bluuebunny/crossref_metadata_2025 huggingface dataset:
A Comparative Study of the Optimum Tuned Mass Damper for High-rise Structures Considering Soil-structure Interaction
Authors: Kaveh Ali , Rezazadeh Ardebili Shaylin
Published: June 2021

The present paper focuses on the optimum design of tuned mass damper (TMD) as a device for control of the structures. The optimum free vibration parameters such as period and damping ratio depend on the soil condition. For this reason, the seven meta-heuristic algorithms namely colliding bodies optimization (CBO), enhanced colliding bodies optimization (ECBO), water strider algorithm (WSA), dynamic water strider algorithm (DWSA), ray optimization (RO) algorithm, teaching-learning-based optimization (TLBO) algorithm and plasma generation optimization (PGO) are used to find the TMD parameters considering soil-structure interaction (SSI) effects. These optimization methods are applied to a benchmark 40-story structure. For comparison, the obtained results of these algorithms are compared. The capability and robustness of the algorithms are investigated through the benchmark problem. The results are shown that the soil type affects the optimum values of the TMD parameters, especially for the soft soil. To evaluate the performance of the obtained parameters in both the frequency and time domains, time history displacement and acceleration transfer function of the top story of the structure are calculated for the model with and without considering the SSI effects.
大规模风电接入对继电保护的影响与对策探究
Authors: 何 鼎
Published: June 2021

文中首先对风电基地继电保护配置与风电并网故障特征简要概述，并分析风电并网存在的问题，然后从继电保护配置、电力系统、电力运行、电路保护、风电脱网、两侧保护等方面分析大规模风电接入对继电保护的影响，最后从明确继电保护影响因素、明确风电接入故障、加强风电操控管理、加强集群线路继电保护、加强并网电路重合闸的优化等方面阐述大规模风电接入继电保护对策。
To substantiation of the list of hazardous highly toxic chemicals that are subject to special control regarding handling, storage, use and disposal. Part 1 (ricin, thallium compounds and organophosphorus compounds)
Authors: Prodanchuk MH , Balan GM , Kravchuk OP , Zhminko PG , Maksymchuk IM , Chermnykh NP
Published: June 2021

ABSTRACT. The Aim of the Research. Based on an analytical review of literature data, to identify a group of highly toxic chemicals which over the past decades are most often used in deliberate criminal and suicidal incidents, sabotage and terrorist act; the traffic, storage, use and disposal of which must be especially carefully monitored by law enforcement agencies. Materials and Methods. An analytical review of scientific publications was carried out using the abstract databases of scientific libraries Pub Med, Medline and text databases of scientific publishing houses Elsevier, Pub Med, Central, BMJ group as well as other VIP databases. Methods of systemic, comparative, and content analysis were used. Results and Conclusions. The scientific publications on hazardous highly toxic chemicals, which over the past quarter century are most often used in the world, notably in deliberate criminal and suicidal incidents, sabotage, and terrorist acts, are being analysed. It was found that these chemicals mainly include ricin, thallium compounds, organophosphorus compounds, as well as chemical warfare agents, arsenic and its compounds, cyanides, and inorganic water-soluble mercury compounds (mercury bichloride, sodium merthiolate), as well as paraquat and diquat pesticides. Based on the analysis of their toxicity, clinical and morphological expression of intoxication with various routes of entry into the body, the need to include them in the List of Highly Hazardous Chemicals, whose traffic, storage, use, and disposal require stricter control of law enforcement agencies, is justified. The first part of this article presents ricin, thallium compounds, organophosphorus compounds, and chemical warfare agents. Key Words: hazardous highly toxic chemicals, ricin, thallium compounds, organophosphorus compounds.
Methodological principles of waste hazardousness classification
Authors: Povyakel LI , Vasetska OP , Petrashenko HI , Bobyliova OO , Krivenchuk VYe , Zubko OS
Published: June 2021

The Aim of the Research. Clarification of the problem of the negative impact of waste on the environment and public health. They appear from the waste formation and at all stages of its handling.

Materials and Methods. One of the priority areas of approximation to the requirements of the European Union in waste management is the harmonization of modern Ukrainian legislation with European standards, adaptation of regulations, including the classification of waste according to the degree of danger. The article provides a comparative analysis of the legal framework for waste hazardousness assessment currently existing in Ukraine with WHO recommendations and EU Directives. The methodological principles of classification of waste according to a degree of hazardousness are substantiated and recommended for implementation.

Results and Conclusions. It is scientifically proven that the assignment of waste to a certain classification category of hazard should be based not only on quantitative calculations of chemical composition and toxicity of constituent ingredients that are part of the waste, but also on experimental testing of samples using alternative methods.

Key Words: waste, EU Directive, classification, biological testing, toxicity, hazard, alternative methods.
MEMBRANES FUNCTIONALIZED WITH 1d, 2d and 3d CARBON MATERIALS
Authors: Rozhdestvenska Liudmyla , Kudelko Kateryna , Kolomiiets Yevhen , Dzyazko Yuliya , Ogenko Volodymyr
Published: June 2021

