bluuebunny/crossref_metadata_2025 huggingface dataset:
Multifractal Properties of Meteorological Drought at Different Time Scales in a Tropical Location
Authors: Ogunjo Samuel Toluwalope
Published: September 2020

Tropical countries, like Nigeria, depend on rainfall for agriculture, power generation, transportation and other economic activities. Drought will hinder the performance of these activities, hence, it poses a significant threat to the economy. Understanding fluctuations and structures in droughts will help in forecasting, planning and mitigating its impact on livelihoods. In this study, the multifractal properties of drought at four temporal scales were investigated over different locations across Nigeria. Drought was computed using the standardized precipitation index from monthly precipitation data from 1980 to 2010. Using multifractal detrended fluctuation analysis, meteorological drought was found to have multifractal properties at 1-, 6-, 12- and 24-month temporal scale. The generalized Hurst exponent of drought at different time-scale showed dependence on scaling exponent. Long-range correlations were found to be main source of multifractality at all temporal scales. The multifractal strength increases with increasing temporal scale except for a few locations. The range of spectrum width were found to be 0.306–0.464 and 0.596–0.993 at 1- and 24-month temporal scale, respectively. No significant trend was found in the degree of multifractality across different climatic zones of Nigeria.
Smoothness of functions versus smoothness of approximation processes
Authors: Kolomoitsev Yu. S. , Tikhonov S. Yu.
Published: September 2020

We provide a comprehensive study of interrelations between different measures of smoothness of functions on various domains and smoothness properties of approximation processes. Two general approaches to this problem have been developed: The first based on geometric properties of Banach spaces and the second on Littlewood–Paley and Hörmander-type multiplier theorems. In particular, we obtain new sharp inequalities for measures of smoothness given by the [Formula: see text]-functionals or moduli of smoothness. As examples of approximation processes we consider best polynomial and spline approximations, Fourier multiplier operators on [Formula: see text], [Formula: see text], [Formula: see text], nonlinear wavelet approximation, etc.
Quantification of potassium concentration with Vis–SWNIR spectroscopy in fresh lettuce
Authors: Xiong Yating , Ohashi Shintaroh , Nakano Kazuhiro , Jiang Weizhong , Takizawa Kenichi , Iijima Kazuyuki , Maniwara Phonkrit
Published: September 2020

Chronic kidney disease (CKD) is becoming a major public health problem worldwide, and excessive potassium intake is a health threat to patients with CKD. In this study, visible–short-wave near-infrared (Vis–SWNIR) spectroscopy and chemometric algorithms were investigated as nondestructive methods for assessing the potassium concentration in fresh lettuce to benefit the CKD patients’ health. Interactance and transmittance measurements were performed and the competencies were compared based on the multivariate methods of partial least-square regression (PLS) and support vector machine regression (SVR). Meanwhile, several preprocessing methods [first- and second-order derivatives in combination with standard normal variate (SNV)] and wavelength selection method of competitive adaptive reweighted sampling (CARS) were applied to eliminate noise and highlight the spectral characteristics. The PLS models yielded better prediction than the SVR models with higher correlation coefficients ([Formula: see text]) and residual predictive deviation (RPD), and lower root-mean-square error of prediction (RMSEP). Excellent prediction of green leaves was obtained by the interactance measurement with [Formula: see text], [Formula: see text][Formula: see text]mg/100[Formula: see text]g, and [Formula: see text]; while the transmittance spectra of petioles provided optimal prediction with [Formula: see text], [Formula: see text][Formula: see text]mg/100[Formula: see text]g, and RPD[Formula: see text]=[Formula: see text]3.34, respectively. Therefore, the results indicated that Vis–SWNIR spectroscopy is capable of intelligently detecting potassium concentration in fresh lettuce to benefit CKD patients around the world in maintaining and enhancing their health.
A decade of development in advanced dielectrics research from JAD’s perspectives
Authors: Bokov Alexei A. , Ye Zuo-Guang , Yao Xi , Wei Xiaoyong , Zhang Nan , Gong Jihui
Published: September 2020

This editorial celebrates the 10th anniversary of Journal of Advanced Dielectrics (JAD) which was launched in January 2011.
What Impact Will Hong Kong Face as an International Financial Center?
Authors: Liang Haiming
Published: September 2020

The National Security Law for Hong Kong has recently implemented by the Chinese National People’s Congress. What effects this action will bring to Hong Kong? The author will judge from the following four critical economic perspectives: stock market, property market, foreign exchange market, and the Sino-US relations. And also, the author will explain why at this moment the National People’s Congress deliberated such a National Security Law for Hong Kong. The conclusion that the implementation of National Security Law could be an outstanding chance for Hong Kong to restart again, if it is not as expected, Hong Kong still has the potential to cope with the challenges and look forward to a bright future will be drawn.
Magnetic Vector Potential: A Review
Authors: Kulkarni Raghavendra G.
Published: September 2020

In this note, we explain in detail the evaluation of the constant appearing in the expression for magnetic vector potential due to an elemental dipole antenna, using a method similar to that adopted for solving Poisson’s equation for static electric potential. The intent of this note is to provide the finer details of the derivations, which are often missing in the textbooks.
Mapping the Geology and Topography of the European Seas (European Marine Observation and Data Network, EMODnet)
Authors: Moses C.A. , Vallius H.
Published: September 2020

Marine engineering geology requires good seabed maps and access to metadata. In 2009 the European Commission established the European Marine Observation and Data Network (EMODnet) programme, which is now in its fourth phase (2019–21). The programme is designed to assemble existing, but fragmented and partly inaccessible, marine data and to create contiguous and publicly available information layers which are interoperable and free of restrictions on use, and which encompass whole marine basins. This collection highlights the use of EMODnet Geology data for better understanding seafloor geology, coastal behaviour and geological events and probabilities. The papers illustrate methodological approaches to harmonizing and representing geological and geohazards information, resultant maps and datasets and their uses, alongside national datasets, for marine spatial planning.

