bluuebunny/crossref_metadata_2025 huggingface dataset:
Manifeste Festival
Authors: Friel Patrick
Published: December 2021

In his introductory preamble, Frank Madlener claimed that audiences would experience and hear The World After Covid during the 2021 edition of IRCAM's annual festival. Luckily a late change in French law allowed me to review an eight-day slice of this monde l’apres in person. (Full disclosure: one of my own pieces was performed at the last concert of the festival as part of a workshop with composer Isabel Mundry.)
A rational explanation for links between the ANS and math
Authors: Libertus Melissa E. , Duong Shirley , Fox Danielle , Elliott Leanne , McGregor Rebecca , Ribner Andrew , Silver Alex M.
Published: December 2021

The proposal by Clarke and Beck offers a new explanation for the association between the approximate number system (ANS) and math. Previous explanations have largely relied on developmental arguments, an underspecified notion of the ANS as an “error detection mechanism,” or affective factors. The proposal that the ANS represents rational numbers suggests that it may directly support a broader range of math skills.
Sizes, ratios, approximations: On what and how the ANS represents
Authors: Ball Brian
Published: December 2021

Clarke and Beck propose that the approximate number system (ANS) represents rational numbers. The evidence cited supports only the view that it represents ratios (and positive integers). Rational numbers are extensive magnitudes (i.e., sizes), whereas ratios are intensities. It is also argued that WHAT a system represents and HOW it does so are not as independent of one another as the authors assume.
Do Legitimate States Have a Right to Do Wrong?
Authors: Wellman Christopher Heath
Published: December 2021

This essay critically assesses Anna Stilz's argument in Territorial Sovereignty: A Philosophical Exploration that legitimate states have a right to do wrong. I concede that individuals enjoy a claim against external interference when they commit suberogatory acts, but I deny that the right to do wrong extends to acts that would violate the rights of others. If this is correct, then one must do more than merely invoke an individual's right to do wrong if one hopes to vindicate a legitimate state's right to commit injustices. Of course, there may be distinctive features of legitimate states that explain why they enjoy moral protections that individuals lack, but I argue that the value of collective self-determination is not up to this task. And even if these arguments fail, self-determination would at most explain why legitimate states enjoy a right to commit injustices against their own citizens; it would provide them no moral protection when they violate the rights of outsiders.
Kant and Recent Philosophies of Art
Authors: Lemos João
Published: December 2021

This article is to be a bridge between Kant’s aesthetics and contemporary art – not by being a paper on Kant and contemporary art, but rather by being on Kant and contemporaryphilosophy of art. I claim that Kant’s views on the appreciation of art can accommodate contextualism as well as ethicism. I argue that not only does contextualism fit Kant’s views on the appreciation of art; in §§51–3 of the thirdCritique, Kant’s appreciation of art is in accordance with contextualism. I go on to argue that not only does ethicism fit Kant’s views on the appreciation of art; in §§51–3, Kant’s appreciation of art is in accordance with ethicism.
Therapists’ perceptions and acceptability of providing internet-delivered guided self-help acceptance and commitment therapy (ACT) for family carers of people with dementia (iACT4CARERS): a qualitative study
Authors: Contreras Milena , Van Hout Elien , Farquhar Morag , Gould Rebecca L. , McCracken Lance M. , Hornberger Michael , Richmond Erica , Kishita Naoko
Published: December 2021

This study aimed to explore therapists’ perceptions and acceptability of providing internet-delivered, therapist-guided, self-help acceptance and commitment therapy (ACT) for family carers of people with dementia (iACT4CARERS). To achieve this, a qualitative approach with semi-structured interviews was employed with eight novice therapists recruited from primary and secondary care services taking part in a feasibility study of iACT4CARERS. The interviews were audio-recorded, transcribed, and analysed using thematic analysis. Four over-arching themes were identified: (1) positive attitudes towards the intervention, (2) therapists’ workload, (3) therapists’ confidence to perform their role, and (4) connecting with family carers in a virtual context. Theme 1 included seeing their involvement as an opportunity for personal growth and perceiving benefits to the family carers, which contributed to greater acceptability. Theme 2 reflected that while workload and the user-friendliness of the online platform were highly acceptable among the therapists, there were also time-consuming cases that increased therapists’ burden. Theme 3 revealed that practical resources provided during the training, continued supervision, and opportunities to learn from other therapists, increased therapist confidence and facilitated greater acceptability. Finally, Theme 4 highlighted that improving the connection between therapists and carers was critical in a virtual context and strategies to improve the therapist–carer relationship were recommended. The implementation of iACT4CARERS was largely acceptable for the therapists involved in the trial. Ways to strengthen the therapeutic relationship in the virtual context and practical strategies to deal with common problems may enhance therapist experience and delivery in a full-scale effectiveness trial.

Key learning aims

(1)

To understand which factors facilitated therapists’ positive perceptions and acceptability of providing internet-delivered guided self-help ACT (iACT4CARERS).

(2)

To understand what challenges acted as barriers to therapists’ positive perceptions and acceptability of providing iACT4CARERS.

