bluuebunny/crossref_metadata_2025 huggingface dataset:
Two‐Dimensional Chiral Polyrotaxane Monolayer with Emergent and Steerable Circularly Polarized Luminescence
Authors: Hu Liangyu , Zhu Xuefeng , Yang Chenchen , Liu Minghua
Published: November 2021

Here, we propose a mechanically interlocked strategy to achieve a 2D chiral polyrotaxane (2DCPR) monolayer with emergent and steerable CPL activity by utilizing β‐cyclodextrin as the chiral wheel and a luminescent dynamic covalent organic framework as 2D polymeric axle. Such methodology, integrating host–guest and dynamic covalent chemistry, enabled the direct construction of a delaminated 2DCPRmonolayer with extraordinarily large size (up to tens of micrometers) and simultaneously endowed chirality to the extended 2DCPRnetwork to generate CPL activity. Importantly, not only the structure but also the CPL performance of the 2DCPRnetwork can be further regulated by the feeding amount of β‐cyclodextrin. This work demonstrated a monolayered 2DCPRwith CPL activity for the first time. The insightful structure–property relationship of the induced CPL will be of benefit for a deeper understanding of the excited‐state chirality of 2D chiral nanomaterials.
Cobalt Single Atom Incorporated in Ruthenium Oxide Sphere: A Robust Bifunctional Electrocatalyst for HER and OER
Authors: Shah Khadim , Dai Ruoyun , Mateen Muhammad , Hassan Zubair , Zhuang Zewen , Liu Chuhao , Israr Muhammad , Cheong Weng‐Chon , Hu Botao , Tu Renyong , Zhang Chao , Chen Xin , Peng Qing , Chen Chen , Li Yadong
Published: November 2021

The development of highly active and stable bifunctional noble‐metal‐based electrocatalysts for the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER) is a crucial goal for clean and renewable energy, which still remains challenging. Herein, we report an efficient and stable catalyst comprising a Co single atom incorporated in an RuO2 sphere for HER and OER, in which the Co single atom in the RuO2 sphere was confirmed by XAS, AC‐STEM, and DFT. This tailoring strategy uses a Co single atom to modify the electronic structures of the surrounding Ru atoms and thereby remarkably elevates the electrocatalytic activities. The catalyst requires ultralow overpotentials, 45 mV for HER and 200 mV for OER, to deliver a current density of 10 mA cm−2. The theoretical calculations reveal that the energy barriers for HER and OER are lowered after incorporation of a cobalt single atom.
Oriented Two‐Dimensional Covalent Organic Framework Membranes with High Ion Flux and Smart Gating Nanofluidic Transport
Authors: Cao Li , Liu Xiaowei , Shinde Digambar B. , Chen Cailing , Chen I‐Chun , Li Zhen , Zhou Zongyao , Yang Zhongyu , Han Yu , Lai Zhiping
Published: November 2021

Nanofluidic ion transport holds high promise in bio‐sensing and energy conversion applications. However, smart nanofluidic devices with high ion flux and modulable ion transport capabilities remain to be realised. Herein, we demonstrate smart nanofluidic devices based on oriented two‐dimensional covalent organic framework (2D COF) membranes with vertically aligned nanochannel arrays that achieved a 2–3 orders of magnitude higher ion flux compared with that of conventional single‐channel nanofluidic devices. The surface‐charge‐governed ion conductance is dominant for electrolyte concentration up to 0.01 M. Moreover, owing to the customisable pH‐responsivity of imine and phenol hydroxyl groups, the COF‐DT membranes attained an actively modulable ion transport with a high pH‐gating on/off ratio of ≈100. The customisable structure and rich chemistry of COF materials will offer a promising platform for manufacturing nanofluidic devices with modifiable ion/molecular transport features.
The effect of silicon dioxide nanoparticle‐covered graphene oxide on mechanical properties, thermal stability and rheological performance of thermoplastic polyurethanes
Authors: Ding Guoxin , Tai Hongxu , Chen Chuanxin , Sun Chenfeng , Tang Zhongfeng , Cheng Guojun , Wan Xianglong , Wang Zhoufeng
Published: November 2021

A two‐step grafting procedure has been used to graft tetraethylenepentamine (TEPA) and nano silicon dioxide (SiO2), onto graphene oxide (GO) surface. The resulting modified GO, that was TGOS, which was used as a reinforcement in thermoplastic polyurethanes (TPUs). Mechanical properties, thermal stability and rheological properties of composites were investigated. Results showed that the addition of TGOS significantly improved the mechanical properties of TPU compared with the pure TPU sample. Tensile strength and elongation at break of TPU were increased by 50.8 and 18.6%, respectively, when the addition amount was only 0.5 wt%. TG results showed that the addition of TGOS improved the heat resistance of TPU. Complex viscosity, storage modulus (G') and loss modulus (G") of TPU composites with different additions were analyzed by rheological tests, the results showed that the addition of TGOS improved the deformation resistance of TPU. Meanwhile, TPU composites present highG',G", and complex viscosity with the increase of TGOS filling amount in the low frequency region.
Nickel‐Catalyzed Asymmetric Hydrogenation for the Synthesis of a Key Intermediate of Sitagliptin
Authors: Sudhakaran Shana , Shinde Prasad G. , Aratikatla Eswar K. , Kaulage Sandeep H. , Rana Priksha , Parit Ratan S. , Kavale Dattatry S. , Senthilkumar Beeran , Punji Benudhar
Published: November 2021