Thematic collection:
This article is part of the Mapping the Geology and Topography of the European Seas (EMODnet) collection available at:
https://www.lyellcollection.org/cc/EMODnet
A Complexity Theoretical Study of Fuzzy
K
-Means
Authors: Blömer Johannes , Brauer Sascha , Bujna Kathrin
Published: September 2020

The fuzzy
K
-means problem is a popular generalization of the well-known
K
-means problem to soft clusterings. In this article, we present the first algorithmic study of the problem going beyond heuristics. Our main result is that, assuming a constant number of clusters, there is a polynomial time approximation scheme for the fuzzy
K
-means problem. As a part of our analysis, we also prove the existence of small coresets for fuzzy
K
-means. At the heart of our proofs are two novel techniques developed to analyze the otherwise notoriously difficult fuzzy
K
-means objective function.
Signals Related to Color in the Early Visual Cortex
Authors: Horwitz Gregory D.
Published: September 2020

Visual images can be described in terms of the illuminants and objects that are causal to the light reaching the eye, the retinal image, its neural representation, or how the image is perceived. Respecting the differences among these distinct levels of description can be challenging but is crucial for a clear understanding of color vision. This article approaches color by reviewing what is known about its neural representation in the early visual cortex, with a brief description of signals in the eye and the thalamus for context. The review focuses on the properties of single neurons and advances the general theme that experimental approaches based on knowledge of feedforward signals have promoted greater understanding of the neural code for color than approaches based on correlating single-unit responses with color perception. New data from area V1 illustrate the strength of the feedforward approach. Future directions for progress in color neurophysiology are discussed: techniques for improved single-neuron characterization, for investigations of neural populations and small circuits, and for the analysis of natural image statistics.
Reaction of Electrogenerated Cyanomethyl Anion with Cyclohexylisocyanate: Synthesis of N-(cyclohexylcarbamoyl)acetamide. An Unexpected Product
Authors: Scarano Vincenzo , Bortolami Martina , Pandolfi Fabiana , Petrucci Rita , Rocco Daniele , Zollo Giuseppe , Feroci Marta
Published: September 2020

The contamination with water of the cathodic ACN-Et4NBF4solution gave us the opportunity to investigate alkyl isocyanate reactivity toward electrogenerated anions. The cathodic reduction of a ACN-Et4NBF4solution led to the formation of both hydroxide and cyanomethyl anions. The reaction of the catholyte with cyclohexylisocyanate led to the exclusive formation of acetamidated product, with no traces of cyanomethylated one. On the contrary, when reacting with benzaldehyde only the cyanomethylated was isolated. Considering that the acetamidated product of benzaldehyde is reported to be unstable (thus its formation cannot be excluded), various experiments were carried out in order to understand the anomalous reactivity of cyclohexylisocyanate. Moreover, computational analysis allowed to state the higher stability of acetamidated product with respect to the cyanomethylated one. The possibility of a concerted reaction, instead of acetamide anion formation prior to the reaction, is still an open question.
Caveolin-1 stabilizes ATP7A, a copper transporter for extracellular SOD, in vascular tissue to maintain endothelial function
Authors: Sudhahar Varadarajan , Okur Mustafa Nazir , O’Bryan John P. , Minshall Richard D. , Fulton David , Ushio-Fukai Masuko , Fukai Tohru
Published: September 2020

Caveolin-1 (Cav-1) is a scaffolding protein and a major component of caveolae/lipid rafts. Previous reports have shown that endothelial dysfunction in Cav-1-deficient (Cav-1−/−) mice is mediated by elevated oxidative stress through endothelial nitric oxide synthase (eNOS) uncoupling and increased NADPH oxidase. Oxidant stress is the net balance of oxidant generation and scavenging, and the role of Cav-1 as a regulator of antioxidant enzymes in vascular tissue is poorly understood. Extracellular SOD (SOD3) is a copper (Cu)-containing enzyme that is secreted from vascular smooth muscle cells/fibroblasts and subsequently binds to the endothelial cells surface, where it scavenges extracellular [Formula: see text] and preserves endothelial function. SOD3 activity is dependent on Cu, supplied by the Cu transporter ATP7A, but whether Cav-1 regulates the ATP7A-SOD3 axis and its role in oxidative stress-mediated vascular dysfunction has not been studied. Here we show that the activity of SOD3, but not SOD1, was significantly decreased in Cav-1−/− vessels, which was rescued by re-expression of Cav-1 or Cu supplementation. Loss of Cav-1 reduced ATP7A protein, but not mRNA, and this was mediated by ubiquitination of ATP7A and proteasomal degradation. ATP7A bound to Cav-1 and was colocalized with SOD3 in caveolae/lipid rafts or perinucleus in vascular tissues or cells. Impaired endothelium-dependent vasorelaxation in Cav-1−/− mice was rescued by gene transfer of SOD3 or by ATP7A-overexpressing transgenic mice. These data reveal an unexpected role of Cav-1 in stabilizing ATP7A protein expression by preventing its ubiquitination and proteasomal degradation, thereby increasing SOD3 activity, which in turn protects against vascular oxidative stress-mediated endothelial dysfunction.
Alveolar CCN1 is associated with mechanical stretch and acute respiratory distress syndrome severity
Authors: Morrell Eric D. , Grazioli Serge , Hung Chi , Kajikawa Osamu , Kosamo Susanna , Stapleton Renee D. , Gharib Sina A. , Amado-Rodríguez Laura , Albaiceta Guillermo , Wurfel Mark M. , Matute-Bello Gustavo
Published: September 2020

