bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of ion mobility spectrometry ‐ mass spectrometry as a screening tool to identify type II kinase inhibitors of FGFR1 kinase
Authors: Beeston Helen S. , Klein Tobias , Norman Richard A. , Tucker Julie A. , Anderson Malcolm , Ashcroft Alison E. , Holdgate Geoffrey A. 
Published: May 2021

RationaleThe protein kinase FGFR1 regulates cellular processes in human development. As over‐activity of FGFR1 is implicated with cancer, effective inhibitors are in demand. Type I inhibitors, which bind to the active form of FGFR1, are less effective than type II inhibitors, which bind to the inactive form. Screening to distinguish between type I and type II inhibitors is required.MethodsX‐ray crystallography was used to indicate whether a range of potential inhibitors bind to the active or inactive FGFR1 kinase conformation. The binding affinity of each ligand to FGFR1 was measured using biochemical methods. Electrospray ionisation ‐ ion mobility spectrometry ‐ mass spectrometry (ESI‐IMS‐MS) in conjunction with collision‐induced protein unfolding generated a conformational profile of each FGFR1–ligand complex. The results indicate that the protein's conformational profile depends on whether the inhibitor is type I or type II.ResultsX‐ray crystallography confirmed which of the kinase inhibitors bind to the active or inactive form of FGFR1 kinase. Collision‐induced unfolding combined with ESI‐IMS‐MS showed distinct differences in the FGFR1 folding landscape for type I and type II inhibitors. Biochemical studies indicated a similar range of FGFR1 affinities for both types of inhibitors, thus providing confidence that the conformational variations detected using ESI‐IMS‐MS can be interpretated unequivocally and that this is an effective screening method.ConclusionsA robust ESI‐IMS‐MS method has been implemented to distinguish between the binding mode of type I and type II inhibitors by monitoring the conformational unfolding profile of FGFR1. This rapid method requires low sample concentrations and could be used as a high‐throughput screening technique for the characterisation of novel kinase inhibitors.
Successful endobronchial occlusion in empyema with broncho‐pleural fistula secondary to COVID‐19 pneumonia: a case report and literature review
Authors: Nakano Takahito , Kawada Masahiro , Minami Kensuke , Kaneda Hiroyuki 
Published: May 2021

AbstractA few cases of empyema secondary to coronavirus disease 2019 (COVID‐19) pneumonia have been reported. Here, we report our experience of a successful endobronchial occlusion using endobronchial Watanabe spigots (EWSs) for empyema with broncho‐pleural fistula secondary to COVID‐19 pneumonia. A 62‐year‐old man was diagnosed with COVID‐19 and progressed to empyema with broncho‐pleural fistula. Computed tomography (CT) imaging showed cyst formation and the right B5b was presumed to be a branch dependent on the cyst. The effusion and air in the pleural cavity were well drained, although the air leak persisted. Endobronchial occlusion was performed for right B5a and B5b using 7‐ and 5‐mm EWSs (Novatech, France), respectively, and the air leak ceased. This is the first report of successful treatment of empyema with bronchial fistula with endobronchial occlusion. Air leak secondary to COVID‐19 pneumonia with a limited number of air cysts may be a good indication for endobronchial occlusion.
Human pegivirus type 1 infection in Asia—A review of the literature
Authors: Zimmerman Joseph , Blackard Jason T. 
Published: May 2021

SummaryThe human pegivirus type 1 (HPgV‐1)—as known as hepatitis G virus and GB virus C—is a common single‐stranded RNA flavivirus. Because few studies have demonstrated an association between HPgV‐1 infection and disease, screening for HPgV‐1 is not performed routinely. Nonetheless, a beneficial impact of HPgV‐1 infection on HIV disease progression has been reported in multiple studies. Given the burden of HIV in Asia and the complex interactions between viral co‐infections and the host, we provide a comprehensive overview of the existing data from Asia on HPgV‐1 infection, including the prevalence and circulating genotypes in all Asian countries with data reported. This review highlights the research conducted thus far and emphasizes the need for additional studies on HPgV‐1 across the Asian continent.
Composite learning adaptive dynamic surface control for uncertain nonlinear strict‐feedback systems with fixed‐time parameter estimation under sufficient excitation
Authors: Wu Zhonghua , Guo Jianfeng , Liu Bojun , Ni Junkang , Bu Xuhui 
Published: May 2021