(3)

To learn what aspects of the training and the intervention can be refined to improve the acceptability to therapists in trials involving internet-delivered guided self-help interventions for family carers.
Massive Multi‐Mission Statistical Study and Analytical Modeling of the Earth's Magnetopause: 1. A Gradient Boosting Based Automatic Detection of Near‐Earth Regions
Authors: Nguyen G. , Aunai N. , Michotte de Welle B. , Jeandet A. , Lavraud B. , Fontaine D.
Published: December 2021

We present an automatic classification method of the three near‐Earth regions, the magnetosphere, the magnetosheath and the solar wind from their in situ data measurement by multiple spacecraft. Based on gradient boosting classifier, this very simple and very fast method outperforms the detection routines based on manually set thresholds. The method is used to identify 15,062 magnetopause crossings and 17,227 bow shock crossings in the data of 11 different spacecraft of the THEMIS, ARTEMIS, Cluster, MMS, and Double Star missions and for a total of 83 cumulated years. These multi‐mission catalogs are easily reproducible, can be automatically enlarged with additional data and their elaboration paves the way for future massive statistical analysis of near‐Earth boundaries.
A Minimal Model to Diagnose the Contribution of the Stratosphere to Tropospheric Forecast Skill
Authors: Charlton‐Perez Andrew J. , Bröcker Jochen , Karpechko Alexey Yu. , Lee Simon H. , Sigmond Michael , Simpson Isla R.
Published: December 2021

Many recent studies have confirmed that variability in the stratosphere is a significant source of surface sub‐seasonal prediction skill during Northern Hemisphere winter. It may be beneficial, therefore, to think about times in which there might be windows‐of‐opportunity for skillful sub‐seasonal predictions based on the initial or predicted state of the stratosphere. In this study, we propose a simple, minimal model that can be used to understand the impact of the stratosphere on tropospheric predictability. Our model purposefully excludes state dependent predictability in either the stratosphere or troposphere or in the coupling between the two. Model parameters are set up to broadly represent current sub‐seasonal prediction systems by comparison with four dynamical models from the Sub‐Seasonal to Seasonal Prediction Project database. The model can reproduce the increases in correlation skill in sub‐sets of forecasts for weak and strong lower stratospheric polar vortex states over neutral states despite the lack of dependence of coupling or predictability on the stratospheric state. We demonstrate why different forecast skill diagnostics can give a very different impression of the relative skill in the three sub‐sets. Forecasts with large stratospheric signals and low amounts of noise are demonstrated to also be windows‐of‐opportunity for skillful tropospheric forecasts, but we show that these windows can be obscured by the presence of unrelated tropospheric signals.
GPR84 signaling promotes intestinal mucosal inflammation via enhancing NLRP3 inflammasome activation in macrophages
Authors: Zhang Qing , Chen Lin-hai , Yang Hui , Fang You-chen , Wang Si-wei , Wang Min , Yuan Qian-ting , Wu Wei , Zhang Yang-ming , Liu Zhan-ju , Nan Fa-jun , Xie Xin
Published: December 2021

The putative medium-chain free fatty acid receptor GPR84 is a G protein-coupled receptor primarily expressed in myeloid cells that constitute the innate immune system, including neutrophils, monocytes, and macrophages in the periphery and microglia in the brain. The fact that GPR84 expression in leukocytes is remarkably increased under acute inflammatory stimuli such as lipopolysaccharide (LPS) and TNFα suggests that it may play a role in the development of inflammatory and fibrotic diseases. Here we demonstrate that GPR84 is highly upregulated in inflamed colon tissues of active ulcerative colitis (UC) patients and dextran sulfate sodium (DSS)-induced colitis mice. Infiltrating GPR84+ macrophages are significantly increased in the colonic mucosa of both the UC patients and the mice with colitis. Consistently, GPR84−/− mice are resistant to the development of colitis induced by DSS. GPR84 activation imposes pro-inflammatory properties in colonic macrophages through enhancing NLRP3 inflammasome activation, while the loss of GPR84 prevents the M1 polarization and properties of proinflammatory macrophages. CLH536, a novel GPR84 antagonist discovered by us, suppresses colitis by reducing the polarization and function of pro-inflammatory macrophages. These results define a unique role of GPR84 in innate immune cells and intestinal inflammation, and suggest that GPR84 may serve as a potential drug target for the treatment of UC.
Retinal ganglion cell loss in an ex vivo mouse model of optic nerve cut is prevented by curcumin treatment
Authors: Buccarello Lucia , Dragotto Jessica , Hassanzadeh Kambiz , Maccarone Rita , Corbo Massimo , Feligioni Marco
Published: December 2021

