depression. Several studies have reported that A1 astrocytes were highly prevalent in human neuroinflammatory and neurodegenerative diseases. However, the precise mechanism by which A1 astrocytes contribute to depression remains unclear. Clinical studies have suggested a correlation between TNF-α, an activator of A1 astrocytes, and the severity of depression. Based on these findings, we hypothesized that TNF-α might worsen depression by activating A1 astrocytes. Our previous studies indicated that Rhodomyrtone (Rho) has the potential to improve depression-like behavior in mice. However, the exact mechanism for this effect has not been fully elucidated. Importantly, it was reported that Rho alleviated skin inflammation in a mouse model of psoriasis by inhibiting the expression of TNF-α. Based on this finding, we hypothesized that rhodomyrtone may exert antidepressant effects by modulating the TNF-α pathway. However, further research is required to investigate and validate these hypotheses, shedding light on the relationships between neuroinflammation, A1 astrocytes, TNF-α, and depression. By obtaining a deeper understanding of the underlying mechanisms, these findings could lead to the development of novel antidepressant strategies that target the TNF-α pathway in the context of neuroinflammation. In vivo, based on the established chronic unpredictable mild stress (CUMS) mouse depression model, we characterized the mechanism of TNF-α and Rho during depression by using several behavioral assays, adeno-associated virus(AAV) transfection, western blotting, immunofluorescence, and other experimental methods. In vitro, we characterized the effect of Rho on inflammation in TNF-α-treated primary astrocytes. TNFR1 expression was significantly increased in the hippocampus of depression-like mice, with increased astrocytes activation and neuronal apoptosis. These processes were further enhanced with increasing levels of TNF-α in the cerebrospinal fluid of mice. However, this process was attenuated by knockdown of TNFR1 and infliximab (Inf; a TNF-α antagonist). Injection of rhodomyrtone decreased the expressions of TNFR1 and TNF-α, resulting in significant improvements in mouse depression-like behaviors and reduction of astrocyte activation. TNF-α could be involved in the pathophysiological process of depression, through mediating astrocytes activation by binding to TNFR1. By blocking this pathway, Rho may be a novel antidepressant.
Deciphering DED assembly mechanisms in FADD-procaspase-8-cFLIP complexes regulating apoptosis
Authors: Yang Chao-Yu , Lien Chia-I , Tseng Yi-Chun , Tu Yi-Fan , Kulczyk Arkadiusz W. , Lu Yen-Chen , Wang Yin-Ting , Su Tsung-Wei , Hsu Li-Chung , Lo Yu-Chih , Lin Su-Chang
Published: May 2024

Fas-associated protein with death domain (FADD), procaspase-8, and cellular FLICE-inhibitory proteins (cFLIP) assemble through death-effector domains (DEDs), directing death receptor signaling towards cell survival or apoptosis. Understanding their three-dimensional regulatory mechanism has been limited by the absence of atomic coordinates for their ternary DED complex. By employing X-ray crystallography and cryogenic electron microscopy (cryo-EM), we present the atomic coordinates of human FADD-procaspase-8-cFLIP complexes, revealing structural insights into these critical interactions. These structures illustrate how FADD and cFLIP orchestrate the assembly of caspase-8-containing complexes and offer mechanistic explanations for their role in promoting or inhibiting apoptotic and necroptotic signaling. A helical procaspase-8-cFLIP hetero-double layer in the complex appears to promote limited caspase-8 activation for cell survival. Our structure-guided mutagenesis supports the role of the triple-FADD complex in caspase-8 activation and in regulating receptor-interacting protein kinase 1 (RIPK1). These results propose a unified mechanism for DED assembly and procaspase-8 activation in the regulation of apoptotic and necroptotic signaling across various cellular pathways involved in development, innate immunity, and disease.
Decarboxylative stereoretentive C–N coupling by harnessing aminating reagent
Authors: Kweon Jeonguk , Park Bumsu , Kim Dongwook , Chang Sukbok
Published: May 2024

