bluuebunny/crossref_metadata_2025 huggingface dataset:
A Microfluidic Device for Long‐Term Maintenance of Organotypic Liver Cultures
Authors: de Hoyos‐Vega José M. , Hong Hye Jin , Loutherback Kevin , Stybayeva Gulnaz , Revzin Alexander
Published: October 2022

Liver cultures may be used for disease modeling, testing therapies, and predicting drug‐induced injury. The complexity of the liver cultures has evolved from hepatocyte monocultures to co‐cultures with non‐parenchymal cells and finally to precision‐cut liver slices. The latter culture format retains liver's native biomolecular and cellular complexity and therefore holds considerable promise for in vitro testing. However, liver slices remain functional for ≈72 h in vitro and display limited utility for some disease modeling and therapy testing applications that require longer culture times. This paper describes a microfluidic device for longer‐term maintenance of functional organotypic liver cultures. This microfluidic culture system is designed to enable direct injection of liver tissue into a culture chamber through a valve‐enabled side port. Liver tissue is embedded in collagen and remained functional for up to 31 days, highlighted by continued production of albumin and urea. These organotypic cultures also express several enzymes involved in xenobiotic metabolism. Conversely, matched liver tissue embedded in collagen in a 96‐well plate loses its phenotype and function within 3–5 days. The microfluidic organotypic liver cultures described here represent a significant advance in liver cultivation and may be used for future modeling of liver diseases or for individualized liver‐directed therapies.
Recent Progress of Noncovalent Interaction‐Driven Self‐Assembly of Photonic Organic Micro‐/Nanostructures
Authors: Ma Ying‐Xin , Yin Hui‐Ling , Yang Jing , Lin Hong‐Tao , Chen Shu‐Hai , Zhou Jin , Zhuo Shu‐Ping , Wang Xue‐Dong
Published: October 2022

Modern organic photonics is heavily reliant on micro‐/nanostructured organic crystalline materials, not least because they exhibit advantageous physicochemical properties and can be easily fabricated by bottom‐up approaches such as self‐assembly driven by weak noncovalent intermolecular interactions (van der Waals forces, π–π interactions, hydrogen bonds, halogen bonds, charge transfer interactions, etc.). Herein, the effects of these interactions on organic crystal nucleation are summarized, the resulting low‐dimensional organic crystal structures and their optoelectronic applications are discussed, and future development prospects are presented to inspire the further investigation of such optofunctional structures.
Noncovalent Bridged Bis(Coumarin‐24‐Crown‐8) Phosphorescent Supramolecular Switch
Authors: Wang Hui‐Juan , Xing Wen‐Wen , Yu Zhen‐Hai , Zhang Heng‐Yi , Xu Wen‐Wen , Liu Yu
Published: October 2022

A multicolor room temperature phosphorescence (RTP) supramolecular photo‐switch encryption film is constructed by the coassembly of coumarin‐24‐crown‐8 (C24C8), diarylethene dicationic alkylammonium derivative (1), rhodamine B (RhB) and poly(vinyl alcohol) (PVA). Benefiting from the tightly binding of C24C8 and secondary alkylammonium ion, 1 formed noncovalent bridged bis(coumarin‐24‐crown‐8), which displayed photo‐switchable RTP with green afterglow (more than 5 s) after coassembly with PVA. Especially doping with RhB gave a photo‐switchable highly efficient phosphorescence‐harvesting system with multicolor through triplet‐to‐singlet Förster‐resonance energy transfer (TS‐FRET). The energy transfer efficiency and antenna effect of C24C8+RhB@PVA film reached 88.3% and 62.6 when the donor/acceptor ratio is 50:1, respectively. Therefore, diarylethene noncovalent bridged bis(coumarin‐24‐crown‐8) supramolecular assembly not only displays a multicolor photoluminescence‐switch, but also presents a phosphorescent photo‐switch with afterglow, which provides a simple and feasible way to construct smart RTP materials through host‐guest strategy.
Merging Gold(I) Catalysis with Amine Transaminases in Cascade Catalysis: Chemoenzymatic Transformation of Propargylic Alcohols into Enantioenriched Allylic Amines
Authors: González‐Granda Sergio , Tzouras Nikolaos V. , Nolan Steven P. , Lavandera Iván , Gotor‐Fernández Vicente
Published: October 2022

The compatibility between gold(I) catalysts and amine transaminases has been explored to transform racemic propargylic alcohols into enantioenriched allylic amines in a straightforward and selective manner. The synthetic approach consists of a gold(I)‐catalysed Meyer‐Schuster rearrangement of a series of 2‐arylpent‐3‐yn‐2‐ols and a subsequent stereoselective enzyme‐catalysed transamination of the resulting α,β‐unsaturated prochiral ketones. The design of cascade processes involving sequential or concurrent approaches has been studied in our search for ideal reaction conditions to produce the desired amines. Thus, the N‐heterocyclic carbene complex [1,3‐bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene]‐[bis(trifluoromethanesulfonyl)‐imide]gold(I) ([Au(IPr)(NTf2)] (A) in aqueous medium was found to be an ideal catalyst, while selective, made‐in‐house and commercial amine transaminases permitted the asymmetric synthesis of both (E)‐4‐arylpent‐3‐en‐2‐amine enantiomers in good isolated yields (53–84%) and excellent stereoselectivities (97 to >99% enantiomeric excess).

