bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of operating parameters on discharge mode of parallel-rail accelerator
Authors: Liu Shuai , Shi Yu-Hao , Lin Tian-Yu , Zhang Yong-Peng , Lu Zhi-Jian , Yang Lan-Jun ,   State Key Laboratory of Electrical Insulation and Power Equipment, Xi’an Jiaotong University, Xi’an 710049, China
Published: October 2021

Electromagnetic plasma accelerators which can generate hypervelocity and high density plasma jets have been widely used in the fields of nuclear physics and astrophysics. In this paper, an experimental platform of parallel-rail accelerator electromagnetically driven plasma is established, and the discharge modes under different discharge currents and gas injection conditions are studied through using magnetic probes, a spectrometer and an ICCD. A fast gas valve is used to inject argon into the rail electrode area. The time delay between the fast valve discharge and the parallel-rail accelerator discharge is fixed to be 450 μs. The waveform of power supply of the parallel-rail accelerator is a sinusoidal wave. The total capacitance is 120 μF, the total inductance is about 400 nH, and the maximum current is 170 kA. The fast valve current waveform is a double exponential waveform with a maximum current of 2.5 kA. When the discharge current is 40 kA, a current sheet with a certain thickness is generated, and the current sheet moves through different detection positions along the rail electrode at a certain velocity. Therefore, the working mode of the parallel-rail accelerator is the snowplow mode. As the discharge current increases, the trailing edge of the current channel is fixed during the current rising phase, and starts to move to the end of the rail during the current falling phase. A diffuse distributed current channel is formed, and the parallel-rail accelerator operates in a deflagration mode. As the gas injection mass increases, the current channel front velocity decreases to form a more concentrated distributed current channel, and the discharge mode turns into the snowplow mode. The stationary current channel in the deflagration mode is maintained mainly by ablating the electrode. The operating parameters mainly affect the rail voltage, which in turn affects the discharge mode of the parallel-rail accelerator. The rail voltage increases when the discharge current or the current rate of change increases. If the rail gap behind the current channel cannot withstand the high rail voltage under large discharge current or large current rate of change, the breakdown occurs, which results in the deflagration mode discharge.
Privacy Is Hard and Seven Other Myths
Authors: Hoepman Jaap-Henk
Published: October 2021

An expert on computer privacy and security shows how we can build privacy into the design of systems from the start.

We are tethered to our devices all day, every day, leaving data trails of our searches, posts, clicks, and communications. Meanwhile, governments and businesses collect our data and use it to monitor us without our knowledge. So we have resigned ourselves to the belief that privacy is hard—choosing to believe that websites do not share our information, for example, and declaring that we have nothing to hide anyway. In this informative and illuminating book, a computer privacy and security expert argues that privacy is not that hard if we build it into the design of systems from the start.

Along the way, Jaap-Henk Hoepman debunks eight persistent myths surrounding computer privacy. The website that claims it doesn't collect personal data, for example; Hoepman explains that most data is personal, capturing location, preferences, and other information. You don't have anything to hide? There's nothing wrong with wanting to keep personal information—even if it's not incriminating or embarrassing—private. Hoepman shows that just as technology can be used to invade our privacy, it can be used to protect it, when we apply privacy by design. Hoepman suggests technical fixes, discussing pseudonyms, leaky design, encryption, metadata, and the benefits of keeping your data local (on your own device only), and outlines privacy design strategies that system designers can apply now.
Command and Persuade
Authors: Baldwin Peter
Published: October 2021

Why, when we have been largely socialized into good behavior, are there more laws that govern our behavior than ever before?

Levels of violent crime have been in a steady decline for centuries—for millennia, even. Over the past five hundred years, homicide rates have decreased a hundred-fold. We live in a time that is more orderly and peaceful than ever before in human history. Why, then, does fear of crime dominate modern politics? Why, when we have been largely socialized into good behavior, are there more laws that govern our behavior than ever before? In Command and Persuade, Peter Baldwin examines the evolution of the state's role in crime and punishment over three thousand years.

Baldwin explains that the involvement of the state in law enforcement and crime prevention is relatively recent. In ancient Greece, those struck by lightning were assumed to have been punished by Zeus. In the Hebrew Bible, God was judge, jury, and prosecutor when Cain killed Abel. As the state's power as lawgiver grew, more laws governed behavior than ever before; the sum total of prohibited behavior has grown continuously. At the same time, as family, community, and church exerted their influences, we have become better behaved and more law-abiding. Even as the state stands as the socializer of last resort, it also defines through law the terrain on which we are schooled into acceptable behavior. This title is also available in an Open Access edition.
Freezing and thawing cycles affect nitrous oxide emissions in rain-fed lucerne (Medicago sativa) grasslands of different ages
Authors: Li Yuan , Shen Yuying , Wang Tao
Published: October 2021