Modification of polymer and ceramic mem­branes by modern one-, two- and three- di­men­sional carbon nanomaterials (carbon nano­tubes, fullerenes and their derivatives, oxi­dized and reduced graphene) is consi­dered. It is shown that carbon materials can be incorporated into membrane matrices both as independent components and as a part of multicomponent modifier. The main methods of modification are the addition of modifiers to the polymer solution with subsequent making of polymer membranes, incorporation of nanoparticles of carbon nanomaterials into the pristine membranes, deposition on the outer membrane surface, formation of nanoparticles directly in the pores of the ceramic matrix. Composite membranes containing carbon nanoparticles are used for pervaporation, gas separation, baromembrane processes and low-temperature fuel cells. The addition of carbon nanomaterials to polymers provides better mechanical strength of the membranes. Hydrophilic carbon modifiers increase the resistance of membranes to fouling by organic substan­ces and biofouling, improves their separation ability. Ion-exchange membranes modified with fullerenol and oxidized graphene maintain high proton conductivity at elevated temperatures and low humidity. Сarbon additives increase membrane productivity in baromembrane processes. This effect is especially evident for materials modified with nanotubes: their smooth surface ensures fast liquid transport. These carbon nanomaterials are characterized by antibacterial activity. Composites consisting of nanotubes and an ion-exchange biopolymer, and composites with oxidized graphene and inorganic ion exchanger, give to membranes selectivity to inorganic ions. Ceramic membranes modified with carbon nanoparticles that were formed in the pores of matrices by carbonization of synthetic polymers and polysaccharides have the same properties. Besides, these composites reject organic dyes too. The separating ability of composite membranes ocuures due to both dimensional and charge effects. Carbon or composite nano­particles block the pores of the membranes. The pores formed by the modifier prevent pene­tration of large particles of organic substances, for example, protein macromolecules. The charge effect is realized due to the functional groups of the modifier. For membranes modified with fullerenols, the retaining of low molecular weight organic substances occurs due to adsorption. Fullerene-modified gas sepa­ration and pervaporation membranes show increased permeability and selectivity.
Effect of Tailored Microstructures in CaO-Added AZ31 Extrusion Material on Tensile, High Cycle Fatigue and Fatigue Crack Propagation Properties
Authors: Kim Young-Kyun , Kim Min-Jong , Hwang Yu-Jin , Kim Shae. K. , Lim Hyun-Kyu , Lee Kee-Ahn
Published: June 2021

The effect of tailored microstructures in 0.5 wt% CaO added AZ31 on tensile, high-cycle fatigue, and fatigue crack growth properties was examined. By adding CaO, the average grain size (AGS) was significantly reduced from 4.25±2.32 μm (conventional AZ31) to 2.42±1.60 μm (CaO-AZ31). The fineprecipitates of CaO-AZ31 were more evenly distributed and their fraction was higher than those of conventional AZ31. The fine-precipitates were identified as Al8Mn4Ca and (Mg, Al)2Ca in CaO-AZ31, meanwhile, were identified as Al8Mn5 and Mg17Al11 in conventional AZ31. The tensile test results showed that the yield strengths of CaO-AZ31 and conventional AZ31 were 238.0 MPa and 206.7 MPa, respectively. The elongation-to-failure also increased when CaO was added. The improved tensile properties of CaO-AZ31 could be explained by grain refinement and precipitation hardening. The high-cycle fatigue limit also increased about 15% with added CaO. The fatigue limits as a function of the tensile strengths of CaO-AZ31 and conventional AZ31 were 0.508 and 0.457, respectively. The origin of the improved fatigue resistance was attributed to inhibition of the formation of DTs, which acted as the fatigue crack source, in CaO-AZ31. In contrast, the fatigue crack growth property did not change when CaO was added. Based on the above findings, the relationships between microstructure, mechanical properties and deformation mechanisms are also discussed.
Investigation of Electrowinning of Mg from MgO Using a Liquid Metal Cathode in MgF2-CaF2-NaF or MgF2-LiF Molten Salt
Authors: Lee Tae-Hyuk , Park HyungKyu , Lee Jin-Young , Kim Young Min , Kang Jungshin
Published: June 2021

A novel magnesium (Mg) production process utilizing an electrolytic method was investigated for the direct reduction of magnesium oxide (MgO). Electrolysis of MgO was carried out with an applied voltage of 3.0 V using a copper (Cu), silver (Ag), or tin (Sn) cathode and carbon (C) or platinum (Pt) anode in magnesium fluoride (MgF2)−calcium fluoride (CaF2)−sodium fluoride (NaF) at 1273 K or MgF2− lithium fluoride (LiF) at 1083−1093 K. After the electrolysis of MgO in MgF2−CaF2−NaF molten salt, Mg alloys such as Mg2Cu, Cu2Mg, or Mg2Sn phases were produced with current efficiencies of 75.8−85.6% when the concentration of Mg in Mg alloys was 9.1−14.6 mass%. In addition, when the electrolysis of MgO was conducted in MgF2–LiF molten salt, Mg alloys such as Mg2Cu or AgMg phase were produced with current efficiencies of 76.2−81.7% when the concentration of Mg in the Mg alloys was 12.5−13.2 mass%. In addition, to produce high-purity Mg metal from Mg alloys, vacuum distillation was conducted. When vacuum distillation was conducted at 1100−1400 K for a duration of 5 h, the concentration of Mg in the Mg alloys feed decreased from 30.2−34.1 mass% to 0.64−1.75 mass%, and Mg metal with a purity of 99.998−99.999% was obtained under certain conditions. Therefore, the molten salt electrolysis using liquid metal cathode (MSE-LMC) process developed here is feasible for the direct reduction of MgO using an effective and environmentally sound method.
First Nations Cultural Loss: Whiteness and theTimber CreekJudgment
Authors: Bird Greta , Bird Jo
Published: June 2021

