bluuebunny/crossref_metadata_2025_split huggingface dataset:
HERC2 deficiency activates C-RAF/MKK3/p38 signalling pathway altering the cellular response to oxidative stress
Authors: Sala-Gaston Joan , Pedrazza Leonardo , Ramirez Juanma , Martinez-Martinez Arturo , Rawlins Lettie E , Baple Emma L , Crosby Andrew H , Mayor Ugo , Ventura Francesc , Rosa Jose Luis 
Published: May 2022

Abstract
HERC2 gene encodes an E3 ubiquitin ligase involved in several cellular processes by regulating the ubiquitylation of different protein substrates. Biallelic pathogenic sequence variants in the HERC2 gene are associated with HERC2 Angelman-like syndrome. In pathogenic HERC2 variants, complete absence or marked reduction in HERC2 protein levels are observed. The most common pathological variant, c.1781C>T (p.Pro594Leu), encodes an unstable HERC2 protein. A better understanding of how pathologic HERC2 variants affect intracellular signalling may aid definition of potential new therapies for these disorders. For this purpose, we studied patient-derived cells with the HERC2 Pro594Leu variant. We observed alteration of mitogen-activated protein kinase signalling pathways, reflected by increased levels of C-RAF protein and p38 phosphorylation. HERC2 knockdown experiments reproduced the same effects in other human and mouse cells. Moreover, we demonstrated that HERC2 and RAF proteins form molecular complexes, pull-down and proteomic experiments showed that HERC2 regulates C-RAF ubiquitylation and we found out that the p38 activation due to HERC2 depletion occurs in a RAF/MKK3-dependent manner. The displayed cellular response was that patient-derived and other human cells with HERC2 deficiency showed higher resistance to oxidative stress with an increase in the master regulator of the antioxidant response NRF2 and its target genes. This resistance was independent of p53 and abolished by RAF or p38 inhibitors. Altogether these findings identify the activation of C-RAF/MKK3/p38 signalling pathway in HERC2 Angelman-like syndrome and highlight the inhibition of RAF activity as a potential therapeutic option for individuals affected with these rare diseases.
Direct Determination of the Topological Thermal Conductance
via Local Power Measurement
Authors: Melcer Ron , Konyzheva Sofia , Heiblum Moty , Umansky Vladimir 
Published: May 2022

Abstract
Thermal conductance measurements, sensitive to charge and chargeless energy flow, are evolving as an essential measurement technique in Condensed Matter Physics. For two-dimensional topological insulators, the measurements of the thermal Hall conductance, κxyT, and the longitudinal one κxxT, are crucial for the understanding of their underlying topological order. Such measurements are thus far lacking, even in the extensively studied quantum Hall effect (QHE) regime. Here, we report a new local power measurement technique that reveals the topological thermal Hall conductance (not the ubiquitous two-terminal one). For example, we find κxy~0 of the challenging ν = 2/3 particle-hole conjugated state. This is in contrast to the two-terminal measurement, which provides a non-universal value that depends on the extent of thermal equilibration between the counter-propagating edge modes. Moreover, we use this technique to study the power carried by the current fluctuations in a partitioned edge mode with an out-of-equilibrium distribution.
Role of air-sea heat flux on the transformation of Atlantic Water as it encircles the Nordic Seas
Authors: Huang Jie , Pickart Robert , Chen Zhuomin , Huang Rui Xin 
Published: May 2022

Abstract
The warm-to-cold densification of Atlantic Water (AW) around the perimeter of the Nordic Seas is a critical component of the Atlantic Meridional Overturning Circulation (AMOC). However, it remains unclear how ongoing changes in air-sea heat flux impact this transformation. Here we use observational data, and a one-dimensional mixing model following the flow, to quantify the role of air-sea heat flux on the cooling of AW. We focus on the Norwegian Atlantic Slope Current (NASC) and Front Current (NAFC), where the primary transformation of AW was found to occur. Our results demonstrate that air-sea heat flux accounts almost entirely for the net cooling of AW along the NAFC, while lateral transfer of heat appears to dominate the temperature change along the NASC. Such differing impacts of air-sea heat fluxes, which explain the long-term change in the cooling of AW since the 1990s, need to be considered when understanding the AMOC variability.
Response of different varieties of maize to nitrogen stress and diagnosis of leaf nitrogen using hyperspectral data
Authors: Lu Yanli , Chao Yaru , song Guipei , Nie Caie , Cui Zhiyue , Wang Lei 
Published: May 2022

