bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptional Activation of Biosynthetic Gene Clusters in Filamentous Fungi
Authors: Mózsik László , Iacovelli Riccardo , Bovenberg Roel A. L. , Driessen Arnold J. M.
Published: July 2022

Filamentous fungi are highly productive cell factories, many of which are industrial producers of enzymes, organic acids, and secondary metabolites. The increasing number of sequenced fungal genomes revealed a vast and unexplored biosynthetic potential in the form of transcriptionally silent secondary metabolite biosynthetic gene clusters (BGCs). Various strategies have been carried out to explore and mine this untapped source of bioactive molecules, and with the advent of synthetic biology, novel applications, and tools have been developed for filamentous fungi. Here we summarize approaches aiming for the expression of endogenous or exogenous natural product BGCs, including synthetic transcription factors, assembly of artificial transcription units, gene cluster refactoring, fungal shuttle vectors, and platform strains.
Simazine Enhances Dark Fermentative H2 Production by Unicellular Halotolerant Cyanobacterium Aphanothece halophytica
Authors: Pansook Sunisa , Incharoensakdi Aran , Phunpruch Saranya
Published: July 2022

The halotolerant cyanobacterium Aphanothece halophytica is a potential H2 producer that induces H2 evolution under nitrogen deprivation. H2 is mainly produced via the catabolism of stored glycogen under dark anaerobic condition. H2 evolution is catalyzed by O2-sensitive bidirectional hydrogenase. The aim of this study was to improve H2 production by A. halophytica using various kinds of inhibitors. Among all types of inhibitors, simazine efficiently promoted the highest H2 production under dark conditions. High simazine concentration and long-term incubation resulted in a decrease in cell and chlorophyll concentrations. The optimal simazine concentration for H2 production by A. halophytica was 25 µM. Simazine inhibited photosynthetic O2 evolution but promoted dark respiration, resulting in a decrease in O2 level. Hence, the bidirectional hydrogenase activity and H2 production was increased. A. halophytica showed the highest H2 production rate at 58.88 ± 0.22 µmol H2 g−1 dry weight h−1 and H2 accumulation at 356.21 ± 6.04 μmol H2 g−1 dry weight after treatment with 25 µM simazine under dark anaerobic condition for 2 and 24 h, respectively. This study demonstrates the potential of simazine for the enhancement of dark fermentative H2 production by A. halophytica.
Multi-Omics Uncover Neonatal Cecal Cell Development Potentials
Authors: Chen Liang , Meng Qingshi , Li Shen , Jiang Yue , Zhang Cong , Tang Shanlong , Zhong Ruqing , Tang Xiangfang , Zhang Sheng , Feng Xiaohui , Zhao Yong , Zhang Hongfu
Published: July 2022

Although, the cecum plays vital roles in absorption of water, electrolytes, and other small molecules, and harbors trillions of commensal bacteria to shape large intestine immune functions, it is unknown the cecum development potentials at single cell level during the very crucial neonatal developmental period. Using singe cell RNA-seq and proteomics, we have characterized six major types of cecal cells: undifferentiated cells; immune cells (Ims); cecumocytes (CCs); goblet, Paneth like cells (PLCs), and enteroendocrine cells (EECs) with specific markers. CCs mature with a gradual decrease in proportion of cells; however, Ims develop with a continuing increase in proportion of cells. Meanwhile, goblet and EEC cells reduced in proportion of cells from do to d14 or d21; PLCs increased in proportion of cells from d0 to d7 then decreased at d14 and d21. The cells exhibit specific development and maturation trends controlled by transcriptional factors, ligand-receptor pairs, and other factors. As piglets grow, cecal content and mucosal microbial diversity increases dramatically with population of beneficial microbiota, such as lactobacillus. Moreover, cecal mucosal-associated and cecal content microbiota are positively correlated and both show significant correlation with different types of cecal cells and plasma metabolites. This is the first presentation of neonatal cecal cell development and maturation naturally at single cell level with transcript, protein, microbiota and metabolism perspectives. Furthermore, this study provides an important tool for the determination of novel interventions in cecal drug delivery and metabolism studies.
Epigenetic Regulation of Phenotypic Sexual Plasticity Inducing Skewed Sex Ratio in Zebrafish
Authors: Hosseini Shahrbanou , Trakooljul Nares , Hirschfeld Marc , Wimmers Klaus , Simianer Henner , Tetens Jens , Sharifi Ahmad Reza , Brenig Bertram
Published: July 2022