The Ngaliwurru and Nungali Peoples of the Country known in white law as Timber Creek commenced three proceedings under the Native Title Act 1993 (Cth) (NTA) in 1999 and 2000. The final judgment in the High Court was hailed as progressive. It was the first time that the Court had awarded damages inter alia for cultural loss under the NTA. The article contends that the compensation awarded was inadequate, being based on white, neo-liberal notions of property that do not acknowledge Aboriginal sovereignty, the depth of connection to country and loss suffered. The case also denied that a fiduciary obligation existed on behalf of the Crown, a possibility that was raised in Mabo and other cases but allowed to atrophy. Given this, it is argued that the judgment is a continuation of the colonial project based on the ‘ terra nullius’ doctrine and can be critiqued from the perspective of the white cultural privilege embedded throughout. The judgment does not disturb the skeleton of white Australia's claims to sovereignty: the taking of the land without consent, the failure to recognise First Nations sovereignty, the neglect to enter into treaties or to provide compensation in any meaningful sense.
Making a Case for Feminist Statistics
Authors: Heilmann Lisanne
Published: June 2021

In contrast to qualitative and theoretical approaches, the mainstream of quantitative research often still finds it difficult to incorporate modern concepts of diversity and intersectionality into its work. This article aims to highlight various aspects in which large studies and their evaluations marginalise or ignore certain parts of the population. In surveying data, large-scale surveys like the Programme for the International Assessment of Adult Competencies (PIAAC) often not only operate on a binary gender concept but also do not differentiate between a person gender identity and their social gender. In addition, commonly used methods keep unequal distributions invisible. Non-binary people are virtually invisible, unequal benefits for women remain hidden and the intersectional diversity inside the broad gender categories poses challenges to the mainstream of quantitative research in adult education. Therefore, there is a need for a feminist approach to statistics and quantitative research.
Production of Glucose 6-Phosphate From a Cellulosic Feedstock in a One Pot Multi-Enzyme Synthesis
Authors: Usvalampi Anne , Li He , Frey Alexander D.
Published: June 2021

Glucose 6-phosphate is the phosphorylated form of glucose and is used as a reagent in enzymatic assays. Current production occurs via a multi-step chemical synthesis. In this study we established a fully enzymatic route for the synthesis of glucose 6-phosphate from cellulose. As the enzymatic phosphorylation requires ATP as phosphoryl donor, the use of a cofactor regeneration system is required. We evaluated Escherichia coli glucokinase and Saccharomyces cerevisiae hexokinase (HK) for the phosphorylation reaction and Pseudomonas aeruginosa polyphosphate kinase 2 (PPK2) for ATP regeneration. All three enzymes were characterized in terms of temperature and pH optimum and the effects of substrates and products concentrations on enzymatic activities. After optimization of the conditions, we achieved a 85% conversion of glucose into glucose 6-phosphate using the HK/PPK2 activities within a 24 h reaction resulting in 12.56 g/l of glucose 6-phosphate. Finally, we demonstrated the glucose 6-phosphate formation from microcrystalline cellulose in a one-pot reaction comprising Aspergillus niger cellulase for glucose release and HK/PPK2 activities. We achieved a 77% conversion of released glucose into glucose 6-phosphate, however at the expense of a lower glucose 6-phosphate yield of 1.17 g/l. Overall, our study shows an alternative approach for synthesis of glucose 6-phosphate that can be used to valorize biomass derived cellulose.
Clinical Use of the Self-Assembling Peptide RADA16: A Review of Current and Future Trends in Biomedicine
Authors: Sankar Sharanya , O’Neill Kate , Bagot D’Arc Maurice , Rebeca Florian , Buffier Marie , Aleksi Elton , Fan Melanie , Matsuda Noriaki , Gil Eun Seok , Spirio Lisa
Published: June 2021

RADA16 is a synthetic peptide that exists as a viscous solution in an acidic formulation. In an acidic aqueous environment, the peptides spontaneously self-assemble into β-sheet nanofibers. Upon exposure and buffering of RADA16 solution to the physiological pH of biological fluids such as blood, interstitial fluid and lymph, the nanofibers begin physically crosslinking within seconds into a stable interwoven transparent hydrogel 3-D matrix. The RADA16 nanofiber hydrogel structure closely resembles the 3-dimensional architecture of native extracellular matrices. These properties make RADA16 formulations ideal topical hemostatic agents for controlling bleeding during surgery and to prevent post-operative rebleeding. A commercial RADA16 formulation is currently used for hemostasis in cardiovascular, gastrointestinal, and otorhinolaryngological surgical procedures, and studies are underway to investigate its use in wound healing and adhesion reduction. Straightforward application of viscous RADA16 into areas that are not easily accessible circumvents technical challenges in difficult-to-reach bleeding sites. The transparent hydrogel allows clear visualization of the surgical field and facilitates suture line assessment and revision. The shear-thinning and thixotropic properties of RADA16 allow its easy application through a narrow nozzle such as an endoscopic catheter. RADA16 hydrogels can fill tissue voids and do not swell so can be safely used in close proximity to pressure-sensitive tissues and in enclosed non-expandable regions. By definition, the synthetic peptide avoids potential microbiological contamination and immune responses that may occur with animal-, plant-, or mineral-derived topical hemostats. In vitro experiments, animal studies, and recent clinical experiences suggest that RADA16 nanofibrous hydrogels can act as surrogate extracellular matrices that support cellular behavior and interactions essential for wound healing and for tissue regenerative applications. In the future, the unique nature of RADA16 may also allow us to use it as a depot for precisely regulated drug and biopharmaceutical delivery.
Nanoparticle-Based Therapies for Turning Cold Tumors Hot: How to Treat an Immunosuppressive Tumor Microenvironment
Authors: Giustarini Giulio , Pavesi Andrea , Adriani Giulia
Published: June 2021