The cellular communication network factor 1 (CCN1) is a matricellular protein that can modulate multiple tissue responses, including inflammation and repair. We have previously shown that adenoviral overexpression of Ccn1 is sufficient to cause acute lung injury in mice. We hypothesized that CCN1 is present in the airspaces of lungs during the acute phase of lung injury, and higher concentrations are associated with acute respiratory distress syndrome (ARDS) severity. We tested this hypothesis by measuring 1) CCN1 in bronchoalveolar lavage fluid (BALF) and lung homogenates from mice subjected to ventilation-induced lung injury (VILI), 2) Ccn1 gene expression and protein levels in MLE-12 cells (alveolar epithelial cell line) subjected to mechanical stretch, and 3) CCN1 in BALF from mechanically ventilated humans with and without ARDS. BALF CCN1 concentrations and whole lung CCN1 protein levels were significantly increased in mice with VILI ( n = 6) versus noninjured controls ( n = 6). Ccn1 gene expression and CCN1 protein levels were increased in MLE-12 cells cultured under stretch conditions. Subjects with ARDS ( n = 77) had higher BALF CCN1 levels compared with mechanically ventilated subjects without ARDS ( n = 45) ( P < 0.05). In subjects with ARDS, BALF CCN1 concentrations were associated with higher total protein, sRAGE, and worse [Formula: see text]/[Formula: see text] ratios (all P < 0.05). CCN1 is present in the lungs of mice and humans during the acute inflammatory phase of lung injury, and concentrations are higher in patients with increased markers of severity. Alveolar epithelial cells may be an important source of CCN1 under mechanical stretch conditions.
Carbon monoxide-releasing molecules inhibit the cystic fibrosis transmembrane conductance regulator Cl−channel
Authors: Rodrat Mayuree , Jantarajit Walailak , Ng Demi R. S. , Harvey Bartholomew S. J. , Liu Jia , Wilkinson William J. , Charoenphandhu Narattaphol , Sheppard David N.
Published: September 2020

The gasotransmitter carbon monoxide (CO) regulates fluid and electrolyte movements across epithelial tissues. However, its action on anion channels is incompletely understood. Here, we investigate the direct action of CO on the cystic fibrosis transmembrane conductance regulator (CFTR) by applying CO-releasing molecules (CO-RMs) to the intracellular side of excised inside-out membrane patches from cells heterologously expressing wild-type human CFTR. Addition of increasing concentrations of tricarbonyldichlororuthenium(II) dimer (CORM-2) (1–300 μM) inhibited CFTR channel activity, whereas the control RuCl3(100 μM) was without effect. CORM-2 predominantly inhibited CFTR by decreasing the frequency of channel openings and, hence, open probability ( Po). But, it also reduced current flow through open channels with very fast kinetics, particularly at elevated concentrations. By contrast, the chemically distinct CO-releasing molecule CORM-3 inhibited CFTR by decreasing Powithout altering current flow through open channels. Neither depolarizing the membrane voltage nor raising the ATP concentration on the intracellular side of the membrane affected CFTR inhibition by CORM-2. Interestingly, CFTR inhibition by CORM-2, but not by CFTRinh-172, was prevented by prior enhancement of channel activity by the clinically approved CFTR potentiator ivacaftor. Similarly, when added after CORM-2, ivacaftor completely relieved CFTR inhibition. In conclusion, CORM-2 has complex effects on wild-type human CFTR consistent with allosteric inhibition and open-channel blockade. Inhibition of CFTR by CO-releasing molecules suggests that CO regulates CFTR activity and that the gasotransmitter has tissue-specific effects on epithelial ion transport. The action of ivacaftor on CFTR Cl−channels inhibited by CO potentially expands the drug’s clinical utility.
Effects of sex and menstrual cycle on volume-regulatory responses to 24-h fluid restriction
Authors: Giersch Gabrielle E. W. , Colburn Abigail T. , Morrissey Margaret C. , Butler Cody R. , Pruchnicki Michaela L. , Kavouras Stavros A. , Charkoudian Nisha , Casa Douglas J.
Published: September 2020

Reproductive hormones have significant nonreproductive physiological effects, including altering fluid regulation. Our purpose was to explore the impact of sex and menstrual cycle (MC) phase on volume-regulatory responses to 24-h fluid restriction (24-h FR). Participants (men: n = 12, 20 ± 2 yr; women: n = 10, 20 ± 1 yr) were assigned two randomized and counterbalanced fluid prescriptions [Euhy: euhydrated, urine specific gravity (USG) < 1.020; Dehy: 24-h FR, USG > 1.020]. Men completed both (MEuhy, MDehy), while women completed both in the late-follicular ( days 10–13; FDehy, FEuhy) and midluteal ( days 18–22; LDehy, LEuhy) phases. We measured body mass, plasma and urine osmolality (Posm, Uosm), urine specific gravity (USG), urine color (Ucol), and serum copeptin; 24-h FR yielded mild dehydration without influence of sex or MC ( P > 0.05). Copeptin increased in men following Dehy (pre: 8.2 ± 5.2, post: 15.8 ± 12.6, P = 0.04) but not in women (FDehy pre: 4.3 ± 1.6, post: 10.5 ± 6.9, P = 0.06; LDehy pre: 5.6 ± 3.5, post: 10.4 ± 6.2, P = 0.16). In FDehy, Posm increased following FR (pre: 288 ± 2, post: 292 ± 1, P = 0.03) but not in men (pre: 292 ± 3, post: 293 ± 2, P = 0.46). No MC differences were observed between body mass loss, Posm, Uosm, USG, and copeptin ( P > 0.05). These results suggest that volume-regulatory responses to 24-h FR were present in men but not in women, without apparent effects of the menstrual cycle.
Disruption of GABA or glutamate release from POMC neurons in the adult mouse does not affect metabolic end points
Authors: Rau Andrew R. , King Connie M. , Hentges Shane T.
Published: September 2020

