bluuebunny/crossref_metadata_2025 huggingface dataset:
Electromagnetohydrodynamic boundary layer flow in hybrid nanofluid with thermal radiation effect: Numerical simulation
Authors: Sulochana C. , Prasanna Kumar T.
Published: March 2022

Hybrid nanofluid boundary layer flow past a stretching surface with zero mass flux boundary condition is explored in this article. The main aim of this article is to analyze the electromagnetohydrodynamic role in a hybrid nanofluid containing silver and molybdenum disulfide nanoparticles. The self‐similar solution is embedded to reduce the governing partial differential equation into algebraic equations and a shooting algorithm is applied to obtain the solution of the resultant boundary value problem. Variation in momentum, energy, and nanoparticle concentration is explained through graphical profiles. Nusselt number and drag force coefficients are computed for various flow parameters and their impact on the nanofluid and hybrid nanofluid is computed and presented and explained in a comparative fashion. It is observed that the velocity profile shows the opposite nature with respect to the electric field and magnetic field. For electric field parameter velocity accelerates whereas for magnetic parameter velocity diminishes. Nusselt number increases with electric field parameter and nanoparticle volume fraction.
Pharmacological role of Vitamin C in stress‐induced cardiac dysfunction via alteration in Gut microbiota
Authors: Anwar Firoz , Alhayyani Sultan , Al‐Abbasi Fahad A. , Nadeem Muhammad Shahid , Kumar Vikas
Published: March 2022

There is emerging evidence exhibiting the strong association of gut microbiota with cardiovascular metabolic functions. Cardiac diseases may alter the richness, diversity, and composition of the gut microbiome. Vitamin C (Vit C) plays an important role in many metabolic activities in cardiovascular diseases. In this study, we induced cardiac remodeling by the forced swim stress model in rats, which resulted in dysbiosis. Adult male Wistar rats were designated into the following groups: (i) normal control (NC), (ii) forced swim induced stress (FSIS) control, (iii) FSIS + Vit C treatment, and (iv) Vit C control. Stool samples were collected for estimation for 90 days, and at the end of the study, the animals were killed and heart tissue was isolated for histochemical analysis. We observed a sharp fall in the operational taxonomic unit in the FSIS control animals as compared to NC animals. Treatment with Vit C exhibited a decrease in Bacteroidetes while raising the abundance of spirochetes. Plasma levels of creatine kinase myocardial band (CKMB) in the treatment group reduced to 175.7 ± 3.41 U/L, from 317.7 ± 34.48 U/L in the diabetic control group. Also, the C‐reactive protein level in the disease control group was 18 ± 0.93 mg/dl, which reduced to the normal level of 7.53 ± 0.20 mg/dl on treatment with Vit C administration. Our results suggest that FSIS induced cardiac complication is also associated with changes in gut microbial abundance. Higher doses of Vit C, which strengthens the immunity, have shown some positive outcomes on cardiac complications. The abundance of gut microbiota is also associated with the immune system, which in turn marks the impact of a disease. More the richness and diversity of the gut microbiome, healthier is the composition that can withstand the external threats of disease and other major challenges in the environment. Hence microbiome abundance plays an important role in the therapies or future prospects of disease. Histopathological studies support the serological and microbiome examination and warrant the cardioprotective influence of Vit C in the stress‐induced cardiac dysfunction model.
microRNA‐486‐5p is implicated in the cisplatin‐induced apoptosis and acute inflammation response of renal tubular epithelial cells by targeting HAT1
Authors: Lin Fang‐You , Han Shang‐Ting , Yu Wei‐Min , Rao Ting , Ruan Yuan , Yuan Run , Li Hao‐Yong , Ning Jin‐Zhuo , Xia Yu‐Qi , Xie Jin‐Na , Qi Yu‐Cheng , Zhou Xiang‐Jun , Cheng Fan
Published: March 2022

The proinflammatory property of cisplatin is potentially destructive and contributes to the pathogenesis of acute kidney injury (AKI). The role and upstream regulatory mechanism of histone acetyltransferase 1 (HAT1) in acute kidney inflammation are still unknown. We performed RNA sequencing to filter differentially expressed microRNAs (miRNAs) in the kidney tissue of mice with AKI induced by cisplatin and ischemia‐reperfusion. Here, we found that miR‐486‐5p was upregulated and that the expression of HAT1 was reduced in AKI mouse models and injured human renal proximal tubular epithelial cell (HK‐2) model induced by cisplatin. miR‐486‐5p is implicated in cisplatin‐induced kidney damage in vivo. Bioinformatics analysis predicted a potential binding site between miR‐486‐5p and HAT1. The Luciferase reporter assay and Western blot confirmed that miR‐486‐5p directly targeted the 3′‐untranslated region of HAT1 mRNA and inhibited its expression in the cytoplasm of HK‐2 cells. In the in vitro study, inhibiting miR‐486‐5p reduced apoptosis, and the expression of proinflammatory mediators was induced by cisplatin in HK‐2 cells. Simultaneously, the downregulation of miR‐486‐5p inhibited the activation of the toll‐like receptor 4 (TLR4) and nuclear factor‐kappa B (NF‐κB). We further found that HAT1 could inhibit apoptosis and the activation of cisplatin on the TLR4/NF‐κB pathway and that the upregulation of miR‐486‐5p reversed this effect. Therefore, the upregulation of miR‐486‐5p targeting HAT1 promoted the cisplatin‐induced apoptosis and acute inflammation response of renal tubular epithelial cells by activating the TLR4/NF‐κB pathway, providing a new basis to highlight the potential intervention of regulating the miR‐486‐5p/HAT1 axis.
2‐mercaptobenzothiazole generates γ‐H2AX via CYP2E1‐dependent production of reactive oxygen species in urothelial cells
Authors: Qi Yonggang , Toyooka Tatsushi , Horiguchi Hyogo , Koda Shigeki , Wang Rui‐Sheng
Published: March 2022