Nanotechnologies are rapidly increasing their role in immuno-oncology in line with the need for novel therapeutic strategies to treat patients unresponsive to chemotherapies and immunotherapies. The tumor immune microenvironment (TIME) has emerged as critical for tumor classification and patient stratification to design better treatments. Notably, the tumor infiltration of effector T cells plays a crucial role in antitumor responses and has been identified as the primary parameter to define hot, immunosuppressed, excluded, and cold tumors. Organic and inorganic nanoparticles (NPs) have been applied as carriers of new targeted therapies to turn cold or altered (i.e., immunosuppressed or excluded) tumors into more therapeutically responsive hot tumors. This mini-review discusses the significant advances in NP-based approaches to turn immunologically cold tumors into hot ones.
Motion Design with Efficient Actuator Placement for Adaptive Structures that Perform Large Deformations
Authors: Sachse Renate , Geiger Florian , von Scheven Malte , Bischoff Manfred
Published: June 2021

Adaptive structures have great potential to meet the growing demand for energy efficiency in buildings and engineering structures. While some structures adapt to varying loads by a small change in geometry, others need to perform an extensive change of shape to meet varying demands during service. In the latter case, it is important to predict suitable deformation paths that minimize control effort. This study is based on an existing motion design method to control a structure between two given geometric configurations through a deformation path that is optimal with respect to a measure of control efficiency. The motion design method is extended in this work with optimization procedures to obtain an optimal actuation system placement in order to control the structure using a predefined number of actuators. The actuation system might comprise internal or external actuators. The internal actuators are assumed to replace some of the elements of the structure. The external actuators are modeled as point forces that are applied to the structure nodes. Numerical examples are presented to show the potential for application of the motion design method to non-load-bearing structures.
Oriented Antibody Covalent Immobilization for Label-Free Impedimetric Detection of C-Reactive Protein via Direct and Sandwich Immunoassays
Authors: Adesina Abiola , Mashazi Philani
Published: June 2021

The detection and monitoring of biological markers as disease indicators in a simple manner is a subject of international interest. In this work, we report two simple and sensitive label-free impedimetric immunoassays for the detection of C-reactive protein (CRP). The gold electrode modified with boronic acid–terminated self-assembled monolayers afforded oriented immobilization of capture glycosylated antibody (antihuman CRP monoclonal antibody, mAb). This antibody-modified surface was able to capture human CRP protein, and the impedance signal showed linear dependence with CRP concentration. We confirmed the immobilization of anti-CRP mAb using surface sensitive X-ray photoelectron spectroscopy (XPS) and electrochemical impedance. The oriented covalent immobilization of mAb was achieved using glycosylated Fc (fragment, crystallizable) region specific to boronic acid. The direct immunoassay exhibited a linear curve for concentration range up to 100 ng ml−1. The limit of detection (LoD) of 2.9 ng ml−1, limit of quantification (LoQ) of 9.66 ng ml−1, and sensitivity of 0.585 kΩ ng−1 ml cm−2 were obtained. The sandwich immunoassay was carried out by capturing polyclonal anti-CRP antibody (pAb) onto the CRP antigen immunoreaction. The impedance signal after pAb capture also showed linear dependence with CRP antigen concentration and acted as a CRP antigen detection signal amplifier. The detection of the CRP antigen using sandwich pAb immunoassay improved LoD to 1.2 ng ml−1, LoQ to 3.97 ng ml−1, and enhanced the sensitivity to 0.885 kΩ ng−1 ml cm−2. The real sample analysis, using newborn calf serum, showed excellent selectivity and % recovery for the human CRP ranging from 91.2 to 96.5%. The method was reproducible to 4.5% for direct immunoassay and 2.3% for sandwich immunoassay.
A Framework for Evaluating Earthquake Early Warning for an Infrastructure Network: An Idealized Case Study of a Northern California Rail System
Authors: Minson Sarah E. , Cochran Elizabeth S. , Wu Stephen , Noda Shunta
Published: June 2021

Earthquake early warning (EEW) systems provide a few to tens of seconds of warning before shaking hits a site. Despite the recent rapid developments of EEW systems around the world, the optimal alert response strategy and the practical benefit of using EEW are still open-ended questions, especially in areas where EEW systems are new or have not yet been deployed. Here, we use a case study of a rail system in California’s San Francisco Bay Area to explore potential uses of EEW for rail systems. Rail systems are of particular interest not only because they are important lifeline infrastructure and a common application for EEW around the world, but also because their geographically broad yet networked infrastructure makes them almost uniquely well suited for utilizing EEW. While the most obvious potential benefit of EEW to the railway is to prevent derailments by stopping trains before the arrival of shaking, the lead time for warnings is usually not long enough to significantly reduce a train’s speed. In reality, EEW’s greatest impact is preventing derailment by alerting trains to slow down or stop before they encounter damaged track. We perform cost-benefit analyses of different decision-making strategies for several EEW system designs to find an optimal alerting strategy. On-site EEW provides better outcomes than source-parameter-based EEW when warning at a threshold of 120 gal (the level of shaking at which damage might occur) regardless of false alarm tolerance. A source-parameter-based EEW system with a lower alerting threshold (e.g., 40 gal) can reduce the exposure to potentially damaged track compared to an on-site system alerting at 120 gal, but a lower alerting threshold comes at the cost of additional precautionary system stops. The optimal EEW approach for rail systems depends strongly on the ratio of the cost of stopping the system unnecessarily to the potential loss from traversing damaged tracks.
Changes in Flood Regime of the Upper Yangtze River
Authors: Zhang Yu , Fang Guohua , Tang Zhengyang , Wen Xin , Zhang Hairong , Ding Ziyu , Li Xin , Bian Xinsheng , Hu Zengyun
Published: June 2021