The plasticity of sexual phenotype in response to environmental conditions results in biased sex ratios, and their variation has an effect on population dynamics. Epigenetic modifications can modulate sex ratio variation in species, where sex is determined by genetic and environmental factors. However, the role of epigenetic mechanisms underlying skewed sex ratios is far from being clear and is still an object of debate in evolutionary developmental biology. In this study, we used zebrafish as a model animal to investigate the effect of DNA methylation on sex ratio variation in sex-biased families in response to environmental temperature. Two sex-biased families with a significant difference in sex ratio were selected for genome-wide DNA methylation analysis using reduced representation bisulfite sequencing (RRBS). The results showed significant genome-wide methylation differences between male-biased and female-biased families, with a greater number of methylated CpG sites in testes than ovaries. Likewise, pronounced differences between testes and ovaries were identified within both families, where the male-biased family exhibited a higher number of methylated sites than the female-biased family. The effect of temperature showed more methylated positions in the high incubation temperature than the control temperature. We found differential methylation of many reproduction-related genes (e.g., sox9a, nr5a2, lhx8a, gata4) and genes involved in epigenetic mechanisms (e.g., dnmt3bb.1, dimt1l, hdac11, h1m) in both families. We conclude that epigenetic modifications can influence the sex ratio variation in zebrafish families and may generate skewed sex ratios, which could have a negative consequence for population fitness in species with genotype-environment interaction sex-determining system under rapid environmental changes.
Toll-Like Receptor 4 Signaling in the Trabecular Meshwork
Authors: Mzyk Philip , Hernandez Humberto , Le Thanh , Ramirez Jose Ricardo , McDowell Colleen M.
Published: July 2022

Primary open-angle glaucoma is one of the leading causes of blindness worldwide. With limited therapeutics targeting the pathogenesis at the trabecular meshwork (TM), there is a great need for identifying potential new targets. Recent evidence has implicated Toll-like receptor 4 (TLR4) and it is signaling pathway in augmenting the effects of transforming growth factor beta-2 (TGFβ2) and downstream extracellular matrix production. In this review, we examine the role of TLR4 signaling in the trabecular meshwork and the interplay between endogenous activators of TLR4 (damage-associated molecular patterns (DAMPs)), extracellular matrix (ECM), and the effect on intraocular pressure
Precise Purity Analysis of High-Purity Lanthanum Oxide by Gravimetric Analysis Assisted With Trace Elemental Analysis by Inductively Coupled Plasma Mass Spectrometry
Authors: Miura Tsutomu , Wada Ayaka
Published: July 2022

Gravimetric analysis was used to determine the purity of high-purity La2O3 by stepwise conversions of the weighing forms. In this study, lanthanum in the sample was converted to La oxalate, La2O3, and La2(SO4)3 to evaluate the stoichiometry of the weighing forms for accurate gravimetric determination. The losses of La in the filtrate, the washing solution of the precipitate, and the mechanical loss of La during filtration were measured using inductively coupled plasma optical emission spectrometry. The weighing forms were evaluated by comparing the observed mass ratio with the theoretical value at each conversion step. The final converted La2(SO4)3 was consistent with the theoretical composition based on the observed mass ratio of La2(SO4)3/La2O3. Additionally, impurities in the high-purity La2O3 were determined by inductively coupled plasma tandem mass spectrometry. The purity of the original La2O3 sample was precisely determined to be 99.977 % ± 0.057% (mass fraction as La2O3; the value following “±” indicates the expanded uncertainty with a coverage factor k = 2.18) by a combination of the gravimetric analysis using the precipitation from the homogeneous solution method and verification of the weighing forms for La compound.
Convergence of Electronic Structure Properties in Ionic Oxides Within a Fragment Approach
Authors: Larsson Ernst D. , Veryazov Valera
Published: July 2022

Embedded-cluster models of crystalline solids are important to allow accurate wave function methods to be applicable to solids. The ab-initio model potential method, in which the crystal is divided into three different fragments, one quantum fragment, one ab-initio model potential fragment and one point-charge fragment, has historically been shown to be a viable tool for describing the electronic structure in ionic solids. The optimal size of these regions is, of course, individual for each crystal. In this study we analyzed the convergence of the electronic structure properties with respect to an increase of the size of the quantum part and the layer of potentials. MgO crystal and Ni: MgO were used for this purpose as examples of an ideal crystal and a crystal with a point defect. We demonstrated that with an increase of the cluster size, the electron density in the inner part of the cluster becomes very similar to the electron density in the periodic model. Clusters, embedded into a layer of model potential and electrostatic field, are a good alternative to periodic description.
Performance of a Three-Dimensional Electrochemical Reactor (3DER) on Bisphenol A Degradation
Authors: Ren Xu , Song Kai , Zhang Qiaoyun , Xu Linghan , Yu Zhuyi , Tang Peixin , Pan Zhicheng
Published: July 2022

This study constructed a three-dimensional electrochemical reactor (3DER) using meshed stainless steel sheets and titanic magnetite particles (TMP) to investigate bisphenol A (BPA) degradation through the synergistic action of electrical current and TMP. We examined some TMP characteristics, such as particle size, specific surface areas, X-ray diffraction, surface imaging, elemental constituents, and electrical resistivity. It was found that TMP was a micron-level material with excellent electrical conductivity, and it could be regarded as a magnetite-based material comprising Fe(II) and Fe(III). The single-factor experiment determined the optimal conditions for BPA removal in 3DER, specifically by introducing 200 ml of BPA-simulated wastewater (10 mg L−1) into 3DER. At the initial pH of 9.00, current and electrodes gap of 300 mA and 15 mm, respectively, and adding 1 ml of 0.5 M potassium peroxymonosulfate and 1 g TMP, > 98% of BPA was removed after 55 min of electrochemical reaction. In addition, liquid chromatography–mass spectrometry identified the intermediates formed during the BPA treatment, showing two possible pathways for BPA degradation. The final degradation intermediates were chain organics with simple molecular structures. This research provided an understanding of the potential application of 3DER for BPA removal in water.
Metagenome Analysis of the Bacterial Characteristics in Invasive Klebsiella Pneumoniae Liver Abscesses
Authors: Zhang Zhijie , Wang Hairui , Guo Yawen , Liu Zhaoyu , Chang Zhihui
Published: July 2022