Lucerne (Medicago sativa L.) is a major component of the crops used in dry-land farming systems in China and its management is associated with notable nitrous oxide (N2O) emissions. A high proportion of these emissions is more likely to occur during periods when the soil undergoes freezing and thawing cycles. In this study, the effects of freeze/thaw cycles on N2O emissions and related factors were investigated in lucerne grasslands. The hypothesis was tested whether increased emissions resulted from a disruption of nitrification or denitrification caused by variations in soil temperatures and water contents. Three days (3 × 24 h) were chosen, where conditions represented freezing and thawing cycles. N2O emissions were measured for a fallow control (F) and two grasslands where lucerne had been cultivated for 4 and 11 years. Soil temperature, soil water content, soil microbial biomass carbon (MBC), soil microbial biomass nitrogen (MBN), soil ammonium nitrogen (NH4+-N), and soil nitrate nitrogen (NO3−-N) contents were measured. Moreover, the quantities of soil nitrification and denitrification microbes were assessed. Variations in N2O emissions were strongly affected by freeze/thaw cycles, and emissions of 0.0287 ± 0.0009, 0.0230 ± 0.0019, and 0.3522 ± 0.0029 mg m−2 h−1 were found for fallow, 4-year-old, and 11-year-old grasslands, respectively. Pearson correlation analyses indicated that N2O emissions were significantly correlated with the soil water content, temperature, NH4+-N content, and the number of nitrosobacteria and denitrifying bacteria at a soil depth of 0–100 mm. The numbers of nitrosobacteria and denitrifying bacteria correlated significantly with soil temperature at this soil depth. MBN and soil NH4+-N contents correlated significantly with soil water content at this depth. Principal component analysis highlighted the positive effects of the number of denitrifying bacteria on N2O emissions during the freeze/thaw period. Furthermore, soil temperature and the number of nitrosobacteria at the tested soil depth (0−100 mm) also played a significant role. This shows that soil freeze/thaw cycles strongly impacted both N2O emissions and the diurnal range, and the number of denitrifying bacteria was mainly influenced by soil temperature and soil NH4+-N content. The number of denitrifying bacteria was the dominant variable affecting N2O emissions from lucerne grasslands during the assessed soil freeze/thaw period on the Loess Plateau, China.
Numerical Simulation of One Step Block Method for Treatment of Second Order Forced Motions in Mass-Spring Systems
Authors: Sabo J. , Kyagya T. Y. , Vashawa W. J.
Published: October 2021

This paper discuss the numerical simulation of one step block method for treatment of second order forced motions in mass-spring systems of initial value problems. The one step block method has been developed with the introduction of off-mesh point at both grid and off- grid points using interpolation and collocation procedure to increase computational burden which may jeopardize the accuracy of the method in terms of error. The basic properties of the one step block method was established and numerical analysis shown that the one step block method was found to be consistent, convergent and zero-stable. The one step block method was simulated on three highly stiff mathematical problems to validate the accuracy of the block method without reduction, and obviously the results shown are more accurate over the existing method in literature.
Existence of Positive Solution For a Fourth-order Differential System
Authors: Kov´acs B.
Published: October 2021

Existence of Positive Solution For a Fourth-order Differential System 

   where µ > 0 is a constant, and the nonlinear terms f, g may be singular with respect to the time and space variables. By fixed point theorem in cones, the existence is established for singular differential system. The results obtained herein generalize and improve some known results including singular and non-singular cases.
In-vitro Testing of Antioxidant, Anti-Parasite Activities, Cytotoxicity, and Chemical Evaluation of Abutilon Pannosum and Cassia Occidentalis Ethanolic Extracts
Authors: A. Elshikh Ahmed , E. M. ElNour Mawahib , H. Elkamali Hatil , S. Kabbashi Ahmed
Published: October 2021

Aims: The aim of this study to detect Anti-giardia, antioxidant activities, cytotoxicity and evaluated the chemical constituent of ethanolic extracts of Abutilon pannosum and Cassia occidentalis.

Study Design:  Various standard methods were used to detect of bioactivity for ethanolic extracts of plants used in this study.

Place and Duration of Study: This study was conducted in the laboratories of microbiology and parasitology and chemistry, the International University of Africa, Khartoum, Sudan, during May 2019.

Methodology: The ethanolic extract of Abutilon pannosum and Cassia occidentalis was used as an anti-giardia and anti-oxidant in-vitro, and toxicity tests were performed using brine shrimp and MTT assay. Also, the compounds of the plants used were detected by the GCMS apparatus.

Results: The ethanolic extracts of Abutilon pannosum showed high Anti-giardia activity (79%) in concentration (500 ppm) after 72 hours, whereas the activity of Cassia occidentalis extract showed (61%). The highest antioxidant activity of ethanolic extract of Cassia occidentalis was (68.7%), while it was weak in Abutilon pannosum ethanolic extract (45%) by using 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The results of cytotoxicity revealed that the ethanolic extracts are highly toxic to brine shrimp, but are not toxic to normal cell line (MTT). Chromatographic analysis using gas chromatography-mass spectroscopy (GCMS) showed good separation of compounds. GCMS detected 22 and14 important compounds in Abutilon pannosum and Cassia occidentalis extracts respectively. The common compound in both plant extracts is n-Hexadecanoic acid. This acid was reported as an antioxidant.

Conclusion: This study revealed that the biological activities of Abutilon pannosum extracts showed high activities of Anti-giardia and antioxidants. Non-cytotoxic in the normal cell line was shown. Cassia occidentalis showed high activity of Anti-giardia and weak activity antioxidant.
Effect of the Rise in Online Motorcycle Taxi Services on the Number of Motorcycles using the Interrupted Time Series Method
Authors: Anindityas Yovita Fabriska Laras , Rizki M. , Joewono T.B.
Published: October 2021

The substantial growth of motorcycle users in Indonesia is hypothesized to be influenced by a government policy on motorcycle purchase waivers and the massive growth of online motorcycle taxis. This study aims to analyse the relationship between the emergence of online motorcycle taxis and government policy changes towards the number of motorcycles and compare the estimation model seen from the consumer and sales sides. The data were collected from the Indonesian Bureau of Statistics, Motorcycle Industry Association, and World Bank. Several estimation models were built using the interrupted time series method. The results showed that changes in government policy and income per capita significantly increased the number of motorcycles. However, the emergence of online motorcycle taxis negatively affected the increasing number of motorcycles. The results also showed that models with data representing motorcycle usage behavior provided better results than the model with motorcycle sales.
Adobe Flash untuk Mendukung Pembelajaran dalam Pelajaran Seni Budaya
Authors: Candra P. Mochamad Okky
Published: October 2021