Ortho (o)‐toluidine is a widely known carcinogenic substance associated with cancers of the human bladder. A study on British chemical factory workers exposed to 2‐mercaptobenzothiazole, phenyl‐β‐naphthylamine, aniline, and o‐toluidine demonstrated the crucial roles of o‐toluidine, 2‐mercaptobenzothiazole, and phenyl‐β‐naphthylamine in the development of bladder cancer. As genotoxic events are crucial steps in the initiation of cancer, in the present study, we aimed to examine the genotoxic potential of the four chemicals using phosphorylated histone H2AX (γ‐H2AX), which is a sensitive and reliable marker of DNA damage, in cultured human urothelial cells. Of the four chemicals, 2‐mercaptobenzothiazole was a particularly potent DNA‐damaging agent. Moreover, mechanistic studies revealed that γ‐H2AX generation by 2‐mercaptobenzothiazole was mainly associated with the generation of reactive oxygen species via cytochrome P450 2E1‐mediated metabolism. The findings of this study may provide information that is important for the assessment of risks associated with chemicals as well as the interpretation of epidemiological studies investigating occupational bladder cancer.
The effect of off‐centerσ‐hole on the atom‐centered partial charges in halogenated molecules
Authors: Leskourová Aneta , Kolář Michal H.
Published: March 2022

Partial atomic charges belong to key concepts of computational chemistry. In some cases, however, they fail in describing the electrostatics of molecules. One such example is the ‐hole, a region of positive electrostatic potential located on halogens and other atoms. In molecular mechanics, the ‐hole is often modeled as a pseudo‐atom with a positive partial charge located off the halogen nucleus. Here we address a question, to what extent the pseudo‐atom affects partial charges of other atoms in the molecule. To this aim, we have thoroughly analyzed partial charges of over 2300 halogenated molecules from the ZINC database calculated by the restricted electrostatic potential (RESP) method and compared them with the charges fitted by RESP including the pseudo‐atom. We show that the pseudo‐atom improves charge fitting for a vast majority of molecules. The ‐hole, modeled as the off‐center charge, affects the atoms within three covalent bonds from the halogen.
No impact of donor sex on the recurrence of hepatocellular carcinoma after liver transplantation
Authors: Taura Kojiro , Shimamura Tsuyoshi , Akamatsu Nobuhisa , Umeshita Koji , Fujiyoshi Masato , Abe Hiroyasu , Morita Satoshi , Uemoto Shinji , Eguchi Susumu , Furukawa Hiroyuki , Takada Yasutsugu , Egawa Hiroto , Ohdan Hideki , Hatano Etsuro ,   the Japanese Liver Transplantation Society
Published: March 2022

Background/Purpose

We aimed to verify a recent theory that female donors reduced the risk of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT).

Methods

A total of 1118 recipients registered in the Japanese Liver Transplantation Society database were evaluated for HCC, of whom 446 received a graft from female donors (F‐D group) and 672 from male donors (M‐D group).

Results

Between the groups, donor age, recipient age and sex, positivity of hepatitis viruses, and graft type were different, whereas tumor‐related factors were all comparable. The 5‐year overall recurrence rates were 14% and 16% in the F‐D and M‐D groups, respectively (P = 0.59). The 5‐year graft recurrence rate was also comparable between the groups (4% and 6%, respectively, P = 0.17). Neither univariate nor multivariate analysis identified donor sex as a significant risk factor for recurrence. Propensity score matching showed similar 5‐year overall recurrence rates (15% in the F‐D group and 14% in the M‐D group, P = 0.63) and graft recurrence rates (5% and 5%, respectively, P = 0.94) between the groups.

Conclusion

Donor sex did not affect post‐LT recurrence of HCC in the Japanese cohort and should not be considered in the process of donor selection or organ allocation.
Biologically active thio‐pyrimidinones from base‐catalyzed thiol‐ene coupling with maleimides
Authors: Feitosa Sidney Gustavo Diniz , Maciel Larissa Gonçalves , dos Anjos Janaína Versiani
Published: March 2022

The synthesis of 2‐thiopyrimidinones through thiol‐ene coupling is reported here, resulting in 35 unpublished molecules. Thiopyrimidinones may exhibit one up to three tautomeric forms, and favoring the thiol tautomer is favored is the key to success of this reaction. Five compounds from all obtained products, those substituted with a carbonyl ester portion in the side chain, were chosen to be tested in a preliminary evaluation for human aldose reductase inhibition. All tested compounds showed an inhibition percentage equal to or >60%.
Synthesis and pyrolysis of two novel pyrrole ester flavor precursors
Authors: Fan Wenpeng , Chu Wenjuan , Tian Haiying , Zhang Zhan , Feng Yingjie , Gao Ziting , Cheng Biao , Ji Xiaoming , Lai Miao
Published: March 2022

In order to develop the high‐temperature‐released pyrrole aroma, two novel flavors precursors of methyl 2‐methyl‐5‐(((2‐methylbutanoyl)oxy)methyl)‐1‐propyl‐1H‐pyrrole‐3‐carboxylate and methyl 2‐methyl‐5‐(((2‐methylbutanoyl)oxy)methyl)‐1‐propyl‐1H‐pyrrole‐3‐carboxylate were synthesized using glucosamine hydrochloride and methyl acetoacetate as raw materials through cyclization, oxidation, alkylation, reduction, and esterification. The target compounds were characterized by nuclear magnetic resonance (1H NMR, 13C NMR), infrared spectroscopy (IR) and high‐resolution mass spectrometry (HRMS). Thermogravimetry (TG), differential scanning calorimeter (DSC) and the pyrolysis‐gas chromatography/mass spectrometry (Py‐GC/MS) methods were used to analyze the heating‐stability of the target compounds, and the pyrolysis mechanism was inferred. Py‐GC/MS results indicated that some fragrance compounds were formed during thermal degradation such as 2‐methylbutyric acid, 2‐methylbutyrate, alkylpyrroles, and benzoic acid, which were important aroma components or flavor additives. This provided a theoretical reference for the application of pyrrole ester in cigarette and heat‐processed food flavoring.
Synthetic approaches toward butenolide‐containing natural products
Authors: Tadiparthi Krishnaji , Venkatesh Swathy
Published: March 2022