Retinal ganglion cell (RGC) loss is a pathologic feature common to several retinopathies associated to optic nerve damage, leading to visual loss and blindness. Although several scientific efforts have been spent to understand the molecular and cellular changes occurring in retinal degeneration, an effective therapy to counteract the retinal damage is still not available. Here we show that eyeballs, enucleated with the concomitant optic nerve cut (ONC), when kept in PBS for 24 h showed retinal and optic nerve degeneration. Examining retinas and optic nerves at different time points in a temporal window of 24 h, we found a thinning of some retinal layers especially RGC’s layer, observing a powerful RGC loss after 24 h correlated with an apoptotic, MAPKs and degradative pathways dysfunctions. Specifically, we detected a time-dependent increase of Caspase-3, -9 and pro-apoptotic marker levels, associated with a strong reduction of BRN3A and NeuN levels. Importantly, a powerful activation of JNK, c-Jun, and ERK signaling (MAPKs) were observed, correlated with a significant augmented SUMO-1 and UBC9 protein levels. The degradation signaling pathways was also altered, causing a significant decrease of ubiquitination level and an increased LC3B activation. Notably, it was also detected an augmented Tau protein level. Curcumin, a powerful antioxidant natural compound, prevented the alterations of apoptotic cascade, MAPKs, and SUMO-1 pathways and the degradation system, preserving the RGC survival and the retinal layer thickness. This ex vivo retinal degeneration model could be a useful method to study, in a short time window, the effect of neuroprotective tools like curcumin that could represent a potential treatment to contrast retinal cell death.
Impact of maternal antibodies and microbiota development on the immunogenicity of oral rotavirus vaccine in African, Indian, and European infants
Authors: Parker Edward P. K. , Bronowski Christina , Sindhu Kulandaipalayam Natarajan C. , Babji Sudhir , Benny Blossom , Carmona-Vicente Noelia , Chasweka Nedson , Chinyama End , Cunliffe Nigel A. , Dube Queen , Giri Sidhartha , Grassly Nicholas C. , Gunasekaran Annai , Howarth Deborah , Immanuel Sushil , Jere Khuzwayo C. , Kampmann Beate , Lowe Jenna , Mandolo Jonathan , Praharaj Ira , Rani Bakthavatsalam Sandya , Silas Sophia , Srinivasan Vivek Kumar , Turner Mark , Venugopal Srinivasan , Verghese Valsan Philip , Darby Alistair C. , Kang Gagandeep , Iturriza-Gómara Miren
Published: December 2021

Identifying risk factors for impaired oral rotavirus vaccine (ORV) efficacy in low-income countries may lead to improvements in vaccine design and delivery. In this prospective cohort study, we measure maternal rotavirus antibodies, environmental enteric dysfunction (EED), and bacterial gut microbiota development among infants receiving two doses of Rotarix in India (n = 307), Malawi (n = 119), and the UK (n = 60), using standardised methods across cohorts. We observe ORV shedding and seroconversion rates to be significantly lower in Malawi and India than the UK. Maternal rotavirus-specific antibodies in serum and breastmilk are negatively correlated with ORV response in India and Malawi, mediated partly by a reduction in ORV shedding. In the UK, ORV shedding is not inhibited despite comparable maternal antibody levels to the other cohorts. In both India and Malawi, increased microbiota diversity is negatively correlated with ORV immunogenicity, suggesting that high early-life microbial exposure may contribute to impaired vaccine efficacy.
Uppermost crustal structure regulates the flow of the Greenland Ice Sheet
Authors: Jones G. A. , Ferreira A. M. G. , Kulessa B. , Schimmel M. , Berbellini A. , Morelli A.
Published: December 2021

The flow of the Greenland Ice Sheet is controlled by subglacial processes and conditions that depend on the geological provenance and temperature of the crust beneath it, neither of which are adequately known. Here we present a seismic velocity model of the uppermost 5 km of the Greenlandic crust. We show that slow velocities in the upper crust tend to be associated with major outlet glaciers along the ice-sheet margin, and elevated geothermal heat flux along the Iceland hotspot track inland. Outlet glaciers particularly susceptible to basal slip over deformable subglacial sediments include Jakobshavn, Helheim and Kangerdlussuaq, while geothermal warming and softening of basal ice may affect the onset of faster ice flow at Petermann Glacier and the Northeast Greenland Ice Stream. Interactions with the solid earth therefore control the past, present and future dynamics of the Greenland Ice Sheet and must be adequately explored and implemented in ice sheet models.
Quantum theory based on real numbers can be experimentally falsified
Authors: Renou Marc-Olivier , Trillo David , Weilenmann Mirjam , Le Thinh P. , Tavakoli Armin , Gisin Nicolas , Acín Antonio , Navascués Miguel
Published: December 2021

Although complex numbers are essential in mathematics, they are not needed to describe physical experiments, as those are expressed in terms of probabilities, hence real numbers. Physics, however, aims to explain, rather than describe, experiments through theories. Although most theories of physics are based on real numbers, quantum theory was the first to be formulated in terms of operators acting on complex Hilbert spaces1,2. This has puzzled countless physicists, including the fathers of the theory, for whom a real version of quantum theory, in terms of real operators, seemed much more natural3. In fact, previous studies have shown that such a ‘real quantum theory’ can reproduce the outcomes of any multipartite experiment, as long as the parts share arbitrary real quantum states4. Here we investigate whether complex numbers are actually needed in the quantum formalism. We show this to be case by proving that real and complex Hilbert-space formulations of quantum theory make different predictions in network scenarios comprising independent states and measurements. This allows us to devise a Bell-like experiment, the successful realization of which would disprove real quantum theory, in the same way as standard Bell experiments disproved local physics.
Experimental evidence for recovery of mercury-contaminated fish populations
Authors: Blanchfield Paul J. , Rudd John W. M. , Hrenchuk Lee E. , Amyot Marc , Babiarz Christopher L. , Beaty Ken G. , Bodaly R. A. Drew , Branfireun Brian A. , Gilmour Cynthia C. , Graydon Jennifer A. , Hall Britt D. , Harris Reed C. , Heyes Andrew , Hintelmann Holger , Hurley James P. , Kelly Carol A. , Krabbenhoft David P. , Lindberg Steve E. , Mason Robert P. , Paterson Michael J. , Podemski Cheryl L. , Sandilands Ken A. , Southworth George R. , St Louis Vincent L. , Tate Lori S. , Tate Michael T.
Published: December 2021