Perkembangan Teknlogi yang kini membuat para pengajar harus meng-upgrade ilmu dan kreativitas dalam proses belajar mengajar, supaya pembelajaran tidak terasa menjemukan. Salah satunya belajar dengan menggunakan animasi komputer untuk memungkinkan siswa belajar secara dinamis dan lebih interaktif. Penggunaan media komputer sebagai media pembelajaran ini menghadirkan banyak manfaat, salah satu program yang mampu mendukung proses pembelajaran adalah program Adobe Flash. Adalah standar program aplikasi yang digunakan untuk membuat vektor animasi dan bitmap yang luar biasa untuk keperluan membuat situs Web yang interaktif dan dinamis. Aplikasi ini diimplementasikan sebagai media belajar. Pesan yang disampaikan melalui media, dalam bentuk konten atau bahan ajar itu harus diterima oleh siswa, dengan menggunakan satu atau kombinasi beberapa organ indera mereka. Bahkan lebih baik, ketika semua perangkat penginderaan yang dimiliki mampu menerima konten pesan yang disampaikan. Melalui makalah sebagai pustaka studi ini yang menggunakan SMP PGRI 5 Taman sebagai objek penelitian, dapat ditemukan bahwa kreativitas sangat diperlukan dalam hal pembelajaran, sedangkan animasi adalah alat dalam proses mengajar yang mampu menjadikan belajar menjadi lebih mudah dipahami oleh para siswa.
Representasi Perempuan dalam Iklan Televisi “Downy” Varian Parfum Collection dan Premium Parfum
Authors: Surya Jessica Alicia , Natadjaja Listia , Febriani Rika
Published: October 2021

Bersamaan dengan diluncurkannya produk Downy Parfum Collection dan Premium Parfum, Downy juga mengeluarkan dua iklan yang ditayangkan di televisi nasional. Kedua iklan ini merepresentasikan tokoh perempuan dengan cara yang berbeda dari iklan-iklan sebelumnya, dimana sebelumnya perempuan selalu digambarkan sebagai ibu rumah tangga. Selain itu, elemen “luar negeri” dan “orang asing” terlihat jelas meski iklan ini ditayangkan di Indonesia. Tujuan dari penelitian ini adalah untuk mengetahui representasi perempuan yang disampaikan dalam iklan Downy tersebut. Penelitian ini bersifat kualitatif dan dianalisis menggunakan semiologi Roland Barthes. Hasil penelitian menunjukkan bahwa Downy merepresentasikan perempuan sebagai figur yang percaya diri, mandiri, dan tidak lagi hanya bekerja di ranah domestik tetapi juga ranah publik. Hal ini sejalan dengan pandangan fenimisme yaitu menyamakan derajat pria dan wanita. Meskipun begitu, perempuan ternyata tetap tunduk kepada tuntutan publik bahwa ia harus selalu tampil wangi dan cantik. Terdapat budaya postkolonial yang terkandung dalam iklan ini, dilihat dari orang Barat yang mengagumi dan memuji tokoh utama (orang Timur). Rasa kagum dan pujian dari orang Barat lebih berkesan bagi orang Timur, karena budaya postkolonial yang masih berlaku saat ini.
Logo “Petitenget Festival 2018” Dalam Budaya Postmodern
Authors: Swandi I Made Dwiarya , Swandi I Wayan , Mudra I Wayan
Published: October 2021

Postmodernisme adalah suatu pergerakan ide yang menggantikan ide-ide zaman modern. Dalam logo “Petitenget Festival 2018” memiliki konteks postmodern. Penelitian ini bertujuan untuk menganalisis logo “Petitenget Festival 2018” dalam budaya postmodern. Penelitian ini juga diharapkan dapat memberikan manfaat untuk memberikan informasi tentang nilai estetika postmodern dan makna yang terdapat pada logo. Teori yang digunakan adalah teori postmodern, dan estetika postmodern. Penelitian ini menggunakan metode deskriptif kualitatif. Hasil dari penelitian ini berupa bagaimana penerapan logo “Petitenget Festival” dalam konteks postmodern. Postmodern itu sendiri dapat diliht melalui nilai estetika yang memiliki idiom idiom yang terkandung di dalam logo tersebut. Idiom estetika postmodern yang paling kuat terkait kasus diatas terdapat pada idiom pastiche. Selain itu, terdapat makna denotasi dan konotasi pada logo “Petitenget Festival 2018”.
Can clarifying instructions mitigate the effects of multifaceted questions on susceptibility to suggestion?
Authors: Chrobak Quin M. , Braun Blair E. , Smith Allison L. , Zaragoza Maria S.
Published: October 2021

When cross‐examining witnesses, lawyers will sometimes use complex questions to “trip‐up” witnesses and thus cast doubt on their testimony. Extending prior research, the present study showed that multifaceted test questions (which contain both a true and false proposition) reduced accuracy for both misled and control participants but had a disproportionate impact on the former. Although misled participants accurately rejected blatant suggestions when tested with simple questions, there was a two‐fold increase in false assents when multifaceted questions were used (Experiment 1). Providing participants with explicit instructions on how to respond to multifaceted questions (i.e., respond “yes” only if all parts of the question are true) improved accuracy slightly but did not mitigate the magnitude of the misinformation effect (Experiment 2). Collectively, the results underscore the importance of assessing eyewitness suggestibility in contexts that mimic those witnesses are likely to encounter in the real world.
Interfacial Engineering of Wide‐Bandgap Perovskites for Efficient Perovskite/CZTSSe Tandem Solar Cells
Authors: Wang Deng , Guo Hongling , Wu Xin , Deng Xiang , Li Fengzhu , Li Zhen , Lin Francis , Zhu Zonglong , Zhang Yi , Xu Baomin , Jen Alex K.‐Y.
Published: October 2021