The butenolide scaffold is ubiquitous in many natural products and pharmaceutical active ingredients. These candidates appeal to organic chemists for the synthesis of products with various biological activities. This review delineates the efforts made in the total synthesis of natural products based on the butenolide core unit such as umbelactones, akolactones, ansepcinolide, lissoclinolide, fugomycin, and muricadienin. Many of the reported syntheses involve chiral pool, enzyme resolution, and chiral auxiliary, or enantioselective approaches as a key step. Overall, this review highlights the synthetic methods involved in the preparation of butenolide‐containing molecules and aims to increase the profile of such scaffolds to the synthetic community.
Synergistic use of glycomics and single‐molecule molecular inversion probes for identification of congenital disorders of glycosylation type‐1
Authors: Abu Bakar Nurulamin , Ashikov Angel , Brum Jaime Moritz , Smeets Roel , Kersten Marjan , Huijben Karin , Keng Wee Teik , Speck‐Martins Carlos Eduardo , de Carvalho Daniel Rocha , de Rizzo Isabela Maria Pinto Oliveira , de Mello Walquiria Domingues , Heiner‐Fokkema Rebecca , Gorman Kathleen , Grunewald Stephanie , Michelakakis Helen , Moraitou Marina , Martinelli Diego , van Scherpenzeel Monique , Janssen Mirian , de Boer Lonneke , van den Heuvel Lambertus P. , Thiel Christian , Lefeber Dirk J.
Published: March 2022

Congenital disorders of glycosylation type 1 (CDG‐I) comprise a group of 27 genetic defects with heterogeneous multisystem phenotype, mostly presenting with nonspecific neurological symptoms. The biochemical hallmark of CDG‐I is a partial absence of complete N‐glycans on transferrin. However, recent findings of a diagnostic N‐tetrasaccharide for ALG1‐CDG and increased high‐mannose N‐glycans for a few other CDG suggested the potential of glycan structural analysis for CDG‐I gene discovery. We analyzed the relative abundance of total plasma N‐glycans by high resolution quadrupole time‐of‐flight mass spectrometry in a large cohort of 111 CDG‐I patients with known (n = 75) or unsolved (n = 36) genetic cause. We designed single‐molecule molecular inversion probes (smMIPs) for sequencing of CDG‐I candidate genes on the basis of specific N‐glycan signatures. Glycomics profiling in patients with known defects revealed novel features such as the N‐tetrasaccharide in ALG2‐CDG patients and a novel fucosylated N‐pentasaccharide as specific glycomarker for ALG1‐CDG. Moreover, group‐specific high‐mannose N‐glycan signatures were found in ALG3‐, ALG9‐, ALG11‐, ALG12‐, RFT1‐, SRD5A3‐, DOLK‐, DPM1‐, DPM3‐, MPDU1‐, ALG13‐CDG, and hereditary fructose intolerance. Further differential analysis revealed high‐mannose profiles, characteristic for ALG12‐ and ALG9‐CDG. Prediction of candidate genes by glycomics profiling in 36 patients with thus far unsolved CDG‐I and subsequent smMIPs sequencing led to a yield of solved cases of 78% (28/36). Combined plasma glycomics profiling and targeted smMIPs sequencing of candidate genes is a powerful approach to identify causative mutations in CDG‐I patient cohorts.
Obesity promotes lipid accumulation in mouse cartilage—A potential role of acetyl‐CoA carboxylase (ACC) mediated chondrocyte de novo lipogenesis
Authors: Liu Huanhuan , Witzigreuter Luke , Sathiaseelan Roshini , Agbaga Martin‐Paul , Brush Richard S. , Stout Michael B. , Zhu Shouan
Published: March 2022