Anthropogenic releases of mercury (Hg)1–3 are a human health issue4 because the potent toxicant methylmercury (MeHg), formed primarily by microbial methylation of inorganic Hg in aquatic ecosystems, bioaccumulates to high concentrations in fish consumed by humans5,6. Predicting the efficacy of Hg pollution controls on fish MeHg concentrations is complex because many factors influence the production and bioaccumulation of MeHg7–9. Here we conducted a 15-year whole-ecosystem, single-factor experiment to determine the magnitude and timing of reductions in fish MeHg concentrations following reductions in Hg additions to a boreal lake and its watershed. During the seven-year addition phase, we applied enriched Hg isotopes to increase local Hg wet deposition rates fivefold. The Hg isotopes became increasingly incorporated into the food web as MeHg, predominantly from additions to the lake because most of those in the watershed remained there. Thereafter, isotopic additions were stopped, resulting in an approximately 100% reduction in Hg loading to the lake. The concentration of labelled MeHg quickly decreased by up to 91% in lower trophic level organisms, initiating rapid decreases of 38–76% of MeHg concentration in large-bodied fish populations in eight years. Although Hg loading from watersheds may not decline in step with lowering deposition rates, this experiment clearly demonstrates that any reduction in Hg loadings to lakes, whether from direct deposition or runoff, will have immediate benefits to fish consumers.
Effect of graphite oxide and exfoliated graphite oxide as a modifier for the voltametric determination of dopamine in presence of uric acid and folic acid
Authors: Vidya H. , Kumara Swamy B. E. , Sharma S. C. , Jayaprakash G. K. , Hariprasad S. A.
Published: December 2021

In the present work, exfoliated graphite oxide (E-GO) was prepared by sonicating graphite oxide (GO) (prepared by modified Hummer’s and Offemam methods). Prepared GO and E-GO were characterized using infrared absorption spectroscopy, X-ray diffraction, and scanning electron microscopy. The electrocatalytic properties of GO and E-GO towards detection of dopamine (DA), uric acid (UA), and folic acid (FA) were investigated using cyclic voltammetry and differential pulse voltammetry. Our results revealed that E-GO has a slighter advantage over the GO as an electrode modifier for detection DA, UA, and FA, which might be ascribed to the good conductivity of E-GO when compared to the GO.
Frequency domain maximum correntropy criterion spline adaptive filtering
Authors: Guo Wenyan , Zhi Yongfeng , Feng Kai
Published: December 2021

A filtering algorithm based on frequency domain spline type, frequency domain spline adaptive filters (FDSAF), effectively reducing the computational complexity of the filter. However, the FDSAF algorithm is unable to suppress non-Gaussian impulsive noises. To suppression non-Gaussian impulsive noises along with having comparable operation time, a maximum correntropy criterion (MCC) based frequency domain spline adaptive filter called frequency domain maximum correntropy criterion spline adaptive filter (FDSAF-MCC) is developed in this paper. Further, the bound on learning rate for convergence of the proposed algorithm is also studied. And through experimental simulations verify the effectiveness of the proposed algorithm in suppressing non-Gaussian impulsive noises. Compared with the existing frequency domain spline adaptive filter, the proposed algorithm has better performance.
Effects of sub-threshold transcutaneous auricular vagus nerve stimulation on cerebral blood flow
Authors: Chen Conan , Mao Yixiang , Falahpour Maryam , MacNiven Kelly H. , Heit Gary , Sharma Vivek , Alataris Konstantinos , Liu Thomas T.
Published: December 2021

Transcutaneous auricular vagus nerve stimulation (taVNS) has shown promise as a non-invasive alternative to vagus nerve stimulation (VNS) with implantable devices, which has been used to treat drug-resistant epilepsy and treatment-resistant depression. Prior work has used functional MRI to investigate the brain response to taVNS, and more recent work has also demonstrated potential therapeutic effects of high-frequency sub-threshold taVNS in rheumatoid arthritis. However, no studies to date have measured the effects of high-frequency sub-threshold taVNS on cerebral blood flow (CBF). The objective of this study was to determine whether high-frequency (20 kHz) sub-threshold taVNS induces significant changes in CBF, a promising metric for the assessment of the sustained effects of taVNS. Arterial spin labeling (ASL) MRI scans were performed on 20 healthy subjects in a single-blind placebo-controlled repeated measures experimental design. The ASL scans were performed before and after 15 min of either sub-threshold taVNS treatment or a sham control. taVNS induced significant changes in CBF in the superior posterior cerebellum that were largely localized to bilateral Crus I and Crus II. Post hoc analyses showed that the changes were driven by a treatment-related decrease in CBF. Fifteen minutes of high-frequency sub-threshold taVNS can induce sustained CBF decreases in the bilateral posterior cerebellum in a cohort of healthy subjects. This study lays the foundation for future studies in clinical populations, and also supports the use of ASL measures of CBF for the assessment of the sustained effects of taVNS.
Novel chemical inhibitor against SOD1 misfolding and aggregation protects neuron-loss and ameliorates disease symptoms in ALS mouse model
Authors: Woo Tae-Gyun , Yoon Min-Ho , Kang So-mi , Park Soyoung , Cho Jung-Hyun , Hwang Young Jun , Ahn Jinsook , Jang Hyewon , Shin Yun-Jeong , Jung Eui-Man , Ha Nam-Chul , Kim Bae-Hoon , Kwon Yonghoon , Park Bum-Joon
Published: December 2021