Wide‐bandgap perovskites have attracted substantial attention due to their important role in serving as a top absorber in tandem solar cells (TSCs). However, wide‐bandgap perovskite solar cells (PVSCs) typically suffer from severe non‐radiative recombination loss and therefore exhibit high open‐circuit voltage (VOC) deficits. To address these issues, a 2D octyl‐diammonium lead iodide interlayer is adopted onto the hole‐transporting layer to induce the formation of an ultrathin quasi‐2D perovskite that is close to the hole‐selective interface. This approach not only accelerates hole transfer and retards hole accumulation but also reduces the trap density in the perovskite layer on top, thereby efficiently suppresses non‐radiative recombination pathways. Consequently, the champion wide‐bandgap device (≈1.66 eV) exhibits a power conversion efficiency (PCE) of 21.05% with a VOC of 1.23 V, where the VOC deficit of 0.43 V is among the lowest values for inverted wide‐bandgap PVSCs. Moreover, by stacking a semi‐transparent perovskite top cell on a 1.1 eV Cu2ZnSn(S,Se)4 (CZTSSe) bottom cell, a 22.27% PCE was achieved on a perovskite/CZTSSe four‐terminal tandem solar cell, paving the way for all‐solution‐processed, low‐cost, and efficient TSCs with mitigated energy loss in the wide‐bandgap top cells.
A Flexible and Stretchable 12‐Lead Electrocardiogram System with Individually Deformable Interconnects
Authors: Wan Chunxue , Gao Shenghan , Shang Xue , Wu Ziyue , Li Tianyu , Ling Wei , Zhou Mingxing , Huo Wenxing , Guo Yu , Huang Xian
Published: October 2021

Dynamic multilead monitoring of cardiovascular health conditions is challenging due to the complexity of constructing a flexible system that covers large surface areas and synchronizes measurement results from different leads. A flexible 12‐lead electrocardiography system that can simultaneously conduct electrocardiogram sensing and 3‐axis acceleration monitoring is developed. The system is fabricated through a modularized printing process, resulting in individual modules that can be assembled reversibly through magnetic connectors. Different levels of stretchability and adjustable length of interconnect can accommodate different body statures and deformations. A wireless flexible circuit with high adaptability can deform through individually deformable interconnectors. The system is used to monitor seven people for more than 2 h, offering comparable accuracy as the commercial system. The accuracy values of R‐peak detection at 12 leads during jogging are higher than 85%, showing improved stability and excellent tolerance to motion. The system is later employed for 24 h monitoring to judge the activities and heart health conditions. All experimental results indicate that the system can be readily applied to accommodate large‐scale manufacturing and large population health monitoring.
Transparent Medium Embedded with CdS Quantum Dots for X‐Ray Imaging
Authors: Fang Zhaohui , Tang Haitao , Yang Ze , Zhang Hao , Peng Qingpeng , Yu Xue , Zhou Dacheng , Qiu Jianbei , Xu Xuhui
Published: October 2021

Scintillators, converting the absorbed high‐energy X‐ray photons into to visible ones, have been used in fields as medical diagnostics, radiation dosimetry, and security inspection. Commercial bulk scintillators generally suffer from time‐consuming production, high‐cost operation, and deteriorated performance especially exposed to humidity. Here, in situ precipitated CdS quantum dots (QDs) within the transparent glass matrix are achieved feasibly. The CdS QDs glass‐ceramic (GC) is explored to be a superior scintillator with an outstanding weather resistance. A profound radioluminescence behavior and long‐term (≈3600 s) stability under X‐ray irradiation of the scintillator with the dose rate of 1 mGyair s−1 are demonstrated. Moreover, the indirect X‐ray imaging of the CdS GC reaches excellent resolution of 10 lp mm−1. Furthermore, the damaged scintillator under a long‐term cumulative dose up to 288 Gyair is recovered via a subsequent thermal treatment. Herein, the explored scintillator of CdS GC executes a promising cost‐effective X‐ray imaging for long‐term operation of the corresponding optoelectronic devices.
A Novel Mechanism of Endoplasmic Reticulum Stress‐ and c‐Myc‐Degradation‐Mediated Therapeutic Benefits of Antineurokinin‐1 Receptor Drugs in Colorectal Cancer
Authors: Shi Yue , Wang Xi , Meng Yueming , Ma Junjie , Zhang Qiyu , Shao Gang , Wang Lingfei , Cheng Xurui , Hong Xiangyu , Wang Yong , Yan Zhibin , Cao Yihai , Kang Jian , Fu Caiyun
Published: October 2021