Obesity promotes the development of osteoarthritis (OA). It is also well‐established that obesity leads to excessive lipid deposition in nonadipose tissues, which often induces lipotoxicity. The objective of this study was to investigate changes in the levels of various lipids in mouse cartilage in the context of obesity and determine if chondrocyte de novo lipogenesis is altered. We used Oil Red O to determine the accumulation of lipid droplets in cartilage from mice fed high‐fat diet (HFD) or low‐fat diet (LFD). We further used mass spectrometry‐based lipidomic analyses to quantify levels of different lipid species. Expression of genes involving in fatty acid (FA) uptake, synthesis, elongation, and desaturation were examined using quantitative polymerase chain reaction. To further study the potential mechanisms, we cultured primary mouse chondrocytes under high‐glucose and high‐insulin conditions to mimic the local microenvironment associated with obesity and subsequently examined the abundance of cellular lipid droplets. The acetyl‐CoA carboxylase (ACC) inhibitor, ND‐630, was added to the culture medium to examine the effect of inhibiting de novo lipogenesis on lipid accumulation in chondrocytes. When compared to the mice receiving LFD, the HFD group displayed more chondrocytes with visible intracellular lipid droplets. Significantly higher amounts of total FAs were also detected in the HFD group. Five out of six significantly upregulated FAs were ω‐6 FAs, while the two significantly downregulated FAs were ω‐3 FAs. Consequently, the HFD group displayed a significantly higher ω‐6/ω‐3 FA ratio. Ether linked phosphatidylcholine was also found to be higher in the HFD group. Fatty acid desaturase (Fad1‐3), fatty acid‐binding protein 4 (Fabp4), and fatty acid synthase (Fasn) transcripts were not found to be different between the treatment groups and fatty acid elongase (Elovl1‐7) transcripts were undetectable in cartilage. Ceramide synthase 2 (Cers‐2), the only transcript found to be changed in these studies, was significantly upregulated in the HFD group. In vitro, chondrocytes upregulated de novo lipogenesis when cultured under high‐glucose, high‐insulin conditions, and this observation was associated with the activation of ACC, which was attenuated by the addition of ND‐630. This study provides the first evidence that lipid deposition is increased in cartilage with obesity and that this is associated with the upregulation of ACC‐mediated de novo lipogenesis. This was supported by our observation that ACC inhibition ameliorated lipid accumulation in chondrocytes, thereby suggesting that ACC could potentially be targeted to treat obesity‐associated OA.
Chemometric approach based on multivariate analysis for discriminating uvaia (Eugenia pyriformis Cambess) fruits during the ripening stages: Physicochemical characteristics, bioactive compounds, and antioxidant activity
Authors: Sganzerla William Gustavo , da Silva Aline Priscilla Gomes , Castro Luiz Eduardo Nochi , da Rosa Cleonice Gonçalves , Komatsu Roberto Akitoshi , Nunes Michael Ramos , Ferrareze Jocleita Peruzzo , Veeck Ana Paula de Lima
Published: March 2022

Background

Uvaia (Eugenia pyriformis Cambess) is a native fruit from the Brazilian Atlantic rainforest with very peculiar aroma and flavor characteristics. However, the behavior of this fruit during the ripening was not reported in the literature. Therefore, this study aimed to evaluate the physicochemical characterization, nutritional composition, bioactive compounds, and antioxidant activity of uvaia fruits collected from six different ripening stages. Hence, chemometric approach based on multivariate analysis was used for discriminating uvaia fruits during the ripening stages.

Results

The results demonstrate that ashes, carbohydrates, and soluble solids increased according to the ripening. The uvaia fruits presented a green color at the first stage and a notable yellow color in the last ripening stage, which is a characteristic of the species. Regarding the phenolic compounds, high content was observed, with the highest accumulation in the last ripening stage, positively correlated with the antioxidant activity. The samples were discriminated by principal component analysis in four different groups, and each group was joined according to the ripening stage. The fruits on the first ripening stage were discriminated mainly by the highest acidity and vitamin C content, and a significant difference was observed in the multivariate analysis between the beginning and the end of the ripening stage of uvaia.

Conclusion

The fruits collected at the end of ripening presented adequate nutritional potential and should be used for fresh consumption. However, depending on the characteristics for industrial processing, the use of fruits from intermediate ripening can be an advantage for the formulation of processed products.
Unique green chromatography method for the determination of serotonin receptor antagonist (Ondansetron hydrochloride) related substances in a liquid formulation, robustness by quality by design‐based design of experiments approach
Authors: Kowtharapu Leela Prasad , Katari Naresh Kumar , Sandoval Christian A , Muchakayala Siva Krishna , Rekulapally Vijay Kumar
Published: March 2022

Serotonin receptor antagonist drug Ondansetron hydrochloride injectable formulation containing all related substances was identified and quantified by a single, simple, sensitive, eco‐friendly, and green high‐performance liquid chromatography method. The disseverment of all impurities was achieved with the Discovery Cyano (250 × 4.6) mm, 5 μm column. The gradient program was composed of pH 5.7 phosphate buffer as mobile phase A and acetonitrile as mobile phase B. The flow rate, column compartment temperature, and detection wavelengths were 0.9 mL/min, 30°C, and 216 nm, respectively. The method was validated as per current regulatory guidelines. The obtained %relative standard deviation for the precision results was between 0.55 and 2.72% for all impurities. The correlation coefficient values from the linearity experiment for impurities and analyte were more than 0.995. The accuracy results were obtained between 88.4 and 113.0% for all impurities. Both sample and standard solutions showed 24 h stability at benchtop and refrigerator conditions. All impurities and analytes met the specificity and mass balance for all forced degradation conditions. Quality‐by‐design‐based design of experiments was utilized to establish the method's robustness. Method greenness was assessed by using the current advanced tool green analytical procedure index, National Environmental Methods Index, and analytical eco‐scale.
Dopamine Functionalized Polyethylene Glycol for Improving Stability of Gold Nanoparticles against Reactive Oxygen Species in Serum
Authors: Kang Jing , Wu Fei‐Zheng , Xue Yao , Li Zhi‐Han , Wang Yu‐Xi , Liu Kun
Published: March 2022

PEGylation is the most effective antifouling method for the surface modification of gold nanoparticles (AuNPs). However, thiol‐terminated polyethylene glycol (PEG) ligands tethered on the AuNPs are instable in serum and can detach from the AuNP surface, resulting in a significant reduce of their antifouling properties. Herein, it is reported that reactive oxygen species (ROS) is a major factor causing the detachment of PEG ligands from AuNP surfaces. By covalently backfilling dopamine‐functionalized PEG on the AuNPs, the stability of PEG ligands on AuNP surface and the antifouling ability of AuNPs can be effectively improved. Tuning the balance between ROS and dopamine‐functionalized PEG can be used as a new strategy to control the self‐assembly of AuNPs and serum proteins.
Technical note: Analysis of brachytherapy source movement by high‐speed camera
Authors: Okamoto Hiroyuki , Iijima Kotaro , Chiba Takahito , Takemori Mihiro , Nakayama Hiroki , Fujii Kyohei , Kon Mitsuhiro , Mikasa Shohei , Nakaichi Tetsu , Urago Yuka , Aikawa Ako , Katsuta Shyouichi , Nakamura Satoshi , Igaki Hiroshi
Published: March 2022

Purpose

To assess the accuracy of the movement of a brachytherapy source using a high‐speed camera for evaluating source position, dwell time, and transit dose.