River flooding affects more people worldwide than other natural hazards. Thus, analysis of the changes in flood regime caused by global warming and increasing anthropogenic activities will help us make adaptive plans for future flood management. The nonstationary flood behavior in the upper Yangtze River was examined comprehensively in terms of trend, change point, and periodicity with co-usage of different methods. Results show that there are decreasing tendencies in the corresponding series of annual maximum flood peak flow and flood volume in four out of six control stations, except Pingshan and Wulong stations in the Jinsha River and the Wu River, respectively, and the flood peak occurrence time appears earlier mostly. The uniformity of flood process increases in four main tributaries, while it decreases in mainstream of the Yangtze River (Yichang and Pingshan stations). The rates of both rising limb and recession limb of all the typical flood process flowing through the six stations were analyzed. 77.8% of the rates of rising limb decrease, while 61.1% of the rates of recession limb increase, which is almost consistent with the variation reflected by the uniformity. The change points of most evaluation indicators happened in 1970s–1990s. The first main periodicity of evaluation indicators in Yichang is about 45 years, while that of other stations is about 20 years. Invalidity of stationarity in the flood series can be attributed to the intensified construction on major water conservancy projects, changes of underlying surface, and influences of climatic variables. The contributions of both climatic control and the Three Gorges Dam (TGD) to the variation of the annual flood peak in Yichang station were further quantitatively evaluated, which has verified that the construction of the TGD has played a positive role in peak-flood clipping.
How to Screen and Prevent Metabolic Syndrome in Patients of PCOS Early: Implications From Metabolomics
Authors: Zhao Xiaoxuan , Feng Xiaoling , Zhao Xinjie , Jiang Yuepeng , Li Xianna , Niu Jingyun , Meng Xiaoyu , Wu Jing , Xu Guowang , Hou Lihui , Wang Ying
Published: June 2021

Background

Polycystic ovary syndrome (PCOS) is a complex reproductive endocrine disorder. And metabolic syndrome (MS) is an important bridge for PCOS patients to develop other diseases, such as diabetes and coronary heart disease. Our aim was to study the potential metabolic characteristics of PCOS-MS and identify sensitive biomarkers so as to provide targets for clinical screening, diagnosis, and treatment.

Methods

In this study, 44 PCOS patients with MS, 34 PCOS patients without MS, and 32 healthy controls were studied. Plasma samples of subjects were tested by ultraperformance liquid chromatography (UPLC) system combined with LTQ-orbi-trap mass spectrometry. The changes of metabolic characteristics from PCOS to PCOS-MS were systematically analyzed. Correlations between differential metabolites and clinical characteristics of PCOS-MS were assessed. Differential metabolites with high correlation were further evaluated by the receiver operating characteristic (ROC) curve to identify their sensitivity as screening indicators.

Results

There were significant differences in general characteristics, reproductive hormone, and metabolic parameters in the PCOS-MS group when compared with the PCOS group and healthy controls. We found 40 differential metabolites which were involved in 23 pathways when compared with the PCOS group. The metabolic network further reflected the metabolic environment, including the interaction between metabolic pathways, modules, enzymes, reactions, and metabolites. In the correlation analysis, there were 11 differential metabolites whose correlation coefficient with clinical parameters was greater than 0.4, which were expected to be taken as biomarkers for clinical diagnosis. Besides, these 11 differential metabolites were assessed by ROC, and the areas under curve (AUCs) were all greater than 0.7, with a good sensitivity. Furthermore, combinational metabolic biomarkers, such as glutamic acid + leucine + phenylalanine and carnitine C 4: 0 + carnitine C18:1 + carnitine C5:0 were expected to be sensitive combinational biomarkers in clinical practice.

Conclusion

Our study provides a new insight to understand the pathogenesis mechanism, and the discriminating metabolites may help screen high-risk of MS in patients with PCOS and provide sensitive biomarkers for clinical diagnosis.
Responses of Habitat Quality and Animal Biodiversity to Grazing Activities on the Qinghai-Tibet Plateau
Authors: Liu Yixuan , Liu Shiliang , Wang Fangfang , Sun Yongxiu , Li Mingqi , Wang Qingbo , Yu Lu
Published: June 2021