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Rapid Plasma Exsolution from an A‐site Deficient Perovskite Oxide at Room Temperature
Authors: Khalid Hessan , Haq Atta ul , Alessi Bruno , Wu Ji , Savaniu Cristian D. , Kousi Kalliopi , Metcalfe Ian S. , Parker Stephen C. , Irvine John T. S. , Maguire Paul , Papaioannou Evangelos I. , Mariotti Davide
Published: October 2022

High‐performance nanoparticle platforms can drive catalysis progress to new horizons, delivering environmental and energy targets. Nanoparticle exsolution offers unprecedented opportunities that are limited by current demanding process conditions. Unraveling new exsolution pathways, particularly at low‐temperatures, represents an important milestone that will enable improved sustainable synthetic route, more control of catalysis microstructure as well as new application opportunities. Herein it is demonstrated that plasma direct exsolution at room temperature represents just such a step change in the synthesis. Moreover, the factors that most affect the exsolution process are identified. It is shown that the surface defects produced initiate exsolution under a brief ion bombardment of an argon low‐pressure and low‐temperature plasma. This results in controlled nanoparticles with diameters ≈19–22 nm with very high number densities thus creating a highly active catalytic material for CO oxidation which rivals traditionally created exsolved samples.
18.9% Efficient Organic Solar Cells Based on n‐Doped Bulk‐Heterojunction and Halogen‐Substituted Self‐Assembled Monolayers as Hole Extracting Interlayers
Authors: Lin Yuanbao , Zhang Yadong , Zhang Junxiang , Marcinskas Mantas , Malinauskas Tadas , Magomedov Artiom , Nugraha Mohamad Insan , Kaltsas Dimitris , Naphade Dipti R. , Harrison George T. , El‐Labban Abdulrahman , Barlow Stephen , De Wolf Stefaan , Wang Ergang , McCulloch Iain , Tsetseris Leonidas , Getautis Vytautas , Marder Seth R. , Anthopoulos Thomas D.
Published: October 2022

The influence of halogen substitutions (F, Cl, Br, and I) on the energy levels of the self‐assembled hole‐extracting molecule [2‐(9H‐Carbazol‐9‐yl)ethyl]phosphonic acid (2PACz), is investigated. It is found that the formation of self‐assembled monolayers (SAMs) of [2‐(3,6‐Difluoro‐9H‐carbazol‐9‐yl)ethyl]phosphonic acid (F‐2PACz), [2‐(3,6‐Dichloro‐9H‐carbazol‐9‐yl)ethyl]phosphonic acid (Cl‐2PACz), [2‐(3,6‐Dibromo‐9H‐carbazol‐9‐yl)ethyl]phosphonic acid (Br‐2PACz), and [2‐(3,6‐Diiodo‐9H‐carbazol‐9‐yl)ethyl]phosphonic acid (I‐2PACz) directly on indium tin oxide (ITO) increases its work function from 4.73 eV to 5.68, 5.77, 5.82, and 5.73 eV, respectively. Combining these ITO/SAM electrodes with the ternary bulk‐heterojunction (BHJ) system PM6:PM7‐Si:BTP‐eC9 yields organic photovoltaic (OPV) cells with power conversion efficiency (PCE) in the range of 17.7%–18.5%. OPVs featuring Cl‐2PACz SAMs yield the highest PCE of 18.5%, compared to cells with F‐2PACz (17.7%), Br‐2PACz (18.0%), or I‐2PACz (18.2%). Data analysis reveals that the enhanced performance of Cl‐2PACz‐based OPVs relates to the increased hole mobility, decreased interface resistance, reduced carrier recombination, and longer carrier lifetime. Furthermore, OPVs featuring Cl‐2PACz show enhanced stability under continuous illumination compared to ITO/PEDOT:PSS‐based cells. Remarkably, the introduction of the n‐dopant benzyl viologen into the BHJ further boosted the PCE of the ITO/Cl‐2PACz cells to a maximum value of 18.9%, a record‐breaking value for SAM‐based OPVs and on par with the best‐performing OPVs reported to date.
The outcome of a multidisciplinary approach incorporating neoadjuvant chemoradiotherapy with S1 for resectable pancreatic ductal adenocarcinoma
Authors: Matsumura Masaru , Honda Goro , Tani Keigo , Nemoto Satoshi , Ome Yusuke , Hayakawa Sara , Suzuki Mizuka , Horiguchi Shin‐ichiro , Kikuyama Masataka , Seyama Yasuji
Published: October 2022

Aim

This study was performed to evaluate the efficacy of a multidisciplinary approach incorporating neoadjuvant chemoradiotherapy with S1 (S1‐NACRT) for resectable pancreatic ductal adenocarcinoma.

Methods

The medical records of 132 patients who received S1‐NACRT for resectable pancreatic ductal adenocarcinoma from 2010 to 2019 were reviewed. The S1‐NACRT regimen consisted of S1 at a dose of 80‐120 mg/body/day together with 1.8 Gy of radiation in 28 fractions. The patients were re‐evaluated 4 weeks after S1‐NACRT completion, and a pancreatectomy was then considered.

Results

Adverse events of S1‐NACRT ≥grade 3 occurred in 22.7% of the patients, and 1.5% discontinued therapy. Of the 112 patients who underwent a pancreatectomy, 109 underwent R0 resection. Adjuvant chemotherapy with relative dose intensity ≥50% was administered to 74.1% of the patients who underwent resection. The median overall survival of all patients was 47 months, and the median overall survival and recurrence‐free survival of patients who underwent resection was 71 and 32 months, respectively. According to the multivariate analyses of prognostic factors for overall survival in patients who underwent resection, negative margin status (hazard ratio: 0.182; P = 0.006) and relative dose intensity of adjuvant chemotherapy ≥50% (hazard ratio 0.294; P < 0.001) were independent prognostic factors of overall survival.