AbstractThis paper presents a novel practical fixed‐time parameter identification algorithm and a composite learning based practical fixed‐time adaptive dynamic surface control (DSC) scheme for nonlinear strict‐feedback systems subject to linear‐in‐parameters uncertainties. The convergence of conventional parameter estimation algorithms often requires a restrictive prerequisite termed persistent excitation (PE) condition. By contrast, a new fixed‐time parameter identification algorithm configured with two layer transformation technique is firstly proposed under relaxed sufficient excitation condition rather than strict PE condition. The key point of avoiding PE condition is by introducing a smooth switching function to adjust the forgetting factor in the filtered regressor dynamics. Instead of using the fractional power of the tracking errors to construct the control laws, a smooth hyperbolic tangent function based adaptive DSC scheme is designed such that the potential singular problem caused by time derivations of virtual control laws in back‐stepping algorithm is avoided. Integrating the parameter identification algorithm into the adaptive DSC scheme, a composite learning based control is formed to guarantee the practical fixed‐time convergence of parameter estimation errors and tracking errors. Comparative simulation results are given to illustrate the effectiveness of the proposed algorithm.
Finite‐time output regulation for a class of nonlinear multi‐agent systems with unity relative degree
Authors: Wu Yanzhi , Liu Lu 
Published: May 2021

AbstractIn this paper, we consider a finite‐time output regulation problem for a class of nonlinear multi‐agent systems with unity relative degree. First, the robust estimation for the system matrix of the exosystem is achieved via a distributed observer, provided that the estimation error converges to zero within a finite time. Second, another observer is developed to estimate the nonlinear output of the exosystem, showing that the estimation error of the output of the exosystem reaches zero within a finite time under the assumption that only a subset of subsystems can obtain the output of the exosystem. Third, adaptive controllers are proposed such that the estimation error between the output of each subsystem and the estimated output of the exosystem converges to zero within a finite time by using the output information of each subsystem. Finally, the global finite‐time output regulation problem of nonlinear multi‐agent systems with unity relative degree is solved under a set of standard assumptions. A numerical example is presented to demonstrate the effectiveness of the proposed adaptive control strategy.
Shareholder activism and firms' voluntary disclosure of climate change risks
Authors: Flammer Caroline , Toffel Michael W. , Viswanathan Kala 
Published: May 2021

AbstractResearch SummaryThis article examines whether—in the absence of mandated disclosure requirements—shareholder activism can elicit greater disclosure of firms' exposure to climate change risks. We find that environmental shareholder activism increases the voluntary disclosure of climate change risks, especially if initiated by institutional investors, and even more so if initiated by long‐term institutional investors. We also find that companies that voluntarily disclose climate change risks following environmental shareholder activism achieve a higher valuation postdisclosure, suggesting that investors value transparency with respect to firms' exposure to climate change risks.Managerial SummaryClimate change poses increasing risks to companies. Yet, despite the growing importance of climate change risks, little is known about companies' exposure to climate change risks, their disclosure of these risks, and what strategic actions they take to manage and mitigate these risks. In this study, we examine whether—in the absence of mandatory disclosure—shareholders can elicit greater corporate transparency with respect to climate change risks. We find that shareholder activism is effective, especially if initiated by long‐term institutional investors. We also find that the stock market reacts positively to companies' climate risk disclosure following environmental shareholder activism, suggesting that investors value transparency with respect to firms' exposure to climate change risks.
Starch Acetate Nanoparticles as Controlled Release Nanocarriers for Piperine
Authors: Chin Suk Fun , Salim Asniar , Pang Suh Cem 
Published: May 2021

