bluuebunny/crossref_metadata_2025 huggingface dataset:
Long non‐coding RNA HOTAIR/microRNA‐761 sponge regulates PPME1 and further influences cell biological functions in thyroid carcinoma
Authors: Guo Runsheng , Ning Yong , Ma Ye , Lin Qianhuang , Shen Na , Shi Peidong
Published: May 2021

Background

Most well‐differentiated thyroid carcinomas display good therapeutic outcomes, but there are still some patients who are not sensitive to the general treatments lose their treatment opportunities. Thus, it is important to understand the molecular mechanisms that cause thyroid carcinoma, so as to find effective diagnostic and therapeutic targets.

Aim of the study

To explore the role of homeobox transcript antisense RNA (HOTAIR) in thyroid carcinoma through protein phosphatase methylesterase 1 (PPME1) by sponging microRNA 761 (miR‐761).

Methods

The regulation network amongst HOTAIR, miR‐761 and PPME1 was predicted by online sources. RT‐PCR was conducted to evaluate the expression of HOTAIR and miR‐761 in tumor tissues. Clinical data was collected and analyzed by Chi‐square test. Cell apoptosis and proliferation was evaluated using three types of cancer cells (HTh‐7, CAL‐62, BCPAP) after treated with si‐HOTAIR and miR‐761inhibitor. The binding site among HOTAIR, miR‐761 and PPME1 was verified by dual luciferase reporter assay. PPME1 expression was measured after HOTAIR and miR‐761 were suppressed by western blot. Survival time was measured in nude mice using log‐rank test.

Results

HOTAIR was expressed to a significantly greater extent than miR‐761 in thyroid tumor tissues (P < .001). miR‐761 and PPME1 were negatively correlated (coef = −1.91, P < .001). HOTAIR competitively binds to miR‐761 and miR‐761 directly targets PPME1. HOTAIR was highly correlated with TNM (χ2 = 5.797, P = .016), tumor size (χ2 = 7.955, P = .005) and lymphatic metastasis (χ2 = 6.0, P = .014). HOTAIR promoted cell proliferation and inhibited cell apoptosis, whereas miR‐761 did not. HOTAIR elevated and miR‐761 suppressed PPME1 expression. HOTAIR expression appears to affect the survival time in vivo.

Conclusion

HOTAIR regulated thyroid cancer cells by binding to miR‐761 through PPME1.
H. pylori infection induces CXCL8 expression and promotes gastric cancer progress through downregulating KLF4
Authors: Liu Zhengxia , Wu Xiao , Tian Yuanyuan , Zhang Wanchun , Qiao Siyuan , Xu Wenting , Liu Yakun , Wang Siying
Published: May 2021

Tumour‐derived CXCL8 facilitates the movement of myeloid‐derived suppressor cells, which are able to restrain antitumour immune responses to the tumour microenvironment. Kruppel‐like factor 4 (KLF4) is a potential tumour suppressor in gastric cancer (GC). However, knowledge regarding correlations between KLF4 and CXCL8 in GC is limited. We use cellular and molecular biological methods to assess whether these two factors interact in GC. Expression CXCL8 and KLF4 was altered in human GC tissues compared to normal gastric tissues in opposite ways. Additionally, cytotoxin‐associated gene A protein (CagA) gene transduction or Helicobacter pylori (H. pylori) infection upregulated CXCL8 expression. Knockdown of KLF4 expression increased CXCL8 protein and RNA expression, whereas its overexpression had the opposite effect. CXCL8‐mediated enhancement of GC cell migration and proliferation was reversed by upregulation of KLF4 expression. Further mechanistic research revealed that KLF4 binds the CXCL8 promoter, suppressing CXCL8 transcription. Moreover, CXCL8 stimulation reduced KLF4 protein expression and promoted GC cell proliferation and migration, eventually promoting neoplasm growth in vivo. Together, our findings demonstrate that CagA promotes CXCL8 and inhibits KLF4. CXCL8 is a decisive downstream target gene of KLF4, and KLF4 negatively regulates CXCL8 in GC. Furthermore, CXCL8's negative regulation of KLF4 in vivo and in vitro, indicates that CagA may downregulate KLF4 by inducing CXCL8 expression, low expression of KLF4 further promotes that of CXCL8, forming a vicious circle in GC. Targeted KLF4 activation might improve the immunosuppressive microenvironment through direct negative regulation of CXCL8, providing a new potential target to strengthen the efficacy of immunotherapy in GC patients.
Superconvergence analysis of nonconforming EQ1rot element for nonlinear parabolic integro‐differential equation
Authors: Liang Conggang , Wang Junjun
Published: May 2021