Conclusions

A multidisciplinary approach incorporating S1‐NACRT for resectable pancreatic ductal adenocarcinoma demonstrated acceptable tolerability and good local control and resulted in comparable survival benefits.
Structure change of atactic polystyrene upon aging
Authors: Abdeldaym Ahmed , Brüning Ralf
Published: October 2022

We report the changes of atactic polystyrene (a‐PS) upon annealing below the glass transition based on X‐ray scattering, volume, and differential scanning calorimetry measurements of samples in the quenched and annealed states. Upon relaxation, an increase of the main diffuse diffraction peak and a decrease of the polymerization peak, typical for a‐PS, are proportional to the enthalpy changes. The relaxation of enthalpy corresponds to a change of the fictive temperature by 6.1 K for annealing at 80°C for 24 h. The changes of the fictive temperature derived from the X‐ray structure factor are between 5.4 and 6.8 K, depending on the range of scattering vector. The relaxation signal has a zero crossing at low scattering angles. The volume of the samples, measured at ambient conditions, did not change upon relaxation. We attribute these observations to localized relaxation processes that involve a small number of phenyl groups.
Modified rod‐shaped calcium carbonate with thiols improving UV‐curing 3D printing resin
Authors: Huang Weibing , Luo Qinghong , Zhu Yong , Liu Xiaoxuan , Xiang Hongping
Published: October 2022

UV‐curing 3D printing technology is one of the additive manufacturing techniques with the best printing accuracy and efficiency, but its advance is being challenged by the high curing shrinkage, poor mechanical strength and low toughness of photosensitive resin. Herein, rod‐shaped calcium carbonate modified by γ‐mercaptopropyl triethoxysilane (RCa‐Si) is used to improve the 3D printing resin. After compositing with RCa‐Si, the photopolymerization conversion of resin is slightly decreased, but it is still possible to 3D print accurate samples with a warpage of 1.0%. By adjusting the grafting ratio of thiols and the content of resultant RCa‐Si, the maximum elastic modulus of 3D printed samples is increased from 990 to 1420 MPa, tensile strength is enhanced from 35 to 63 MPa, and impact strength is also increased from 2.1 to 4.6 kJ/m2, owing to its anchoring effect between printing layers. Moreover, the thermal decomposition temperature of 3D printed sample containing 1.0 wt% of RCa1‐Si1 is increased to 325°C, and its Vicat softening point temperature is also increased to 193°C. Therefore, the comprehensive properties of 3D printing resin can be greatly improved by modified rod‐shaped calcium carbonate with thiols, guaranteeing the future large‐scale applications.
Determination of residual stresses in amorphous thermoplastic polymers by DMA
Authors: Huskić Miroslav , Kusić Dragan , Pulko Irena , Nardin Blaž
Published: October 2022

The processing of polymers and polymeric materials always leaves some residual stresses in the final product, which can have a positive but usually a negative effect on the properties of the final product. Polycarbonate was injection molded into the mold, which was heated to 50, 60, or 70°C to produce test specimens with different amounts of residual stresses. They were then annealed at various temperatures below Tg to partially remove the stresses or heated to 145°C (above Tg) to completely remove them. Comparison between annealed and as‐molded samples showed a strong influence of residual stresses on mechanical properties. Dynamic mechanical analysis (DMA) analysis showed that the loss modulus can be divided into the intrinsic loss modulus, which is a material property, and the residual stress, which can be relaxed at a given temperature. The stress relaxation curve, obtained by subtracting the loss modulus of the annealed sample from the loss modulus of the as‐molded sample gives us the ability to estimate the residual stresses that have been or can still be relaxed by heating to a given temperature.
A rare case of partial skull and brain duplication in a hatchling Alligator mississippiensis
Authors: Pritz Michael B. , Elsey Ruth M. , Thompson Tyler N. , Hsu Edward W.
Published: October 2022

Errors in development occur in all vertebrates. When severe, these anomalies are lethal and frequently escape attention. In rare cases, animals with profound malformations are born and can provide a glimpse into structures and their respective function that would otherwise go unnoticed. A rare abnormality in a hatchling Alligator mississippiensis is described in which duplication of the skull, face, and brain was incomplete. The rostral skull, face, and associated forebrain, including the olfactory apparatus, were duplicated. However, the caudal skull and brainstem were not. These observations were made with advanced imaging using both computed tomography and magnetic resonance coupled with gross brain dissections. These abnormal features emphasize the complex and intertwined relationship between the development of the brain, face, and skull which are influenced by certain signaling molecules, possible gene mutation(s), and potential environmental factors.
The sailing performance of ancient Polynesian canoes and the early settlement of East Polynesia
Authors: Irwin Geoffrey , Flay Richard G.J. , Dudley Loughlin , Johns Dilys
Published: October 2022

Scholarly estimates and opinions of the sailing performance of ancient Pacific canoes vary widely. This paper measures performance by testing real sails in a wind tunnel and hulls in a towing tank. The sails were three East Polynesian Oceanic spritsails of late eighteenth century type, held by the British Museum, collected from New Zealand, Tahiti and Hawaii/Marquesas, which conform to the first historical records. Also tested was a hypothetical generic ancestral sail, and the Māori sail was tested in different ways to accommodate different views. Tests of hull form found that upwind sailing performance improved as underwater hull profile changed from U‐shape to V‐shape and some archaeological hulls can be assigned to this scale. Velocity prediction programs (VPPs) were calculated for a range of different canoes and simulated voyages by the fourteenth century AD archaeological canoe (waka) found at Anaweka, New Zealand retraced real voyages made by the experimental Polynesian replica canoe Hōkūle'a between 1980 and 2000, in the same recorded weather. Both canoes could average speeds of up to four knots and sail upwind at 75° to the true wind angle (TWA), as proposed by Lewis and Finney. The paper identifies a package of technological innovations involved in the settlement of East Polynesia following the “long pause” in Pacific settlement in West Polynesia. Two innovations previously suggested by linguistics were the Oceanic spritsail and the double canoe, and a third was the development of complex composite planked hulls and V‐shaped underwater hull forms. East Polynesian canoes were capable of two‐way voyaging and some migrations were planned, as in the case of New Zealand.
Kinetic‐model‐based pathway optimization with application to reverse glycolysis in mammalian cells
Authors: Lu Yen‐An , Brien Conor M. O' , Mashek Douglas G. , Hu Wei‐Shou , Zhang Qi
Published: October 2022