Proopiomelanocortin (POMC) neurons contribute to the regulation of many physiological processes; the majority of which have been attributed to the release of peptides produced from the POMC prohormone such as α-MSH, which plays key roles in food intake and metabolism. However, it is now clear that POMC neurons also release amino acid transmitters that likely contribute to the overall function of POMC cells. Recent work indicates that constitutive deletion of these transmitters can affect metabolic phenotypes, but also that the expression of GABAergic or glutamatergic markers changes throughout development. The goal of the present study was to determine whether the release of glutamate or GABA from POMC neurons in the adult mouse contributes notably to energy balance regulation. Disturbed release of glutamate or GABA specifically from POMC neurons in adult mice was achieved using a tamoxifen-inducible Cre construct ( Pomc-CreERT2) expressed in mice also carrying floxed versions of Slc17a6 (vGlut2) or Gad1 and Gad2, encoding the vesicular glutamate transporter type 2 and GAD67 and GAD65 proteins, respectively. All mice in the experiments received tamoxifen injections, but control mice lacked the tamoxifen-inducible Cre sequence. Body weight was unchanged in Gad1- and Gad2- or vGlut2-deleted female and male mice. Additionally, no significant differences in glucose tolerance or refeeding after an overnight fast were observed. These data collectively suggest that the release of GABA or glutamate from POMC neurons in adult mice does not significantly contribute to the metabolic parameters tested here. In light of prior work, the data also suggest that amino acid transmitter release from POMC cells may contribute to separate functions in the adult versus the developing mouse.
Foreground stimuli and task engagement enhance neuronal adaptation to background noise in the inferior colliculus of macaques
Authors: Rocchi Francesca , Ramachandran Ramnarayan
Published: September 2020

Auditory neuronal responses are influenced by maskers and distractors. However, it is still unclear whether the neuronal sensitivity to the masker stimulus is influenced by task-dependent factors. Our study represents one of the first attempts to investigate how task involvement influences the neural representation of background sounds in the subcortical, midbrain auditory neurons of behaving animals.
Dendritic distributions of L-type Ca2+ and SKL channels in spinal motoneurons: a simulation study
Authors: Mousa Mohamed H. , Elbasiouny Sherif M.
Published: September 2020

Recent experimental findings on L-type Ca2+ channels challenge fundamental assumptions used in interpreting experimental and computational modeling data. Here, we incorporated recent experimental data into an updated, high-fidelity computational model to explain apparent inconsistencies and better elucidate the distributions, expression patterns, and functional roles of L-type Ca2+ and SKL channels. Our results indicate that punctate expression of L-type Ca2+ and SKL channels is a potent mechanism for regulating motoneuron excitability, providing a strong neuroprotective effect.
TLR4/AP-1-Targeted Anti-Inflammatory Intervention Attenuates Insulin Sensitivity and Liver Steatosis
Authors: Hu Xiang , Zhou Jing , Song Sha-sha , Kong Wen , Shi Yan-Chuan , Chen Lu-Lu , Zeng Tian-Shu
Published: September 2020

Insulin resistance has been shown to be the common pathogenesis of many metabolic diseases. Metainflammation is one of the important characteristics of insulin resistance. Macrophage polarization mediates the production and development of metainflammation. Toll-like receptor 4 (TLR4) mediates macrophage activity and is probably the intersection of immunity and metabolism, but the detailed mechanism is probably not fully understood. Activated protein 1 (AP1) signaling pathway is very important in macrophage activation-mediated inflammation. However, it is unclear whether AP1 signaling pathway mediates metabolic inflammation in the liver. We aimed to investigate the effects of macrophage TLR4-AP1 signaling pathway on hepatocyte metabolic inflammation, insulin sensitivity, and lipid deposition, as well as to explore the potential of TLR4-AP1 as new intervention targets of insulin resistance and liver steatosis. TLR4 and AP1 were silenced in the RAW264.7 cells by lentiviral siRNA transfection. In vivo transduction of lentivirus was administered in mice fed with high-fat diet. Insulin sensitivity and inflammation were evaluated in the treated cells or animals. Our results indicated that TLR4/AP-1 siRNA transfection alleviated high-fat diet-induced systemic and hepatic inflammation, obesity, and insulin resistance in mice. Additionally, TLR4/AP-1 siRNA transfection mitigated palmitic acid- (PA-) induced inflammation in RAW264.7 cells and metabolic abnormalities in cocultured AML hepatocytes. Herein, we propose that TLR4-AP1 signaling pathway activation plays a crucial role in high fat- or PA-induced metabolic inflammation and insulin resistance in hepatocytes. Intervention of the TLR4 expression regulates macrophage polarization and metabolic inflammation and further alleviates insulin resistance and lipid deposition in hepatocytes.
Simulation of Nonradiative Energy Transfer in Photosynthetic Systems Using a Quantum Computer
Authors: Guimarães José Diogo , Tavares Carlos , Barbosa Luís Soares , Vasilevskiy Mikhail I.
Published: September 2020