The neurokinin‐1 receptor (NK‐1R) antagonists are approved as treatment for chemotherapy‐associated nausea and vomiting in cancer patients. The emerging role of the substance P‐NK‐1R system in oncogenesis raises the possibility of repurposing well‐tolerated NK‐1R antagonists for cancer treatment. This study reports that human colorectal cancer (CRC) patients with high NK‐1R expression have poor survival, and NK‐1R antagonists SR140333 and aprepitant induce apoptotic cell death in CRC cells and inhibit CRC xenograft growth. This cytotoxicity induced by treatment with NK‐1R antagonists is mediated by induction of endoplasmic reticulum (ER) stress. ER stress triggers calcium release, resulting in the suppression of prosurvival extracellular signal‐regulated kinase (ERK)‐c‐Myc signaling. Along with ER calcium release, one ER stress pathway mediated by protein kinase RNA‐like ER kinase (PERK) is specifically activated, leading to increased expression of proapoptotic C/EBP‐homologous protein (CHOP). Moreover, NK‐1R antagonists enhance the efficacy of chemotherapy by increasing the sensitivity and overcoming resistance to 5‐fluorouracil in CRC cells through the induction of sustained ER stress and the consequent suppression of ERK‐c‐Myc signaling both in vitro and in vivo. Collectively, the findings provide novel mechanistic insights into the efficacy of NK‐1R antagonists either as a single agent or in combination with chemotherapy for cancer treatment.
Classical Analog of Quantum Light Cones in 1D and 2D Dipole Systems
Authors: Batle Josep , Cerdà Joan J. , Pons Miquel
Published: October 2021

The speed at which the magnetic perturbation or information propagates along a chain of classical dipoles is discussed. While in the quantum information counterpart for long‐range interacting spins, where the speed of propagation of the information plays a paramount role, it is not strictly clear whether a light cone exists or not, numerical evidence that interacting dipoles do posses a linear light cone shortly after a perturbation takes place in classical systems is provided. Specifically, a power‐law expansion occurs which is followed by a linear propagation of the associated perturbation. As opposed to the quantum case, and in analogy with the so‐called speed of gravity problem, it is found that the speed of propagation of information can be arbitrarily large in the classical context. While it is true that quantum information outperforms any classical treatment regarding many processes and properties, it is shown that for the case of spin buffers, classical chains of dipoles can indeed play a role as auxiliary tools in both quantum communications and processing.
Dimensionality Control of Inorganic and Hybrid Perovskite Nanocrystals by Reaction Temperature: From No‐Confinement to 3D and 1D Quantum Confinement
Authors: Otero‐Martínez Clara , García‐Lojo Daniel , Pastoriza‐Santos Isabel , Pérez‐Juste Jorge , Polavarapu Lakshminarayana
Published: October 2021

This work focuses on the systematic investigation of the shape, size, and composition‐controlled synthesis of perovskite nanocrystals (NCs) under inert gas‐free conditions and using pre‐synthesized precursor stock solutions. In the case of CsPbBr3 NCs, we find that the lowering of reaction temperature from ∼175 to 100 °C initially leads to a change of morphology from bulk‐like 3D nanocubes to 0D nanocubes with 3D‐quantum confinement, while at temperatures below 100 °C the reaction yields 2D nanoplatelets (NPls) with 1D‐quantum confinement. However, to our surprise, at higher temperatures (∼215 °C), the reaction yields CsPbBr3 hexapod NCs, which have been rarely reported. The synthesis is scalable, and their halide composition is tunable by simply using different combinations of precursor solutions. The versatility of the synthesis is demonstrated by applying it to relatively less explored shape‐controlled synthesis of FAPbBr3 NCs. Despite the synthesis carried out in the air, both the inorganic and hybrid perovskite NCs exhibit nearly‐narrow emission without applying any size‐selective separation, and it is precisely tunable by controlling the reaction temperature.
Copper‐Catalyzed Intermolecular Enantioselective Radical Oxidative C(sp3)−H/C(sp)−H Cross‐Coupling with Rationally Designed Oxazoline‐Derived N,N,P(O)‐Ligands
Authors: Liu Lin , Guo Kai‐Xin , Tian Yu , Yang Chang‐Jiang , Gu Qiang‐Shuai , Li Zhong‐Liang , Ye Liu , Liu Xin‐Yuan
Published: October 2021

The intermolecular asymmetric radical oxidative C(sp3)−C(sp) cross‐coupling of C(sp3)−H bonds with readily available terminal alkynes is a promising method to forge chiral C(sp3)−C(sp) bonds because of the high atom and step economy, but remains underexplored. Here, we report a copper‐catalyzed asymmetric C(sp3)−C(sp) cross‐coupling of (hetero)benzylic and (cyclic)allylic C−H bonds with terminal alkynes that occurs with high to excellent enantioselectivity. Critical to the success is the rational design of chiral oxazoline‐derived N,N,P(O)‐ligands that not only tolerate the strong oxidative conditions which are requisite for intermolecular hydrogen atom abstraction (HAA) processes but also induce the challenging enantiocontrol. Direct access to a range of synthetically useful chiral benzylic alkynes and 1,4‐enynes, high site‐selectivity among similar C(sp3)−H bonds, and facile synthesis of enantioenriched medicinally relevant compounds make this approach very attractive.
Duloxetine ameliorates valproicacid‐inducedhyperactivity, anxiety‐like behavior, and social interaction deficits in zebrafish
Authors: Joseph Thomson Patrick , Zhou Fang , Sai Liu Yang , Chen Hanyu , Lin Stanley Li , Schachner Melitta
Published: October 2021