Over the last two decades, model‐based metabolic pathway optimization tools have been developed for the design of microorganisms to produce desired metabolites. However, few have considered more complex cellular systems such as mammalian cells, which requires the use of nonlinear kinetic models to capture the effects of concentration changes and cross‐regulatory interactions. In this study, we develop a new two‐stage pathway optimization framework based on kinetic models that incorporate detailed kinetics and regulation information. In Stage 1, a set of optimization problems are solved to identify and rank the enzymes that contribute the most to achieving the metabolic objective. Stage 2 then determines the optimal enzyme interventions for specified desired numbers of enzyme adjustments. It also incorporates multi‐scenario optimization, which allows the simultaneous consideration of multiple physiological conditions. We apply the proposed framework to find enzyme adjustments that enable a reverse glucose flow in cultured mammalian cells, thereby eliminating the need for glucose feed in the late culture stage and enhancing process robustness. The computational results demonstrate the efficacy of the proposed approach; it not only captures the important regulations and key enzymes for reverse glycolysis but also identifies differences and commonalities in the metabolic requirements for different carbon sources.
Development of a UPLC–MS/MS method for the simultaneous determination of atorvastatin, 2‐hydroxy atorvastatin, and naringenin in rat plasma and its application to pharmacokinetic interaction studies
Authors: Li Wenchao , Xu Xiaolan , Wang Simeng , Li Yingchao , Zhang Yawei , Zhang Tianhong
Published: October 2022

Recent studies have revealed that the combination therapy of atorvastatin (ATV) with naringenin (NG) can offer meaningful benefits in the treatment of hypercholesterolemia, while decreasing adverse side effects. To investigate whether there are pharmacokinetic interactions among ATV, its metabolite 2‐hydroxy atorvastatin (2‐ATV), and NG, in the current study, we developed and validated a simple, rapid, and specific UPLC–MS/MS method to simultaneously determine the concentrations of these analytes in the rat plasma. Sample preparation was performed using simple protein precipitation. Chromatographic analysis was carried out on an Acquity UPLC BEH C18 column (1.7 μm, 2.1 × 100 mm) using gradient elution mode, and these three analytes were detected using a Xevo® TQD triple quadrupole tandem mass spectrometer, in the positive ion electrospray ionization interface. The developed method showed good linearity over the following concentrations in rat plasma samples: 3–1200 ng/ml (r = 0.9965) for ATV, 1.5–600 ng/ml (r = 0.9934) for 2‐ATV, and 3–1200 ng/ml (r = 0.9964) for NG. The assays were validated and satisfied the acceptance criteria recommended by U.S. Food and Drug Administration guidelines. Upon successful application of the method to a pharmacokinetic interaction study, the results indicated that NG significantly enhanced the bioavailability of ATV and 2‐ATV.
Bumetanide attenuates sevoflurane‐induced neuroapoptosis in the developing dentate gyrus and impaired behavior in the contextual fear discrimination learning test
Authors: Wei Kai , Liu Yiheng , Yang Xiamin , Liu Jin , Li Yuan , Deng Meng , Wang Yingwei
Published: October 2022

Introduction

Sevoflurane acts as a gamma‐aminobutyric acid subtype A receptor agonist and can induce widespread apoptosis of immature dentate granule cells in postnatal day 21 mice. The dentate granule cells of postnatal day 21 mice undergo a developmental stage when gamma‐aminobutyric acid (GABA) shifts from inducing the depolarization of neurons to causing hyperpolarization. However, it is unclear whether sevoflurane induces apoptosis of immature granule cells by facilitating the depolarization or hyperpolarization of neurons.

Methods

We utilized bumetanide, an Na+–K+–2Cl− cotransporter isoform 1 (NKCC1) antagonist, to determine whether the NKCC1‐mediated GABA depolarization of neurons plays a role in sevoflurane‐induced neuroapoptosis. We also investigated whether sevoflurane exposure is related to long‐term cognitive dysfunction in postnatal day 21 mice and explored the possible protective effects of bumetanide.

Results

Bumetanide attenuated the sevoflurane‐induced apoptosis of dentate granule cells in postnatal day 21 mice. Exposure to sevoflurane at postnatal day 21 mice did not affect their motor ability or anxiety level, and it had no effect on spatial learning or memory functions. However, sevoflurane exposure at postnatal day 21 impaired the pattern separation ability in the contextual fear discrimination test; bumetanide mitigated this effect of sevoflurane as well.