In recent decades, strategies involving transition-metal catalyzed carbon-carbon or carbon-heteroatom bond coupling have emerged as potent synthetic tools for constructing intricate molecular architectures. Among these, decarboxylative carbon-nitrogen bond formation using abundant carboxylic acids or their derivatives has garnered notable attention for accessing alkyl- or arylamines, one of key pharmacophores. While several decarboxylative amination methods have been developed, the involvement of a common carboradical intermediate currently poses challenges in achieving stereospecific transformation toward chiral alkylamines. Herein, we present a base-mediated, stereoretentive decarboxylative amidation by harnessing 1,4,2-dioxazol-5-one as a reactive and robust amidating reagent under transition-metal-free ambient conditions, encompassing all types of primary, secondary and tertiary carboxylic acids, thereby providing access to the important pharmacophore, α-chiral amines. This method exhibits high functional group tolerance, convenient scalability, and ease of applicability for 15N-isotope labeling, thus accentuating its synthetic utilities. Experimental and computational mechanistic investigations reveal a sequence of elementary steps: i) nucleophilic addition of carboxylate to dioxazolone, ii) rearrangement to form a dicarbonyl N-hydroxy intermediate, iii) conversion to hydroxamate, followed by a Lossen-type rearrangement, and finally, iv) reaction of the in situ generated isocyanate with carboxylate leading to C–N bond formation in a stereoretentive manner.
Machine learning-based prediction of polaron-vacancy patterns on the TiO2(110) surface
Authors: Birschitzky Viktor C. , Sokolović Igor , Prezzi Michael , Palotás Krisztián , Setvín Martin , Diebold Ulrike , Reticcioli Michele , Franchini Cesare
Published: May 2024

The multifaceted physics of oxides is shaped by their composition and the presence of defects, which are often accompanied by the formation of polarons. The simultaneous presence of polarons and defects, and their complex interactions, pose challenges for first-principles simulations and experimental techniques. In this study, we leverage machine learning and a first-principles database to analyze the distribution of surface oxygen vacancies (VO) and induced small polarons on rutile TiO2(110), effectively disentangling the interactions between polarons and defects. By combining neural-network supervised learning and simulated annealing, we elucidate the inhomogeneous VOdistribution observed in scanning probe microscopy (SPM). Our approach allows us to understand and predict defective surface patterns at enhanced length scales, identifying the specific role of individual types of defects. Specifically, surface-polaron-stabilizing VO-configurations are identified, which could have consequences for surface reactivity.
A hierarchical kidney outcome using win statistics in patients with heart failure from the DAPA-HF and DELIVER trials
Authors: Kondo Toru , Jhund Pardeep S. , Gasparyan Samvel B. , Yang Mingming , Claggett Brian L. , McCausland Finnian R. , Tolomeo Paolo , Vadagunathan Muthiah , Heerspink Hiddo J. L. , Solomon Scott D. , McMurray John J. V.
Published: May 2024

Win statistics offer a new approach to the analysis of outcomes in clinical trials, allowing the combination of time-to-event and longitudinal measurements and taking into account the clinical importance of the components of composite outcomes, as well as their relative timing. We examined this approach in a post hoc analysis of two trials that compared dapagliflozin to placebo in patients with heart failure and reduced ejection fraction (DAPA-HF) and mildly reduced or preserved ejection fraction (DELIVER). The effect of dapagliflozin on a hierarchical composite kidney outcome was assessed, including the following: (1) all-cause mortality; (2) end-stage kidney disease; (3) a decline in estimated glomerular filtration rate (eGFR) of ≥57%; (4) a decline in eGFR of ≥50%; (5) a decline in eGFR of ≥40%; and (6) participant-level eGFR slope. For this outcome, the win ratio was 1.10 (95% confidence interval (CI) = 1.06–1.15) in the combined dataset, 1.08 (95% CI = 1.01–1.16) in the DAPA-HF trial and 1.12 (95% CI = 1.05–1.18) in the DELIVER trial; that is, dapagliflozin was superior to placebo in both trials. The benefits of treatment were consistent in participants with and without baseline kidney disease, and with and without type 2 diabetes. In heart failure trials, win statistics may provide the statistical power to evaluate the effect of treatments on kidney as well as cardiovascular outcomes.
A road surface reconstruction dataset for autonomous driving
Authors: Zhao Tong , Xie Yichen , Ding Mingyu , Yang Lei , Tomizuka Masayoshi , Wei Yintao
Published: May 2024