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by selective death of motor neurons. Mutations in Cu, Zn-superoxide dismutase (SOD1) causing the gain of its toxic property are the major culprit of familial ALS (fALS). The abnormal SOD1 aggregation in the motor neurons has been suggested as the major pathological hallmark of ALS patients. However, the development of pharmacological interventions against SOD1 still needs further investigation. In this study, using ELISA-based chemical screening with wild and mutant SOD1 proteins, we screened a new small molecule, PRG-A01, which could block the misfolding/aggregation of SOD1 or TDP-43. The drug rescued the cell death induced by mutant SOD1 in human neuroblastoma cell line. Administration of PRG-A01 into the ALS model mouse resulted in significant improvement of muscle strength, motor neuron viability and mobility with extended lifespan. These results suggest that SOD1 misfolding/aggregation is a potent therapeutic target for SOD1 related ALS.
Cadmium exposure modulates the gut-liver axis in an Alzheimer’s disease mouse model
Authors: Zhang Angela , Matsushita Megumi , Zhang Liang , Wang Hao , Shi Xiaojian , Gu Haiwei , Xia Zhengui , Cui Julia Yue
Published: December 2021

The human Apolipoprotein E4 (ApoE4) variant is the strongest known genetic risk factor for Alzheimer’s disease (AD). Cadmium (Cd) has been shown to impair learning and memory at a greater extent in humanized ApoE4 knock-in (ApoE4-KI) mice as compared to ApoE3 (common allele)-KI mice. Here, we determined how cadmium interacts with ApoE4 gene variants to modify the gut-liver axis. Large intestinal content bacterial 16S rDNA sequencing, serum lipid metabolomics, and hepatic transcriptomics were analyzed in ApoE3- and ApoE4-KI mice orally exposed to vehicle, a low dose, or a high dose of Cd in drinking water. ApoE4-KI males had the most prominent changes in their gut microbiota, as well as a predicted down-regulation of many essential microbial pathways involved in nutrient and energy homeostasis. In the host liver, cadmium-exposed ApoE4-KI males had the most differentially regulated pathways; specifically, there was enrichment in several pathways involved in platelet activation and drug metabolism. In conclusion, Cd exposure profoundly modified the gut-liver axis in the most susceptible mouse strain to neurological damage namely the ApoE4-KI males, evidenced by an increase in microbial AD biomarkers, reduction in energy supply-related pathways in gut and blood, and an increase in hepatic pathways involved in inflammation and xenobiotic biotransformation.
Male fire ant neurotransmitter precursors trigger reproductive development in females after mating
Authors: Vander Meer Robert K. , Chinta Satya P. , Jones Tappey H. , O’Reilly Erin E. , Adams Rachelle M. M.
Published: December 2021

Social insect queens have evolved mechanisms to prevent competition from their sexual daughters. For Solenopsis invicta, the fire ant, queens have evolved a primer pheromone that retards reproductive development in their winged reproductive daughters. If these daughters are removed from the influence of the queen, it takes about a week to start reproductive development; however, it starts almost immediately after mating. This dichotomy has been unsuccessfully investigated for several decades. Here we show that male fire ants produce tyramides, derivatives of the biogenic amine tyramine, in their reproductive system. Males transfer tyramides to winged females during mating, where the now newly mated queens enzymatically convert tyramides to tyramine. Tyramine floods the hemolymph, rapidly activating physiological processes associated with reproductive development. Tyramides have been found only in the large Myrmicinae ant sub-family (6,800 species), We suggest that the complex inhibition/disinhibition of reproductive development described here will be applicable to other members of this ant sub-family.
Spatial pattern of lake evaporation increases under global warming linked to regional hydroclimate change
Authors: Zhou Wenyu , Wang Linying , Li Dan , Leung L. Ruby
Published: December 2021

Lakes are critical natural resources that are vulnerable to climate change. In a warmer climate, lake evaporation is projected to increase globally, but with substantial variation between regions. Here, based on ensemble projections of climate and lake models and an attribution method, we show that future lake evaporation increase is strongly modulated by regional hydroclimate change. Specifically, a drying hydroclimate will amplify evaporation increase by enlarging surface vapor pressure deficit and reducing cloud shortwave reflection. Future lake evaporation increase is amplified in tropical America, the Mediterranean and Southeast China with drier future hydroclimates, and dampened in high latitudes and the Tibetan Plateau with wetter future hydroclimates. Such spatially coupled changes in lake evaporation and hydroclimate have important implications on regional lake water balance and volume change, which can aggravate water scarcity and flood risks.
Linker Design and Impact on ADC Properties
Authors: Frigerio M. , Camper N.
Published: December 2021

Antibody–drug conjugates (ADCs) represent one of the most complex classes of drugs currently under development. The aim of an ADC is to improve the therapeutic index with respect to traditional chemotherapy by combining the targeting properties of an antibody with a high cytotoxicity payload that is attached via an appropriate linker. The linker represents an important and critical element of the overall ADC design, and the different structural elements of the linker can be evaluated using a developability assessment to modulate ADC functionality, safety, and manufacturability in order to establish an appropriate and stage-specific target product profile (TPP). This chapter describes the many varied and different approaches that have been applied to linker design and its subsequent impact on ADC properties, and ultimately how an optimal linker design drives the success of ADC programs.
Protease-sensitive Linkers
Authors: Johannes S. , Sommer A. , Lerchen H.-G.
Published: December 2021