In this paper, superconvergent analysis for nonlinear parabolic integro‐differential equation is studied with nonconforming element. A linearized Galerkin finite element method is introduced, and a time‐discrete system is constructed to split the error into two parts. On the one hand, a rigorous analysis for the regularity of the time‐discrete system is presented based on the temporal error estimation skillfully. On the other hand, the spatial error is deducedτ‐independently with the above achievements. With the help of typical characters of this element, the superclose result of order in the brokenH1‐norm is derived without any restriction ofτ. At last, numerical results are provided to confirm the theoretical analysis. Here,his the subdivision parameter, andτis the time step.
The number of Dirac‐weighted eigenvalues of Sturm–Liouville equations with integrable potentials and an application to inverse problems
Authors: Chen Xiao , Qi Jiangang
Published: May 2021

In this paper, we further Meirong Zhang et al.'s work by computing the number of weighted eigenvalues for Sturm–Liouville equations, equipped with general integrable potentials and Dirac weights, under Dirichlet boundary condition. We show that, for a Sturm–Liouville equation with a general integrable potential, if its weight is a positive linear combination of n Dirac delta functions, then it has at most n (may be less than n, or even be 0) distinct real Dirichlet eigenvalues, or every complex number is a Dirichlet eigenvalue; in particular, under some sharp condition, the number of Dirichlet eigenvalues is exactly n. Our main method is to introduce the concepts of characteristics matrix and characteristics polynomial for Sturm–Liouville problem with Dirac weights and put forward a general and direct algorithm used for computing eigenvalues. As an application, a class of inverse Dirichlet problems for Sturm–Liouville equations involving single Dirac distribution weights is studied.
Using Population Dynamics to Model Harvest Regulation Impacts to Channel Catfish in the Monongahela River, West Virginia
Authors: Chestnut-Faull Kristen L. , Phelps Quinton E. , Smith Dustin M. , Wellman David I.
Published: May 2021

Channel Catfish Ictalurus punctatus were collected during 2018 and 2019 from the Monongahela River in West Virginia using hoop nets to estimate population dynamics. Length, weight, sex, fecundity, and age data were obtained from collected individuals. Population characteristics (e.g., relative abundance, size structure, age structure, growth, etc.) were modeled under three proposed length limits of 300, 375, and 450 mm. Simulation results indicated that growth overfishing may occur when exploitation rates reach 36% under a 300-mm minimum length limit. Furthermore, recruitment overfishing began to occur at 40% exploitation under a 300-mm minimum length limit. Additionally, simulations suggest that no recruitment or growth overfishing occur at minimum length limits of 375 mm or 450 mm until extremely high exploitation levels (>90%) are reached. Thus, future consideration should be given for implementation of a 375-mm minimum length limit of Channel Catfish in the Monongahela River to prevent growth and recruitment overfishing while also ensuring anglers are still able to harvest Channel Catfish.
NONMEM population pharmacokinetics and Monte Carlo dosing simulations of imipenem in critically ill patients with life‐threatening severe infections during support with or without extracorporeal membrane oxygenation in an intensive care unit
Authors: Jaruratanasirikul Sutep , Boonpeng Apinya , Nawakitrangsan Monchana , Samaeng Maseetoh
Published: May 2021

Study Objectives

The objectives of this study were (i) to determine the population pharmacokinetic (PK) of imipenem in critically ill patients with life‐threatening severe infections, (ii) to investigate the impact of extracorporeal membrane oxygenation (ECMO) on the population PK of imipenem during support with ECMO compared to those without ECMO support, and (iii) to assess the probability of target attainment (PTA) for finding the optimal dosage regimens of imipenem in critically ill patients with life‐threatening severe infections.

Design

Open‐label, PK study.

Setting

Academic tertiary care medical center.

Patients

Fifty critically ill patients with or without ECMO by pooling data from previously published studiesand unpublished data from 14 patients.

Intervention and Measurements

The population PK of imipenem was determined using NONMEM and a Monte Carlo simulation was performed to determine the PTAs of achieving 40% and 75% exposure times during which the plasma drug concentrations remained above the MIC.

Main Results

The values of volume of distribution and total clearance were 30.5 L and 13.3 L/h, respectively. The ECMO circuit did not show a significant influence on the PK parameters of imipenem. For pathogens with a MIC of 4 mg/L, the PTA target of 75% fT>MIC in patients with normal renal function was achieved when the imipenem was administered by a 4‐h infusion of 1 g q6h.