AbstractThis paper aims to synthesize starch acetate nanoparticles for controlled release of piperine. Starch acetate is synthesized by chemically modified sago starch with acetylation reaction. Starch acetate nanoparticles with mean particle sizes of 110 nm are obtained by controlled precipitation through drop‐wise addition of dissolved starch acetate solution into excess absolute ethanol. Piperine is loaded onto starch acetate nanoparticles and native starch nanoparticles via the in situ nanoprecipitation process. Starch acetate nanoparticles exhibit higher piperine loading capacity as compared to native starch nanoparticles with the maximum loading capacity of 0.46 and 0.33 mg mg–1, respectively. Piperine is observed to release from starch acetate nanoparticles in a slow and sustained manner at pH 1.2 for 24 h. In contrast, piperine is observed to fully release from native starch nanoparticles after 16 h.
Glyburide attenuates B(a)p and LPS‐induced inflammation‐related lung tumorigenesis in mice
Authors: Li Mengyuan , Liu Hong , Shao Hua , Zhang Peng , Gao Min , Huang Li , Shang Pingping , Zhang Qiao , Wang Wei , Feng Feifei 
Published: May 2021

AbstractGlyburide (Gly) could inhibit NLRP3 inflammasome, as well as could be treated with Type 2 diabetes as a common medication. Despite more and more studies show that Gly could influence cancer risk and tumor growth, it remains unclear about the effect of Gly in lung tumorigenesis. To evaluate whether Gly inhibited lung tumorigenesis and explore the possible mechanisms, a benzo(a)pyrene [B(a)p] plus lipopolysaccharide (LPS)‐induced non‐diabetes mice model was established with B(a)p for 4 weeks and once a week (1 mg/mouse), then instilled with LPS for 15 weeks and once every 3 weeks (2.5 μg/mouse) intratracheally. Subsequently, Gly was administered by gavage (10 μl/g body weight) 1 week before B(a)p were given to the mice until the animal model finished (when Gly was first given named Week 0). At the end of the experiment called Week 34, we analyzed the incidence, number and histopathology of lung tumors, and detected the expression of NLRP3, IL‐1β, and Cleaved‐IL‐1β protein. We found that vehicles and tricaprylin+Gly could not cause lung carcinogenesis in the whole process. While the incidence and mean tumor count of mice in B(a)P/LPS+Gly group were decreased compared with B(a)p/LPS group. Moreover, Gly could alleviate inflammatory changes and reduce pathological tumor nest numbers compared with mice administrated with B(a)p/LPS in histopathological examination. The B(a)p/LPS increased the expression of NLRP3, IL‐1β, and Cleaved‐IL‐1β protein significantly than Vehicle, whereas decreased in B(a)P/LPS+Gly (0.96 mg/kg) group compared with B(a)p/LPS group. Results suggested glyburide might inhibit NLRP3 inflammasome to attenuate inflammation‐related lung tumorigenesis caused by intratracheal instillation of B(a)p/LPS in non‐diabetes mice.
Autoimmune polyendocrine syndrome in a standard poodle with concurrent non‐endocrine immune‐mediated diseases
Authors: Kuijlaars Margaux , Yool Donald A. , Ridyard Alison E. 
Published: May 2021

AbstractA 6‐year‐old female neutered standard poodle was referred with a 4‐week history of rapidly progressive weight loss, muscle atrophy, hyporexia, hind limb weakness and lethargy. In the preceding 3‐month period, the dog had been diagnosed with both keratoconjunctivitis sicca (KCS) and hypoadrenocorticism. Clinical deterioration had occurred despite treatment for hypoadrenocorticism. Following referral, the dog was diagnosed with concurrent hypothyroidism, exocrine pancreatic insufficiency (EPI) and suspected generalised myositis. Treatment with hormone replacement therapy, pancreatic enzyme supplementation and immunosuppressive doses of prednisolone and mycophenolate resulted in marked clinical improvement. This case describes a rapidly progressive, presumed autoimmune, polyglandular endocrinopathy in a dog with concurrent non‐endocrine autoimmune diseases.
Anaesthetic and perioperative management of a dog with biventricular congestive heart failure and advanced second‐degree atrioventricular block
Authors: Foster Andrew , Seo Joonbum , Veres‐Nyéki Kata 
Published: May 2021