The development and maturation of protease-cleavable linkers as an efficient and flexible linker strategy, compatible with a variety of payload classes, is described. Lysosomal proteases such as cathepsins and legumain have been employed successfully to release active payloads from antibody–drug conjugates (ADCs) with peptide linkers composed of appropriate substrate sequences for respective cleavage enzymes and on demand, with additional self-immolative spacer fragments. Case studies of approved ADCs are reviewed, along with further improvements of linker stability, cleavage specificity, and reduced tendency for aggregate formation. Initial investigations to expand the scope to extracellular payload release from non-internalizing ADCs by proteases in the tumor microenvironment such as cathepsin B and matrix metalloproteinases complete the overview.
ADC Linkers Strategies for the Release of Alcohol-containing Payloads
Authors: Miller Jared T. , Tumey L. Nathan
Published: December 2021

In spite of tremendous advances in the design of ADC linkers, there continue to be limited options for the release of payloads that do not contain a free amino group. Herein, we review a variety of cleavable linker strategies that have been employed for both phenolic and aliphatic alcohols. We highlight the advantages and shortcomings of each approach, particularly focusing on technology that has advanced into the clinic and those approaches that are broadly applicable to structurally diverse alcohol-containing payloads.
Precision synthesis of linear oligorotaxanes and polyrotaxanes achieving well-defined positions and numbers of cyclic components on the axle
Authors: Masai Hiroshi , Oka Yuki , Terao Jun
Published: December 2021

This article provides an overview of the “defined” oligo- and polyrotaxanes with controlled number density, sequence, and positions of the cyclic components on the axle, focusing on the synthetic methodologies as well as functionalities.
Atom-economic amide synthesis by using an iron-substituted polyoxometalate catalyst
Authors: Wang Aiping , Xie Ya , Wang Jingjing , Shi Da , Yu Han
Published: December 2021

A practical strategy for amidation of various amines and carboxylic acids by using an inorganic–ligand supported iron catalyst.
Remote difunctionalization of 2H-indazoles using Koser's reagents
Authors: Bhattacharjee Suvam , Laru Sudip , Hajra Alakananda
Published: December 2021

We report a regioselective remote difunctionalization of unreactive C–H bonds of 2H-indazoles with Koser's reagents to provide C-4,7 substituted 2H-indazole derivatives.
In situ ortho-lithiation/functionalization of pentafluorosulfanyl arenes
Authors: Le Thanh V. , Daugulis Olafs
Published: December 2021

A general method forortho-functionalization of pentafluorosulfanyl arenes has been developed.
Homochiral porous coordination polymer of EuIII for metal ion sensing and enantioselective adsorption
Authors: Dong Yingling , Chen Rui , Zhu Xu , Niu Caoyuan , Wu Benlai , Yu Ajuan
Published: December 2021

A novel multifunctional homochiral porous metal–organic framework was obtained by combining the luminescent component Eu(iii) with an enantiopure triangular polycarboxylic ligand.
The extensive solid-form landscape of sulfathiazole: geometrical similarity and interaction energies
Authors: Hughes David S. , Bingham Ann L. , Hursthouse Michael B. , Threlfall Terry L. , Bond Andrew D.
Published: December 2021

Sulfathiazole shows one of the most extensive solid-form landscapes known to date for an active pharmaceutical ingredient. A standardised structure set of 5 polymorphs, 59 co-crystals, 29 salts, and 3 other structures is established.
Correction: Micro- and nanoplastic transfer in freezing saltwater: implications for their fate in polar waters
Authors: Pradel Alice , Gautier Maud , Bavay Dominique , Gigault Julien
Published: December 2021

Correction for ‘Micro- and nanoplastic transfer in freezing saltwater: implications for their fate in polar waters’ by Alice Pradel et al., Environ. Sci.: Processes Impacts, 2021, 23, 1759–1770, DOI: 10.1039/D1EM00280E.
Metabolomic and bioenergetic responses of human hepatocellular carcinoma cells following exposure to commercial copper hydroxide nanopesticide
Authors: Li Xiaoyu , Qin Yingju , Kong Long , Yan Xiliang , Zhang Wei , Martyniuk Christopher J. , Wang Xiaohong , Yan Bing
Published: December 2021

Copper hydroxide (Cu(OH)2) nanopesticide formulas are becoming more frequently used in agriculture; however, human exposure risks are not completely characterized.
Direct catalytic benzene hydroxylation under mild reaction conditions by using a monocationic μ-nitrido-bridged iron phthalocyanine dimer with 16 peripheral methyl groups
Authors: Yamada Yasuyuki , Teoh Chee-Ming , Toyoda Yuka , Tanaka Kentaro
Published: December 2021

Direct catalytic benzene hydroxylation under mild reaction conditions was achieved using a monocationic μ-nitrido-bridged iron phthalocyanine dimer with 16 peripheral methyl groups.
Photo-oxidative cross-linking of thiol polydimethylsiloxane co-polymers via disulfide formation
Authors: Wright Taylor , Zhang Ziyue , Michal Carl A. , Hatzikiriakos Savvas G. , Wolf Michael O.
Published: December 2021

Disulfide bonds are often employed as reductively cleavable sites in biomaterials and polymers. Here we demonstrate the aerobic photo-cross-linking of thiol-containing polymers through disulfide formation using a sensitizer and telluride catalyst.
A Ni(ii)-catalyzed reductive cross-coupling reaction of oxalates and thiosulfonates/selenosulfonates
Authors: Chen Ying , Wang Fei , Liu Bo-Xi , Rao Wei-Dong , Wang Shun-Yi
Published: December 2021