Abstract
Spectral technology is theoretically effective in diagnosing N stress in maize (Zea mays L.), but its application is affected by varietal differences. In this study, the responses to N stress, leaf N spectral diagnostic models and the differences between two maize varieties were analyzed. Variety Jiyu 5817 exhibited a greater response to different N stresses in the 12-leaf stage (V12), while Zhengdan 958 displayed a greater response in the silking stage (R1). Correlation analysis showed that the spectral bands sensitive to the leaf N content were 548–556 nm and 706–721 nm at the V12 stage in Jiyu 5817 and 760–1142 nm at the R1 stage in Zhengdan 958. Compared with those of the model established without considering the differences in varieties, the coefficient of determination (R2) and root mean square error (RMSE) of the N spectral diagnosis model established according to each variety were improved by 10.6% and 29.2%, respectively. It was concluded that the V12 stage of Jiyu 5817 and the R1 stage of Zhengdan 958 were the best diagnostic stages and were more sensitive to N stress, which can further guide fertilization decision-making in precision fertilization.
Combining network pharmacology and bioinformatics analysis to identify the molecular mechanisms of UDCA in the treatment of carotid atherosclerosis
Authors: Xu Xiankai , Zhang Yueqi , Lu Xiaojin , Shi Baolin 
Published: May 2022

Abstract
Ursodeoxycholic acid (UDCA) can be used to prevent atherosclerosis. However, the molecular mechanism of UDCA on carotid atherosclerosis is not known. A combination of bioinformatics, network pharmacology, and molecular docking was used to unravel the potential molecular mechanisms of UDCA in alleviating carotid atherosclerosis. The results of weighted gene co-expression network analysis (WGCNA) combined with differential expression analysis were used to screen for potent targets in carotid atherosclerosis. A typical target for UDCA in the treatment of carotid atherosclerosis was obtained by network pharmacology, and a protein-protein interaction network was constructed. Nine core targets were obtained using four algorithms of the cytoHubba plugin of Cytoscape 3.9.0, and molecular docking was completed using Autodock Vina 1.1.2. GO, and KEGG enrichment pathway analysis was performed based on the Metascape platform. The results showed that CD4, PTPRC, CCL5, MMP9, CD38, CASP1, CCR2, EGFR, and SYK were the targets of action of UDCA in the treatment of carotid atherosclerosis. The enrichment analysis results showed that these targets were significantly enriched in pathways associated with inflammation. In conclusion, this study highlights some of the molecular mechanisms of UDCA in the treatment of carotid atherosclerosis and provides a theoretical basis for future studies.
Association between hepatic steatosis and fibrosis with measures of insulin sensitivity in patients with severe obesity and type 2 diabetes - a cross-sectional study
Authors: Seeberg Kathrine Aglen , Hofsø Dag , Borgeraas Heidi , Grimnes John Olav , Fatima Farhat , Seeberg Lars Thomas , Kvan Nils Petter , Svanevik Marius , Hertel Jens Kristoffer , Hjelmesæth Jøran 
Published: May 2022

Abstract
BackgroundObesity, non-alcoholic fatty liver disease (NAFLD) and insulin resistance are three pathological conditions highly correlated, but this relationship is not fully elucidated. Hence, we aimed to assess the association of hepatic steatosis and fibrosis with different measures of insulin sensitivity in patients with severe obesity and type 2 diabetes mellitus (T2DM).MethodsA cross-sectional study (Oseberg trial) including patients with T2DM referred for bariatric surgery at Vestfold Hospital Trust, Norway. Magnetic resonance imaging (MRI) and the enhanced liver fibrosis (ELF) test was used for estimation of liver fat fraction (LFF) and degree of fibrosis, respectively. Oral and intravenous glucose tolerance tests were applied for estimation of insulin sensitivity (HOMA2S, Matsuda ISI and MinMod SI).ResultsA total of 100 patients (mean [SD] age 47.5 [9.7] years, 65% women, BMI 42.0 [5.3] kg/m² and 98% with metabolic syndrome) were included in the analyses. The mean (SD) LFF in the total population was 19.1 (11.5), and the mean (SD) ELF score was 8.46 (0.84), a value representing moderate fibrosis. LFF was inversely associated with HOMA2S and Matsuda ISI, and both measures were significantly higher in the no or low-grade steatosis group compared with the medium-to-high grade steatosis group (mean difference [95% CI] 5.9 [2.2-9.6]%, Cohen’s d=0.75), and (0.7 [0.3-1.1], Cohen’s d=0.80, respectively). There was no association between LFF, as a categorical or continuous variable, and MinMod SI. The proportions of patients with none to mild fibrosis, moderate fibrosis and severe fibrosis were 14, 78 and 6%, respectively, and there were no significant associations between level of fibrosis and measures of insulin sensitivity. ConclusionsPatients with morbid obesity and T2DM demonstrated high levels of liver fat fraction, and we showed that hepatic steatosis, but not the degree of liver fibrosis, was associated with different measures of insulin sensitivity in patients with severe obesity and T2DM. Further, our results might indicate that the LFF is primarily associated with hepatic, and not peripheral insulin sensitivity. To improve the diagnosis of NAFLD and the prediction of its progression, more studies are needed to reveal the pathological mechanistic pathways involved in NAFLD and insulin sensitivity.Trial RegistrationClinicalTrials.gov:NCT01778738
Spectral properties of a high quantum yield, novel aminocoumarin with a vicinal hydroxyl group
Authors: Knoor Leah H. , Hoogewerf Liam P. , Jonker Isaac B. , Doty Elizabeth A. , Du Laney George R. , Blankespoor Ronald L. , Muyskens Mark A. 
Published: May 2022