Photosynthesis is an important and complex physical process in nature, whose comprehensive understanding would have many relevant industrial applications, for instance, in the field of energy production. In this paper, we propose a quantum algorithm for the simulation of the excitonic transport of energy, occurring in the first stage of the process of photosynthesis. The algorithm takes in account the quantum and environmental effects (pure dephasing), influencing the quantum transport. We performed quantum simulations of such phenomena, for a proof of concept scenario, in an actual quantum computer, IBM Q, of 5 qubits. We validate the results with the Haken-Ströbl model and discuss the influence of environmental parameters on the efficiency of the energy transport.
The Effects of Open Innovation Platform Knowledge Strategies on Participants: Evolutionary Game Research
Authors: Zhang Mo , Lin Chaoran , Guan Jun , Lin Yan
Published: September 2020

Based on previous research on open innovation and appropriability strategies, using knowledge production functions and evolutionary game methods, this paper describes the process of dynamic cooperation between open innovation platforms and their participants. This paper specifically analyzes the influence of open innovation platform’s knowledge appropriability/knowledge sharing strategies, as well as participants’ exit/nonexit strategy, on the cooperative relationship. Through simulation analysis, this paper draws the following conclusions: first, the knowledge appropriability strategy of the open innovation platform and the participant’s nonexit strategy is an important strategic point of the cooperation between open innovation platforms and participants; second, the amount of knowledge production affects the strategic choices of open innovation platforms, while the knowledge increment affects the strategic choices of participants; third, the appreciation coefficient of complementary assets determines the direction of evolution of the cooperation process.
Certain Subclasses of β-Uniformly q-Starlike and β-Uniformly q-Convex Functions
Authors: AbuJarad Eman S. A. , AbuJarad Mohammed H. A. , Abdeljawad Thabet , Jarad Fahd
Published: September 2020

In this paper, the authors introduced certain subclasses β-uniformly q-starlike and β-uniformly q-convex functions of order α involving the q-derivative operator defined in the open unit disc. Coefficient bounds were also investigated.
The Beneficial Roles of SIRT1 in Neuroinflammation-Related Diseases
Authors: Jiao Fangzhou , Gong Zuojiong
Published: September 2020

Sirtuins are the class III of histone deacetylases whose deacetylate of histones is dependent on nicotinamide adenine dinucleotide (NAD+). Among seven sirtuins, SIRT1 plays a critical role in modulating a wide range of physiological processes, including apoptosis, DNA repair, inflammatory response, metabolism, cancer, and stress. Neuroinflammation is associated with many neurological diseases, including ischemic stroke, bacterial infections, traumatic brain injury, Alzheimer’s disease (AD), and Parkinson’s disease (PD). Recently, numerous studies indicate the protective effects of SIRT1 in neuroinflammation-related diseases. Here, we review the latest progress regarding the anti-inflammatory and neuroprotective effects of SIRT1. First, we introduce the structure, catalytic mechanism, and functions of SIRT1. Next, we discuss the molecular mechanisms of SIRT1 in the regulation of neuroinflammation. Finally, we analyze the mechanisms and effects of SIRT1 in several common neuroinflammation-associated diseases, such as cerebral ischemia, traumatic brain injury, spinal cord injury, AD, and PD. Taken together, this information implies that SIRT1 may serve as a promising therapeutic target for the treatment of neuroinflammation-associated disorders.
Subcritical Phase Separation and Occurrence of Deep-Seated Brines at the NW Caldera Vent Field, Brothers Volcano: Evidence from Fluid Inclusions in Hydrothermal Precipitates
Authors: Diehl Alexander , de Ronde Cornel E. J. , Bach Wolfgang
Published: September 2020

The northwestern caldera wall of Brothers volcano in the southern Kermadec arc features several clusters of hydrothermal venting in a large area that extends from near the caldera floor (~1700 mbsl) almost up to the crater rim (~1300 mbsl). Abundant black smoker-type hydrothermal chimneys and exposed stockwork mineralization in this area provide an excellent archive of hydrothermal processes that form seafloor massive sulfide deposits. Using sulfate precipitates from chimneys and stockwork recently recovered by remotely operated vehicles, we conducted fluid inclusion microthermometry and Sr isotope studies to determine the role of phase separation and mixing between vent fluid and seawater. The variability in the vast majority of fluid inclusion salinities (i.e., 0.1–5.25 wt.% NaCl eq.) and entrapment temperatures of up to 346°C are indicative of phase-separated hydrothermal fluids. Large salinity variations in samples with entrapment temperatures mostly below the boiling temperature for the sample’s depth show that the majority of fluids ascending below the NW Caldera are phase separating in the subsurface and cooling, prior to discharge. In several samples, entrapment temperatures of over 343°C suggest that phase-separating fluids have at least sporadically exited the seafloor at the NW Caldera site. Isobaric-isenthalpic mixing trends between coexisting phase-separated vapors and brines with seawater are consistent with phase-separated fluids at near-seafloor pressures of ~170 bar and suggest that the vast majority of the ascending fluids continue to phase separate to within tens to hundreds of meters below seafloor prior to mixing with seawater. A small subset of the most saline fluid inclusions (up to 18.6 wt.% NaCl eq.) is unlikely formed by near-seafloor phase separation and is considered to be produced either by supercritical phase separation or by the contribution of a magmatic brine from near the magmatic-hydrothermal interface. 87Sr/86Sr values of sulfate samples range from 0.7049 (i.e., near hydrothermal end-member) to 0.7090 (i.e., near seawater) and show that the crystals grew from vapor- and brine-derived fluids in a hydrothermally dominated mixing regime. Our work provides new insights into mineral growth conditions, mixing regimes, and in particular, the extent and character of subseafloor phase separation during the formation of hydrothermal vents and their underlying stockwork in seawater-dominated, arc-related hydrothermal systems.
Evaluation of Temperature-Based Empirical Models and Machine Learning Techniques to Estimate Daily Global Solar Radiation at Biratnagar Airport, Nepal
Authors: Dhakal Sandeep , Gautam Yogesh , Bhattarai Aayush
Published: September 2020