AbstractA 7‐year‐old male neutered Cocker Spaniel presented with a 6‐hour history of severe tachypnoea. Cardiac evaluation revealed advanced second‐degree atrioventricular block (2AVB) and biventricular congestive heart failure (CHF). Due to concerns of impending respiratory arrest, mechanical ventilation (MV) and emergency transvenous pacemaker implantation were planned. General anaesthesia was achieved using methadone premedication, midazolam and etomidate induction and isoflurane in oxygen maintenance. On intubation, large volumes of serosanguinous fluid poured from the airway with haemoglobin oxygen saturation (SPO2) reading 10%. Suctioning of the airway and initiation of MV improved SPO2to 85%. Temporary cardiac pacing was achieved with transthoracic pacing pads. Following uneventful pacemaker implantation, the dog continued on MV for 12 h with gradual resolution of pulmonary oedema assessed using serial thoracic ultrasound. The dog was successfully discharged 24 h later. This report highlights anaesthetic considerations and management of a critically ill bradycardic dog, with biventricular CHF.
Performance and responses of aerobic granular sludge at different concentrations of graphene oxide after a single administered dose
Authors: Tian Yuan , Yu Deshuang , Wang Yanyan , Chen Guanghui 
Published: May 2021

AbstractTo investigate the impact of graphene oxide (GO) under different concentrations (0, 50, 100, 150, and 200 mg/L) on aerobic granular sludge (AGS) after a single administered dose, the performance of nitrogen removal, microbial enzymatic activity, extracellular polymeric substances (EPSs), and microbial community structure was analyzed in batch tests. The results showed that the impact of GO concentrations on AGS was dose‐ and time‐dependent. Short‐term GO exposure could accelerate the nitrification process of AGS, while relatively concentrations (≥100 mg/L) inhibited the process when present for extended periods of time. The microbial enzymatic activity showed similar tendency. The production of lactate dehydrogenase release (LDH) in 200 mg/L group was increased 48.04% and EPS contents decreased 30.06% compared to the control group at 30th day and showed that high concentrations of GO have toxic effects on AGS. The microbial bacteria responded differently to the stimulation of different concentrations of GO.Practitioner points

GO affected AGS system performance in concentration‐ and time‐dependent manners.
The nitrification rate of AGS increased in the short term and reversed over time.
Long‐term exposure to high GO concentrations caused toxicity to AGS.
Different microorganisms had diverse responses to GO concentrations.
Identifying and Mastering Legal Uncertainty Concerning Autonomous Systems
Authors: Joggerst Laura , Wendt Janine 
Published: May 2021

Abstract
The level of uncertainty concerning the use of autonomous systems is still very high. This also poses a liability risk for manufactures, which can impede the pace of innovation. Legal uncertainty also contributes to this factor. This paper will discuss existing legal uncertainty. The identified uncertainty can stem from different sources. Categorizing these sources will be our first step when trying to master legal uncertainty. On the basis of these categories, we will be able to evaluate where the focus for mastering legal uncertainty should lie. This approach promises to identify true legal uncertainty, which can only be mastered by new legislation, and separate it from other forms of legal uncertainty which can stem from unclear legal guidelines or uncertainty regarding the application and scope of existing rules and guidelines. Mastering the latter could be possible by specifying said existing rules and guidelines or even by clarifying the scope of their application, a much less drastic solution. Establishing how to deal with different categories of legal uncertainty will then contribute to minimizing liability risks for manufacturers.
Reconstructing Stress Resultants in Wind Turbine Towers Based on Strain Measurements
Authors: Kinne Marko , Schneider Ronald , Thöns Sebastian 
Published: May 2021

AbstractSupport structures of offshore wind turbines are subject to cyclic stresses generated by different time-variant random loadings such as wind, waves, and currents in combination with the excitation by the rotor. In the design phase, the cyclic demand on wind turbine support structure is calculated and forecasted with semi or fully probabilistic engineering models. In some cases, additional cyclic stresses may be induced by construction deviations, unbalanced rotor masses and structural dynamic phenomena such as, for example, the Sommerfeld effect. Both, the significant uncertainties in the design and a validation of absence of unforeseen adverse dynamic phenomena necessitate the employment of measurement systems on the support structures. The quality of the measurements of the cyclic demand on the support structures depends on (a) the precision of the measurement system consisting of sensors, amplifier and data normalization and (b) algorithms for analyzing and converting data to structural health information. This paper presents the probabilistic modelling and analysis of uncertainties in strain measurements performed for the purposes of reconstructing stress resultants in wind turbine towers. It is shown how the uncertainties in the strain measurements affect the uncertainty in the individual components of the reconstructed forces and moments. The analysis identifies the components of the vector of stress resultants that can be reconstructed with sufficient precision.
Robust Topology Optimization of Truss-Like Space Structures
Authors: Hartisch Michael , Reintjes Christian , Marx Tobias , Lorenz Ulf 
Published: May 2021