Conclusion

The ECMO circuit had little effect on enhancing the PK changes of imipenem that had already occurred in these patients. A high dosage of imipenem may be required for achieving the PK/pharmacodynamic targets against less susceptible pathogens, however, the dosage regimens in patients with renal impairment may not need to be as high as those required in patients with normal renal function.

ClinicalTrials.gov: NCT03858387.
Decay mechanisms in CdS‐buffered Cu(In,Ga)Se2thin‐film solar cells after exposure to thermal stress: Understanding the role of Na
Authors: Yetkin Hasan A. , Kodalle Tim , Bertram Tobias , Villanueva‐Tovar Alejandra , Rusu Marin , Klenk Reiner , Szyszka Bernd , Schlatmann Rutger , Kaufmann Christian A.
Published: May 2021

Due to their tunable bandgap energy, Cu(In,Ga)Se2(CIGSe) thin‐film solar cells are an attractive option for use as bottom devices in tandem configurations. In monolithic tandem devices, the thermal stability of the bottom device is paramount for reliable application. Ideally, it will permit the processing of a top device at the required optimum process temperature. Here, we investigate the degradation behavior of chemical bath deposited (CBD) CdS‐buffered CIGSe thin‐film solar cells with and without Na incorporation under thermal stress in ambient air and vacuum with the aim to gain a more detailed understanding of their degradation mechanisms. For the devices studied, we observe severe degradation after annealing at 300°C independent of the atmosphere. The electrical and compositional properties of the samples before and after a defined application of thermal stress are studied. In good agreement with literature reports, we find pronounced Cd diffusion into the CIGS absorber layer. In addition, for Na‐containing samples, the observed degradation can be mainly explained by the formation of Na‐induced acceptor states in the TCO front contact and a back contact barrier formation due to the out‐diffusion of Na. Supported by numerical device simulation using SCAPS‐1D, various possible degradation models are discussed and correlated with our findings.
Effect of gas pressure on the microstructure of parts foamed with the novel microcellular injection molding technology Ku‐Fizz™
Authors: Simon Sara Andrea , Hain Jörg , Osswald Tim
Published: May 2021

The increasing demand for lightweight and economical automotive components boosts investigation of advanced materials and new lightweighting technologies. This work employs the novel microcellular injection molding technology Ku‐Fizz™. The process introduces gas with granulates at moderate low pressures into the feed zone of the injection molding machine. Ku‐Fizz is controlled by gas pressure; thus, a simple plate geometry was molded and the effect of various gas contents on the microstructure was analyzed. The material used was a chemically coupled glass fiber‐reinforced polypropylene compound. Optical microscopy was employed to measure the foam microstructure. Microcomputed tomography was used to quantify the fiber volume fraction and the orientation tensors. Results of the fully characterized microstructure showed cell density increasing and cell size decreasing with gas pressure and melt flow direction. Fiber length increased with gas content. Cell growth displaced fibers from the center of the part towards the mold surface, changing the fiber concentration and global fiber orientation.
Three‐dimensional printed realistic pediatric static and dynamic airway models for bronchoscopy and foreign body removal training
Authors: Maier Pia , Silvestro Elizabeth , Goldfarb Samuel B. , Piccione Joseph , Phinizy Pelton A. , Andronikou Savvas
Published: May 2021

For mastering bronchoscope handling, positioning, and directing of the bronchoscope in response to the intraluminal view provided by the bronchoscope camera, sufficient training is necessary, especially in infants and toddlers who have smaller airways, faster respiratory rates, and higher airway collapsibility. With the use of three‐dimensional printing, we aimed to develop a set of anatomically accurate and low‐cost airway models for teaching and training of bronchoscopy technique and foreign body removal: a translucent airway box model, a static airway model, and a dynamic airway model consisting of a flexible tree model connected to a pump that allows simulation of airway collapsibility during breathing. Computed tomography (CT) patient data of three different ages (1, 5, and 18 years of age) was imported into Materialise Mimics, segmented, and printed using VisoClear and soft Tango+ material. The models were evaluated by three pediatric pulmonology attendings for anatomical accuracy and usefulness for teaching and training. The translucent airway box model was preferred for the initial presentation of bronchoscope handling and learning anatomy in three dimensions. The static and flexible tree models were used to train bronchoscope handling and foreign body removal. The dynamic model provided the most realistic representation of a pediatric airway throughout the respiratory cycle with increased patency during inspiration and relative collapse during exhalation. Objective verification of anatomical accuracy and physiology of breathing motion was obtained by comparing CT scans of the model with original images and by application of 4D dynamic CT airway imaging protocols, respectively.
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

Rationale

The 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.