Recent developments in intelligent robot systems, especially autonomous vehicles, put forward higher requirements for safety and comfort. Road conditions are crucial factors affecting the comprehensive performance of ground vehicles. Nonetheless, existing environment perception datasets for autonomous driving lack attention to road surface areas. In this paper, we introduce the road surface reconstruction dataset, providing multi-modal, high-resolution, and high-precision data collected by real-vehicle platform in diverse driving conditions. It covers common road types containing approximately 16,000 pairs of stereo images, point clouds, and ground-truth depth/disparity maps, with accurate data processing pipelines to ensure its quality. Preliminary evaluations reveal the effectiveness of our dataset and the challenge of the task, underscoring substantial opportunities of it as a valuable resource for advancing computer vision techniques. The reconstructed road structure and texture contribute to the analysis and prediction of vehicle responses for motion planning and control systems.
Laboratory parameters related to disease severity and physical performance after reconvalescence of acute COVID-19 infection
Authors: Gietl Mario , Burkert Francesco , Hofer Stefanie , Gostner Johanna M. , Sonnweber Thomas , Tancevski Ivan , Pizzini Alex , Sahanic Sabina , Schroll Andrea , Brigo Natascha , Egger Alexander , Bellmann-Weiler Rosa , Löffler-Ragg Judith , Weiss Günter , Kurz Katharina
Published: May 2024

Research into the molecular basis of disease trajectory and Long-COVID is important to get insights toward underlying pathophysiological processes. The objective of this study was to investigate inflammation-mediated changes of metabolism in patients with acute COVID-19 infection and throughout a one-year follow up period. The study enrolled 34 patients with moderate to severe COVID-19 infection admitted to the University Clinic of Innsbruck in early 2020. The dynamics of multiple laboratory parameters (including inflammatory markers [C-reactive protein (CRP), interleukin-6 (IL-6), neopterin] as well as amino acids [tryptophan (Trp), phenylalanine (Phe) and tyrosine (Tyr)], and parameters of iron and vitamin B metabolism) was related to disease severity and patients’ physical performance. Also, symptom load during acute illness and at approximately 60 days (FU1), and one year after symptom onset (FU2) were monitored and related with changes of the investigated laboratory parameters: During acute infection many investigated laboratory parameters were elevated (e.g., inflammatory markers, ferritin, kynurenine, phenylalanine) and enhanced tryptophan catabolism and phenylalanine accumulation were found. At FU2 nearly all laboratory markers had declined back to reference ranges. However, kynurenine/tryptophan ratio (Kyn/Trp) and the phenylalanine/tyrosine ratio (Phe/Tyr) were still exceeding the 95th percentile of healthy controls in about two thirds of our cohort at FU2. Lower tryptophan concentrations were associated with B vitamin availability (during acute infection and at FU1), patients with lower vitamin B12 levels at FU1 had a prolonged and more severe impairment of their physical functioning ability. Patients who had fully recovered (ECOG 0) presented with higher concentrations of iron parameters (ferritin, hepcidin, transferrin) and amino acids (phenylalanine, tyrosine) at FU2 compared to patients with restricted ability to work. Persistent symptoms at FU2 were tendentially associated with IFN-γ related parameters. Women were affected by long-term symptoms more frequently. Conclusively, inflammation-mediated biochemical changes appear to be related to symptoms of patients with acute and Long Covid.
Determining sea-level rise in the Caribbean: A shift from temperature to mass control
Authors: Maitland Deron O. , Richter Kristin , Raj Roshin P. , Bonaduce Antonio , Nisancioglu Kerim H. , Taylor Michael A. , Stephenson Tannecia S.
Published: May 2024