AbstractDue to the additional design freedom and manufacturing possibilities of additive manufacturing compared to traditional manufacturing, topology optimization via mathematical optimization gained importance in the initial design of complex high-strength lattice structures. We consider robust topology optimization of truss-like space structures with multiple loading scenarios. A typical dimensioning method is to identify and examine a suspected worst-case scenario using experience and component-specific information and to incorporate a factor of safety to hedge against uncertainty. We present a quantified programming model that allows us to specify expected scenarios without having explicit knowledge about worst-case scenarios, as the resulting optimal structure must withstand all specified scenarios individually. This leads to less human misconduct, higher efficiency and, thus, to cost and time savings in the design process. We present three-dimensional space trusses with minimal volume that are stable for up to 100 loading scenarios. Additionally, the effect of demanding a symmetric structure and explicitly limiting the diameter of truss members in the model is discussed.
Modelling of Resilient Coping Strategies within the Framework of the Resilience Design Methodology for Load-Carrying Systems in Mechanical Engineering
Authors: Schulte Fiona , Kloberdanz Hermann , Kirchner Eckhard 
Published: May 2021

AbstractDuring the development of load-carrying systems uncertainty caused by nescience can be handled applying resilience design. With this systematic approach, in addition to robust design, resilient system properties can be achieved. The resilience design methodology comprises new and extended models and methods. The central aspect of resilient properties is an adaptivity of the system. The procedure for resilience design starts with choosing a ‘general coping strategy’ appropriate for the design task. Based on this, a more detailed ‘system coping strategy’ is developed. This concrete strategy is based on the resilience functions responding, monitoring, anticipating and learning. The coping strategies always contain the function ‘responding’ because it represents the actual adaption of the system. The central, most abstract synthesis model for developing robust and resilient systems is the functional structure model. In this model the system functions and their interconnection by signals, material and energy flows are depicted. However, the realisation of resilience properties requires additional signals and flows. Hitherto, the functional structure for robust systems is static, whereas adaptivity requires flexible control of functions and flows. Therefore, an extension of the functional structure model is proposed to be able to depict the resilient system coping strategy and adaptivity. Within the resilient system the coping strategy is depicted by adaption functions based on the four resilience functions. Via an introduced interface and an enabler-structure the adaption functions are connected to the robust functional structure. The application of the proposed extension is illustrated by the example of a by-wire car brake system.
Comparability of Water Infrastructure Resilience of Different Urban Structures
Authors: Lorenz Imke-Sophie , Pouls Kevin , Pelz Peter F. 
Published: May 2021

AbstractUrban water distribution systems (WDS) ensure the demand-driven supply of a city at multiple ends. Well-being of the population as well as multiple economic sectors depend on its viability and thereby classify it as a critical infrastructure. Therefore, its behavior when exposed to changes is of interest to water suppliers as well as local decision-makers. It can be determined by resilience metrics, assessing the capability to meet and recover its functioning when exposed to disturbances. These disturbances can occur in form of changes in the water availability, the WDS topology, or the water demand pattern. Since networks as WDS are studied by graph theory, also different graph-theoretical resilience metrics were derived. In this work a well-established topology-based resilience metric is adapted and deployed to assess the present resilience of the urban main-line WDS of the German city of Darmstadt as well as of a suburb in the Rhine-Main region. Thereby, the intercomparability of the resilience for the different urban structures were of interest. Based on this analysis the comparability of different urban main-line WDS regarding their resilience is facilitated. Additionally, the conducted approach to allow for the comparability of absolute resilience values of urban structures of varying size can be applied to different resilience metrics as well as technical systems.