A Ni(ii)-catalyzed reductive cross-coupling reaction of oxalates and thiosulfonates/selenosulfonates to synthesize benzylic sulfides/selenides under mild conditions is developed.
One-pot synthesis of natural-product inspired spiroindolines with anti-cancer activities
Authors: Li Shi-Qiang , Yan Wei , He Liu-Jun , Zhang Ming , Tang Dian-Yong , Li Hong-yu , Chen Zhong-Zhu , Xu Zhi-Gang
Published: December 2021

A post-Ugi/diastereoselective cascade reaction was developed to construct the spiroindoline scaffold through a 5-exo-dig indole cyclization and the intramolecular trapping of the spiro intermediate forming a quaternary carbon center.
Polymyxin B engineered polystyrene-divinylbenzene microspheres for the adsorption of bilirubin and endotoxin
Authors: Yang Kangle , Peng Yaotian , Wang Lin , Ren Li
Published: December 2021

A new adsorbent for hemoperfusion was successfully prepared by grafting polymyxin B (PMB) on the surface of polystyrene divinylbenzene (PS-DVB) microspheres. It showed good biocompatibility and could adsorb both bilirubin and endotoxin.
Proton-coupled electron transfer of catechin in tea wine: the enhanced mechanism of anti-oxidative capacity
Authors: Xia Yirong , Wang Xintong , Sun Hechen , Huang Ximing
Published: December 2021

Tea wine is a Chinese traditional alcoholic drink made by cereal and tea leaves.
Student teachers’ problem-based investigations of chemical phenomena in the nearby outdoor environment
Authors: Höper Jan , Jegstad Kirsti Marie , Remmen Kari Beate
Published: December 2021

Learning science outdoors can enhance the understanding of theoretical scientific content taught in the classroom. However, learners are rarely afforded the opportunity to go outdoors to learn chemistry. This study investigates how problem-based learning outdoors can facilitate the understanding of basic chemistry in teacher education. A teaching unit was designed according to which student teachers at two Norwegian universities were asked to examine and identify corroded metals in the nearby outdoor environment and propose solutions to avoid this corrosion. Video data from this task were collected by using chest-mounted cameras for four groups of student teachers (N = 17). A thematic analysis of the videos yielded four themes related to the student teachers’ use of content knowledge and experimental competence. Based on these findings, three learning opportunities were deduced for how the nearby outdoor environment allows learners to use everyday phenomena for learning basic chemistry. First, the availability of different corrosion incidents allowed the student teachers to choose and solve one of interest to them. Second, the proximity of the outdoor location to the classroom enabled the seamless continuity of discussions when switching between the learning arenas, and allowed for different approaches to solve the task. Third, being asked to conduct analyses outside customary laboratory routines led to an unexpected awareness of health and safety issues among the student teachers, indicating that outdoor chemistry is an overlooked opportunity for teaching these.
Correction: Electrochromic triphenylamine-based cobalt(ii) complex nanosheets
Authors: Liu Yurong , Sakamoto Ryota , Ho Cheuk-Lam , Nishihara Hiroshi , Wong Wai-Yeung
Published: December 2021

Correction for ‘Electrochromic triphenylamine-based cobalt(ii) complex nanosheets’ by Yurong Liu et al., J. Mater. Chem. C, 2019, 7, 9159–9166, DOI: 10.1039/C9TC02257K.
Circular RNAs in stem cells: from basic research to clinical implications
Authors: Lu Hui-Juan , Li Juan , Yang Guodong , Yi Cun-Jian , Zhang Daping , Yu Fenggang , Ma Zhaowu
Published: December 2021

Circular RNAs (circRNAs) are a special class of endogenous RNAs with a wide variety of pathophysiological functions via diverse mechanisms, including transcription, microRNA (miRNA) sponge, protein sponge/decoy, and translation. Stem cells are pluripotent cells with unique properties of self-renewal and differentiation. Dysregulated circRNAs identified in various stem cell types can affect stem cell self-renewal and differentiation potential by manipulating stemness. However, the emerging roles of circRNAs in stem cells remain largely unknown. This review summarizes the major functions and mechanisms of action of circRNAs in stem cell biology and disease progression. We also highlight circRNA-mediated common pathways in diverse stem cell types and discuss their diagnostic significance with respect to stem cell-based therapy.
BaTiO3‐doped silicon nanocomposite anodes capacity enhancement for ultra‐high capacity rechargeable lithium‐ion batteries
Authors: Amli Hatem , Walwyn Graham , Ahmed Waqar
Published: December 2021

Silicon anodes are vital for the next generation ultra‐high capacity rechargeable lithium‐ion batteries. This study investigates ultrasmall silicon nanopowder (30–40 nm) as an anode material. Its high capacity > 3700 mAh/g makes it attractive, given the current theoretical capacity of graphite is ten times lower (370 mAh/g). However, it has severe instability due to volume expansion of silicon particles during charging. Hence, BaTiO3 nanomaterial was used to stabilise the cycling ability and improve the capacity. This study showed that silicon anode with BaTiO3 retained 40% of its original capacity after the 100th cycle where the silicon anode without BaTiO3 lost almost all of its capacity. The silicon anode with BaTiO3 also managed to regain and sustain ∼800 mAh/g of its capacity at slow charging rate compared to the silicon anode without BaTiO3. Water was used as a solvent and the basic changes in oxidation states of the silicon anode were investigated using X‐ray photoemission spectroscopy and proved the creation of COx at different rates of repeated cycling. The work also provides detailed mapping of the different stages as the silicon nanopowder undergoes cycling. It provides a simple and effective way of synthesising and testing nearly pure silicon anodes.
Coronal condensation as the source of transition-region supersonic downflows above a sunspot
Authors: Chen Hechao , Tian Hui , Li Leping , Peter Hardi , Chitta Lakshmi Pradeep , Hou Zhenyong
Published: December 2021

Context. Plasma loops or plumes rooted in sunspot umbrae often harbor downflows with speeds of 100 km s−1. These downflows are supersonic at transition region temperatures of ∼0.1 MK. The source of these flows is not well understood.