Syndromic autism spectrum disorders (ASDs) are characterized by impaired social communication and repetitive/stereotyped behaviors. Currently available therapeutic agents against ASD have limited efficacy. Thus, searching for novel and effective drugs ameliorating core symptoms, in particular social deficits, is of utmost importance. Duloxetine (DLX), an antidepressant that has been identified as an agonist mimetic for the cell adhesion molecule L1, exhibits beneficial functions in vitro and in vivo. Therefore, in this study, we focused on the rapid and persistent neuroprotective function of DLX following valproic acid (VPA)‐triggered hyperactivity, anxiety‐like behavior and social deficits in zebrafish. Embryonic exposure to VPA reduced survival in a dose‐ and time‐dependent manner, delayed hatching, and also resulted in a significant number of malformed larvae. After initial dose–response experiments in zebrafish larvae, 10 μM VPA exposure between 0.33 and 4.5 days post fertilization (dpf) was identified as an effective concentration that led to an early and persistent ASD‐like phenotype in zebrafish. ASD‐like elevated acetylcholine esterase (AChE) activity and reduced Akt–mTOR signaling was observed in zebrafish whole brain. Acute administration of DLX (4.5–6 dpf) reduced the VPA‐induced ASD‐like phenotype in zebrafish larvae. Additionally, such early‐life acute DLX treatment had long‐term effects in ameliorating social impairments, hyperactivity, and anxiety‐like behaviors through adulthood. This was accompanied by reduced AChE activity and by normalized Akt–mTOR signaling. Overall, DLX treatment showed a long‐term therapeutic effect on autistic‐like behaviors, and alteration of AChE activity and Akt–mTOR signaling were identified as crucial in the VPA‐induced ASD zebrafish model.
The immunomodulatory activity of lenvatinib prompts the survival of patients with advanced hepatocellular carcinoma
Authors: Zhu Jie , Fang Peiqi , Wang Chong , Gu Meixiu , Pan Baishen , Guo Wei , Yang Xinrong , Wang Beili
Published: October 2021

Background

Lenvatinib is a novel multiple receptor tyrosine kinase inhibitor used for hepatocellular carcinoma (HCC) treatment. Although its main function is to suppress VEGFR and FGFR pathway, its immunomodulatory activity in HCC is not elucidated. Thus, this study aimed to investigate the immunomodulatory capability of lenvatinib in HCC.

Material and methods

Totally 47 patients with HCC were enrolled in this study, and the immune cells and serum cytokine profiles before initiation of treatment and after 1 and 3 months were measured. The immune checkpoint receptors on the immune cells were also evaluated. Kaplan–Meier survival estimate and log rank tests were used to assess the prognostic value.

Result

The frequency of T helper (Th) cells and T regulatory (Treg) cells reduced after lenvatinib treatment, while cytotoxic T lymphocyte (CTL) cells increased significantly. The cytokine profiles showed IL‐2, IL‐5, IFN‐γ increased; other cytokines including IL‐6, IL‐10, TNF‐ α and TNF‐ β decreased with lenvatinib therapy. Furthermore, the PD‐1 and TIM‐3 expressed on CTL had greatly decreased; the expression of TIM‐3 and CTLA‐4 was reduced on Treg cells as well. Besides, the new index CTL/Treg ratio was created, and low ratio was associated with the unfavorable outcome of HCC patients.

Conclusion

Our results confirmed that lenvatinib is capable of improving patients’ immune status, saving the effector cells from exhaustion status and inhibiting the number and function of immunosuppressive cells. The novel index CTL/Treg ratio qualifies as a predictor for the outcome of patients with lenvatinib therapy.
First report of invasive Aspergillus rhinosinusitis in a critically ill COVID‐19 patient affected by acute myeloid leukemia, northeastern Iran
Authors: Hosseinikargar Neginsadat , Basiri Reza , Asadzadeh Mohammad , Najafzadeh Mohammad Javad , Zarrinfar Hossein
Published: October 2021

This is a report of established invasive Aspergillus rhinosinusitis in a patient diagnosed with COVID‐19 and afflicted by AML, which was initially considered to be rhinocerebral mucormycosis.
COVID‐19 outbreak as a probable cause of increased risk of intracranial rebleeding in partially treated cerebral arteriovenous malformations
Authors: Ghorbani Mohammad , Lafta Ghazwan , Rahbarian Farhad
Published: October 2021

Patients who are infected with COVID‐19 and have cerebral arteriovenous malformations which are partially treated or untreated may be more liable to rupture or bleed than not infected patients.
Hereditary hemochromatosis and JAK2‐positive polycythemia vera
Authors: Radwan Ahmed , Othman Ibraheem
Published: October 2021

A 59‐year‐old man was diagnosed with JAK2‐positive polycythemia vera. Subsequently, further laboratory testing revealed elevated ferritin and iron saturation. Genetic testing for HFE gene mutation screen revealed that the patient was positive for heterozygous C282Y mutation. The patient was ultimately diagnosed with both polycythemia vera and hereditary hemochromatosis.
Scanning Electrochemical Cell Microscopy in a Glovebox: Structure‐Activity Correlations in the Early Stages of Solid‐Electrolyte Interphase Formation on Graphite
Authors: Martín‐Yerga Daniel , Kang Minkyung , Unwin Patrick R.
Published: October 2021

Understanding the formation and properties of the solid‐electrolyte interphase (SEI) will enable the development of enhanced Li‐ion batteries (LiBs) and other battery types. Herein, we report scanning electrochemical cell microscopy (SECCM) in a glovebox to characterize the SEI formation on the basal surface of highly oriented pyrolytic graphite (HOPG) as a model system of negative LiB electrodes with nonaqueous electrolytes. Different grades of HOPG have been studied, which provide a range of step edge densities on the basal surface. The high‐throughput and spatially‐resolved character of SECCM allows thousands of measurements across a surface, revealing how surface heterogeneity in graphite affects the early stages of the SEI formation and its properties. Step edges promote electrolyte reduction resulting in a more passivating SEI than that formed on smoother surfaces. A strongly insulating but relatively unstable SEI is detected under fast formation conditions, while slow formation rates induce the steady growth of an increasingly passivating SEI. This work provides new insights on the SEI dynamic formation and demonstrates SECCM as a powerful technique to probe the effect of local structure in heterogeneous battery materials under inert atmosphere. The demonstration that SECCM can readily be deployed in a glovebox serves as a foundation for future experiments to explore high resolution electrochemical imaging of battery electrode materials.
Push‐Pull Stiff‐Stilbene: Proton‐Gated Visible‐Light Photoswitching and Acid‐Catalyzed Isomerization
Authors: Villarón David , Duindam Nol , Wezenberg Sander J.
Published: October 2021