Methods

A high‐speed camera was used to record the source position of an Ir‐192 source relative to a ruler within a custom positioning jig in a remote afterloading system. The analyzed frames can be used to assess dwell positions and times. Treatment plans had multiple dwell times equal to 0.1, 0.5, 1.0, and 2.0 s in 2.5‐ and 5‐mm step sizes. Images were acquired at a rate of 146 frames/s. Acquired images were processed to automatically track the actual source using the correlation between a template image and each frame. The brachytherapy dose calculation formalism (AAPM TG43‐U1) was applied to each frame to evaluate the transit dose contribution to the total dose.

Results

The differences in measured source positions from the nominal for dwell times equal to 0.1, 0.5, 1.0, and 2.0 s in treatment plans were approximately ≤1 mm. The corresponding differences in measured dwell times from the nominal values at 5 mm steps were −15, −9, −5, and 5 ms, respectively. The source velocities at 5 mm steps were approximately 393 mm/s. The dose differences at 5 mm from the source movement with and without the transit dose for these dwell times were 38%, 7%, 3%, and 2%, respectively.

Conclusions

Recording a brachytherapy source using a high‐speed camera allowed the evaluation of positional and dwell time accuracies as well as dosimetry assessments, such as the transit dose, based on the application of AAPM TG‐43U1.
A free‐interface component mode synthesis of moving contact multibodies and its application to gear contacts
Authors: Yao Jia‐Lun , Shu Xuan‐Bo , Ren Ge‐Xue
Published: March 2022

Moving contact components are common in mechanical systems, and they exhibit a large rigid motion with linear‐elastic deflection under contact boundary conditions. The finite element method can capture local deformation and high gradient stresses, but finely meshed contact interfaces lead to numerous degrees of freedom. Model order reduction techniques for multibodies are effective, but moving contact interfaces also introduce multiple interface degrees of freedom. In the present method, the interface degrees of freedom are retained to ensure the accuracy of the local response induced by contacts, but the computational scale is not further enlarged. The motion of moving contact components is described by the floating frame of reference formulation. A free‐interface component mode synthesis method is proposed for model order reduction. Kept free‐interface normal modes represent global flexibility and residual modes accurately compensate for the local quasi‐static responses of omitted modes induced by contacts. The contribution of residual modes is represented by interface load coordinates, which can be directly evaluated by contact forces. The contacts are calculated with the present contact algorithm. The accuracy and efficiency of the proposed method are fully demonstrated through correlation with the finite element method in gear meshing simulations.
Assessment of pharmacokinetic linearity after repeated drug administration
Authors: Bauer Alexander , Kagedal Matts , Wolfsegger Martin J.
Published: March 2022

The prediction of drug concentration time courses after different dosing scenarios is greatly facilitated if the pharmacokinetics (PK) can be assumed linear. The assumption of linear PK thus needs careful evaluation for any new drug in development. Under linear PK, exposure is proportional to dose (linear PK across doses) and exposure at steady state can be predicted from a single dose based on the superposition principle (linear PK over time). While investigation of dose‐proportionality is common practice, evaluation of time dependent PK has received less attention in the literature. In particular, the superposition principle can be used to assess whether the observed extent of accumulation after repeated administration is expected under the premise of linear PK. This work emphasizes the importance of the time related aspect of linear PK by introducing the predictability ratio (PR). Linear PK over time can be concluded if PR = 1. Accumulation is higher than expected if PR >1, and lower if PR <1. If PK data from multiple dose cohorts are available, the PR is assessed for each dose cohort and a supportive hypothesis test can be applied to test for potential differences between doses in PR.
Block sparse design of distributed controllers for dynamical network systems
Authors: Adachi Ryosuke , Yamashita Yuh , Kobayashi Koichi
Published: March 2022

This study proposes a controller design method based on block sparse optimization for dynamical network systems. The objective of the controller is to stabilize dynamical network systems with a given convergence rate. The block sparse optimization minimizes the number of controlled nodes. This study is unique in that the structure of the controller is constrained by the network topology of the system. Additionally, the proposed design problem is separable in terms of the distributed optimization over networks. The proposed method is applicable to controller design for the pinning control of consensus systems and the optimal vaccine allocation for epidemic spreading processes.
A switching adaptive scheme for global output‐feedback stabilization of inherent nonlinear systems with unknown control direction
Authors: Man Yongchao , Liu Yungang
Published: March 2022

This article is devoted to the global output‐feedback stabilization of nonlinear systems with unknown control directions and unmeasured states dependent growth whose rate is an unknown arbitrary function of output. In view of limited capability of continuous feedback in compensating system uncertainties and nonlinearities, a novel switching adaptive scheme is proposed. The scheme involves a logic‐based switching mechanism, based on which, a proper controller is selected (from a family of candidate controllers) to act on the system during its execution interval. The main differences between the proposed scheme and those in the related works are as follows. First, the set of candidate controllers is determined online, rather than specified in advance, which provides foundations for compensating arbitrary function‐of‐output growth rate. Second, an iterative function composed of system memory signals is introduced into the switching mechanism, aiming to evaluate the differences between the system states and observe states. Finally, when switching stops, only by introducing an extra transformation and adopting elaborate analysis, can the boundedness of the closed‐loop system signals be obtained, rather than those in the related works where the boundedness can be naturally established once switching stops. The constructed switching adaptive controller guarantees that all the signals of the resulting closed‐loop system are bounded and ultimately converge to zero.
Water repellency prediction in high‐organic Greenlandic soils: Comparing vis–NIRS to pedotransfer functions
Authors: Blaesbjerg Natasha H. , Weber Peter L. , de Jonge Lis Wollesen , Moldrup Per , Greve Mogens H. , Arthur Emmanuel , Knadel Maria , Hermansen Cecilie
Published: March 2022