Nickel‐catalyzed enantioselective hydrogenation of enamines leading to the efficient synthesis of 3‐R‐Boc‐amino‐4‐(2,4,5‐trifluorophenyl)butyric esters, the key intermediate of the blockbuster antidiabetic drug (R)‐SITAGLIPTIN, is described. The sitagliptin motifs were isolated in more than 99% yield and with 75–92% ee using the earth‐abundant nickel catalyst. Upon chiral resolution with (R)‐ and (S)‐1‐phenylethylamines, the partially enantioenriched (R)‐ and (S)‐Boc‐3‐amino‐4‐(2,4,5‐trifluorophenyl)butanoic acids provided >99.5% ee of the crucial sitagliptin intermediate. The asymmetric hydrogenation protocol was scaled up to 10 g with consistency in yield and ee, and has been reproduced in multiple batches.
A cyclic non‐homogeneous Markov chain model for resource availability optimization in a two‐parking lots system with priority classes and resource reservation
Authors: Koutras Vasilis P. , Kadrefi Athanasia , Platis Agapios N.
Published: November 2021

Resource availability optimization has gained a lot of research effort recently, especially in client–server systems. A parking lot can be considered such a client–server system. Parking lot resource availability importance increased during the last decades since there is a tremendous increase of vehicles' usage not only in urban areas but in rural areas too. Academia and industry have extensively studied the problem of parking availability under various constraints and limitations. In this article, we extend previous work on parking lot resource availability optimization by providing an integrated theoretical framework for modeling resource reservation in a two‐parking lot problem which can be accessed by clients of different priorities under nonconstant arrival and service rates. The aim is to determine the optimal parking place reservation policy, which minimizes the blocking probability for each clients' class at each parking lot for different traffic periods. Under the optimal policy, we compute two different performance indicators; from clients' perspective we compute the total expected walking time from the parking lot to the point of interest, and from company's point of view, the total expected hourly profit. To model the fact that clients' arrival and service rates are time dependent, we use a cyclic nonhomogeneous Markov chain to model the entire system's evolution in time. Additionally, an empirical numerical case study is provided to examine the effectiveness of the proposed resource reservation approach.
Accretion mode and jet collimation in active galactic nuclei
Authors: Boccardi Bia , Madika Eftychia , Ricci Luca
Published: November 2021

In this article, we summarize our recent progress in observational studies of jet collimation in active galactic nuclei. We focus on the investigation of a relation between the properties of the collimation zone and the AGN accretion mode, recently proposed by Boccardi, B., Perucho, M., Casadio, C. et al., 2021, A&A, 647, A67. We also discuss the efforts made by our team to increase the still limited number of sources that can be imaged on sufficiently small spatial scales to probe such zone, and we present first results for new candidates.
“Honecker's Vassal” or a Prehistorian in the Service of Science? The Evaluation of Former East German Scholarship and the Concept ofthe Scholarin the Debate on Joachim Herrmann in Reunified Germany
Authors: Kluger Anne
Published: November 2021

The evaluation and transformation process of the GDR research system in the wake of German reunification 1989/90 was immediately accompanied not only by debates within the scientific community, but also by an extensive discussion about the value and future perspectives of East German scholarship and its protagonists in the nationally circulated press. In 1990, the focus turned temporarily to the prominent East German prehistorian Joachim Herrmann after his election to the board of an international historical association. The article uses the example of Herrmann and the public discussion about him as a case study to examine the status of, and changes in, the authority of scholarship and the scholar in the context of the evaluation and restructuring of the East German research landscape in the early 1990s. A selection of press articles from nationwide German newspapers and newsmagazines, as well as archival letters exchanged between different participants in the debate serve as prisms carving out the central arguments and subjacent structures of the discussion. Therefore, Herrmann's case exposes generic characteristics of (different concepts of) scientific authority and the close connection between its negotiation and the search for identity in the newly reunited German academic sphere.
Corporate ESG reporting quantity, quality and performance: Where to now for environmental policy and practice?
Authors: Arvidsson Susanne , Dumay John
Published: November 2021

Environmental, social and governance (ESG) issues are driving corporate strategy and performance. However, does this mean more ESG reporting is being done? If so, is the quality of ESG reports improving? And what about ESG performance? In this paper, we examine these three trends in ESG reporting—quantity, quality and corporate ESG performance. With a Swedish multinational corporate focus, we analyse data from Sustainalytics, corporateregister.com and the Alliance for Corporate Transparency to answer our research questions. Our analysis shows that, while the quality of ESG information in Sweden has steadily improved, performance plateaued around 2015. Mitigating problems such as the impacts of climate change and COVID‐19 call for improved ESG performance, not improved ESG reporting quantity or quality. Thus, rather than focusing on improving ESG reporting regulations, we need to redirect our focus towards creating better ESG outcomes. Therefore, we argue that companies must be asked to provide data that are more timely, relevant, credible and comparable and that demonstrate improved ESG performance. With this information, financial analysts and investors can redirect and accelerate capital flows towards corporate investments that help tackle important problems related to climate crises and the reaching of a sustainable development. Our analysis reveals that we need more research focusing on consumers, investors and policymakers. Future scholars could explore how changing consumer preferences are driving improvements in ESG performance and how changing capital market allocations affect ESG performance.
Founder CEOs and corporate environmental violations: Evidence from S&P 1500 firms
Authors: Abebe Michael A. , Acharya Keshab
Published: November 2021