Conclusion

Bumetanide attenuates sevoflurane‐induced apoptosis and is a promising prospect for protecting against anesthesia‐induced neurotoxicity in the developing brain.
Metallic Catalysts for Oxidative Dehydrogenation of Propane Using CO2
Authors: Xing Feilong , Furukawa Shinya
Published: October 2022

The oxidative dehydrogenation of propane using CO2 (CO2−ODP) is a promising technique for realizing high‐yield propylene production and CO2 usage. Developing a highly efficient catalyst for CO2−ODP is essential and beneficial to the chemical industry and for realizing net‐zero emissions. Many studies have investigated metal oxide‐based catalysts, revealing that rapid deactivation and low selectivity remain limiting factors for their industrial applications. In recent years, metallic nanoparticle catalysts have become increasingly attractive due to their unique properties. Therefore, we summarize the performance of metal‐based catalysts in CO2−ODP reactions by considering catalyst design concepts, different mechanisms in the reaction process, and the role of CO2.
Walking Cations: Transition‐Metal Free Benzyl Cation‐Triggered sp2 C—H Phosphorylation and Etherification
Authors: Liu Kuan , Song Bin , Dang Qi , Liu Long , Tang Jie , Huang Tianzeng , Li Chunya , Tang Zhi , Chen Tieqiao
Published: October 2022

Comprehensive Summary

A novel benzyl cation‐triggered site‐selective sp2 C—H phosphorylation and etherification was developed. This reaction was conducted under the transition metal‐free conditions through cation migration via dearomatization. Under the reaction conditions, the derivatives of naphthalenes, benzofurans and benzo[b]thiophenes all can be transformed into the corresponding products in good to excellent yields. It provides a method to construct sp2 C—P and sp2 C—O bonds as well as a new strategy for benzylic activation‐triggered sp2 C—H functionalization.
Recycling and Upgrading Utilization of Polymer Plastics†
Authors: Hu Huilin , Chen Yana , You Feng , Yao Junlong , Yang Huan , Jiang Xueliang , Xia Bao Yu
Published: October 2022

Comprehensive Summary

Due to the current situation of massive waste consumption and accumulation, the recycling and upgrading utilization of polymer materials is an effective technology to solve environmental pollution. In this work, the recycling and upgrading methods of polymers are summarized, and the latest progress in polymer upcycling is discussed from the perspective of upgrading materials. The common polymer recovery methods, including mechanical recovery, chemical recovery, biocatalysis, and photocatalytic recovery, are discussed based on their mechanism and industrialized application. The upgrading products of polymers are divided into monomers, fuels and fine chemicals. The challenges and prospects of polymer degradation technology are discussed.
Considerations for Use of Pharmacodynamic Biomarkers to Support Biosimilar Development – (II) A Randomized Trial with IL‐5 Antagonists
Authors: Gershuny Victoria , Sun Qin , Schrieber Sarah J. , Matta Murali K. , Weaver James L. , Ji Ping , Sheikhy Morasa , Hsiao Cheng‐Hui , Vegesna Giri , Shah Aanchal , Prentice Kristin , Deering Jennifer , Wang Yow‐Ming , Strauss David G. , Florian Jeffry
Published: October 2022

The US Food and Drug Administration (FDA) guidance describes how pharmacodynamic (PD) biomarkers can be used to address residual uncertainty and demonstrate no clinically meaningful differences between a proposed biosimilar and its reference product without relying on clinical efficacy end point(s). Pilot studies and modeling can inform dosing for such PD studies. To that end, we conducted a randomized, double‐blinded, placebo‐controlled, single‐dose, parallel‐arm clinical study in healthy participants to evaluate approaches to address information gaps, inform best practices for analysis of biomarker samples and study results, and apply emerging technologies in biomarker characterization. Seventy‐two healthy participants (n = 8 per arm) received either placebo or 1 of 4 doses of the interleukin‐5 inhibitors mepolizumab (3–24 mg) or reslizumab (0.1–0.8 mg/kg). A clinical study using doses lower than approved therapeutic doses was combined with modeling and simulation to evaluate the dose–response relationship of the biomarker eosinophils. There was no dose–response relationship for eosinophil counts due to variability, although the mepolizumab 24 mg and reslizumab 0.8 mg/kg doses showed clear effects. Published indirect‐response models were used to explore eosinophil data across doses from this study and the unstudied therapeutic doses. Simulations were used to calculate typical PD metrics, such as baseline‐adjusted area under the effect curve and maximum change from baseline. The simulation results demonstrate sensitivity of eosinophils as a PD biomarker and indicate doses lower than the approved doses would have PD responses overlapping with variability in the placebo arm. The simulation results further highlight the utility of model‐based approaches in supporting use of PD biomarkers in biosimilar development.
Hydrogen Bond Activation by Pyridinic Nitrogen for the High Proton Conductivity of Covalent Triazine Framework Loaded with H3PO4
Authors: Liu Manying , Deng Wei‐Hua , Wang Xueqing , Liu Jing , Jin Shangbin , Xu Gang , Tan Bien
Published: October 2022

Under high temperature anhydrous conditions, it is still a formidable challenge to improve the performance of proton‐conducting materials based on H3PO4 and elucidate its proton conduction mechanism. Herein, a highly stable covalent triazine frameworks (CTFs) based on H3PO4 is reported. The more pyridinic nitrogen CTFs contain, the higher proton conductivity is. Compared with H3PO4@CTF−L with less pyridinic nitrogen, H3PO4@CTF−H has a higher proton conductivity of 1.6×10−1 S cm−1 at 150 °C under anhydrous conditions, which does not decay after about 18 months exposure in air. The high proton conductivity is associated with the formation and breaking of the activated Ntriazine⋯H+⋯H2PO4− pairs by pyridinic nitrogen of CTFs. The outstanding long‐term stability is mainly attributed to the ultra‐strong triazine skeleton structure of CTFs.
Simplifying the design of harmonic‐suppressing power amplifiers adopting capacitance‐splitting method
Authors: Han Kefeng , Geng Li
Published: October 2022