Global solar radiation (GSR) is a critical variable for designing photovoltaic cells, solar furnaces, solar collectors, and other passive solar applications. In Nepal, the high initial cost and subsequent maintenance cost required for the instrument to measure GSR have restricted its applicability all over the country. The current study compares six different temperature-based empirical models, artificial neural network (ANN), and other five different machine learning (ML) models for estimating daily GSR utilizing readily available meteorological data at Biratnagar Airport. Amongst the temperature-based models, the model developed by Fan et al. performs better than the rest with anR2of 0.7498 and RMSE of2.0162 MJm−2d−1. Feed-forward multilayer perceptron (MLP) is utilized to model daily GSR utilizing extraterrestrial solar radiation, sunshine duration, maximum and minimum ambient temperature, precipitation, and relative humidity as inputs. ANN3 performs better than other ANN models with anR2of 0.8446 and RMSE of1.4595 MJm−2d−1. Likewise, stepwise linear regression performs better than other ML models with anR2of 0.8870 and RMSE of1.5143 MJm−2d−1. Thus, the model developed by Fan et al. is recommended to estimate daily GSR in the region where only ambient temperature data are available. Similarly, a more robust ANN3 and stepwise linear regression models are recommended to estimate daily GSR in the region where data about sunshine duration, maximum and minimum ambient temperature, precipitation, and relative humidity are available.
Somatic Mutations Drive Specific, but Reversible, Epigenetic Heterogeneity States in AML
Authors: Li Sheng , Chen Xiaowen , Wang Jiahui , Meydan Cem , Glass Jacob L. , Shih Alan H. , Delwel Ruud , Levine Ross L. , Mason Christopher E. , Melnick Ari M.
Published: September 2020

Epigenetic allele diversity is linked to inferior prognosis in acute myeloid leukemia (AML). However, the source of epiallele heterogeneity in AML is unknown. Herein we analyzed epiallele diversity in a genetically and clinically annotated AML cohort. Notably, AML driver mutations linked to transcription factors and favorable outcome are associated with epigenetic destabilization in a defined set of susceptible loci. In contrast, AML subtypes linked to inferior prognosis manifest greater abundance and highly stochastic epiallele patterning. We report an epiallele outcome classifier supporting the link between epigenetic diversity and treatment failure. Mouse models with TET2 or IDH2 mutations show that epiallele diversity is especially strongly induced by IDH mutations, precedes transformation to AML, and is enhanced by cooperation between somatic mutations. Furthermore, epiallele complexity was partially reversed by epigenetic therapies in AML driven by TET2/IDH2, suggesting that epigenetic therapy might function in part by reducing population complexity and fitness of AMLs.

Significance:

We show for the first time that epigenetic clonality is directly linked to specific mutations and that epigenetic allele diversity precedes and potentially contributes to malignant transformation. Furthermore, epigenetic clonality is reversible with epigenetic therapy agents.

This article is highlighted in the In This Issue feature, p. 1775
Pharmacologic Suppression of B7-H4 Glycosylation Restores Antitumor Immunity in Immune-Cold Breast Cancers
Authors: Song Xinxin , Zhou Zhuan , Li Hongchun , Xue Yifan , Lu Xinghua , Bahar Ivet , Kepp Oliver , Hung Mien-Chie , Kroemer Guido , Wan Yong
Published: September 2020

Despite widespread utilization of immunotherapy, treating immune-cold tumors has proved to be a challenge. Here, we report that expression of the immune checkpoint molecule B7-H4 is prevalent among immune-cold triple-negative breast cancers (TNBC), where its expression inversely correlates with that of PD-L1. Glycosylation of B7-H4 interferes with its interaction/ubiquitination by AMFR, resulting in B7-H4 stabilization. B7-H4 expression inhibits doxorubicin-induced cell death through the suppression of eIF2α phosphorylation required for calreticulin exposure vis-à-vis the cancer cells. NGI-1, which inhibits B7-H4 glycosylation causing its ubiquitination and subsequent degradation, improves the immunogenic properties of cancer cells treated with doxorubicin, enhancing their phagocytosis by dendritic cells and their capacity to elicit CD8+ IFNγ-producing T-cell responses. In preclinical models of TNBC, a triple combination of NGI-1, camsirubicin (a noncardiotoxic doxorubicin analogue) and PD-L1 blockade was effective in reducing tumor growth. Collectively, our findings uncover a strategy for targeting the immunosuppressive molecule B7-H4.

Significance:

This work unravels the regulation of B7-H4 stability by ubiquitination and glycosylation, which affects tumor immunogenicity, particularly regarding immune-cold breast cancers. The inhibition of B7-H4 glycosylation can be favorably combined with immunogenic chemotherapy and PD-L1 blockade to achieve superior immuno-infiltration of cold tumors, as well as improved tumor growth control.