Soil water repellency (SWR) is a common phenomenon across agricultural soils of South Greenland that can negatively affect soil functions. Existing methods to measure SWR as a function of water content (w) are laborious. This study was conducted to compare the potential of visible–near‐infrared spectroscopy (vis–NIRS) as an alternative method to pedotransfer functions (PTFs) for predicting four SWR indices in 143 agricultural soils from South Greenland (clay, 0.016–0.172 kg kg–1; organic carbon (OC), 0.009–0.241 kg kg–1). Pedotransfer functions were established by multiple linear regression based on OC, clay, and pH. Partial least squares regression (PLS‐R) and interval PLS‐R were applied to build vis–NIRS prediction models (vis–NIR range 400–2,500 nm). The area under the SWR–w curve (SWRarea) and the critical soil water content (wnon) were accurately predicted by PTFs (R2 = .90; R2adj = .91) while the SWR after 60 °C pretreatment (SWR60), and the integrative repellency dynamic index (IRDI) were predicted less accurately (R2adj = .36; R2adj = .27). Vis‐NIRS models with variable selection performed at a better or close to the same level of accuracy as PTFs (SWRarea, R2 = .88; wnon, R2 = .90; SWR60, R2 = .63; IRDI, R2 = .54). This study demonstrated vis–NIRS as a valuable alternative to PTFs for rapid assessment of SWR and as a tool for SWR mitigation for farmers in South Greenland. The results may well apply to other regions with similar texture and OC ranges, but further testing is required.
The effect of impurities Pb, Bi, and PbO on erosion properties of Lead‐Bismuth Eutectic alloy on Fe3O4 oxide film by first principle calculations
Authors: Zhang Sun Jing Kang , Cai Jun , Yang Fu An
Published: March 2022

The first‐principle calculation was performed to study the effect of impurities Pb, Bi, and PbO on erosion properties of liquid lead‐bismuth eutectic alloy on the metal oxide (Fe3O4) and its surfaces. We found that whether in the bulk or on the surface of Fe3O4 the formation energy by substitution of Fe with Bi is slightly larger than that with Pb substitution and the formation energy by substitution of Fe with PbO is much larger than those with Pb and Bi, indicating that PbO has weaker corrosion potential than Pb/Bi. The calculation results show that a tetrahedral site in Fe3O4 should be the weakest position where Fe3O4 is attacked by these exotic impurities. The corrosion process on the oxide film will be initialized at that position. It can be seen that for the doping case the dissociation energy of Fe atom in the (110) surface has the smallest value, a medium value in (100) surface, and the largest value in (111) surface. Correspondingly, the corrosion resistance of doping Fe3O4 film in (110) surface is the weakest one among these surfaces. For the doping‐free case, the (100) surface has the weakest corrosion resistance. By comparing the doping case with no‐doping case it can be seen that the impurities of Pb, Bi, and PbO will weaken the corrosion resistance of Fe3O4 film further. The doping has a negative impact on the stability of the structure and on the corrosion resistance of Fe3O4 film. From present results, it is also seen that the replacement of Fe in Fe3O4 by multiple impurities is more likely to occur than the replacement of only single impurity.
Highly Efficient One‐pot Aerobic Synthesis of α‐Aminophosphonate from Alcohols: Dual Catalytic Effect of Tetrabutylammonium Tribromide (TBATB)
Authors: Kazemi Foad , Shariati Yadollah , Kaboudin Babak
Published: March 2022

In this work, a simple, metal‐free, and homogeneous two steps one‐pot method for the synthesis of α‐aminophosphonate in the presence of tetrabutylammonium tribromide (TBATB) from alcohol was reported. Interestingly TBATB showed catalytic effect for both photo tuanable aerobic oxidation of alcohol (including electron rich and poor) and α‐aminophosphonate synthesis from in situ prepared aldehyde. Also, more interestingly efficiency of the synthesis is higher for starting from alcohols than aldehyde. The optimized condition including: solvent, catalyst amounts, photo and thermal factors was considered. Various derivatives of benzyl alcohol and aniline participated well in this reaction and produced the corresponding α‐aminophosphonates efficiently.
Catalysts Based on the C−H⋅⋅⋅M Weak Interaction: Synthesis, Characterization and Catalytic Application of Bis(pyrazolyl)borate Cu(I) Complexes in Carbene Insertion into Heteroatom Hydrogen Bonds
Authors: Zhao Qianyi , Yao Qiu‐Yue , Dou Ting , Xu Ting , Zhang Jie , Chen Xuenian
Published: March 2022

A series of new copper(I) complexes [BBN(3‐R1‐4‐R2‐5‐R3‐pz)2]Cu(I) (BBN=9‐borabicyclo[3.3.1]nonane; pz=pyrazole) have been synthesized and fully characterized. Single crystal studies of these complexes showed weak intramolecular C−H⋅⋅⋅Cu interactions which can be assigned as agostic or anagostic interactions. Their catalytic application in carbene insertion into N−H and B−H bonds demonstrates wide substrate scope, high yields and selectivity.
Low‐Loss Tunable Infrared Plasmons in the High‐Mobility Perovskite (Ba,La)SnO3
Authors: Yang Hongbin , Konečná Andrea , Xu Xianghan , Cheong Sang‐Wook , Garfunkel Eric , García de Abajo F. Javier , Batson Philip E.
Published: March 2022