In this paper, an effective strategy for harmonic‐suppressing power amplifier (HS‐PA) design is proposed. To ease the design of HS‐PAs with harmonic‐suppressing output matching networks (HS‐OMN), the capacitance‐splitting method is proposed to tactically incorporate harmonic‐reflecting λ/4 stubs into the HS‐OMN. Benefits from the proposed method, normally complex iterative tunings on HS‐OMN parameters are avoided in implementing HS‐PAs. Two prototype designs are presented to verify the effectiveness and generality of the proposed methodology. One prototype operates in Class AB, which achieves saturated output powers of 47.8 ± 0.2 dBm, peak efficiencies of 70 ± 3%, and harmonic suppressing ratios of better than 70 dB on both the second and third harmonics over 2.3–2.7 GHz. Another prototype is a Doherty HS‐PA, which achieves a saturated output power of 43.2 dBm, saturated/6 dB back‐off efficiencies of 77%/63%, and suppression ratio of better than 60 dB on both the 2nd and 3rd harmonics at 1.95 GHz.
An energy‐efficient level shifter based on a differential cascade voltage switch structure
Authors: Zhang Haineng , Liu Zhongyang , Bi Dawei , Zhang Zhengxuan , Xiao Zhiyi , Dai Ruofan
Published: October 2022

Based on differential cascade voltage switch architecture, this paper proposes a level shifter with optimized energy consumption, constructed by stacking diode‐connected NMOS and PMOS transistors and splitting input signals of the two output stages. Eventually, the overlap time of input signals of the two output stages has been reduced, during which there is a considerable short‐current from high voltage source to ground. When implemented in a 110 nm CMOS process, post‐layout netlist simulations show that the proposed level shifter exhibits a 2.31 ns switching delay and 819 fJ energy consumption when converting a 1.5 V input signal into 4.5 V with 10 MHz operational frequency and 15 fF output load.
Laguerre polynomial function‐based inverter control with low‐voltage ride‐through capabilities
Authors: Pandey Amarendra , Singh Alka
Published: October 2022

This work discusses the design of a Laguerre polynomial (LP)‐based control technique to govern the functioning of a single‐phase grid connected to a voltage source converter (VSC). The controller is trained online using the least means square (LMS) approach to compute the load fundamental current. The controller is designed to alleviate power quality (PQ) issues and work in different modes. Apart from the normal operation mode, the controller is provided with an additional capability to ride over voltage sags caused by grid faults. During this low‐voltage ride‐through (LVRT) mode, the VSC injects the required reactive power to grid. The work demonstrates the results under normal grid conditions when the system can function in unity power factor (UPF) as well as in abnormal grid conditions when it needs to operate in LVRT mode. Extensive simulation and experimental results under various cases have been discussed with the proposed LP‐based controller to demonstrate the feasibility of the approach.
A modified Cued Recall Test for detecting prodromal AD in adults with Down syndrome
Authors: Krinsky‐McHale Sharon J. , Hartley Sigan , Hom Christy , Pulsifer Margaret , Clare Isabel C.H. , Handen Benjamin L. , Lott Ira T. , Schupf Nicole , Silverman Wayne ,   for the Alzheimer's Biomarker Consortium—Down Syndrome (ABC‐DS) Investigators
Published: October 2022

Introduction

The development of valid methods to diagnose prodromal Alzheimer's disease (AD) in adults with Down syndrome (DS) is one of the many goals of the Alzheimer's Biomarkers Consortium—Down Syndrome (ABC‐DS).

Methods

The diagnostic utility of a modified Cued Recall Test (mCRT) was evaluated in 332 adults with DS ranging from 25 to 81 years of age. Total recall was selected a priori, as the primary indicator of performance. Multiple regression and receiver‐operating characteristic (ROC) analyses were used to compare diagnostic groups.

Results

Performance on the mCRT, as indicated by the total recall score, was highly sensitive to differences between diagnostic groups. ROC areas under the curve (AUCs) ranging from 0.843 to 0.955, were observed.,

Discussion

The mCRT has strong empirical support for its use in clinical settings, as a valuable tool in studies targeting biomarkers of AD, and as a potential outcome measure in clinical trials targeting AD in this high‐risk population.
Knockdown of IGF2BP3 inhibits the tumorigenesis of gallbladder cancer and modifies tumor microenvironment
Authors: Qin Yiyu , Zhang Mingdi , Lei Haiming , Wu Hongyan , Huang Cheng , Zhou Xin , Fu Yang , Weng Mingzhe , Ma Mingzhe
Published: October 2022

Gallbladder cancer (GBC) ranks seventh among the gastrointestinal cancers. Messenger RNAs (mRNAs) could regulate the progression of GBC. For the purpose of exploring the targets for GBC treatment, RNA sequencing was used to identify the differential expressed mRNAs between GBC and adjacent tissues. Next, CCK8 assay was used to assess the cell viability, and cell proliferation was investigated by colony formation assay. Flow cytometry was performed to evaluate the cell apoptosis. Protein and mRNA expression were analyzed by western blot and RT‐qPCR, respectively. Transwell was performed to evaluate the cell metastasis. GBC‐derived exosomes were isolated with ultracentrifugation. To evaluate the function of exosomes in GBC, in vivo model of GBC was constructed. The data revealed IGF2BP3 was identified to be upregulated in GBC, and IGF2BP3 silencing was able to decrease GBC cell proliferation by promoting the apoptosis. The migration and invasion of GBC cells were reduced by IGF2BP3 knockdown. Silencing of IGF2BP3 obviously suppressed the level of p‐STAT3 in GBC cells. Meanwhile, GBC cell‐derived exosomes notably promoted macrophage M2 polarization via carrying IGF2BP3, and then the polarized macrophages promoted the malignant behavior of GBC cells. Furthermore, exosomes markedly promoted the tumor growth of GBC via promoting macrophage M2 polarization. In summary, knockdown of IGF2BP3 suppressed the malignant behavior of GBC cells. Additionally, knockdown of IGF2BP3 modified tumor microenvironment during the progression of GBC. Thus, these findings might provide a new theoretical basis for exploring a strategies against GBC.
Seismic behavior of novel low‐damage precast infill walls with sliding joints for reinforced concrete frame
Authors: Zhang Chao , Yu Tianhao , Chen Zhangyan , Huang Weiyuan , Zhang Shaohua , Zhou Yun , Lu Dehui , Lin Zexin
Published: October 2022