The Chief Executive Officer (CEO), as the principal leader of the firm, plays an essential role in the prevention of corporate misconduct. While all CEOs have a responsibility to reduce incidents of corporate misconduct, not all are equally effective in doing so. In this study, we propose that given their central role in the inception of the firm, their psychological attachment, and stewardship mentality, founder CEO‐led firms exhibit less likelihood and frequency of environmental violations, which are major types of corporate misconduct. Additionally, we explore the possibility that founder CEOs' ability to reduce environmental violations may decline over time as the firm gets older and larger, using insights from organizational life cycle theory. Our analyses of data from major environmental violation incidents among S&P 1500 firms between 2009 and 2018 provide some support for our arguments. Specifically, we found that founder CEO leadership is indeed associated with a reduced likelihood and frequency of environmental violations. Furthermore, we observed that the normally negative relationship between founder CEO leadership and the occurrence of environmental violations turns positive as the firm gets older, consistent with organizational life cycle theory predictions. Implications for research and practice are discussed.
Oligo Pools as an Affordable Source of Synthetic DNA for Cost‐Effective Library Construction in Protein‐ and Metabolic Pathway Engineering
Authors: Kuiper Bastiaan P. , Prins Rianne C. , Billerbeck Sonja
Published: November 2021

The construction of custom libraries is critical for rational protein engineering and directed evolution. Array‐synthesized oligo pools of thousands of user‐defined sequences (up to ∼350 bases in length) have emerged as a low‐cost commercially available source of DNA. These pools cost ≤10 % (depending on error rate and length) of other commercial sources of custom DNA, and this significant cost difference can determine whether an enzyme engineering project can be realized on a given research budget. However, while being cheap, oligo pools do suffer from a low concentration of individual oligos and relatively high error rates. Several powerful techniques that specifically make use of oligo pools have been developed and proven valuable or even essential for next‐generation protein and pathway engineering strategies, such as sequence‐function mapping, enzyme minimization, or de‐novo design. Here we consolidate the knowledge on these techniques and their applications to facilitate the use of oligo pools within the protein engineering community.
An ESIPT‐Dependent AIE Fluorophore Based on HBT Derivative: Substituent Positional Impact on Aggregated Luminescence and its Application for Hydrogen Peroxide Detection
Authors: Zeng Guanling , Liang Zhenhao , Jiang Xiao , Quan Tingting , Chen Tongsheng
Published: November 2021

Aiming to develop the facile organic fluorophore possessing excited state intramolecular proton transfer (ESIPT) and aggregation‐induced emission (AIE), we designed and synthesized two isomers with different linkage site between hydroxyl of 2‐(2‐hydroxyphenyl) benzothiazole (HBT) and a benzothiazole substituent (para position refers to p‐BHBT and ortho position refers to o‐BHBT). Fluorescence emission properties of p‐BHBT and o‐BHBT in THF/water mixtures with different water volume fractions indicated an opposite luminescence in aggregates, in which p‐BHBT showed an ESIPT‐dependent AIE properties while o‐BHBT displayed ESIPT effect and aggregation‐caused quenching (ACQ) qualities. A possible mechanism for molecular actions to illustrate the aggregating luminescence alteration of these two isomers had been proposed and verified by theoretical and experimental studies. More importantly, Probe‐1, generated from dual ESIPT‐AIE fluorophore p‐BHBT, was successfully used as a ratiometric fluorescent chemosensor for highly selective (above 15‐fold over other ROS) and sensitive (69‐fold fluorescence enhancement with 0.22 μM of detection limit) detection of hydrogen peroxide in aqueous solution and living cells, respectively.
Understanding the Effects of Binders in Gas Sorption and Acidity of Aluminium Fumarate Extrudates
Authors: Rivera‐Torrente Miguel , Kroon Danny , Coulet Marie‐Vanessa , Marquez Carlos , Nikolopoulos Nikolaos , Hardian Rifan , Bourrelly Sandrine , De Vos Dirk , Whiting Gareth T. , Weckhuysen Bert M.
Published: November 2021

Understanding the impact of shaping processes on solid adsorbents is critical for the implementation of MOFs in industrial separation processes or as catalytic materials. Production of MOF‐containing shaped particles is typically associated with loss of porosity and modification of acid sites, two phenomena that affect their performance. Herein, we report a detailed study on how extrusion affects the crystallinity, porosity, and acidity of the aluminium fumarate MOF with clays or SiO2 gel binders. Thorough characterization showed that the clay binders confer the extrudates a good mechanical robustness at the expense of porosity, while silica gel shows an opposite trend. The CO2 selectivity towards CH4, of interest for natural gas separation processes, is maintained upon the extrusion process. Moreover, probe FTIR spectroscopy revealed no major changes in the types of acid sites. This study highlights that these abundant and inexpensive clay materials may be used for scaling MOFs as active adsorbents.
Visible‐Light‐Promoted [3 + 2] Cycloaddition of 2H‐Azirines with Quinones: Access to Substituted Benzo[f]isoindole‐4,9‐diones
Authors: Wang Lijia , Liu Chuang , Li Lei , Wang Xin , Sun Ran , Zhou Ming‐Dong , Wang He
Published: November 2021

Comprehensive Summary

A visible‐light‐promoteded [3 + 2] cycloaddition reaction of 2H‐azirines with quinones has been developed under mild reaction conditions. The reaction provides a general and efficient strategy for the synthesis of the benzo[f]isoindole‐4,9‐diones scaffold via a tandem [3 + 2] cyclization/oxidative aromatization with molecular oxygen. Furthermore, preliminary studies for photocatalytic properties show that the benzo[f]isoindole‐4,9‐diones 3 can be used as photocatalysts in several organic transformations.
Solid‐State C−N Cross‐Coupling Reactions with Carbazoles as Nitrogen Nucleophiles Using Mechanochemistry
Authors: Kubota Koji , Endo Tsubura , Uesugi Minami , Hayashi Yuta , Ito Hajime
Published: November 2021