See related commentary by Pearce and Läubli, p. 1789.

This article is highlighted in the In This Issue feature, p. 1775
Hydroxychloroquine Blocks Autophagy and Promotes Apoptosis of the Prostate after Castration in Rats
Authors: Ling Sheng-Tao , Deng Chun-Lei , Huang Li , Yao Qi-Sheng , Liu Cui , Sun Chuan-Tao , Wang Li , Yang Yong , Gong Xiao-Xin , Chen Cong-Bo
Published: September 2020

Autophagy is an important pro-survival mechanism and closely related to apoptosis. The aim of this study was to investigate whether hydroxychloroquine (HCQ) blocks autophagy and promotes apoptosis of the prostate after castration. Methods: Thirty-six male SD rats were randomly divided into 3 groups (n = 12): control group (sham operation), castration group, and HCQ group (castrated and treated with HCQ). On day 7, all mice were executed and prostates were isolated. The morphological changes of prostates were observed by light microscope, and the ultrastructure changes were observed under scanning electron microscope (SEM). The protein expression of Beclin-l, P62, caspase-3, Bcl-2, and Bax was assessed by immunohistochemical analyses. The mRNA expression of microtubule-associated protein light chain 3 (LC3) and autophagy-related gene 5 (Atg5) was detected by RT-PCR. Results: Prostates of castration group shrank remarkably and prostates of HCQ group shrank more remarkably than castration group. Cytolysosomes were visible in the prostates of the castration group under SEM. Immunohistochemistry showed that the protein of Beclin-1 increased in the castration group compared to the control group, while decreased in the HCQ group compared to the castration group. While P62 protein moderately dyed in the control group and weakly dyed in the castration group, it strongly dyed in the HCQ group. Caspase-3 and Bax protein were weakly dyed in the control group but moderately dyed in the castration group and strongly dyed in the HCQ group. The expressions of apoptosis suppressor Bcl-2 were reduced in the castration group and further reduced in the HCQ group compared to the castration group. RT-PCR revealed that the mRNA of LC3 and Atg5 in the castration group increased compared to the control group, while decreased after treated with HCQ. Conclusion: Autophagy increased after castrated in prostates, while decreased after treated with HCQ; all these indicated that HCQ blocked autophagy and then promoted prostate apoptosis of castrated mice.
Characterization of Tissue-Engineered Human Periosteum and Allograft Bone Constructs: The Potential of Periosteum in Bone Regenerative Medicine
Authors: Yu Qing , DiFeo Jacquet Robin , Landis William J.
Published: September 2020

Delayed-union or non-union between a host bone and a graft is problematic in clinical treatment of segmental bone defects in orthopedic cases. Based on a preliminary study of human periosteum allografts from this laboratory, the present work has extensively investigated the use of human cadaveric tissue-engineered periosteum-allograft constructs as an approach to healing such serious orthopedic surgical situations. In this current report, human cadaveric periosteum-wrapped bone allografts and counterpart controls without periosteum were implanted subcutaneously in athymic mice (nu/nu) for 10, 20, and, for the first time, 40 weeks. Specimens were then harvested and assessed by histological and gene expression analyses. Compared to controls, the presence of new bone formation and resorption in periosteum-allograft constructs was indicated in both histology and gene expression results over 40 weeks of implantation. Of several genes also examined for the first time, RANKL and SOST expression levels increased in a statistically significant manner, data suggesting that bone formation and the presence of increasing numbers of osteocytes in bone matrices had increased with time. The tissue-engineering strategy described in this study provides a possible means of improving delayed-union or non-union at the healing sites of segmental bone defects or bone fractures. The potential of periosteum and its resident cells could thereby be utilized effectively in tissue-engineering methods and tissue regenerative medicine.
The Cycle of Abuse: Emotional Availability in Resilient and Non-Resilient Mothers with Early Life Maltreatment
Authors: Mielke Emilia Louisa , Neukel Corinne , Fuchs Anna , Hillmann Karen , Zietlow Anna-Lena , Bertsch Katja , Reck Corinna , Möhler Eva , Herpertz Sabine C.
Published: September 2020

Background: Early life maltreatment (ELM) has a high risk of transmission across generations, known as “the cycle of abuse.” ELM is also an important risk factor for developing mental disorders, and having a mental disorder increases the risk of child abuse. Both the abuse potential in mothers with ELM and in mothers with a history of mental disorders might be associated with a disturbed mother-child interaction. Objective: The current study examined differences in emotional availability between mothers with a history of ELM and previous or current mental disorders (non-resilient), mothers with ELM without mental disorders (resilient), and control mothers without ELM and without mental disorders. Methods: Thirty-three non-resilient mothers, 18 resilient mothers, and 37 control mothers and their 5- to 12-year-old children participated in a standardized mother-child interaction task. Videotaped interactions were rated by three independent, trained raters based on the Emotional Availability Scales (EA Scales) and compared between the groups. Results: The non-resilient mothers and their children showed reduced maternal sensitivity, structuring, non-intrusiveness, non-hostility, responsiveness, and involvement compared to the resilient mothers and their children and the control mothers and their children (p = 0.006, ηp2 = 0.12). No differences on any of the EA Scales were found between resilient mothers and control mothers. Conclusions: These deficits in mother-child interaction in non-resilient mothers might contribute to mechanisms that could explain the cycle of abuse. Interestingly, resilient mothers, who did not develop a mental disorder despite having experienced ELM, did not show these deficits. Thus, prevention programs promoting resilience might be a key to break the cycle of abuse.
Functional Communication Profiles of Children and Youth with Autism: A Roadmap to Therapeutic and Educational Interventions
Authors: Hus Yvette , Segal Osnat
Published: September 2020