Grazing activities perhaps lead to habitat quality degradation and animal biodiversity loss while the effects on the Qinghai-Tibet Plateau (QTP) is still relatively poorly studied. Based on the Integrated Valuation of Ecosystem Services and Tradeoffs model, geographical detector model and generalized linear mixed model, the responses of habitat quality and animal biodiversity to grazing activities at 5 km grid scale were analyzed. Results showed that the overall habitat quality on the QTP was high with 76.43% of the total area, and poor level accounted for 19.56%. High level habitat was mainly distributed in the southern part, while the poor level in the northern part. The mean grazing activity explanatory ability to habitat quality, bird species richness and mammal richness were 0.346, 0.430, and 0.354. The interaction effects between slope and grazing activities on habitat quality, bird species richness and mammal richness were the most important interaction effects, and the area affected by the interaction was 73.82, 46.00, and 46.17% of habitat quality, bird species richness and mammal richness, respectively. The interaction effects on habitat quality, bird species richness and mammal richness all showed “low in the northwest and high in the southeast”. Grazing activities and habitat quality had a positive correlation while bird species richness, and mammal richness negative correlations. The spatial relationship of grazing activities of habitat quality was “higher in the middle and lower around the periphery”, while the spatial distribution of grazing activities of bird species richness and mammal richness was “higher in the east and lower in the west”. This study explicitly revealed the responses of habitat quality and animal biodiversity to grazing activities, thus providing references for biodiversity conservation on the QTP.
Continuous Exposure to Non-Soluble β-Glucans Induces Trained Immunity in M-CSF-Differentiated Macrophages
Authors: Moerings Bart G. J. , de Graaff Priscilla , Furber Matthew , Witkamp Renger F. , Debets Reno , Mes Jurriaan J. , van Bergenhenegouwen Jeroen , Govers Coen
Published: June 2021

Beta-glucans enable functional reprogramming of innate immune cells, a process defined as “trained immunity”, which results in enhanced host responsiveness against primary (training) and/or secondary infections (resilience). Trained immunity holds great promise for promoting immune responses in groups that are at risk (e.g. elderly and patients). In this study, we modified an existing in vitro model for trained immunity by actively inducing monocyte-to-macrophage differentiation using M-CSF and applying continuous exposure. This model reflects mucosal exposure to β-glucans and was used to study the training effects of a variety of soluble or non-soluble β-glucans derived from different sources including oat, mushrooms and yeast. In addition, trained immunity effects were related to pattern recognition receptor usage, to which end, we analyzed β-glucan-mediated Dectin-1 activation. We demonstrated that β-glucans, with different sources and solubilities, induced training and/or resilience effects. Notably, trained immunity significantly correlated with Dectin-1 receptor activation, yet Dectin-1 receptor activation did not perform as a sole predictor for β-glucan-mediated trained immunity. The model, as validated in this study, adds on to the existing in vitro model by specifically investigating macrophage responses and can be applied to select non-digestible dietary polysaccharides and other components for their potential to induce trained immunity.
Neutrophils and COVID-19: Active Participants and Rational Therapeutic Targets
Authors: Hazeldine Jon , Lord Janet M.
Published: June 2021

Whilst the majority of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen of COVID-19, experience mild to moderate symptoms, approximately 20% develop severe respiratory complications that may progress to acute respiratory distress syndrome, pulmonary failure and death. To date, single cell and high-throughput systems based analyses of the peripheral and pulmonary immune responses to SARS-CoV-2 suggest that a hyperactive and dysregulated immune response underpins the development of severe disease, with a prominent role assigned to neutrophils. Characterised in part by robust generation of neutrophil extracellular traps (NETs), the presence of immature, immunosuppressive and activated neutrophil subsets in the circulation, and neutrophilic infiltrates in the lung, a granulocytic signature is emerging as a defining feature of severe COVID-19. Furthermore, an assessment of the number, maturity status and/or function of circulating neutrophils at the time of hospital admission has shown promise as a prognostic tool for the early identification of patients at risk of clinical deterioration. Here, by summarising the results of studies that have examined the peripheral and pulmonary immune response to SARS-CoV-2, we provide a comprehensive overview of the changes that occur in the composition, phenotype and function of the neutrophil pool in COVID-19 patients of differing disease severities and discuss potential mediators of SARS-CoV-2-induced neutrophil dysfunction. With few specific treatments currently approved for COVID-19, we conclude the review by discussing whether neutrophils represent a potential therapeutic target for the treatment of patients with severe COVID-19.
Type I Interferon Dependent hsa-miR-145-5p Downregulation Modulates MUC1 and TLR4 Overexpression in Salivary Glands From Sjögren’s Syndrome Patients
Authors: Jara Daniela , Carvajal Patricia , Castro Isabel , Barrera María-José , Aguilera Sergio , González Sergio , Molina Claudio , Hermoso Marcela , González María-Julieta
Published: June 2021

Sjögren’s syndrome (SS) is an autoimmune disease that mainly affects salivary glands (SG) and is characterized by overactivation of the type I interferon (IFN) pathway. Type I IFNs can decrease the levels of hsa-miR-145-5p, a miRNA with anti-inflammatory roles that is downregulated in SG from SS-patients. Two relevant targets of hsa-miR-145-5p, mucin 1 (MUC1) and toll-like receptor 4 (TLR4) are overexpressed in SS-patients and contribute to SG inflammation and dysfunction. This study aimed to evaluate if hsa-miR-145-5p modulates MUC1 and TLR4 overexpression in SG from SS-patients in a type I IFN dependent manner. Labial SG (LSG) biopsies from 9 SS-patients and 6 controls were analyzed. We determined hsa-miR-145-5p levels by TaqMan assays and the mRNA levels of MUC1, TLR4, IFN-α, IFN-β, and IFN-stimulated genes (MX1, IFIT1, IFI44, and IFI44L) by real time-PCR. We also performedin vitroassays using type I IFNs and chemically synthesized hsa-miR-145-5p mimics and inhibitors. We validated the decreased hsa-miR-145-5p levels in LSG from SS-patients, which inversely correlated with the type I IFN score, mRNA levels of IFN-β, MUC1, TLR4, and clinical parameters of SS-patients (Ro/La autoantibodies and focus score). IFN-α or IFN-β stimulation downregulated hsa-miR-145-5p and increased MUC1 and TLR4 mRNA levels. Hsa-miR-145-5p overexpression decreased MUC1 and TLR4 mRNA levels, while transfection with a hsa-miR-145-5p inhibitor increased mRNA levels. Our findings show that type I IFNs decrease hsa-miR-145-5p expression leading to upregulation of MUC1 and TLR4. Together, this suggests that type I interferon-dependent hsa-miR-145-5p downregulation contributes to the perpetuation of inflammation in LSG from SS-patients.
Local Respiratory Allergy: From Rhinitis Phenotype to Disease Spectrum
Authors: Testera-Montes Almudena , Salas Maria , Palomares Francisca , Ariza Adriana , Torres María J. , Rondón Carmen , Eguiluz-Gracia Ibon
Published: June 2021