Donor‐acceptor substituted stiff‐stilbene is shown to undergo isomerization induced by visible light avoiding the need for harmful UV light. This visible‐light photoswitching is inhibited by protonation of the dimethylamino‐donor unit, disrupting the push‐pull character and thus, gating of the photochromic properties is allowed by acid/base addition. Remarkably, the addition of a mild acid also triggers fast thermal back‐isomerization, which is unprecedented for stiff‐stilbene photoswitches usually having a very high energy barrier for this process. These combined features offer unique orthogonal control over switching behavior by light and protonation, which is investigated in detail by 1H NMR and UV/Vis spectroscopy. In addition, TD‐DFT calculations are used to gain further insight into the absorption properties. Our results will help elevating the level of control over dynamic behavior in stiff‐stilbene applications.
A diffuse interface method for simulation‐based screening of heat transfer processes with complex geometries
Authors: Monte Elizabeth J. , Lowman James , Abukhdeir Nasser Mohieddin
Published: October 2021

Frequently, the simulation‐based design of physicochemical processes requires screening of large numbers of alternative designs with complex geometries. These geometries may result in conformal meshes which introduce stability issues, significant computational complexity, and require user‐interaction for their creation. In this work, a method for simulation of heat transfer using the diffuse interface method to capture a complex geometry is presented as an alternative to conformal meshing, with analysis and comparisons given. The methods presented include automated non‐iterative generation of phase fields from CAD geometries and an extension of the diffuse interface method for mixed boundary conditions. Simple measures of diffuse interface quality are presented and used to predict performance. The method is applied to a realistic three‐dimensional heat transfer problem (LED heat sink) and compared to the traditional conformal mesh approach. It is found to enable reasonable accuracy at an order‐of‐magnitude reduction in simulation time or comparable accuracy for equivalent simulation times.
Biomarker‐Informed Model‐Based Risk Assessment of Organic Anion Transporting Polypeptide 1B Mediated Drug‐Drug Interactions
Authors: Kimoto Emi , Costales Chester , West Mark A. , Bi Yi‐an , Vourvahis Manoli , David Rodrigues A. , Varma Manthena V. S.
Published: October 2021

Quantitative prediction of drug‐drug interactions (DDIs) involving organic anion transporting polypeptide (OATP)1B1/1B3 inhibition is limited by uncertainty in the translatability of experimentally determined in vitro inhibition potency (half‐maximal inhibitory concentration (IC50)). This study used an OATP1B endogenous biomarker‐informed physiologically‐based pharmacokinetic (PBPK) modeling approach to predict the effect of inhibitor drugs on the pharmacokinetics (PKs) of OATP1B substrates. Initial static analysis with about 42 inhibitor drugs, using in vitro IC50 values and unbound liver inlet concentrations (Iin,max,u), suggested in vivo OATP1B inhibition risk for drugs with R‐value (1+ Iin,max,u/IC50) above 1.5. A full‐PBPK model accounting for transporter‐mediated hepatic disposition was developed for coproporphyrin I (CP‐I), an endogenous OATP1B biomarker. For several inhibitors (cyclosporine, diltiazem, fenebrutinib, GDC‐0810, itraconazole, probenecid, and rifampicin at 3 different doses), PBPK models were developed and verified against available CP‐I plasma exposure data to obtain in vivo OATP1B inhibition potency—which tend to be lower than the experimentally measured in vitro IC50 by about 2‐fold (probenecid and rifampicin) to 37‐fold (GDC‐0810). Models verified with CP‐I data are subsequently used to predict DDIs with OATP1B probe drugs, rosuvastatin and pitavastatin. The predicted and observed area under the plasma concentration‐time curve ratios are within 20% error in 55% cases, and within 30% error in 89% cases. Collectively, this comprehensive study illustrates the adequacy and utility of endogenous biomarker‐informed PBPK modeling in mechanistic understanding and quantitative predictions of OATP1B‐mediated DDIs in drug development.
Scope, Limitations and Mechanistic Analysis of the HyperBTM‐Catalyzed Acylative Kinetic Resolution of Tertiary Heterocyclic Alcohols**
Authors: Smith Samuel M. , Greenhalgh Mark D. , Feoktistova Taisiia , Walden Daniel M. , Taylor James E. , Cordes David B. , Slawin Alexandra M. Z. , Cheong Paul Ha‐Yeon , Smith Andrew D.
Published: October 2021

The full scope and limitations of the catalytic acylative kinetic resolution of a range of tertiary heterocyclic alcohols (78 examples,sup to >200) is reported under operationally‐simple conditions, using low loadings of a commercially available Lewis basic isothiourea catalyst, HyperBTM (generally 1 mol %). The protocol is highly effective for the kinetic resolution of 3‐substituted 3‐hydroxyoxindole and α‐substituted α‐hydroxylactam derivatives bearing up to three potential recognition motifs at the stereogenic tertiary carbinol center. The full power of this methodology has been showcased through the synthesis of highly enantioenriched biologically‐active target compounds in both enantiomeric forms. To provide further insight into the reaction mechanism, a detailed kinetic analysis of this Lewis base‐catalyzed acylation of tertiary alcohols is reported using the variable time normalization analysis (VTNA) method.
Use composite coating of chitosan‐chia seed gum enriched with microliposomes of Bay laurel essential oil to increase the shelf life of quail fillets
Authors: Eslamian Amiri Motahareh , Ahmady Mohammad , Ariaii Peiman , Golestan Leila , Ghorbani‐HasanSaraei Azade
Published: October 2021