Abstract
Knightletin is a novel, high quantum-yield, substituted coumarin in the group of fluorescent aminocoumarins. The molecule reveals the influence of a hydroxyl group on the aminocoumarin structure through its absorbance-fluorescence properties and interaction with several solvents. The substitution on the benzene ring of the coumarin affects electronic states, the molecular dipole moment and hydrogen bonding between vicinal groups as well as hydrogen bonding with solvents. This report describes the synthesis of knightletin, its absorbance-fluorescence characteristics in three solvents of varying polarity, and insights on its conformation from density functional theory modeling. The quantum yield of 0.81 in methanol is remarkable. The modeling indicates a ground state geometry with a pyramidal NH2 group interacting with the OH in an NH-donor hydrogen bond and predicts spectroscopic characteristics consistent with the experimental observations.
Pirates Swarm Search Algorithm: A Meta-Heuristic Search Algorithm for optimization problems
Authors: Siahkali Milad Abolhasani , Mirvaziri Hamid , Bahrololoum Abbas 
Published: May 2022

Abstract
In this study, we have suggested a meta-heuristic algorithm based on swarm intelligence for single-objective optimization problems. Our inspiration comes from historical and behavioral fashions of pirates at 1600s and 1700s which also is known as the golden age of piracy. They navigate in the oceans to find treasures and we search the problem space to find a better solution. Triangle trade is the search space and each pirate ship is a search agent. A bunch of well-known benchmark functions are used to run some qualitative, quantitative and statistically tests to see the outcome of the suggested algorithm. Obtained results shows that the algorithm is able to explore and exploit in search space as expected and also has the ability of improving the average fitness of population and improving the best so far solution. At the end; results of suggested algorithm comparing to other well-known ones such as Particle Swarm Optimization, Gravity Search Algorithm, Ranking Genetic Algorithm and Sparrow search algorithm shows that it is able to outperform these algorithms in most of the studied cases.
The effect of lightweight aggregate on drying shrinkage and properties of one-part alkali activated slag concrete
Authors: Kadkhodaei Razieh , Behfarnia Kiachehr , Shahidi Marjan 
Published: May 2022

Abstract
In the present study, the result of slag grade, dosage of activator and aggregate combination on the compressive strength and drying shrinkage of one-part alkali-activated slag concrete was considered. Also, water curing and plastic cover curing were selected to investigate the effect of curing condition on drying shrinkage and compressive strength of this type of concrete. Two aggregate combinations, one containing lightweight fine (LAF) and normal weight coarse (NAC) aggregates and one other containing both lightweight fine and coarse aggregates, were considered for making the lightweight concrete and conducting the experimental tests. Compressive strength of the specimens were measured at 7, 28 and 90 days, as well as drying shrinkage strain up to 180 days. According to the results, in most of the mixtures, slump and setting time decreased with increasing slag and activator content, while compressive strength and drying shrinkage increased. Examination of curing condition of one-part lightweight alkali-activated slag concrete showed that drying shrinkage increased and compressive strength decreased with plastic cover curing at later age.
Quantifying the Missing Half of Daily NOx Emissions over South, Southeast and East Asia
Authors: Liu Jian , Cohen Jason 
Published: May 2022