BaSnO3 exhibits the highest carrier mobility among perovskite oxides, making it ideal for oxide electronics. Collective charge carrier oscillations known as plasmons are expected to arise in this material, thus providing a tool to control the nanoscale optical field for optoelectronics applications. Here, the existence of relatively long‐lived plasmons supported by high‐mobility charge carriers in La‐doped BaSnO3 (BLSO) is demonstrated. By exploiting the high spatial and energy resolution of electron energy‐loss spectroscopy with a focused beam in a scanning transmission electron microscope, the dispersion, confinement ratio, and damping of infrared localized surface plasmons (LSPs) in BLSO nanoparticles are systematically investigated. It is found that LSPs in BLSO exhibit a high degree of spatial confinement compared to those sustained by noble metals and have relatively low losses and high quality factors with respect to other doped oxides. Further analysis clarifies the relation between plasmon damping and carrier mobility in BLSO. The results support the use of nanostructured degenerate semiconductors for plasmonic applications in the infrared region and establish a solid alternative to more traditional plasmonic materials.
Controllable Preparation of 2D Vertical van der Waals Heterostructures and Superlattices for Functional Applications
Authors: Li Jia , Liang Jingyi , Yang Xiangdong , Li Xin , Zhao Bei , Li Bo , Duan Xidong
Published: March 2022

2D van der Waals heterostructures (vdWHs) and superlattices (SLs) with exotic physical properties and applications for new devices have attracted immense interest. Compared to conventionally bonded heterostructures, the dangling‐bond‐free surface of 2D layered materials allows for the feasible integration of various materials to produce vdWHs without the requirements of lattice matching and processing compatibility. The quality of interfaces in artificially stacked vdWHs/vdWSLs and scalability of production remain among the major challenges in the field of 2D materials. Fortunately, bottom‐up methods exhibit relatively high controllability and flexibility. The growth parameters, such as the temperature, precursors, substrate, and carrier gas, can be carefully and comprehensively controlled to produce high‐quality interfaces and wafer‐scale products of vdWHs/vdWSLs. This review focuses on three types of bottom‐up methods for the assembly of vdWHs and vdWSLs with atomically clean and electronically sharp interfaces: chemical/physical vapor deposition, metal‐organic chemical vapor deposition, and ultrahigh vacuum growth. These methods can intuitively illustrate the great flexibility and controllability of bottom‐up methods for the preparation of vdWHs/vdWSLs. The latest progress in vdWHs and vdWSLs, related physical phenomena, and (opto)electronic devices are summarized. Finally, the authors discuss current challenges and future perspectives in the synthesis and application of vdWHs and vdWSLs.
Urea‐Mediated Monoliths Made of Nitrogen‐Enriched Mesoporous Carbon Nanosheets for High‐Performance Aqueous Zinc Ion Hybrid Capacitors
Authors: Shang Ping , Liu Min , Mei Yingying , Liu Yuanhao , Wu Lisha , Dong Yanfeng , Zhao Zongbin , Qiu Jieshan
Published: March 2022

Aqueous zinc ion hybrid capacitors (aZHCs) are of great potential for large‐scale energy storage and flexible wearable devices, of which the specific capacity and energy density need to be further enhanced for practical applications. Herein, a urea‐mediated foaming strategy is reported for the efficient synthesis of monoliths consisting of nitrogen‐enriched mesoporous carbon nanosheets (NPCNs) by prefoaming drying a solution made of polyvinylpyrrolidone, zinc nitrate, and urea at low temperatures, foaming and annealing at high temperatures, and subsequent acid etching. NPCNs have a large lateral size of ≈40 µm, thin thickness of ≈55 nm, abundant micropores and mesopores (≈3.8 nm), and a high N‐doping value of 9.7 at.%. The NPCNs as the cathode in aZHCs provide abundant zinc storage sites involving both physical and chemical adsorption/desorption of Zn2+ ions, and deliver high specific capacities of 262 and 115 mAh g−1 at 0.2 and 10 A g−1, and a remarkable areal capacity of ≈0.5 mAh cm−2  with a mass loading of 5.3 mg cm−2, outperforming most carbon cathodes reported thus far. Moreover, safe and flexible NPCNs based quasi‐solid‐state devices are fabricated, which can withstand drilling and mechanical bending, suggesting their potential applications in wearable devices.
A three‐range approach enhances the prognostic utility of CSF biomarkers in Alzheimer's disease
Authors: Brum Wagner S. , de Bastiani Marco Antônio , Bieger Andrei , Therriault Joseph , Ferrari‐Souza João P. , Benedet Andréa L. , Saha‐Chaudhuri Paramita , Souza Diogo O. , Ashton Nicholas J. , Zetterberg Henrik , Pascoal Tharick A. , Karikari Thomas , Blennow Kaj , Rosa‐Neto Pedro , Zimmer Eduardo R. ,   Alzheimer's Disease Neuroimaging Initiative (ADNI)
Published: March 2022

Introduction

Alzheimer's disease consensus recommends biomarker dichotomization, a practice with well‐described clinical strengths and methodological limitations. Although neuroimaging studies have explored alternative biomarker interpretation strategies, a formally defined three‐range approach and its prognostic impact remains under‐explored for cerebrospinal fluid (CSF) biomarkers .

Methods

With two‐graph receiver‐operating characteristics based on different reference schemes, we derived three‐range cut‐points for CSF Elecsys biomarkers. According to baseline CSF status, we assessed the prognostic utility of this in predicting risk of clinical progression and longitudinal trajectories of cognitive decline and amyloid–beta (Aβ) positron emission tomography (PET) accumulation in non‐demented individuals (Alzheimer's Disease Neuroimaging Initiative [ADNI]; n = 1246). In all analyses, we compared herein‐derived three‐range CSF cut‐points to previously described binary ones.