The palladium‐catalyzed solid‐state C−N cross‐coupling of carbazoles with aryl halides via a high‐temperature ball‐milling technique has been reported. This reaction allowed simple, fast, and efficient synthesis of N‐arylcarbazole derivatives in good to excellent yields without the use of large amounts of organic solvents in air. Importantly, the developed solid‐state coupling approach enabled the cross‐coupling of poorly soluble aryl halides with large polyaromatic structures that are barely reactive under conventional solution‐based conditions.
HCl‐Catalyzed Aerobic Oxidation of Alkylarenes to Carbonyls
Authors: Niu Kaikai , Shi Xiaodi , Ding Ling , Liu Yuxiu , Song Hongjian , Wang Qingmin
Published: November 2021

The construction of C−O bonds through C−H bond functionalization remains fundamentally challenging. Here, a practical chlorine radical‐mediated aerobic oxidation of alkylarenes to carbonyls was developed. This protocol employed commercially available HCl as a hydrogen atom transfer (HAT) reagent and air as a sustainable oxidant. In addition, this process exhibited excellent functional group tolerance and a broad substrate scope without the requirement for external metal and oxidants. The mechanistic hypothesis was supported by radical trapping,18O labeling, and control experiments.
Asymmetric allelic introgression across a hybrid zone of the coal tit (Periparus ater) in the central Himalayas*
Authors: Wolfgramm Hannes , Martens Jochen , Töpfer Till , Vamberger Melita , Pathak Abhinaya , Stuckas Heiko , Päckert Martin
Published: November 2021

In the Himalayas, a number of secondary contact zones have been described for vicariant vertebrate taxa. However, analyses of genetic divergence and admixture are missing for most of these examples. In this study, we provide a population genetic analysis for the coal tit (Periparus ater) hybrid zone in Nepal. Intermediate phenotypes between the distinctive western “spot‐winged tit” (P. a. melanolophus) and Eastern Himalayan coal tits (P. a. aemodius) occur across a narrow range of <100 km in western Nepal. As a peculiarity, another distinctive cinnamon‐bellied form is known from a single population so far. Genetic admixture of western and eastern mitochondrial lineages was restricted to the narrow zone of phenotypically intermediate populations. The cline width was estimated 46 km only with a center close to the population of the cinnamon‐bellied phenotype. In contrast, allelic introgression of microsatellite loci was asymmetrical from easternP. a. aemodiusinto far western populations of phenotypicP. a. melanolophusbut not vice versa. Accordingly, the microsatellite cline was about 3.7 times wider than the mitochondrial one.
Morphological variability in Lophyra flexuosa (Fabricius, 1787) (Coleoptera, Cicindelidae) in desert countries is affected by sexual dimorphism and geographic aspect
Authors: Jaskuła Radomir , Schwerk Axel , Płóciennik Mateusz
Published: November 2021

Lophyra flexuosa, a eurytopic tiger beetle characterized by long phenological activity, wide geographic and altitudinal distribution, and occurring in the highest number of habitats among all Cicindelidae known from North Africa, was chosen to study its geographic variation in morphology and sexual dimorphism. Here, we found significant sexual dimorphism exhibited in larger body size of females and longer mandibles in males, which can be explained by different roles of particular sexes in courtship. Moreover, we recorded significant differences in body sizes between western and eastern Maghreb populations which could suggest genetic isolation between these populations. As the species is related to habitats placed close to the water reservoirs, which in the desert countries are under significant human pressure (including climate change), we expect a reduction of habitat occupied by this taxon. Therefore, the geographic morphological variability that we observe today in the tiger beetle Lophyra flexuosa in the future could lead to speciation.
Decay of similarity across tropical forest communities: integrating spatial distance with soil nutrients
Authors: Peguero Guille , Ferrín Miquel , Sardans Jordi , Verbruggen Erik , Ramírez‐Rojas Irene , Van Langenhove Leandro , Verryckt Lore T. , Murienne Jerome , Iribar Amaia , Zinger Lucie , Grau Oriol , Orivel Jerome , Stahl Clément , Courtois Elodie A. , Asensio Dolores , Gargallo‐Garriga Albert , Llusià Joan , Margalef Olga , Ogaya Romà , Richter Andreas , Janssens Ivan A. , Peñuelas Josep
Published: November 2021