Abstract

Rapid urbanization and broad use of biomass burning have led to significant changes in NOx emissions across South, Southeast, and East Asia, frequently occurring on day-to-day time scales and over areas not identified by existing emissions databases. This work computes NOx emissions using remotely sensed NO2 and a model-free mass-conserving inverse method, resulting respectively in 61kt/day and 40kt/day from biomass burning in Northern and Southern Continental Southeast Asia, and 14.3kt/day and 3.7kt/day from urbanization in China and Eastern South Asia. This is a net increase of more than double the 55.7kt/day existing inventories. This method offers three additional constraints: NO2 accounts for 22%-90% of NOx emissions, NOx has an in-situ lifetime of 4.3hours-24hours, and NOx transports up to 480km, all of which are larger than chemical transport modeling studies, yet still consistent with theory. This result provides quantitative support for mitigation efforts targeting specific extreme events, processes, or geographies.
High in-vivo Stability and First-in-human Experience with [18F]AlF-RESCA-MIRC213: A 18F-Labeled Nanobody as PET Radiotracer for Diagnosis of HER2-Positive Cancers
Authors: Qin xue , Guo Xiaoyi , Liu Tianyu , Li Liqiang , Zhou Nina , Ma Xiaopan , Meng Xiangxi , Liu Jiayue , Zhu Hua , Jia Bing , Yang Zhi 
Published: May 2022

Abstract
Purpose [18F]AlF-RESCA was introduced as a core particularly useful for 18F-labeling of heat-sensitive biomolecules. However, no translational studies have been reported up to now. Herein, we reported the first-in-human evaluation of an 18F-labeled anti-HER2 nanobody MIRC213 as a PET radiotracer for imaging HER2-positive cancers.Methods In this study, [18F]AlF-RESCA-MIRC213 was prepared at room temperature. Small-animal PET/CT and bio-distribution were performed on HER2-positive subcutaneous xenografts. Six breast cancer patients (3 HER2-positive and 3 HER2-negative patients) were included, and PET/CT images were acquired at 2 h and 4 h after injection of 222 ± 18.5 MBq of [18F]AlF-RESCA-MIRC213. All patients underwent [18F]-FDG PET/CT within a week for comparison purpose. Bio-distribution and dosimetry were calculated. Standardized uptake values (SUV) were measured in tumors and normal organs.Results [18F]AlF-RESCA-MIRC213 was prepared within 20 min at room temperature with the radiochemical yield of 50.48 ± 7.6% and radiochemical purity of > 98% (n > 10). The 2 h cellular uptake of [18F]AlF-RESCA-MIRC213 in NCI-N87 cells was 11.22 ± 0.60 %IA/105 cells. Its binding affinity Kd value was determined to be 1.23 ± 0.58 nM using SK-OV-3 cells. After 2 h injection, the xenografted SK-OV-3 tumors could be readily detected by [18F]AlF-RESCA-MIRC213 PET with SUVmax of 4.73 ± 1.18 ID%/g and 1.70 ± 0.13 ID%/g for the blocking group (p < 0.05). No significant radioactivity was seen in the bone in tumor-bearing animals. After approved by ethics committee (No.2021KT108). First-in-human PET translational study was conducted. In six all patients, there was no adverse reactions during study. The uptake of [18F]AlF-RESCA-MIRC213 was mainly in lacrimal gland, parotid gland, submandibular gland, thyroid gland, gallbladder, kidneys, liver, and intestine. There was no significant radioactivity accumulation in the bone of cancer patients. [18F]AlF-RESCA-MIRC213 had significantly higher tumor uptake in HER2-positive lesions than that in HER2-negative lesions (SUVmax of 3.62 ± 1.56 vs. 1.41 ± 0.41, p = 0.0012) at 2 h post-injection. Kidneys received the highest radiation dose of 2.17×10-2 mGy/MBq, and the effective dose was 1.76×10-2 mSv/MBq. Conclusions [18F]AlF-RESCA-MIRC213 could be prepared with high radiolabeling yield under mild conditions. [18F]AlF-RESCA-MIRC213 has relatively high stability both in vitro and in vivo. The results from clinical transformation suggest that [18F]AlF-RESCA-MIRC213 PET/CT is a safe procedure with favorable pharmacokinetics and dosimetry profile, and it is a promising new PET radiotracer for noninvasive diagnosis of HER2-positive cancers.
Investigation of optimal convolutional neural network conditions for thyroid ultrasound image analysis
Authors: Lee Joon-Hyop , Kim Young-Gon , Ahn Youngbin , Park Seyeon , Kong Hyoun-Joong , Choi June Young , Kim Kwangsoon , Nam Inn-Chul , Lee Myung-Chul , Masuoka Hiroo , Miyauchi Akira , Kim Sungwan , Kim Young A , Choe Eun Kyung , Chai Young Jun 
Published: May 2022