Background

Klebsiella pneumoniae liver abscess (KPLA) combined with extrahepatic migratory infection (EMI) is defined as invasive KPLA (IKPLA) and is associated with a poor prognosis. The mechanism of IKPLA formation is yet to be elucidated. In this study, metagenomic sequencing was used to compare the bacterial characteristics between IKPLA and KPLA to explore the underlying mechanism of invasiveness.

Methods

Clinical details, imaging, and microbial features were retrospectively evaluated by medical record review. Metagenomic sequencing was performed on the pus samples of liver abscesses whose culture results were indicative of monomicrobial Klebsiella pneumoniae (K. pneumoniae). Bacterial diversity and composition in IKPLA and KPLA were comparatively analyzed, and the key pathways and genes that may affect invasiveness were further explored.

Results

Sixteen patients were included in this study. Five patients with EMI were included in the IKPLA group, and the other eleven patients without EMI were assigned to the KPLA group. There was no statistical difference in the hypermucoviscous phenotype and serotype of K. pneumoniae between the two groups. The bacterial diversity of IKPLA was lower than that of KPLA. The abundant taxa in the IKPLA group were primarily species of unclassified Enterobacteriaceae and K. pneumoniae. The KPLA group had a high abundance of the genera Tetrasphaera and Leuconostoc. Metabolic pathway genes represented most of the enriched genes in IKPLA. Fourteen pathogenic genes with significant differences in abundance were identified between the two groups, including ybtS, fepC, phoQ, acrB, fimK, magA, entC, arnT, iucA, fepG, oqxB, entA, tonB, and entF (p < 0.001).

Conclusion

The diversity and bacterial composition of IKPLA were significantly different from those of KPLA. Microbiological changes in the abscess, activation of the related metabolic pathways, and the pathogenic gene expression may constitute a novel mechanism that regulates the invasiveness of KPLA.
XCast: A python climate forecasting toolkit
Authors: Hall Kyle Joseph Chen , Acharya Nachiketa
Published: July 2022

Climate forecasts, both experimental and operational, are often made by calibrating Global Climate Model (GCM) outputs with observed climate variables using statistical and machine learning models. Often, machine learning techniques are applied to gridded data independently at each gridpoint. However, the implementation of these gridpoint-wise operations is a significant barrier to entry to climate data science. Unfortunately, there is a significant disconnect between the Python data science ecosystem and the gridded earth data ecosystem. Traditional Python data science tools are not designed to be used with gridded datasets, like those commonly used in climate forecasting. Heavy data preprocessing is needed: gridded data must be aggregated, reshaped, or reduced in dimensionality in order to fit the strict formatting requirements of Python's data science tools. Efficiently implementing this gridpoint-wise workflow is a time-consuming logistical burden which presents a high barrier to entry to earth data science. A set of high-performance, easy-to-use Python climate forecasting tools is needed to bridge the gap between Python's data science ecosystem and its gridded earth data ecosystem. XCast, an Xarray-based climate forecasting Python library developed by the authors, bridges this gap. XCast wraps underlying two-dimensional data science methods, like those of Scikit-Learn, with data structures that allow them to be applied to each gridpoint independently. XCast uses high-performance computing libraries to efficiently parallelize the gridpoint-wise application of data science utilities and make Python's traditional data science toolkits compatible with multidimensional gridded data. XCast also implements a diverse set of climate forecasting tools including traditional statistical methods, state-of-the-art machine learning approaches, preprocessing functionality (regridding, rescaling, smoothing), and postprocessing modules (cross validation, forecast verification, visualization). These tools are useful for producing and analyzing both experimental and operational climate forecasts. In this study, we describe the development of XCast, and present in-depth technical details on how XCast brings highly parallelized gridpoint-wise versions of traditional Python data science tools into Python's gridded earth data ecosystem. We also demonstrate a case study where XCast was used to generate experimental real-time deterministic and probabilistic forecasts for South Asian Summer Monsoon Rainfall in 2022 using different machine learning-based multi-model ensembles.
Low α2-Plasmin Inhibitor Antigen Levels on Admission Are Associated With More Severe Stroke and Unfavorable Outcomes in Acute Ischemic Stroke Patients Treated With Intravenous Thrombolysis
Authors: Székely Edina Gabriella , Orbán-Kálmándi Rita , Szegedi István , Katona Éva , Baráth Barbara , Czuriga-Kovács Katalin Réka , Lóczi Linda , Vasas Nikolett , Fekete István , Fekete Klára , Berényi Ervin , Oláh László , Csiba László , Bagoly Zsuzsa
Published: July 2022

Background

Intravenous administration of recombinant tissue plasminogen activator (rt-PA) fails to succeed in a subset of acute ischemic stroke (AIS) patients, while in approximately 6–8% of cases intracerebral hemorrhage (ICH) occurs as side effect.