Methods

X‐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.

Results

X‐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.

Conclusions

A 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

A 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

The 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

This 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

In 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.
Experimental study and thermal spike modeling of sputtering in SiO2 thin films under MeV Auq+ heavy ion irradiation
Authors: Boubir Abir , Mammeri Ster , Dib Amel , Ammi Hakim , Msimanga Mandla , Bouldjedri Abdelhamid , Matshali Christopher , Mlungisi Nkosi
Published: May 2021

The sputtering of silicon dioxide (SiO2/Si) thin films deposited onto silicon substrates and irradiated by swift Auq+ heavy ions (q = +4 to +9) has been investigated both by experiment and via numerical modeling by varying the kinetic energy from 10 to 40 MeV. The induced sputtering yields were determined experimentally via the Rutherford backscattering spectrometry (RBS) technique using a 2‐MeV He+ ion beam. The obtained experimental results were first plotted versus the target electronic stopping power together with previous data available for the same projectile‐target system at high kinetic energies, indicating increased sputtering yields with increasing electronic energy loss. Then, the whole data were compared with numerical sputtering yield values derived both from the inelastic thermal spike model and the SRIM‐2013 simulation code by including, respectively, nonlinear elastic spikes and linear elastic collision cascades. A good agreement was observed between the measured sputtering yield data and i‐TS predicted values over higher incident energies used by using refined parameters of the ion slowing down with reduced thermophysical properties of the SiO2 thin film. Finally, the synergy between electronic and nuclear energy loss processes inducing sputtering at low incident energies was discussed through the comparison between experimental and numerical yield data.
Shareholder activism and firms' voluntary disclosure of climate change risks
Authors: Flammer Caroline , Toffel Michael W. , Viswanathan Kala
Published: May 2021

Research Summary

This 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 Summary

Climate 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.
Over 13% Efficient Organic Solar Cells Based on Low‐Cost Pentacyclic A‐DA′D‐A‐Type Nonfullerene Acceptor
Authors: Song Jiage , Cai Fangfang , Zhu Can , Chen Honggang , Wei Qingya , Li Dongxu , Zhang Chujun , Zhang Rui , Yuan Jun , Peng Hongjian , So Shu Kong , Zou Yingping
Published: May 2021

Recent studies have almost focused on finding active layer materials with extended π‐conjugation structures for high‐performance organic solar cells (OSCs). However, with the extension of conjugate length, the synthesis difficulty and cost of materials will increase. Achieving high efficiency while reducing material costs is a prerequisite for the commercialization of OSCs. Herein, two low‐cost A‐DA′D‐A‐type (where A and D represent an electron‐withdrawing unit and an electron‐donating unit, respectively) nonfullerene acceptors (Y25,Y26) are synthesized with pentacyclic fused backbone as the DA′D electron‐deficient core and 5,6‐difluoro‐3‐(dicyandiamethyl) indigo as the end groups. Compared with classical Y series acceptors with heptacyclic backbone, although Y25 and Y26 own the reduced conjugated length, they still show moderate performance (11.65% and 13.34%), and the cost of synthesis is significantly reduced. Therefore, we provide a new molecular design idea for commercially efficient nonfullerene OSCs acceptors. We also find that adding alkyl chains to the β site of thiophenes is beneficial to obtaining the reduced energetic disorder, dominant molecular stacking, and desirable morphology, which can facilitate charge carrier transport and prompt higher short‐circuit current density (Jsc) as well as fill factor.
Starch Acetate Nanoparticles as Controlled Release Nanocarriers for Piperine
Authors: Chin Suk Fun , Salim Asniar , Pang Suh Cem
Published: May 2021

This 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

Glyburide (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

A 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

A 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

To 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

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

Support 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

Due 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

During 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

Urban 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.
Dealing with Uncertainties in Fatigue Strength Using Deep Rolling
Authors: Yüksel Berkay , Görtan Mehmet Okan
Published: May 2021