Abstract
Neural network models have been used to analyze thyroid ultrasound (US) images and stratify malignancy risk of the thyroid nodules. We investigated the optimal neural network condition for thyroid US image analysis. We compared scratch and transfer learning models, performed stress tests in 10% increments, and compared the performance of three threshold values. All validation results indicated superiority of the transfer learning model over the scratch model. Stress test indicated that training the algorithm using 3902 images (70%) resulted in a performance which was similar to the full dataset (5575). Threshold 0.3 yielded high sensitivity (1% false negative) and low specificity (72% false positive), while 0.7 gave low sensitivity (22% false negative) and high specificity (23% false positive). Here we showed that transfer learning was more effective than scratch learning, about 3900 images were minimally required to demonstrate an acceptable performance, and algorithm performance can be customized according to the population characteristics by adjusting threshold value.
Genome-wide Computational Analysis of DIR Genes inSolanum lycopersicum
Authors: Saddique Muhammad Abu Bakar 
Published: May 2022

Abstract
Background: Extensive Dirigent proteins impart a key role in the development of organic products in plants. They confer conformational influence on processes that lack stereoselectivity and regioselectivity through processes that are mostly understood. Dirrigent proteins are required to produce lignans, a unique and widely distributed family of plant secondary metabolites with intriguing pharmacological characteristics and potential use in plant development as well. The dirigent (DIR) proteins, which are implicated in the process of lignification, also protect plants from environmental stresses including Biotic and Abiotic. Nevertheless, there is no research have been done so far on the DIR proteins in Solanum lycopersicum. This study provides a detailed information of DIRs protein in the in tomato.Results:The Conserved Domain analysis, Phylogeny, Evolutionary Adaptation, cis-acting Elements, Proteomic analysis, Transmembrane Potential Analysis, Sequence Identity and Similarity Analysis, gene assembly, genomic localization, duplication of gene analysis, and evolutionary linkage of all 31 potential dirigent genes (SlDIRs) were revealed in this investigation. Conclusion:This research provides an in - depth and comprehensive explanation of the detailed molecular process and structural characterization of SlDIR genes in the genome of Solanum lycopersicum, laying the groundwork for future plant genetic engineering and crop development exploration. This study will aid future research on the DIR gene family and give helpful information for enabling appropriate DIRs genes in higher plants.
Complementary descriptions of Euler characteristics of simplicial incidence pseudographs
Authors: ZHANG Zhiguo , WANG Yanying , ZHANG Conglei , ZHAO Suqian 
Published: May 2022

Abstract

We introduce incidence pseudographs and simplicial incidence pseudographs with a poset topology, which provide discrete representation of continuous objects and helpful tools in digital image analysis. We prove closed or open sub-pseudograph matching theorems in a regular incidence pseudograph. By embedding a finite simplicial incidence pseudograph into an optimal simplicial incidence pseudograph, we obtain several formulae which give complementary descriptions of Euler characteristics of finite simplicial incidence pseudographs and its relative pseudographs. These descriptions provide new methods of calculating Euler characteristics by boundary counts rather than all nodes and make it possible, in some cases, to simplify the complexity of computing Euler characteristic of finite simplicial incidence pseudographs.
GCC countries strategic options in a global transition to zero-net emissions
Authors: Babonneau Frédéric , Badran Ahmed , Haurie Alain , Schenckery Maxime , Vielle Marc 
Published: May 2022

Abstract
Using a multi-level perspective approach combined with top-down macroeconomic models, we analyse the situation of the GCC countries in the perspective of a global transition to zero-net emissions before the end of the century. Based on these analyses we propose strategic and political options for these oil and gas exporting countries. We show that it would be unwise for GCC member states to adopt an obstruc-tionist strategy in international climate negotiations. On the contrary, these countries could be proactive in developing international emissions trading market and exploiting negative emissions obtained from CO2 direct reduction technologies, in particular Direct Air Capture with CO2 sequestration, and thus contribute to a global net-zero-emissions regime in which clean fossil fuels are still used.