Local respiratory allergy (LRA) is defined by the negativity of atopy tests, a clinical history suggestive of airway allergy and a positive response to the nasal and/or bronchial allergen challenge. The clinical spectrum of LRA is comprised of three conditions: local allergic rhinitis (LAR) and local allergic asthma in non-atopic patients, and dual allergic rhinitis (coexistence of allergic rhinitis and LAR) in atopic individuals. LRA is an independent disease phenotype not progressing to atopy over time, but naturally evolving to the clinical worsening and the onset of comorbidities. Published data suggests that LRA is mediated through the mucosal synthesis of allergen-specific (s)IgE, which binds to FcϵRI on resident mast cells, and in >50% of cases traffics to the blood stream to sensitize circulating basophils. To date, 4 clinical trials have demonstrated the capacity of allergen immunotherapy (AIT) to decrease nasal, conjunctival and bronchial symptoms, to improve quality of life, to increase the threshold dose of allergen eliciting respiratory symptoms, and to induce serum sIgG4 in LRA individuals. Collectively, these data indicate that local allergy is a relevant disease mechanisms in both atopic and non-atopic patients with airway diseases.
Reduction of Low-Frequency Vessel Noise in Monterey Bay National Marine Sanctuary During the COVID-19 Pandemic
Authors: Ryan John P. , Joseph John E. , Margolina Tetyana , Hatch Leila T. , Azzara Alyson , Reyes Alexis , Southall Brandon L. , DeVogelaere Andrew , Peavey Reeves Lindsey E. , Zhang Yanwu , Cline Danelle E. , Jones Brent , McGill Paul , Baumann-Pickering Simone , Stimpert Alison K.
Published: June 2021

Low-frequency sound from large vessels is a major, global source of ocean noise that can interfere with acoustic communication for a variety of marine animals. Changes in vessel activity provide opportunities to quantify relationships between vessel traffic levels and soundscape conditions in biologically important habitats. Using continuous deep-sea (890 m) recordings acquired ∼20 km (closest point of approach) from offshore shipping lanes, we observed reduction of low-frequency noise within Monterey Bay National Marine Sanctuary (California, United States) associated with changes in vessel traffic during the onset of the COVID-19 pandemic. Acoustic modeling shows that the recording site receives low-frequency vessel noise primarily from the regional shipping lanes rather than via the Sound Fixing and Ranging (SOFAR) channel. Monthly geometric means and percentiles of spectrum levels in the one-third octave band centered at 63 Hz during 2020 were compared with those from the same months of 2018–2019. Spectrum levels were persistently and significantly lower during February through July 2020, although a partial rebound in ambient noise levels was indicated by July. Mean spectrum levels during 2020 were more than 1 dB re 1 μPa2 Hz–1 below those of a previous year during 4 months. The lowest spectrum levels, in June 2020, were as much as 1.9 (mean) and 2.4 (25% exceedance level) dB re 1 μPa2 Hz–1 below levels of previous years. Spectrum levels during 2020 were significantly correlated with large-vessel total gross tonnage derived from economic data, summed across all California ports (r = 0.81, p < 0.05; adjusted r2 = 0.58). They were more highly correlated with regional presence of large vessels, quantified from Automatic Identification System (AIS) vessel tracking data weighted according to vessel speed and modeled acoustic transmission loss (r = 0.92, p < 0.01; adjusted r2 = 0.81). Within the 3-year study period, February–June 2020 exhibited persistently quiet low-frequency noise and anomalously low statewide port activity and regional large-vessel presence. The results illustrate the ephemeral nature of noise pollution by documenting how it responds rapidly to changes in offshore large-vessel traffic, and how this anthropogenic imprint reaches habitat remote from major ports and shipping lanes.
Randomised, Double-Blind, Placebo-Controlled Study of Iguratimod in the Treatment of Active Spondyloarthritis
Authors: Li Yan , Li Kunpeng , Zhao Zheng , Wang Yanyan , Jin Jingyu , Guo Junhua , Zhang Jie , Zhang Jianglin , Zhu Jian , Huang Feng
Published: June 2021

Background and Purpose: The effect of Iguratimod in the treatment of rheumatoid arthritis was confirmed in past studies. In terms of the mechanism of the effect and clinical application experience, Iguratimod has a potential value in the treatment of spondyloarthritis (SpA). This study evaluated the efficacy and safety of Iguratimod on active SpA.

Methods: Subjects with active SpA were enrolled and randomly divided into two groups at a ratio of 1:2 (placebo vs. Iguratimod). On the basis of non-steroidal anti-inflammatory drugs, combined treatment with Iguratimod or placebo, followed by follow-up every 4 weeks for 24 weeks. The primary efficacy endpoint was to evaluate the alleviation rate of ASAS20; the important improvement of ASDAS and the efficacy of spinal mobility, physical function and quality of life at the 24th week.