Understanding the mechanisms that drive the change of biotic assemblages over space and time is the main quest of community ecology. Assessing the relative importance of dispersal and environmental species selection in a range of organismic sizes and motilities has been a fruitful strategy. A consensus for whether spatial and environmental distances operate similarly across spatial scales and taxa, however, has yet to emerge. We used censuses of four major groups of organisms (soil bacteria, fungi, ground insects, and trees) at two observation scales (1‐m2 sampling point vs. 2,500‐m2 plots) in a topographically standardized sampling design replicated in two tropical rainforests with contrasting relationships between spatial distance and nutrient availability. We modeled the decay of assemblage similarity for each taxon set and site to assess the relative contributions of spatial distance and nutrient availability distance. Then, we evaluated the potentially structuring effect of tree composition over all other taxa. The similarity of nutrient content in the litter and topsoil had a stronger and more consistent selective effect than did dispersal limitation, particularly for bacteria, fungi, and trees at the plot level. Ground insects, the only group assessed with the capacity of active dispersal, had the highest species turnover and the flattest nonsignificant distance−decay relationship, suggesting that neither dispersal limitation nor nutrient availability were fundamental drivers of their community assembly at this scale of analysis. Only the fungal communities at one of our study sites were clearly coordinated with tree composition. The spatial distance at the smallest scale was more important than nutrient selection for the bacteria, fungi, and insects. The lower initial similarity and the moderate variation in composition identified by these distance‐decay models, however, suggested that the effects of stochastic sampling were important at this smaller spatial scale. Our results highlight the importance of nutrients as one of the main environmental drivers of rainforest communities irrespective of organismic or propagule size and how the overriding effect of the analytical scale influences the interpretation, leading to the perception of greater importance of dispersal limitation and ecological drift over selection associated with environmental niches at decreasing observation scales.
Additional burden of iron deficiency in heart failure patients beyond the cardio‐renal anaemia syndrome: findings from the BIOSTAT‐CHF study
Authors: Alnuwaysir Ridha I.S. , Grote Beverborg Niels , Hoes Martijn F. , Markousis‐Mavrogenis George , Gomez Karla A. , van der Wal Haye H. , Cleland John G.F. , Dickstein Kenneth , Lang Chim C. , Ng Leong L. , Ponikowski Piotr , Anker Stefan D. , van Veldhuisen Dirk J. , Voors Adriaan A. , van der Meer Peter
Published: November 2021

Aims

Whereas the combination of anaemia and chronic kidney disease (CKD) has been extensively studied in patients with heart failure (HF), the contribution of iron deficiency (ID) to this dysfunctional interplay is unknown. We aimed to assess clinical associates and pathophysiological pathways related to ID in this multimorbid syndrome.

Methods and results

We studied 2151 patients with HF from the BIOSTAT‐CHF cohort. Patients were stratified based on ID (transferrin saturation <20%), anaemia (World Health Organization definition) and/or CKD (estimated glomerular filtration rate <60 ml/min/1.73 m2). Patients were mainly men (73.3%), with a median age of 70.5 (interquartile range 61.4–78.1). ID was more prevalent than CKD and anaemia (63.3%, 47.2% and 35.6% respectively), with highest prevalence in those with concomitant CKD and anaemia (77.5% vs. 59.3%; p < 0.001). There was a considerable overlap in biomarkers and pathways between patients with isolated ID, anaemia or CKD, or in combination, with processes related to immunity, inflammation, cell survival and cancer amongst the common pathways. Key biomarkers shared between syndromes with ID included transferrin receptor, interleukin‐6, fibroblast growth factor‐23, and bone morphogenetic protein 6. Having ID, either alone or on top of anaemia and/or CKD, was associated with a lower overall summary Kansas City Cardiomyopathy Questionnaire score, an impaired 6‐min walk test and increased incidence of hospitalizations and/or mortality in multivariable analyses (all p < 0.05).

Conclusion

Iron deficiency, CKD and/or anaemia in patients with HF have great overlap in biomarker profiles, suggesting common pathways associated with these syndromes. ID either alone or on top of CKD and anaemia is associated with worse quality of life, exercise capacity and prognosis of patients with worsening HF.
Synthesis and Studies of Potential Inhibitors of CD73 Based on a Triazole Scaffold
Authors: Grosjean Félix , Cros‐Perrial Emeline , Braka Abdenour , Uttaro Jean‐Pierre , Chaloin Laurent , Jordheim Lars Petter , Peyrottes Suzanne , Mathé Christophe
Published: November 2021

The ecto‐5′‐nucleotidase CD73 is involved in the production of immunosuppressive adenosine in the tumoral microenvironment and recently became a validated target in immuno‐oncology. To avoid formation of CD73‐produced adenosine, several series of potential inhibitors of the target enzyme based on a triazole scaffold were synthetized and evaluated on recombinant purified hCD73 and in cell‐based assays.
Ring Opening and Closure Reactions of β‐Propiolactone in the Superacids HF/MF5 (M=Sb, As)
Authors: Beck Stefanie , Jessen Christoph , Kornath Andreas J.
Published: November 2021

Transformations of β‐propiolactone in the binary superacidic systems HF/MF5 (M=Sb, As) were investigated at different temperatures. Salts of monoprotonated 3‐hydroxypropanoyl fluoride [H2O(CH2)2C(O)F][SbF6] (1) and [H2O(CH2)2C(O)F][AsF6] (2) were obtained by performing the reactions at temperatures lower than −40 °C. In contrast, temperatures higher than −40 °C yield the respective salts [C9H15O6][SbF6]3 (3) and [C9H15O6][AsF6]3 (4) containing a cyclic trication. The protonated species of β‐propiolactone was not observed. All salts were characterized by low temperature Raman and IR spectroscopy. In addition, single‐crystal X‐ray analyses were performed for (1) and (3). For both cations the existence of a cationic acyl species as a reactive intermediate in the form of [HO(CH2)2CO][MF6] is assumed. The formation of the acyl cation, based on protonated β‐propiolactone, was investigated by quantum chemical calculations on the MP2/aug‐cc‐pVTZ level of theory.
Heterostructural NiCo2O4 Nanocomposites for Nonenzymatic Electrochemical Glucose Sensing
Authors: Yang Shuying , Wang Yahui , Sheng Qinglin
Published: November 2021