The detrimental infill‐frame interaction and vulnerable nature of the traditional solid infill walls might change the seismic behavior of the infilled reinforced concrete frames. To mitigate the adverse infill‐frame interaction and protect the fragile infill walls, in this paper, an innovative solution by partitioning the infill wall panels with low‐strength mortar sliding joints and uncoupling the infill from the boundary frame by flexible materials is presented for the reinforced concrete frames. Three 1/2 scale specimens designed in this context were examined experimentally and numerically, and a simplified model is developed for the proposed infill system. Test results show that the presented low‐damage infill system could effectively mitigate the adverse infill‐frame interaction and considerably prevent corner crushing or damage to the infill wall panels so that the reinforced concrete frame with the proposed infill system behaves similarly to the bare frame. Thanks to the working mechanism of the infill system, the proposed wall panels have a relatively high energy conversion efficiency from inter‐story displacement to the energy dissipation capacity of the infilled frame. Moreover, the developed simplified infill model could well capture the hysteretic behaviors of the proposed low‐damage infill system and improve the calculation efficiency. Parametric analysis results indicate that the friction factor of the sliding joints plays a significant role in enhancing the seismic behavior of the novel low‐damage infilled system.
Morphology and architectural analysis ofCopaifera pubifloraseedlings (Detarioideae, Leguminosae)
Authors: Silva Lealdina Miranda e , Rodrigues Rodrigo Schütz
Published: October 2022

CopaiferaL. is a woody legume genus with 42 species that produce valuable terpenoid oleoresins used in medicine and industrial activities.Copaiferabelongs to the Detarieae (Detarioideae) and is part of a clade together with five other genera. We describe the seedling morphology ofCopaifera pubifloraBenth. based on plant architectural analysis to shed light on its post‐seminal shoot development. Seeds of this species were collected from a wild population in Roraima State, Brazil. Seedlings ofC. pubiflorahave preformed shoots with determinate and rhythmic growth. Each growth unit has two reduced leaf scales that correspond to a pair of prophylls followed by two or three scale‐like stipules and one distal eophyll. Besides,C. pubiflorahas a monochasial sympodial branching with delayed branches. Current evidence indicates that mostCopaiferaspecies, includingC. pubiflora, have phanerocotylar, epigeal, reserve seedlings with a cataphyll‐free epicotyl and scale‐like structures on the first internode after the epicotyledonary axis. Based on the available data, a comprehensive view ofCopaiferaseedlings from both the Old and New Worlds is also presented.
A dynamic performance evaluation of distress prediction models
Authors: Mousavi Mohammad Mahdi , Ouenniche Jamal , Tone Kaoru
Published: October 2022

So far, the dominant comparative studies of competing distress prediction models (DPMs) have been restricted to the use of static evaluation frameworks and as such overlooked their performance over time. This study fills this gap by proposing a Malmquist Data Envelopment Analysis (DEA)‐based multi‐period performance evaluation framework for assessing competing static and dynamic statistical DPMs and using it to address a variety of research questions. Our findings suggest that (1) dynamic models developed under duration‐dependent frameworks outperform both dynamic models developed under duration‐independent frameworks and static models; (2) models fed with financial accounting (FA), market variables (MV), and macroeconomic information (MI) features outperform those fed with either MVMI or FA, regardless of the frameworks under which they are developed; (3) shorter training horizons seem to enhance the aggregate performance of both static and dynamic models.
Commodity tail risks
Authors: Ammann Manuel , Moerke Mathis , Prokopczuk Marcel , Würsig Christoph Matthias
Published: October 2022

In this study, we investigate the cross‐section of option‐implied tail risks in commodity markets. In contrast to findings from equity markets, left and right tail risks implied by option markets are both large. Commodity‐specific variables exert the largest influence on tail risk, while there is no evidence of systematic commodity factors that are linked to tail risk. Additionally, we find strong links to the equity markets, but also comovements to macroeconomic factors. Left or right tail risks are largely independent of variance risk premiums. Finally, both left and right tail risks are priced in the cross‐section of commodity futures returns.
Both brain size and biological sex contribute to variation in white matter microstructure in middle‐aged healthy adults
Authors: Eikenes Live , Visser Eelke , Vangberg Torgil , Håberg Asta K.
Published: October 2022

Whether head size and/or biological sex influence proxies of white matter (WM) microstructure such as fractional anisotropy (FA) and mean diffusivity (MD) remains controversial. Diffusion tensor imaging (DTI) indices are also associated with age, but there are large discrepancies in the spatial distribution and timeline of age‐related differences reported. The aim of this study was to evaluate the associations between intracranial volume (ICV), sex, and age and DTI indices from WM in a population‐based study of healthy individuals (n = 812) aged 50–66 in the Nord‐Trøndelag health survey. Semiautomated tractography and tract‐based spatial statistics (TBSS) analyses were performed on the entire sample and in an ICV‐matched sample of men and women. The tractography results showed a similar positive association between ICV and FA in all major WM tracts in men and women. Associations between ICV and MD, radial diffusivity and axial diffusivity were also found, but to a lesser extent than FA. The TBSS results showed that both men and women had areas of higher and lower FA when controlling for age, but after controlling for age and ICV only women had areas with higher FA. The ICV matched analysis also demonstrated that only women had areas of higher FA. Age was negatively associated with FA across the entire WM skeleton in the TBSS analysis, independent of both sex and ICV. Combined, these findings demonstrated that both ICV and sex contributed to variation in DTI indices and emphasized the importance of considering ICV as a covariate in DTI analysis.
Modelling the depth‐dependent VASO and BOLD responses in human primary visual cortex
Authors: Akbari Atena , Bollmann Saskia , Ali Tonima S. , Barth Markus
Published: October 2022