Results: A total of 48 cases in the Iguratimod group and 25 cases in the placebo group were included in the final analysis. On the 24th week, the percentage of responders to ASAS20 (80 vs. 44%) and ASAS40 (56 vs. 20%) treated with Iguratimod were significantly higher than that in the placebo group (P < 0.05). Twelve cases had gastrointestinal discomfort, of which eight were in the Iguratimod group (16.7%, one case withdrew from the study due to diarrhoea) and four were in the placebo group (16.0%). No significant difference was found between the two groups (P < 0.05). Three cases of elevated transaminase were observed in the Iguratimod group and none in the placebo group, with no significant difference (P < 0.05).

Conclusion: Iguratimod could significantly reduce the symptoms and signs of patients with active SpA. It could improve the physical function and quality of life of these patients and the overall safety and tolerance are good.
Case Report: Lipoprotein Glomerulopathy Complicated by Atypical Hemolytic Uremic Syndrome
Authors: Kollbrunner Lara , Hirt-Minkowski Patricia , Sanz Javier , Bresin Elena , Neuhaus Thomas J. , Hopfer Helmut , Jehle Andreas W.
Published: June 2021

Lipoprotein glomerulopathy (LPG) is a rare inherited disease caused by mutations in the APOE gene, encoding apolipoprotein E (apoE). Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy (TMA) characterized by overactivation of the alternative complement pathway. Here we report the case of a 21-year-old man with LPG who developed aHUS. A functional complement assay demonstrated an overactivation of the complement system. Complementary genetic analysis revealed a homozygous aHUS risk allele for complement factor-H related 1 (CFHR1), CFHR1*B. To the best of our knowledge, this is the first report of an aHUS in a patient with LPG.
Combined Analysis of the Time-Resolved Transcriptome and Proteome of Plant Pathogen Xanthomonas oryzae pv. oryzae
Authors: Kim Seunghwan , Jang Wooyoung Eric , Park Jihwan , Kim Min-Sik , Kim Jeong-Gu , Kang Lin-Woo
Published: June 2021

Xanthomonas oryzae pv. oryzae (Xoo) is a plant pathogen responsible for causing bacterial blight in rice. The immediate alterations in Xoo upon initial contact with rice are essential for pathogenesis. We studied time-resolved genome-wide gene expression in pathogenicity-activated Xoo cells at the transcriptome and proteome levels. The early response genes of Xoo include genes related to cell motility, inorganic ion transport, and effectors. The alteration of gene expression is initiated as early as few minutes after the initial interaction and changes with time. The time-resolved comparison of the transcriptome and proteome shows the differences between transcriptional and translational expression peaks in many genes, although the overall expression pattern of mRNAs and proteins is conserved. The discrepancy suggests an important role of translational regulation in Xoo at the early stages of pathogenesis. The gene expression analysis using time-resolved transcriptome and proteome provides unprecedented valuable information regarding Xoo pathogenesis.
Model Selection Reveals the Butyrate-Producing Gut Bacterium Coprococcus eutactus as Predictor for Language Development in 3-Year-Old Rural Ugandan Children
Authors: Kort Remco , Schlösser Job , Vazquez Alan R. , Atukunda Prudence , Muhoozi Grace K. M. , Wacoo Alex Paul , Sybesma Wilbert F. H. , Westerberg Ane C. , Iversen Per Ole , Schoen Eric D.
Published: June 2021

Introduction

The metabolic activity of the gut microbiota plays a pivotal role in the gut-brain axis through the effects of bacterial metabolites on brain function and development. In this study we investigated the association of gut microbiota composition with language development of 3-year-old rural Ugandan children.

Methods

We studied the language ability in 139 children of 36 months in our controlled maternal education intervention trial to stimulate children’s growth and development. The dataset includes 1170 potential predictors, including anthropometric and cognitive parameters at 24 months, 542 composition parameters of the children’s gut microbiota at 24 months and 621 of these parameters at 36 months. We applied a novel computationally efficient version of the all-subsets regression methodology and identified predictors of language ability of 36-months-old children scored according to the Bayley Scales of Infant and Toddler Development (BSID-III).

Results

The best three-term model, selected from more than 266 million models, includes the predictors Coprococcus eutactus at 24 months of age, Bifidobacterium at 36 months of age, and language development at 24 months. The top 20 four-term models, selected from more than 77 billion models, consistently include C. eutactus abundance at 24 months, while 14 of these models include the other two predictors as well. Mann–Whitney U tests suggest that the abundance of gut bacteria in language non-impaired children (n = 78) differs from that in language impaired children (n = 61). While anaerobic butyrate-producers, including C. eutactus, Faecalibacterium prausnitzii, Holdemanella biformis, Roseburia hominis are less abundant, facultative anaerobic bacteria, including Granulicatella elegans, Escherichia/Shigella and Campylobacter coli, are more abundant in language impaired children. The overall predominance of oxygen tolerant species in the gut microbiota was slightly higher in the language impaired group than in the non-impaired group (P = 0.09).

Conclusion

Application of the all-subsets regression methodology to microbiota data established a correlation between the relative abundance of the anaerobic butyrate-producing gut bacterium C. eutactus and language development in Ugandan children. We propose that the gut redox potential and the overall bacterial butyrate-producing capacity in the gut are important factors for language development.