Hierarchical nanocomposites consisting of NiCo2O4 nanorods and NiCo2O4 nanoparticles through a straightforward two‐step hydrothermal process was employed as a working electrode to examine the electrochemical behavior of glucose. The NiCo2O4@NiCo2O4 heterostructures was confirmed by the scanning electron microscopy (SEM), transmission electron microscopy (TEM), X‐ray powder diffractometer (XRD), X‐ray photoelectron spectroscopy (XPS) and electrochemistry analysis. Results indicated that glucose is electrochemically oxidized with improved sensitivity at the NiCo2O4@NiCo2O4 sensor, compared to NiCo2O4 sensors. Analytical parameters such as the optimal potential (0.45 V), linear range from 0.4 μM to 5.2 mM, limit of detection (1.1 μΜ) (S/N=3), stability and repeatability (2.7 %) demonstrate the suitability of the prepared sensor for glucose analysis. Moreover, the proposed sensor could be used for actual samples analysis in complex matrices.
Applying intensified design of experiments to mammalian cell culture processes
Authors: Nold Verena , Junghans Lisa , Bisgen Lorenzo , Drerup Raphael , Presser Beate , Gorr Ingo , Schwab Thomas , Knapp Bettina , Wieschalka Stefan
Published: November 2021

The analysis of data collected using design of experiments (DoE) is the current gold standard to determine the influence of input parameters and their interactions on process performance and product quality. In early development, knowledge on the bioprocess of a new product is limited. Many input parameters need to be investigated for a thorough investigation. For eukaryotic cell cultures, intensified DoE (iDoE) has been proposed as efficient tool, requiring fewer bioreactor runs by introducing setpoint changes during the bioprocess. We report the first successful application of iDoE to mammalian cell culture, performing sequential setpoint changes in the growth phase for the selected input parameters temperature and dissolved oxygen. The process performance data were analyzed using ordinary least squares regression. Our results indicate iDoE to be applicable to mammalian bioprocesses and to be a cost‐efficient option to inform modeling early on during process development. Even though only half the number of bioreactor runs were used in comparison to a classical DoE approach, the resulting models revealed comparable input‐output relations. Being able to examine several setpoint levels within one bioreactor run, we confirm iDoE to be a promising tool to speed up biopharmaceutical process development.
Development of Fluoride Protective Values for Aquatic Life Using Empirical Bioavailability Models
Authors: Parker Samuel P. , Wilkes Austin E. , Long Gary R. , Goulding Nigel W. E. , Ghosh Rajat S.
Published: November 2021

The derivation of protective values for aquatic life can be enhanced by the development and use of bioavailability models. Recent advances to metals bioavailability modeling are applicable to other analyte groups and should be widely considered. We conducted a meta-analysis of the available aquatic toxicity literature for fluoride to evaluate the utility of hardness, alkalinity, and chloride as toxicity-modifying factors (TMFs) in empirical bioavailability models of freshwater taxa. The resulting optimal multiple linear regression model predicting acute fluoride toxicity to the invertebrate Hyalella azteca included all three TMFs (observed vs. predicted 50% lethal concentrations, R2 = 0.88) and the optimal model predicting toxicity to the fish Oncorhynchus mykiss included alkalinity and hardness (R2 = 0.37). At >20 mg/L chloride, the preliminary final acute values for fluoride were within 1 order of magnitude and ranged from approximately 18.1 to 56.3 mg/L, depending on water chemistry. Sensitivity of H. azteca to low-chloride conditions increased model uncertainty when chloride was <20 mg/L. Because of limited toxicity data, chronic bioavailability models were not developed, and final chronic values were derived using an acute-to-chronic ratio (ACR) approach. Accounting for TMFs, the geometric mean ACR was 5.4 for fish and invertebrate taxa (n = 6). The present assessment highlights the need to expand bioavailability modeling to include inorganic anions, particularly fluoride, and demonstrates that existing promulgated protective values for fluoride are likely overly conservative. More toxicological studies are recommended to further refine multivariate empirical bioavailability models for inorganic anions. Environ Toxicol Chem 2022;41:396–409. © 2021 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Abstract

Hardness, alkalinity, and chloride are toxicity-modifying factors that influence the bioavailability of fluoride to freshwater taxa. Toxicity-modifying factors need to be considered when assessing protective values for aquatic life, such as the final acute value. FAV = final acute value; TMF = toxicity-modifying factor.
Dynamic of recovery growth of intercropped soybean after maize harvest in maize–soybean relay strip intercropping system
Authors: Wu Yushan , Gong Wanzhuo , Yang Feng , Wang Xiaochun , Yong Taiwen , Liu Jiang , Pu Tian , Yan Yanhong , Yang Wenyu
Published: November 2021

Recovery growth is common in relay intercropping systems and is a useful practice to increase total productivity of these systems. A field experiment was conducted during 2014–2016 to investigate the phenotypic and physiological traits related to light interception and utilization changes and cultivars difference of soybean during the recovery growth period. Two cropping patterns (maize–soybean relay strip intercropping (RSI), analogous soybean monoculture (CK)) and two soybean cultivars (shade‐tolerant Nandou12 and shade non‐tolerant Jiuyuehuang) were evaluated. During the co‐growth period, the growth of both two soybean cultivars was suppressed and showed a series of shade avoidance traits. After maize harvest, the LAI and leaflet number of intercropped soybean exhibited rapid growth, the LAI of Nandou12 (3.09) and Jiuyuehuang (1.32) recovered to 79% and 43% of corresponding CK level, respectively. Subsequently, final biomass of Nandou12 (3972.7 kg ha−1) and Jiuyuehuang (2263.3 kg ha−1) recovered 85.7% and 52% of corresponding CK level, respectively. Leaf blade thickness of Nandou12 recovered to the corresponding CK level, while Jiuyuehuang was not. Pn recovered to 84.5% and 82.8% of sole Pn at 80 days after soybean sowing in 2015 and to 72% and 91.2% at 66 days after soybean sowing in 2016 for Nandou12 and Jiuyuehuang, respectively. The above recovery process promoted the recovery of pod formation and grain yield. The yield of Nandou12 (1159.5 kg ha−1) has no significant difference between the CK level (1325.5 kg ha−1) but significantly higher than that of Jiuyuehuang (566.8 kg ha−1). Taken together, some recovery growth did occur in Jiuyuehuang, but it did not completely compensate for the growth reduction that occurred during the co‐growth period. Shade‐tolerant soybean cultivar has more stronger recovery growth ability in LAI, leaflet number, leaf thickness, and photosynthesis after maize harvest, which promoted the recovery growth of aboveground biomass and grain yield.
Degradation studies using machine learning on novel solid oxide cell database
Authors: Padinjarethil, Aiswarya Krishnakumar , Pollok, Stefan , Hagen, Anke
Published: November 2021