Objective

Here, we aimed to investigate α2-plasmin inhibitor (α2-PI) levels during thrombolysis and to find out whether they predict therapy outcomes in AIS patients.

Patients/Methods

In this prospective, observational study, blood samples of 421 AIS patients, all undergoing i.v. thrombolysis by rt-PA within 4.5 h of their symptom onset, were taken before and 24 h after thrombolysis. In a subset of patients (n = 131), blood was also obtained immediately post-lysis. α2-PI activity and antigen levels were measured by chromogenic assay and an in-house ELISA detecting all forms of α2-PI. α2-PI Arg6Trp polymorphism was identified in all patients. Stroke severity was determined by NIHSS on admission and day 7. Therapy-associated ICH was classified according to ECASSII. Long-term outcomes were defined at 3 months post-event by the modified Rankin Scale (mRS).

Results

Median α2-PI activity and antigen levels showed a significant drop immediately post-lysis and increased to subnormal levels at 24 h post-event. Admission α2-PI levels showed a significant negative stepwise association with stroke severity. Patients with favorable long-term outcomes (mRS 0–1) had significantly higher admission α2-PI antigen levels (median:61.6 [IQR:55.9–70.5] mg/L) as compared to patients with poor outcomes (mRS 2–5: median:59.7 [IQR:54.5–69.1] and mRS 6: median:56.0 [IQR:48.5–61.0] mg/L, p < 0.001). In a Kaplan–Meier survival analysis, patients with an α2-PI antigen in the highest quartile on admission showed significantly better long-term survival as compared to those with α2-PI antigen in the lowest quartile (HR: 4.54; 95%CI:1.92–10.8, p < 0.001); however, in a multivariate analysis, a low admission α2-PI antigen did not prove to be an independent risk factor of poor long-term outcomes. In patients with therapy-related ICH (n = 34), admission α2-PI antigen levels were significantly, but only marginally, lower as compared to those without hemorrhage.

Conclusions

Low α2-PI antigen levels on admission were associated with more severe strokes and poor long-term outcomes in this cohort. Our results suggest that in case of more severe strokes, α2-PI may be involved in the limited efficacy of rt-PA thrombolysis.
Evidence for reciprocal network interactions between injured hearts and cancer
Authors: Guler Melisa N. , Tscheiller Nathalie M. , Sabater-Molina Maria , Gimeno Juan R. , Nebigil Canan G.
Published: July 2022

Heart failure (HF) and cancer are responsible for 50% of all deaths in middle-aged people. These diseases are tightly linked, which is supported by recent epidemiological studies and case control studies, demonstrating that HF patients have a higher risk to develop cancer such as lung and breast cancer. For HF patients, a one-size-fits-all clinical management strategy is not effective and patient management represents a major economical and clinical burden. Anti-cancer treatments-mediated cardiotoxicity, leading to HF have been extensively studied. However, recent studies showed that even before the initiation of cancer therapy, cancer patients presented impairments in the cardiovascular functions and exercise capacity. Thus, the optimal cardioprotective and surveillance strategies should be applied to cancer patients with pre-existing HF. Recently, preclinical studies addressed the hypothesis that there is bilateral interaction between cardiac injury and cancer development. Understanding of molecular mechanisms of HF-cancer interaction can define the profiles of bilateral signaling networks, and identify the disease-specific biomarkers and possibly therapeutic targets. Here we discuss the shared pathological events, and some treatments of cancer- and HF-mediated risk incidence. Finally, we address the evidences on bilateral connection between cardiac injury (HF and early cardiac remodeling) and cancer through secreted factors (secretoms).
Quality of reporting in AI cardiac MRI segmentation studies – A systematic review and recommendations for future studies
Authors: Alabed Samer , Maiter Ahmed , Salehi Mahan , Mahmood Aqeeb , Daniel Sonali , Jenkins Sam , Goodlad Marcus , Sharkey Michael , Mamalakis Michail , Rakocevic Vera , Dwivedi Krit , Assadi Hosamadin , Wild Jim M. , Lu Haiping , O’Regan Declan P. , van der Geest Rob J. , Garg Pankaj , Swift Andrew J.
Published: July 2022

Background

There has been a rapid increase in the number of Artificial Intelligence (AI) studies of cardiac MRI (CMR) segmentation aiming to automate image analysis. However, advancement and clinical translation in this field depend on researchers presenting their work in a transparent and reproducible manner. This systematic review aimed to evaluate the quality of reporting in AI studies involving CMR segmentation.

Methods

MEDLINE and EMBASE were searched for AI CMR segmentation studies in April 2022. Any fully automated AI method for segmentation of cardiac chambers, myocardium or scar on CMR was considered for inclusion. For each study, compliance with the Checklist for Artificial Intelligence in Medical Imaging (CLAIM) was assessed. The CLAIM criteria were grouped into study, dataset, model and performance description domains.