In this study, the effect of composite chitosan‐chia seed coating (CH‐CG) with Bay laurel (Laurus nobilis) essential oil (BE) in two forms including free and nanocapsulated on the shelf life of quail fillets during the 16‐day refrigeration (4 ± 1℃) period was investigated. For this purpose, first, BE was extracted by Clevenger apparatus. Then, nanoliposomes BE were produced, and the properties of BE and nanoliposomes BE were investigated. In order to investigate the shelf life of quail, 6 treatments were produced including 1: control (C), 2: CH‐CG, CH‐CG+BE at 800 ppm, 3: CH‐CG+BE at 1600 ppm, 4: CH‐CG+nano BE at 800 ppm, 5: CH‐CG+nano BE at 1600 ppm, and periodically chemical parameters (peroxide value, free fatty acid, total volatile basic nitrogen, texture firmness, and chewing ability) and microbial (total viable bacteria (TVC) and psychrotrophic bacteria), and the effect of different treatments on control in Escherichia coli and Staphylococcus aureus inoculated populations in quail was also investigated. The BE had high antioxidant and antimicrobial properties. The particle size and microencapsulation efficiency of BE nanoliposome were 98.3 nm and 75.95%, respectively. The results of chemical and microbial analysis showed that in general, the coating with essential oil slowed down the increasing trend of oxidation and microbial indices compared to the control treatment and nanocapsulation of essential oil has increased its antimicrobial and antioxidant properties (p < .05). At the end of storage period, in all tests, treatments of 3, 4, and 5 had the allowed microbial and chemical range and they also inhibited the growth of these bacteria (p < .05). Overall, considering the higher sensory score of treatment 4 and economic efficiency, it seems that this treatment can be used as a natural preservative in the meat industry.
Development and Molecular Understanding of a Pd‐Catalyzed Cyanation of Aryl Boronic Acids Enabled by High‐Throughput Experimentation and Data Analysis
Authors: De Jesus Silva Jordan , Bartalucci Niccolò , Jelier Benson , Grosslight Samantha , Gensch Tobias , Schünemann Claas , Müller Bernd , Kamer Paul C. J. , Copéret Christophe , Sigman Matthew S. , Togni Antonio
Published: October 2021

A synthetic method for the palladium‐catalyzed cyanation of aryl boronic acids using bench stable and non‐toxic N‐cyanosuccinimide has been developed. High‐throughput experimentation facilitated the screen of 90 different ligands and the resultant statistical data analysis identified that ligand σ‐donation, π‐acidity and sterics are key drivers that govern yield. Categorization into three ligand groups – monophosphines, bisphosphines and miscellaneous – was performed before the analysis. For the monophosphines, the yield of the reaction increases for strong σ‐donating, weak π‐accepting ligands, with flexible pendant substituents. For the bisphosphines, the yield predominantly correlates with ligand lability. The applicability of the designed reaction to a wider substrate scope was investigated, showing good functional group tolerance in particular with boronic acids bearing electron‐withdrawing substituents. This work outlines the development of a novel reaction, coupled with a fast and efficient workflow to gain understanding of the optimal ligand properties for the design of improved palladium cross‐coupling catalysts.
Long‐term risk of colorectal cancer after removal of adenomas during screening colonoscopies in a large community‐based population in China
Authors: Zhu Yingshuang , Huang Yanqin , Hu Yeting , Fang Yimin , Kong Xiangxing , Xiao Qian , He Jinjie , Zhu Yunfeng , Li Qilong , Yang Jinhuan , Dong Qi , Jin Mingjuan , Wang Meilin , Chen Kun , Zheng Shu , Ding Kefeng
Published: October 2021

Patients with conventional adenoma removal are recommended to undergo colonoscopy surveillance to prevent colorectal cancer (CRC). However, evidence supporting the guidelines of colonoscopy surveillance is limited, especially among the Chinese population. We investigated the association between colonoscopy adenoma findings and CRC risk among individuals aged 40 to 74 years who underwent baseline colonoscopy from 2007 to 2016 in Jiashan and Haining, Zhejiang, China; 34 382 participants were categorized into advanced adenoma, nonadvanced adenoma and no adenoma based on adenoma findings. A multivariable Cox regression model was used to estimate the hazard ratio (HR) of CRC incidence with adjustment for potential confounding factors. After a median follow‐up time of 7.7 years, 113 incident cases of CRC were identified (18 occurred in 1632 participants with advanced adenoma, 16 in 3973 participants with nonadvanced adenoma and 79 in 28 777 participants with no adenoma). Compared to no adenoma group, the adjusted HR for CRC in advanced adenoma group was 4.01 (95% CI, 2.37‐6.77). For nonadvanced adenomas, individuals with ≥3 adenomas showed an increased risk of CRC (HR, 3.65; 95% CI, 1.43‐9.31), but no significantly increased risk of CRC was found for 1 to 2 nonadvanced adenomas, compared to those with no adenoma. Our study suggested that the risk of subsequent CRC increased in individuals with high‐risk adenoma (at least one advanced adenoma or ≥3 nonadvanced adenomas), but not in those with 1 to 2 nonadvanced adenomas. These results provide the first evidence from the Chinese population for the current surveillance guidelines.