With the current progress in solid oxide cell (SOC) technology towards commercial products, better durability is vital. Continuous advancements in technology and material discovery demand the understanding of underlying degradation mechanisms. It remains a challenge to experimentally assess the lifetime using conventional mapping by long‐term testing.

In this work, a statistical approach based on machine learning was utilized for assessing the lifetime of SOCs. An in‐house SOC dataset consisting of about 2135 tests under different test conditions over the past ca. 20 years with different cell materials was used as the basis for a novel database. Degradation parameters were defined using values obtained from impedance analysis at open‐circuit voltage before (and after) durability testing and parameters recorded during the durability tests. To apply machine learning approaches, data visualization was first carried out, followed by correlation analysis between the different input parameters. Machine learning approaches such as single and multivariable linear regression were applied. Such a study on a diverse dataset would enable an inclusive lifetime prediction for wider datasets, independent of changes in testing environments as well as for various cell operation modes.
Pcsk9 Deletion Promotes Murine Nonalcoholic Steatohepatitis and Hepatic Carcinogenesis: Role of Cholesterol
Authors: Ioannou George N. , Lee Sum P. , Linsley Peter S. , Gersuk Vivian , Yeh Matthew M. , Chen Yen‐Ying , Peng Yi‐Jen , Dutta Moumita , Mascarinas Gabby , Molla Bruk , Cui Julia Yue , Savard Christopher
Published: November 2021

Proprotein convertase subtilisin/kexin type 9 (Pcsk9) binds to hepatic low‐density lipoprotein receptor (LDLR) and induces its internalization and degradation. Pcsk9 inhibition increases LDLR expression by hepatocytes, which causes increased uptake of circulating LDL, thereby reducing plasma LDL‐cholesterol. However, by increasing the uptake of LDL by the liver, Pcsk9 inhibition increases the exposure of the liver to cholesterol, which may result in higher risk of steatohepatitis and ever carcinogenesis. We compared Pcsk9‐/‐ knockout (KO) mice and appropriate wild‐type (WT) controls of the same strain assigned to a high‐fat (15%, wt/wt) diet for 9 months supplemented with 0.25%, 0.5%, or 0.75% dietary cholesterol. Pcsk9 KO mice on a high‐fat, high‐cholesterol diet exhibited higher levels of hepatic free cholesterol loading and hepatic cholesterol crystallization than their WT counterparts. Pcsk9 KO mice developed crown‐like structures of macrophages surrounding cholesterol crystal‐containing lipid droplets and hepatocytes, exhibited higher levels of apoptosis, and developed significantly more hepatic inflammation and fibrosis consistent with fibrosing steatohepatitis, including 5‐fold and 11‐fold more fibrosis at 0.5% and 0.75% dietary cholesterol, respectively. When injected with diethylnitrosamine, a hepatic carcinogen, early‐in‐life Pcsk9 KO mice were more likely to develop liver cancer than WT mice. Conclusion: Pcsk9 KO mice on high‐cholesterol diets developed increased hepatic free cholesterol and cholesterol crystals and fibrosing steatohepatitis with a higher predisposition to liver cancer compared with WT mice. Future studies should evaluate whether patients on long‐term treatment with anti‐PSCK9 monoclonal antibodies are at increased risk of hepatic steatosis, steatohepatitis or liver cancer, while accounting for concurrent use of statins.
Outcome of patients with mantle cell lymphoma after autologous stem cell transplantation in the pre‐CAR T‐cell era
Authors: Mathys Anina , Bacher Ulrike , Banz Yara , Legros Myriam , Mansouri Taleghani Behrouz , Novak Urban , Pabst Thomas
Published: November 2021

Mantle cell lymphoma (MCL) patients can be treated with intensive induction therapy, followed by high dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT) for consolidation and subsequent anti‐CD20 maintenance. For patients relapsing after bruton tyrosine kinase (BTK) inhibitors, CAR T‐cell therapy became available in late 2020 fueling the interest in outcomes of relapsing MCL patients. We retrospectively analyzed the outcome of MCL patients receiving HDCT/ASCT at our center between 2000 and 2021, thus, before availability of CAR‐T cells. We identified 97 MCL patients undergoing HDCT/ASCT in this period with a median follow‐up of 52 months. 43 (44%) patients ultimately relapsed, and 29 (30%) have died. The median progression‐free survival (PFS) for the entire cohort was 48 months and overall survival (OS) was 202 months. Relapsing patients had a median PFS of only 28 months and median OS of 105 months. The OS of relapsing patients receiving BTK inhibitors was 148 versus 78 months in patients who never received BTK inhibitors (p = 0.1175). Even after HDCT/ASCT, a substantial proportion of MCL patients will relapse and ultimately die of the disease, emphasizing the need for new therapeutic options including CAR T‐cell treatment for this lymphoma subtype.
Reassessing the Pediatric Dosing Recommendations for Unfractionated Heparin Using Real‐World Data: A Pharmacokinetic–Pharmacodynamic Modeling Approach
Authors: Salem Ahmed M. , Niu Tao , Li Chao , Moffett Brady S. , Ivaturi Vijay , Gopalakrishnan Mathangi
Published: November 2021