Results

209 studies published between 2012 and 2022 were included in the analysis. Studies were mainly published in technical journals (58%), with the majority (57%) published since 2019. Studies were from 37 different countries, with most from China (26%), the United States (18%) and the United Kingdom (11%). Short axis CMR images were most frequently used (70%), with the left ventricle the most commonly segmented cardiac structure (49%). Median compliance of studies with CLAIM was 67% (IQR 59–73%). Median compliance was highest for the model description domain (100%, IQR 80–100%) and lower for the study (71%, IQR 63–86%), dataset (63%, IQR 50–67%) and performance (60%, IQR 50–70%) description domains.

Conclusion

This systematic review highlights important gaps in the literature of CMR studies using AI. We identified key items missing—most strikingly poor description of patients included in the training and validation of AI models and inadequate model failure analysis—that limit the transparency, reproducibility and hence validity of published AI studies. This review may support closer adherence to established frameworks for reporting standards and presents recommendations for improving the quality of reporting in this field.

Systematic Review Registration

[www.crd.york.ac.uk/prospero/], identifier [CRD42022279214].
Marine Paleoproductivity From the Last Glacial Maximum to the Holocene in the Southwestern Atlantic: A Coccolithophore Assemblage and Geochemical Proxy Perspective
Authors: Pedrão Guilherme A. , Hirama Marcus V. , Tomazella Mariana O. , Albuquerque Ana Luiza S. , Chiessi Cristiano M. , Costa Karen B. , Toledo Felipe A. L.
Published: July 2022

In this study, we associated the variations in coccolithophore assemblages with the variability in major elements (Fe, Ca, and Ti) from the continental slope of the western South Atlantic by investigating two marine sediment cores (GL-824 and GL-1109) to reconstruct paleoceanographic and paleoproductivity changes from the Last Glacial Maximum (LGM) to the present. Terrigenous-supply proxies (Fe/Ca and Ti/Ca) showed a very similar pattern compared with the fine-fraction sediments, higher values throughout the LGM and lower values during the Holocene. The dominant species in the coccolithophore assemblages were Emiliania huxleyi, Gephyrocapsa spp., and Florisphaera profunda, with these species together representing between 82 and 99% of the total assemblage. Additionally, we used three other subordinate species (Umbellosphaera ssp., Rhabdosphaera spp., and Syracosphaera spp.) for paleoproductivity reconstruction. The estimates of primary production using F. profunda and Gephyrocapsa spp. exhibited a similar trend, with higher productivity values during the LGM. Paleoproductivity decreased toward the Late Holocene. Analyzing these results, we observed that the oscillation of relative sea level was the process that controlled paleoproductivity, primarily by changing the position of the main flow of the Brazil Current (BC). During periods of high sea level (low Fe/Ca and Ti/Ca), the BC transported warm and oligotrophic water to the upper slope, preventing any nutrient transport from deeper layers or coastal water. In contrast, during low sea-level periods (high Fe/Ca and Ti/Ca), the offshore displacement of the BC allowed the presence of coastal water (more nutrient-rich than tropical water) and the erosion of the exposed shelf that along with a more enhanced fluvial input provided more nutrients to the photic zone, thus enhancing primary productivity.
Stuck in the Wild—The Hydrology of the Teklanika River (Alaska) in the Summer of 1992
Authors: Hill David F. , Aragon Christina
Published: July 2022

In late spring of 1992, Christopher McCandless crossed the Teklanika River, west of Healy, Alaska (United States). His summer has been well documented both in the book and the movie ‘Into the Wild.’ In early summer of 1992, he attempted to cross back over the river, but was stopped by high waters and he died later that summer. This paper investigates the hydrologic conditions of the Teklanika River watershed. We consider both climatological conditions and also conditions during the summer of 1992. We run process-based snowpack and runoff models in order to estimate the river hydrograph at the point of Mr. McCandless’ attempted crossing. Our results demonstrate that the Teklanika river is very flashy during the summer, responding rapidly to strong episodic rainfall events. The main snowmelt signal occurred in mid-to-late May, after Mr. McCandless’ first crossing and before his second attempt. The specific day of his attempted re-crossing corresponded to a large runoff event, driven by rainfall. We conclude that Mr. McCandless had unfortunate timing and that, had he tried to cross a day or two earlier or later, the outcome may have been different. This paper is also an opportunity to explore the hydrologic compromises that must be made when trying to study ungauged, or poorly gauged, areas. There is a spectrum of choices regarding input datasets and methodological simplifications and the correct location on that spectrum will depend on the particular watershed the objectives and expectations of the study.
Luminescence Sensitivity of Quartz From Rocks Under in situ Chemical Weathering Conditions
Authors: Cao Zheng , Jiang Yingying , Xu Jiandong , Zhao Juxing , Zhao Cheng
Published: July 2022