Background: Autism spectrum disorder (ASD) entails varied developmental pathways along the entire lifespan, demanding early and ongoing diverse and responsive interventions to children’s needs. This study examined in situ education and development attained by children and youth with ASD in a school with a therapeutic and educational curriculum. Objectives: (1) Construct individual communication profiles in educational and developmental aspects. (2) Examine for associations between variables. (3) Demonstrate the clinical and educational utility of including cognitive-linguistic integrative variables. (4) Showcase how the profiles guide interventions tailored to students’ individual needs. Methods: Functional communication profiles (FCPs) of 21 students, aged 5.0–16.8 years, mostly from bilingual middle-high socioeconomic status families, were constructed with input from their educational and therapeutic staff. Students’ performance was examined with an array of instruments and tasks, including person and clock drawings, false belief, and bouba-kiki metaphor screens. Qualitative and quantitative analyses were performed to uncover associations, weaknesses, and strengths. Results: The profiles revealed associations between cognitive, linguistic, social, and educational abilities, indicating that some abilities from different domains tend to co-occur. Conclusions: Including cognitive linguistic integrative variables was a novelty that revealed additional aspects of the children’s abilities. Staff feedback confirmed the utility of FCPs in providing “a roadmap” to needed individual and common curriculum adjustments.
The Level of Public Knowledge about Inflammatory Bowel Disease in Christchurch, New Zealand
Authors: Vernon-Roberts Angharad , Gearry Richard B. , Day Andrew S.
Published: September 2020

Introduction: There is a high degree of perceived stigma among adults with inflammatory bowel disease (IBD), with up to 84% considering a social stereotype against them due to their condition. This may negatively impact their treatment adherence and quality of life, as well as practical issues such as gaining urgent access to public bathroom facilities. It has been demonstrated that higher public knowledge levels can reduce public stigma, yet little is known about the general level of understanding of IBD in the community. A study was performed to ascertain the public knowledge levels of IBD in Christchurch, New Zealand, using a validated assessment tool. Objectives: The aims of this study were to implement a validated knowledge survey (IBD-KID2) among members of the general public in Christchurch, New Zealand, and to assess the level of understanding about IBD. Methods: Recruitment took place at a Health Research and Education showcase event at the University of Otago (Christchurch), which is a free event open to members of the public. All people over the age of 8 years were invited to participate. Demographic information was collected and the disease-specific knowledge assessment survey IBD-KID2 completed by all participants consenting to the research. Results: One hundred people consented to the study, and the mean age 39.9 was years (SD 20, range 12–82 years). Of these 100 participants, 71 were female and 71 had a post-secondary education. Twelve participants had a family history of IBD. The mean IBD-KID2 score was 8.7 (SD 2.9), equal to a percentage total score of 58%. No independent variable was found to be significantly associated with IBD-KID2 scores. The frequency of correct answers showed knowledge deficiencies in the areas of nutrition, treatment, growth, and the cause of IBD. Conclusions: This study highlighted knowledge deficiencies among members of the general public in Christchurch, New Zealand. These topics may be addressed with awareness campaigns in order to maximise community support for adults and children with IBD.
Pharmacokinetics and Safety of Intravenous, Intravesical, Rectal, Transdermal, and Vaginal Melatonin in Healthy Female Volunteers: A Cross-Over Study
Authors: Zetner Dennis , Andersen Lars Peter Kloster , Alder Rasmus , Jessen Majken Lyhne , Tolstrup Anders , Rosenberg Jacob
Published: September 2020

Introduction: We aimed to investigate the pharmacokinetic properties and safety of melatonin administered by alternative routes of administration. Methods: This study employed a cross-over design in healthy female volunteers. Twenty-five milligrams of melatonin was administered intravenously, intravesically, rectally, transdermally, and vaginally. Blood samples were collected at specified time points up to 24 h following intravenous, intravesical, rectal, and vaginal administration, and up to 48 h following transdermal administration. Plasma melatonin concentrations were determined by radioimmunoassay. Sedation was evaluated by a simple reaction-time test, and sleepiness was assessed by the Karolinska Sleepiness Scale. Adverse events were registered for each route of administration. Results: Ten participants were included. We documented a mean (SD) time to maximal concentration of 51 (29) min for intravesical, 24 (20) min for rectal, 21 (8) h for transdermal, and 147 (56) min for vaginal administration. The mean (SD) elimination half-life was 47 (6) min for intravenous, 58 (7) min for intravesical, 60 (18) min for rectal, 14.6 (11.1) h for transdermal, and 129 (17) min for vaginal administration. The mean (SD) bioavailability was 3.6 (1.9)% for intravesical, 36.0 (28.6)% for rectal, 10.0 (5.7)% for transdermal, and 97.8 (31.7)% for vaginal administration. No significant changes in reaction times were observed following administration of melatonin by any of the administration routes. Increased tiredness was documented following transdermal administration only. No serious adverse effects were documented. Conclusion: Rectally and vaginally administered melatonin may serve as relevant alternatives to standard oral melatonin therapy. Transdermal delivery of melatonin displayed an extended absorption and can be applied if prolonged effects are intended. Intravesical administration displayed, as expected, a very limited bioavailability. Melatonin administered by these routes of administration was safe.