Optimal pediatric dosing of unfractionated heparin (UFH) is challenging because of the paucity of clinical outcome and pharmacokinetic–pharmacodynamic (PK/PD) studies in pediatrics. This study aimed to: (i) develop a PK/PD model for UFH, quantified by anti‐factor Xa assay, and the UFH effect, measured by activated partial thromboplastin time (aPTT); and (ii) use simulations to evaluate pediatric UFH infusions for achieving the anti‐factor Xa (0.3–0.7 IU/mL) therapeutic target. Electronic health record data were retrospectively collected from 633 patients aged <19 years admitted to Texas Children's Hospital. The PK/PD model was developed using a 70% (training)/30% (testing) split‐sample approach. A 1‐compartment PK model with linear elimination adequately described the UFH PK. An allometrically scaled body weight on clearance (CL) and volume of distribution (Vd) with an age‐dependent maturation function of extracellular water on Vd were the covariates identified. Comparable with literature, the typical values for CL and Vd were 3.28 L/(h·50 kg) and 8.83 L/50 kg, respectively. A linear model adequately described the UFH–aPTT relationship with an estimated slope of 150 seconds/(IU/mL). Simulations of the currently recommended starting infusions (28 IU/h/kg for pediatrics <1 year old or 20 IU/h/kg for pediatrics >1 year old) showed that the anti‐factor Xa therapeutic target was achieved only in 15.3%, 14.6%, 36.9%, and 45.11% of subjects in the age groups of <1 year, 1–6 years, 6–12 years, and 12–19 years, respectively. In conclusion, the UFH anti‐factor Xa target is not achieved initially, especially in young pediatrics, suggesting the need to optimize UFH dosing to achieve higher therapeutic success.
Rethinking the role of team mindfulness in team relationship conflict: A conflict management perspective
Authors: Ni Dan , Zheng Xiaoming , Liang Lindie H.
Published: November 2021

Why and when does team mindfulness help to reduce team relationship conflict? To answer this question, we develop and test a theoretical model that builds on Deutsch's theory of cooperation and competition. A two‐wave time‐lagged survey was conducted with 68 teams in an airline food service company located in China. The results showed that team mindfulness was negatively related to team relationship conflict via an increased cooperative conflict approach and a decreased competitive conflict approach. Further, high team job demands were shown to weaken the positive direct effect of team mindfulness on a cooperative conflict approach, as well as the indirect effect of team mindfulness on team relationship conflict via a cooperative approach. Theoretical contributions and practical implications are discussed.
Towards a historical precipitation database for West Africa: Overview, quality control and harmonization
Authors: Bliefernicht Jan , Salack Seyni , Waongo Moussa , Annor Thompson , Laux Patrick , Kunstmann Harald
Published: November 2021

Reliable long‐term observations from precipitation stations are often required for climatological studies but are strongly limited in many regions of the world. To improve this limitation for West Africa, we compiled daily and monthly observations from more than 20 national, continental and global databases, to establish a historical precipitation archive with a focus on four countries (Burkina Faso, Ghana, Benin and Togo). The new archive contains long‐term daily and monthly precipitation measurements from 1819 to 2013 for more than 1,000 sites. It is, therefore, the most comprehensive historical dataset with daily and monthly precipitation observations for this region. To produce a quality‐controlled and harmonized precipitation dataset for the focal region, various statistical algorithms have been implemented. These algorithms rely on straightforward geostatistical approaches (e.g., spatial correlograms) and corresponding statistical tests for identification and elimination of unreliable time series, in addition to various standard approaches used by global data centers. Although the quality control revealed various data errors and uncertainties for measurements and meta‐information (e.g., unit conversion errors, temporal offsets, frequent and long data gaps), a spatial interpolation using the quality‐controlled and harmonized dataset produced relatively reliable precipitation patterns for different target variables (e.g., monthly precipitation amount and daily precipitation probability). A major remaining challenge is providing free access to this database for research and other noncommercial purposes, due to national data protection regulations. However, several further tasks have been initiated and implemented (e.g., free provision of gridded precipitation datasets and point statistics) to improve the access and availability of station‐based precipitation observations and related data products for this climatologically challenging region.
On new abundant exact traveling wave solutions to the local fractional Gardner equation defined on Cantor sets
Authors: Wang Kang‐Jia
Published: November 2021

In this article, we derive a new local fractional Gardner equation based on the local fractional derivative. A novel traveling wave transform of the non‐differentiable type is utilized to convert the local fractional Gardner equation into a nonlinear local fractional ordinary differential equation. Then a new method called the Mittag–Leffler function based method is proposed for the first time ever to construct the abundant traveling wave solutions. By this method, three families (six sets) of the traveling wave solutions on Cantor set are obtained. Finally, the performances of the various solutions on Cantor set are presented through the three‐dimensional contours. It shows that the proposed method is straightforward, powerful and can provide more forms of the traveling wave solutions for the local fractional equations, which is expected to be helpful for the study of the traveling wave theory for local fractional equations.