In provenance investigation of Quaternary sediments, quartz luminescence sensitivity (QLS) has been employed as a technique. The weathering and influence on the earliest signs of luminescence sensitivity of sedimentary quartz require more consideration. In this study, the QLS properties of eight samples of Permian biotite monzogranite from a borehole in the southern tropics of China are investigated. The degree of chemical weathering does not correspond with the QLS values of samples that have undergone varying degrees ofin situweathering. We hypothesize that the variation of the irradiation field during thein situchemical weathering process may affect the QLS, but not considerably within 200 ka. In addition, we discovered that quartz from the same source undergoes varying degrees ofin situchemical weathering, but has a constant response to irradiation-bleaching cycles (IBCs). The presence of variances in the thermal activation curves (TACs) of the same rock body indicates that further research is required to apply TAC as a provenance indicator.
PEGylated Recombinant Human Growth Hormone Jintrolong® Exhibits Good Long-Term Safety in Cynomolgus Monkeys and Human Pediatric Growth Hormone Deficiency Patients
Authors: Wu Wei , Zhou Juan , Wu Chuandong , Zhou Qian , Li Xiaoyu , Zhang Yanlin , Zuo Conglin , Yin Jun , Hou Ling , Wang Shuyang , Gao Hongyang , Luo Tianhong , Jin Lei , Zhong Enhong , Wang Yingwu , Luo Xiaoping
Published: July 2022

Jintrolong® is a long-acting PEGylated recombinant human growth hormone (PEG-rhGH) developed for weekly injection in patients with pediatric growth hormone deficiency (PGHD). Although PEG modification of therapeutic proteins is generally considered safe, concerns persist about the potential for adverse vacuolation in tissues with long-term exposure to PEG-included therapies, particularly in children. We assessed the safety of Jintrolong® in cynomolgus monkeys with an examination of vacuolation in the brain choroid plexus (CP) and reported long-term clinical safety data obtained from children with PGHD. The toxicity of Jintrolong® was assessed following the 52-week administration with doses at 0.3, 1, or 3 mg/kg/week. The levels of vacuolation of CP in animals were dose-dependent and at least partially reversible after a 104- or 157-week recovery period. Vacuolation in the CP epithelium did not lead to obvious subcellular structural or cell functional abnormalities. Compared with the clinical dose of 0.2 mg/kg/week Jintrolong® in PGHD patients, exposure in monkeys under NOAEL 3 mg/kg/week exhibited safety margins greater than 120.5, the predicted minimum dose to induce vacuolation in monkeys is equivalent to 1.29 mg/kg/week in humans, which is 6.45-fold higher than the clinical dose. The safety data acquired in clinical trials for Jintrolong® were also analyzed, which included phase III (360 patients), phase IV (3,000 patients) of 26-week treatment, and a follow-up study with treatment lasting for 3 years. There was no statistically significant difference in the incidence of adverse reactions between the Jintrolong® group and the daily rhGH control group (no PEG), and no new adverse effects (AE) were observed in the Jintrolong® group at the clinical therapeutic dose of 0.2 mg/kg/week.
Data-Driven Short-Term Voltage Stability Assessment Considering Sample Imbalance and Overlapping
Authors: Zhu Ruijin , Wang Dafei , Su Zhilin
Published: July 2022

In recent years, data-driven methods have shown great potential for the practical application of short-term voltage stability (STVS) assessment. However, most existing research works overlook the problem of sample imbalance and overlap in STVS assessment. To tackle this issue, a novel self-adaptive data-driven method for real-time STVS is proposed in this study. First, min-redundancy and max-relevance (mRMR) is employed for feature selection to reduce the computational burden. Taking the key features as inputs, a cascaded LightGBM (CasLightGBM) model is constructed to mine STVS informatization. Based on the LightGBM and cascaded structure, CasLightGBM can enhance the assessment accuracy without sacrificing the assessment earliness. Then, focal loss (FL) is embedded into both offline and online phases of the CasLightGBM to mitigate the loss of accuracy caused by sample imbalance and overlapping, thus deriving a highly comprehensive and reliable classification model for real-time STVS assessment. Extensive numerical tests are conducted on the IEEE 118-bus system, and the simulation results demonstrate that the proposed method outperforms traditional algorithms and exhibits favorable robustness to measurement noise.
Communicationless Adaptive Control Strategy for Effective Reactive Power Sharing in a Grid-Independent AC Microgrid
Authors: D Suchitra , D Anitha , S George Fernandez , Alaas Zuhair Muhammed , Ali Ziad M. , Abdel Aleem Shady H. E.
Published: July 2022

The microgrid (MG) ensures a reliable power supply as it can work in a grid-independent mode. This mode requires a coordinated control strategy among distributed generators (DGs). One major challenge in a grid-independent MG is the reactive power-sharing issue. The reactive power sharing is affected by the mismatch of feeder impedance and private loads. This study thus proposed a proportionate reactive power-sharing scheme in a grid-independent mode by mathematically computing the equivalent impedance without the need for communication lines. A mathematical formula is derived to compute the equivalent impedance as a function of the total power output of DG and the power fed to the feeder. Based on the computed equivalent impedance, the virtual impedance is added to each feeder. The inclusion of virtual impedance in each line compensates the mismatch in feeder impedance and private loads providing accurate reactive power sharing among DGs. MATLAB Simulink was used to verify the effectiveness of the proposed control strategy. Furthermore, the real-time OPAL-RT simulator was used to verify the results.
Wind Speed Interval Prediction Based on the Hybrid Ensemble Model With Biased Convex Cost Function
Authors: Long Huan , Geng Runhao , Zhang Chen
Published: July 2022