Mechanical properties inherently possess uncertainties. Among these properties, fatigue behavior data generally shows significant scatter which introduces a challenge in the safe design of dynamically loaded components. These uncertainties in fatigue behavior are mainly results of factors related to surface state including: Roughness, tensile residual stresses, scratches and notches at surface. Therefore, controlling these parameters allows one to increase fatigue strength and reduce scatter and uncertainties in fatigue behavior. Mechanical surface treatments are applied on parts to increase fatigue strength via introducing compressive residual stresses and work-hardening at surface. Two of the most common among these treatments are shot peening and deep rolling. Shot peening has found many applications in industry because of its flexibility. However, it introduces irregularities at the surface and may increase roughness which causes uncertainties in the fatigue behavior data; especially for low-medium strength materials. Unlike shot peening, deep rolling reduces surface roughness. Therefore, it has the capability to reduce uncertainty in the fatigue behavior. To this date, rolling direction of deep rolling was selected as tangential direction to turning direction for axisymmetric parts. Nonetheless, the authors believe that the rolling direction has an apparent effect on the fatigue behavior. In this study, longitudinal direction was also applied for deep rolling operation and the results of these two direction applications on the EN-AW-6082 aluminum alloy were investigated. It was shown that, longitudinal rolling had yielded less scatter and uncertainty in the fatigue behavior than the tangential rolling together with the higher fatigue strength.
RiskStructures
: A design algebra for risk-aware machines
Authors: Gleirscher Mario , Calinescu Radu , Woodcock Jim
Published: May 2021

Machines, such as mobile robots and delivery drones, incorporate controllers responsible for a task while
handling risk
(e.g. anticipating and mitigating hazards; preventing and alleviating accidents). We refer to machines with this capability as risk-awaremachines.
Risk awareness
includes robustness and resilience and complicates monitoring (i.e., introspection, sensing, prediction), decision making, and control. From an engineering perspective, risk awareness adds a range of dependability requirements to
system assurance
. Such assurance mandates a correct-by-construction approach to controller design, based on mathematical theory.We introduce RiskStructures, an algebraic framework for risk modelling intended to support the design of
safety controllers
for risk-aware machines. Using the concept of a
risk factor
as a modelling primitive, this framework provides facilities to construct, examine, and assure these controllers.We prove desirable algebraic properties of these facilities, and demonstrate their applicability by using them to specify key aspects of safety controllers for risk-aware automated driving and collaborative robots.
Enhancing Probabilistic Model Checking with Ontologies
Authors: Dubslaff Clemens , Koopmann Patrick , Turhan Anni-Yasmin
Published: May 2021

Probabilistic model checking (PMC) is a well-established method for the quantitative analysis of state based operational models such as Markov decision processes. Description logics (DLs) provide a well-suited formalism to describe and reason about knowledge and are used as basis for the web ontology language (OWL). We investigate how such knowledge described by DLs can be integrated into the PMC process, introducingontology-mediatedPMC. Specifically, we proposeontologized programsas a formalism that links ontologies to behaviors specified by probabilistic guarded commands, the de-facto standard input formalism for PMC tools such as Prism. Through DL reasoning, inconsistent states in the modeled system can be detected. We present three ways to resolve these inconsistencies, leading to different Markov decision process semantics. We analyze the computational complexity of checking whether an ontologized program is consistent under these semantics. Further, we present and implement a technique for the quantitative analysis of ontologized programs relying on standard DL reasoning and PMC tools. This way, we enable the application of PMC techniques to analyze knowledge-intensive systems.We evaluate our approach and implementation on amulti-server systemcase study,where different DL ontologies are used to provide specifications of different server platforms and situations the system is executed in.
“To be or not to be” located in a cluster?—A descriptive meta-analysis of the firm-specific cluster effect
Authors: Grashof Nils , Fornahl Dirk
Published: May 2021

In the twenty-first century, clusters can be observed in most developed economies. However, the scientific results regarding the effect of clusters on firm performance are highly contradictive. The inconsistencies in the empirical results make it difficult to infer general conclusions about the firm-specific cluster effect, or in other words, the effect from being located in a cluster on firm performance (e.g. derived through the externalities within clusters). Therefore, this paper aims to reconcile the contradictory empirical findings. It investigates whether the prevalent assumption that clusters are a beneficial location for firms is unconditionally true or whether doubts about the alleged positive effect of clusters on firm performance are justified. By conducting a descriptive meta-analysis of the empirical literature, based on four different performance variables from four separate publication databases, the study investigates the direction of the effect as well as possible moderating influences. We find evidence for a rather positive firm-specific cluster effect. However, we identify several variables from the micro-, meso- and macro-level that directly or interactively moderate the relationship between clusters and firm success. For example, the results demonstrate that a negative firm-specific cluster effect occurs more frequently in low-tech industries than in high-tech industries. “To be or not to be” located in a cluster is therefore not the question, but it rather depends on the specific conditions.