Tropical Small Island Developing States (SIDS), such as those in the Caribbean, are among the most vulnerable to the impacts of climate change, most notably sea-level rise. The current sea-level rise in the Caribbean is 3.40 ± 0.3 mm/year (1993–2019), which is similar to the 3.25 ± 0.4 mm/year global mean sea-level (GMSL) rise (1993–2018). Throughout the year, Caribbean seasonal sea-level variability is found to respond to sea surface temperature variability. Over the past few decades, the trend in Caribbean Sea-level rise is also found to be variable. Satellite altimetry and steric sea-level records of the Caribbean region reveal a shift in the late 2003-early 2004, which separates two distinct periods of sea-level rise. Thermal expansion dominates the sea-level trend from 1993–2003. Following this period, there is an increased trend in sea-level rise, with a dominance of mass changes from 2004–2019, as confirmed by GRACE data. During this period, the sea-level trend is 6.15 ± 0.5 mm/year, which is 67% faster than the most recent estimates of global mean sea-level rise provided by the Intergovernmental Panel on Climate Change (3.69 ± 0.5 mm/year for the period 2006–2018). Despite its reduced importance, increasing temperatures contribute greatly to sea-level rise in the Caribbean region through thermal expansion of ocean water, hence there is a need to limit the current trend of global warming.
Effective small crack detection based on tunnel crack characteristics and an anchor-free convolutional neural network
Authors: Wang Li , Tang Chao
Published: May 2024

Tunnel cracks are thin and narrow linear targets, and their pixel proportions in images are usually very low, less than 6%; therefore, a method is needed to better detect small crack targets. In this study, a crack detection method based on crack characteristics and an anchor-free framework is investigated. First, the characteristics of cracks are analyzed to obtain the real crack texture, interference noise texture, and targets appearing near each crack as the context information for the model to filter and remove noise. We discuss the crack detection performance of anchor-based and anchor-free algorithms. Then, an optimized anchor-free algorithm is proposed in this paper for crack detection. Based on the advantages of YOLOX-x, we add a semantic enhancement module to better use contextual information. The experimental results show that the anchor-free algorithm performs slightly better than other algorithms in crack detection situations. In addition, the proposed method displays better detection performance for slender and inconspicuous cracks, with an average precision of 0.858.
2D signal estimation for sparse distributed target photon counting data
Authors: Hayman Matthew , Stillwell Robert A. , Carnes Josh , Kirchhoff Grant J. , Spuler Scott M. , Thayer Jeffrey P.
Published: May 2024

In this study, we explore the utilization of penalized likelihood estimation for the analysis of sparse photon counting data obtained from distributed target lidar systems. Specifically, we adapt the Poisson Total Variation processing technique to cater to this application. By assuming a Poisson noise model for the photon count observations, our approach yields denoised estimates of backscatter photon flux and related parameters. This facilitates the processing of raw photon counting signals with exceptionally high temporal and range resolutions (demonstrated here to 50 Hz and 75 cm resolutions), including data acquired through time-correlated single photon counting, without significant sacrifice of resolution. Through examination involving both simulated and real-world 2D atmospheric data, our method consistently demonstrates superior accuracy in signal recovery compared to the conventional histogram-based approach commonly employed in distributed target lidar applications.
A Japanese herbal medicine (kampo), hochuekkito (TJ-41), has anti-inflammatory effects on the chronic obstructive pulmonary disease mouse model
Authors: Yuki Masaaki , Ishimori Taro , Kono Shiho , Nagoshi Saki , Saito Minako , Isago Hideaki , Tamiya Hiroyuki , Fukuda Kensuke , Miyashita Naoya , Ishii Takashi , Matsuzaki Hirotaka , Hiraishi Yoshihisa , Saito Akira , Jo Taisuke , Nagase Takahide , Mitani Akihisa
Published: May 2024

Chronic obstructive pulmonary disease (COPD) is a progressive disease that is characterized by chronic airway inflammation. A Japanese herbal medicine, hochuekkito (TJ-41), is prominently used for chronic inflammatory diseases in Japan. This study aimed to analyze the anti-inflammatory effect of TJ-41 in vivo and its underlying mechanisms. We created a COPD mouse model using intratracheal administration of porcine pancreatic elastase and lipopolysaccharide (LPS) and analyzed them with and without TJ-41 administration. A TJ-41-containing diet reduced inflammatory cell infiltration of the lungs in the acute and chronic phases and body weight loss in the acute phase. In vitro experiments revealed that TJ-41 treatment suppressed the LPS-induced inflammatory cytokines in BEAS-2B cells. Furthermore, TJ-41 administration activated the AMP-activated protein kinase (AMPK) pathway and inhibited the mechanistic target of the rapamycin (mTOR) pathway, both in cellular and mouse experiments. We concluded that TJ-41 administration reduced airway inflammation in the COPD mouse model, which might be regulated by the activated AMPK pathway, and inhibited the mTOR pathway.