This study proposes a combination interval prediction based hybrid ensemble (CIPE) model for short-term wind speed prediction. The combination interval prediction (CIP) model employs the extreme learning machine (ELM) as the predictor with a biased convex cost function. To relieve the heavy burden of the hyper-parameter selection of the biased convex cost function, a hybrid ensemble technique is developed by combining the bagging and stacking ensemble methods. Multiple CIP models with random hyper-parameters are first trained based on the sub-datasets generated by the bootstrap resampling. The linear regression (LR) is utilized as the meta model to aggregate the CIP models. By introducing the binary variables, the LR meta model can be formulated as a mixed integer programming (MIP) problem. With the benefit of the biased convex cost function and ensemble technique, the high computational efficiency and stable performance of the proposed prediction model is guaranteed simultaneously. Multi-step ahead 10-min wind speed interval prediction is conducted based on actual wind farm data. Comprehensive experiments are carried out to verify the superiority of the proposed interval prediction model.
Study of the Effect of China’s Emissions Trading Scheme on Promoting Regional Industrial Carbon Emission Reduction
Authors: Feng Rui , Lin Peina , Hou Chenxue , Jia Shuaishuai
Published: July 2022

The creation of carbon emissions trading markets is a core policy for realizing China’s twin objectives of reaching a peak in CO2 emissions before 2030 and achieving carbon neutrality by 2060. Given that industry is the most significant energy consumer and CO2 emitter, it is imperative to implement carbon reducing initiatives to attain these goals. Following the implementation of carbon emissions trading pilots in China, this article theoretically analyzes the mechanisms of action and paths of influence of China’s carbon trading policies on regional industrial carbon emissions. Then, regarding the trading rights policies launched in 2013 as a quasi-natural experiment, this study uses provincial panel data and industry data from 2003 to 2016 to empirically test the effect of carbon trading on industrial emissions by employing the difference-in-difference and difference-in-difference-in-difference methods. It was found that carbon emissions trading can promote a reduction in regional industrial carbon emissions, achieving the dual aims of reducing total emissions and reducing emission intensity. The reduction effect occurs after the implementation of the carbon trading market policies. The carbon trading policies reduced regional industrial emissions by optimizing regional industrial structures and increasing regional technological innovation. It was also found that reductions in carbon emissions were heterogeneous among industries. These research conclusions will help to improve the top-level design of China’s industrial energy saving and carbon reduction policies and to achieve low-carbon and green industrial development.
Resource and Environment Constraints and Promotion Strategies of Rural Vitality: An Empirical Analysis of Rural Revitalization Model Towns
Authors: Yang Zhiheng , Liu Tiantian , Shen Nengneng , Guan Mei , Zheng Yanfeng , Jiang Huailong
Published: July 2022

In response to the challenges of rural chronic poverty caused by insufficient self-development ability, establishing a development model conducive to poverty alleviation and stimulating rural development potential have become core tasks of deepening rural revitalization. Resources and environment play an important role in invigorating rural vitality. Based on symbiosis theory, we have constructed a new conceptual framework to analyze dynamic performance of rural areas in population, industry and facilities, and dynamic constraints in resources and environment. Using an improved TOPSIS evaluation method and panel Tobit model, we have selected 106 rural revitalization model towns from Shandong province as research samples, empirically analyzed the performance of rural vitality and its resources and environment constraints, explored differences of rural vitality performance and vitality constraints of different village types, and put forward long-term mechanisms to maintain rural vitality. Results show that from 2012 to 2019, rural vitality of rural revitalization model towns in Shandong province was gradually improved, among which industrial development had contributed the most; agriculture-tourism towns are more dynamic than industrialized agriculture towns and characteristic agricultural towns. Through analysis of resources and environment constraints on rural vitality, we found that resources had the greatest impact on rural vitality, and the short-term constraints of total amount restriction on rural vitality were not obvious; binding force of ecological environment on rural vitality changed from weak to strong and increasingly became the bottleneck restricting rural vitality. We have further proposed a long-term mechanism to stimulate rural vitality from the aspects of promoting comprehensive utilization of rural residential land, strengthening concept of ecological priority and green development, taking the road of urban–rural integration, and promoting integrated development of rural industries.
Synchrony and Stability in Trophic Metacommunities: When Top Predators Navigate in a Heterogeneous World
Authors: Quévreux Pierre , Loreau Michel
Published: July 2022

Ecosystem stability strongly depends on spatial aspects since localized perturbations spread across an entire region through species dispersal. Assessing the synchrony of the response of connected populations is fundamental to understand stability at different scales because if populations fluctuate asynchronously, the risk of their simultaneous extinction is low, thus reducing the species' regional extinction risk. Here, we consider a metacommunity model consisting of two food chains connected by dispersal and we review the various mechanisms governing the transmission of small perturbations affecting populations in the vicinity of equilibrium. First, we describe how perturbations propagate vertically (i.e., within food chains through trophic interactions) and horizontally (i.e., between food chains through dispersal) in metacommunities. Then, we discuss the mechanisms susceptible to alter synchrony patterns such as density-depend dispersal or spatial heterogeneity. Density-dependent dispersal, which is the influence of prey or predator abundance on dispersal, has a major impact because the species with the highest coefficient of variation of biomass governs the dispersal rate of the dispersing species and determines the synchrony of its populations, thus bypassing the classic vertical transmission of perturbations. Spatial heterogeneity, which is a disparity between patches of the attack rate of predators on prey in our model, alters the vertical transmission of perturbations in each patch, thus making synchrony dependent on which patch is perturbed. Finally, by combining our understanding of the impact of each of these mechanisms on synchrony, we are able to full explain the response of realistic metacommunities such as the model developed by Rooney et al. (2006). By disentangling the main mechanisms governing synchrony, our metacommunity model provides a broad insight into the consequences of spacial aspects on food web stability.
Gene Editing to Tackle Facioscapulohumeral Muscular Dystrophy
Authors: Mariot Virginie , Dumonceaux Julie
Published: July 2022