Functional magnetic resonance imaging (fMRI) using a blood‐oxygenation‐level‐dependent (BOLD) contrast is a common method for studying human brain function noninvasively. Gradient‐echo (GRE) BOLD is highly sensitive to the blood oxygenation change in blood vessels; however, the spatial signal specificity can be degraded due to signal leakage from activated lower layers to superficial layers in depth‐dependent (also called laminar or layer‐specific) fMRI. Alternatively, physiological variables such as cerebral blood volume using the VAscular‐Space‐Occupancy (VASO) contrast have shown higher spatial specificity compared to BOLD. To better understand the physiological mechanisms such as blood volume and oxygenation changes and to interpret the measured depth‐dependent responses, models are needed which reflect vascular properties at this scale. For this purpose, we extended and modified the “cortical vascular model” previously developed to predict layer‐specific BOLD signal changes in human primary visual cortex to also predict a layer‐specific VASO response. To evaluate the model, we compared the predictions with experimental results of simultaneous VASO and BOLD measurements in a group of healthy participants. Fitting the model to our experimental data provided an estimate of CBV change in different vascular compartments upon neural activity. We found that stimulus‐evoked CBV change mainly occurs in small arterioles, capillaries, and intracortical arteries and that the contribution from venules and ICVs is smaller. Our results confirm that VASO is less susceptible to large vessel effects compared to BOLD, as blood volume changes in intracortical arteries did not substantially affect the resulting depth‐dependent VASO profiles, whereas depth‐dependent BOLD profiles showed a bias towards signal contributions from intracortical veins.
Cortical structural changes after subcortical stroke: Patterns and correlates
Authors: Liu Jingchun , Wang Caihong , Qin Wen , Ding Hao , Peng Yanmin , Guo Jun , Han Tong , Cheng Jingliang , Yu Chunshui
Published: October 2022

Subcortical ischemic stroke can lead to persistent structural changes in the cerebral cortex. The evolution of cortical structural changes after subcortical stroke is largely unknown, as are their relations with motor recovery, lesion location, and early impairment of specific subsets of fibers in the corticospinal tract (CST). In this observational study, cortical structural changes were compared between 181 chronic patients with subcortical stroke involving the motor pathway and 113 healthy controls. The impacts of acute lesion location and early impairments of specific CSTs on cortical structural changes were investigated in the patients by combining voxel‐based correlation analysis with an association study that compared CST damage and cortical structural changes. Longitudinal patterns of cortical structural change were explored in a group of 81 patients with subcortical stroke using a linear mixed‐effects model. In the cross‐sectional analyses, patients with partial recovery showed more significant reductions in cortical thickness, surface area, or gray matter volume in the sensorimotor cortex, cingulate gyrus, and gyrus rectus than did patients with complete recovery; however, patients with complete recovery demonstrated more significant increases in the cortical structural measures in frontal, temporal, and occipital regions than did patients with partial recovery. Voxel‐based correlation analysis in these patients showed that acute stroke lesions involving the CST fibers originating from the primary motor cortex were associated with cortical thickness reductions in the ipsilesional motor cortex in the chronic stage. Acute stroke lesions in the putamen were correlated with increased surface area in the temporal pole in the chronic stage. The early impairment of the CST fibers originating from the primary sensory area was associated with increased cortical thickness in the occipital cortex. In the longitudinal analyses, patients with partial recovery showed gradually reduced cortical thickness, surface area, and gray matter volume in brain regions with significant structural damage in the chronic stage. Patients with complete recovery demonstrated gradually increasing cortical thickness, surface area, and gray‐matter volume in the frontal, temporal, and occipital regions. The directions of slow structural changes in the frontal, occipital, and cingulate cortices were completely different between patients with partial and complete recovery. Complex cortical structural changes and their dynamic evolution patterns were different, even contrasting, in patients with partial and complete recovery, and were associated with lesion location and with impairment of specific CST fiber subsets.
Numerical study of film cooling effectiveness of a gas turbine blade under variable blowing ratio and turbulence intensity
Authors: Baghernejad Ali , Hatami Matin , Aslanzadeh Elnaz
Published: October 2022

The present paper investigates a three‐dimensional simulation of film cooling on a C3X turbine blade with a single hole at a suction surface. The Reynolds averaged Navier–Stokes approach with k–ε realizable turbulence model and enhanced wall function are used for the numerical simulation. To simulate the jet flows, the length of the jet input approximately 4.5 times the diameter of the hole is added to the geometry so that the jet outlet flow is closer to the actual condition. The density ratio of the cooling flow to the mainstream flow is assumed about 2. The numerical results in four blowing ratios of 0.5, 0.7, 1.0, and 1.4, and at the low turbulence intensity (0.02%), and high turbulence intensity (12%) are extracted and compared for the turbine blade with a single hole. The results show that the turbulence intensity has a dual effect on the film cooling effectiveness and a higher blowing ratio increases the strength of the jet against the cross‐flow. Moreover, it is illustrated that the distribution of the film cooling effectiveness in higher blowing ratios and high turbulence intensity is more uniform than the low blowing ratios and low turbulence intensity.