Results

In our main longitudinal analyses, we highlight CSF p‐tau181/Aβ1‐42 three‐range cut‐points derived based on the cognitively normal Aβ‐PET negative versus dementia Aβ‐PET positive reference scheme for best depicting a prognostically relevant biomarker abnormality range. Longitudinally, our approach revealed a divergent intermediate cognitive trajectory undetected by dichotomization and a clearly abnormal group at higher risk for cognitive decline, with power analyses suggesting the latter group as potential trial enrichment candidates. Furthermore, we demonstrate that individuals with intermediate‐range CSF status have similar rates of Aβ deposition to those in the clearly abnormal group.

Discussion

The proposed approach can refine clinico‐biological prognostic assessment and potentially enhance trial recruitment, as it captures faster biomarker‐related cognitive decline in comparison to binary cut‐points. Although this approach has implications for trial recruitment and observational studies, further discussion is needed regarding clinical practice applications.
Olive polyphenols and bioavailable glutathione: Promising results in patients diagnosed with mild Alzheimer's disease
Authors: Marianetti Massimo , Pinna Silvia , Venuti Angelo , Liguri Gianfranco
Published: March 2022

Introduction

Recent studies highlighted the role of olive polyphenols in disrupting the ordered structure of highly cytotoxic amyloid beta protofibrils and the efficacy of a derivatized form of glutathione to counteract neuronal oxidative stress affecting specific brain regions at early stages of Alzheimer's disease (AD) pathogenesis. We performed a randomized cross‐over clinical trial to evaluate their potential benefits in mild AD.

Methods

Oleuropein and S‐acetyl glutathione were administered as dietary supplement for 6 months to 18 patients diagnosed for probable mild AD according to International Working Group 2 criteria. Patients underwent an extensive cognitive and behavioral neuropsychological test battery at the beginning and end of the study to evaluate cognitive deterioration, memory, visuospatial abilities, attention, language, executive functions, and behavioral disorders. We compared patients receiving treatment to patients receiving no treatment.

Results

All the measured neurocognitive parameters stabilized or improved after the treatment in all patients.

Discussion

Dietary supplement with olive polyphenols and bioavailable glutathione could be useful for patients diagnosed with mild AD.
Cover Image, Volume 9, Issue 2
Authors: Huang Zeqing , Zhao Tongtiegang
Published: March 2022

The cover image is based on the Advanced Review Predictive performance of ensemble hydroclimatic forecasts: Verifi cation metrics, diagnostic plots and forecast attributes by Zeqing Huang and Tongtiegang Zhao https://doi.org/10.1002/wat2.1580.

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The averaged null energy condition on holographic evaporating black holes
Authors: Ishibashi Akihiro , Maeda Kengo
Published: March 2022

Abstract

We examine the averaged null energy condition (ANEC) for strongly coupled fields, along the event horizon of an evaporating black hole by using the AdS/CFT duality. First, we consider a holographic model of a 3-dimensional evaporating black hole with a perturbed 4-dimensional black droplet geometry as the bulk dual, and investigate how negative energy flux going into the boundary black hole horizon appears. We show that the ingoing negative energy flux always appears at the boundary black hole horizon when the horizon area decreases. Second, we test the ANEC in a holographic model whose boundary geometry is a 4-dimensional asymptotically flat spacetime, describing the formation and subsequent evaporation of a spherically symmetric black hole. By applying the “bulk-no-shortcut principle”, we show that the ANEC is always satisfied when the local null energy is averaged with a weight function along the incomplete null geodesic on the event horizon from beginning of the formation to the final instant of the black hole evaporation. Our results indicate that the total ingoing negative energy flux is compensated by a large amount of positive energy flux in the early stage of the black hole formation.
N-terminome analyses underscore the prevalence of SPPL3-mediated intramembrane proteolysis among Golgi-resident enzymes and its role in Golgi enzyme secretion
Authors: Hobohm Laura , Koudelka Tomas , Bahr Fenja H. , Truberg Jule , Kapell Sebastian , Schacht Sarah-Sophie , Meisinger Daniel , Mengel Marion , Jochimsen Alexander , Hofmann Anna , Heintz Lukas , Tholey Andreas , Voss Matthias
Published: March 2022

Golgi membrane proteins such as glycosyltransferases and other glycan-modifying enzymes are key to glycosylation of proteins and lipids. Secretion of soluble Golgi enzymes that are released from their membrane anchor by endoprotease activity is a wide-spread yet largely unexplored phenomenon. The intramembrane protease SPPL3 can specifically cleave select Golgi enzymes, enabling their secretion and concomitantly altering global cellular glycosylation, yet the entire range of Golgi enzymes cleaved by SPPL3 under physiological conditions remains to be defined. Here, we established isogenic SPPL3-deficient HEK293 and HeLa cell lines and applied N-terminomics to identify substrates cleaved by SPPL3 and released into cell culture supernatants. With high confidence, our study identifies more than 20 substrates of SPPL3, including entirely novel substrates. Notably, our N-terminome analyses provide a comprehensive list of SPPL3 cleavage sites demonstrating that SPPL3-mediated shedding of Golgi enzymes occurs through intramembrane proteolysis. Through the use of chimeric glycosyltransferase constructs we show that transmembrane domains can determine cleavage by SPPL3. Using our cleavage site data, we surveyed public proteome data and found that SPPL3 cleavage products are present in human blood. We also generated HEK293 knock-in cells expressing the active site mutant D271A from the endogenous SPPL3 locus. Immunoblot analyses revealed that secretion of select novel substrates such as the key mucin-type O-glycosylation enzyme GALNT2 is dependent on endogenous SPPL3 protease activity. In sum, our study expands the spectrum of known physiological substrates of SPPL3 corroborating its significant role in Golgi enzyme turnover and secretion as well as in the regulation of global glycosylation pathways.