Facioscapulohumeral dystrophy (FSHD) is a skeletal muscle disease caused by the aberrant expression of the DUX4 gene in the muscle tissue. To date, different therapeutic approaches have been proposed, targeting DUX4 at the DNA, RNA or protein levels. The recent development of the clustered regularly interspaced short-palindromic repeat (CRISPR) based technology opened new avenues of research, and FSHD is no exception. For the first time, a cure for genetic muscular diseases can be considered. Here, we describe CRISPR-based strategies that are currently being investigated for FSHD. The different approaches include the epigenome editing targeting the DUX4 gene and its promoter, gene editing targeting the polyadenylation of DUX4 using TALEN, CRISPR/cas9 or adenine base editing and the CRISPR-Cas9 genome editing for SMCHD1. We also discuss challenges facing the development of these gene editing based therapeutics.
Application of the 3C Method to Study the Developmental Genes in Drosophila Larvae
Authors: Bylino Oleg V. , Ibragimov Airat N. , Digilio Filomena Anna , Giordano Ennio , Shidlovskii Yulii V.
Published: July 2022

A transition from one developmental stage to another is accompanied by activation of developmental programs and corresponding gene ensembles. Changes in the spatial conformation of the corresponding loci are associated with this activation and can be investigated with the help of the Chromosome Conformation Capture (3C) methodology. Application of 3C to specific developmental stages is a sophisticated task. Here, we describe the use of the 3C method to study the spatial organization of developmental loci in Drosophila larvae. We critically analyzed the existing protocols and offered our own solutions and the optimized protocol to overcome limitations. To demonstrate the efficiency of our procedure, we studied the spatial organization of the developmental locus Dad in 3rd instar Drosophila larvae. Differences in locus conformation were found between embryonic cells and living wild-type larvae. We also observed the establishment of novel regulatory interactions in the presence of an adjacent transgene upon activation of its expression in larvae. Our work fills the gap in the application of the 3C method to Drosophila larvae and provides a useful guide for establishing 3C on an animal model.
CircRNA ITCH: Insight Into Its Role and Clinical Application Prospect in Tumor and Non-Tumor Diseases
Authors: Liu Tong , Huang Tao , Shang Mei , Han Gang
Published: July 2022

CircRNA E3 ubiquitin protein ligase (ITCH) (circRNA ITCH, circ-ITCH), a stable closed-loop RNA derived from the 20q11.22 region of chromosome 20, is a new circRNA discovered in the cytoplasm in recent decades. Studies have shown that it does not encode proteins, but regulates proteins expression at different levels. It is down-regulated in tumor diseases and is involved in a number of biological activities, including inhibiting cell proliferation, migration, invasion, and promoting apoptosis. It can also alter disease progression in non-tumor disease by affecting the cell cycle, inflammatory response, and critical proteins. Circ-ITCH also holds a lot of promise in terms of tumor and non-tumor clinical diagnosis, prognosis, and targeted therapy. As a result, in order to aid clinical research in the hunt for a new strategy for diagnosing and treating human diseases, this study describes the mechanism of circ-ITCH as well as its clinical implications.
The Utility of Small Fishes for the Genetic Study of Human Age-Related Disorders
Authors: Dohi Eisuke , Matsui Hideaki
Published: July 2022

Animal models have been used to model human diseases, and among them, small fishes have been highlighted for their usefulness in various ways, such as the low cost of maintenance, ease of genetic modification, small size for easy handling, and strength in imaging studies due to their relative transparency. Recently, the use of turquoise killifish, Nothobranchius furzeri, which is known to exhibit various aging phenotypes in a short period, has attracted attention in research on aging and age-related diseases. However, when using animal models, it is important to keep their genetic background and interspecies differences in mind for translating them into human diseases. In this article, we obtained the gene symbols of protein-coding genes of turquoise killifish, medaka, zebrafish, and humans from NCBI datasets and extracted common shared genes among four species to explore the potential of interspecies translational research and to apply small fish models for human age-related disorders. Common shared protein-coding genes were analyzed with the Reactome Pathway Database to determine the coverage of these genes in each pathway in humans. We applied common shared genes to the Orphanet database to establish a list of human diseases that contain common shared genes among the four species. As examples, the senescence-related pathways and some pathways of human age-related diseases, such as Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, nonalcoholic fatty liver disease, progeria, hepatocellular carcinoma, and renal cell carcinoma, were extracted from the curated pathway and disease list to discuss the further utility of fish models for human age-related disorders.