Aims. We aim to investigate the source of sunspot supersonic downflows (SSDs) in active region 12740 using simultaneous spectroscopic and imaging observations.

Methods. We identified SSD events from multiple raster scans of a sunspot by the Interface Region Imaging Spectrograph, and we calculated the electron densities, mass fluxes, and velocities of these SSDs. The extreme-ultraviolet (EUV) images provided by the Atmospheric Imaging Assembly onboard the Solar Dynamics Observatory and the EUV Imager onboard the Solar Terrestrial Relations Observatory were employed to investigate the origin of these SSDs and their associated coronal rain.

Results. Almost all the identified SSDs appear at the footpoints of sunspot plumes and are temporally associated with the appearance of chromospheric bright dots inside the sunspot umbra. Dual-perspective EUV imaging observations reveal a large-scale closed magnetic loop system spanning the sunspot region and a remote region. We observed that the SSDs are caused by repeated coronal rain that forms and flows along these closed magnetic loops toward the sunspot. One episode of coronal rain clearly indicates that reconnection near a coronal X-shaped structure first leads to the formation of a magnetic dip. Subsequently, hot coronal plasma catastrophically cools from ∼2 MK in the dip region via thermal instability. This results in the formation of a transient prominence in the dip, from which the cool gas mostly slides into the sunspot along inclined magnetic fields under the gravity. This drainage process manifests as a continuous rain flow, which lasts for ∼2 h and concurrently results in a nearly steady SSD event. The total mass of condensation (1.3 × 1014 g) and condensation rate (1.5 × 1010 g s−1) in the dip region were found to be sufficient to sustain this long-lived SSD event, which has a mass transport rate of 0.7 − 1.2 × 1010 g s−1.

Conclusions. Our results demonstrate that coronal condensation in magnetic dips can result in the quasi-steady sunspot supersonic downflows.
Dependence of the ROT effect on the energy of different light charged particles and on the incident neutron energy
Authors: Guseva Irina , Gagarski Alexei , Gönnenwein Friedrich , Gusev Yuri
Published: December 2021

The shift of the angular distribution of different light charged particles in ternary fission of235U induced by polarized neutrons, the so-called ROT effect, was estimated by modified trajectory calculations, which take into account the rotation of the compound nucleus. In previous publications onlyα-particles were considered. It is shown here that inclusion of tritons significantly improves the agreement of the energy dependence of the ROT effect with experiment while the inclusion of5He particles practically does not influence this dependence. In particular, the change in the magnitude of the ROT effect depending on the energy of incident neutrons is correctly predicted. Also, the ROT effect for gamma quanta and neutrons in binary fission is discussed along the same lines, because all mentioned effects are proportional to the effective angular velocity of the compound nucleus at the moment of scission.
Energy sharing based on microscopic level densities
Authors: Randrup Jørgen , Albertsson Martin , Carlsson Gillis , Døssing Thomas , Möller Peter , Åberg Sven
Published: December 2021

The transformation of a moderately excited heavy nucleus into two excited fission fragments is modeled as a strongly damped evolution of the nuclear shape. The resulting Brownian motion in the multi-dimensional deformation space is guided by the shape-dependent level density which has been calculated microscopically for each of nearly ten million shapes (given in the three-quadratic-surfaces parametrization) by using a previously developed combinatorial method that employs the same single-particle levels as those used for the calculation of the pairing and shell contributions to the five-dimensional macroscopic-microscopic potential-energy surface.

The stochastic shape evolution is followed until a small critical neck radius is reached, at which point the mass, charge, and shape of the two proto-fragments are extracted. The available excitation energy is divided statistically on the basis of the microscopic level densities associated with the two distorted fragments. Specific fragment structure features may cause the distribution of the energy disvision to deviate significantly from expectations based on a Fermi-gas level density.

After their formation at scission, the initially distorted fragments are being accelerated by their mutual Coulomb repulsion as their shapes relax to their equilibrium forms. The associated distortion energy is converted to additional excitation energy in the fully accelerated fragments. These subsequently undergo sequential neutron evaporation which is calculated using again the appropriate microscopic level densities. The resulting dependence of the mean neutron multiplicity on the fragment mass, as well as the dependence of on the initial excitation energy of the fissioning compound nucleus, exhibit features that are similar to the experimentally observed behavior, suggesting that the microscopic energy sharing mechanism plays an important role in low-energy fission.
The system of tax incentives in regional tax policy
Authors: Glotko Andrey , Lyaskin Gennady
Published: December 2021

The article analyzes the problem of optimization of tax benefits in formation of tax policy at the regional level. The application of a systematic approach in improving the regional tax regime has been substantiated. The content and functions of tax benefits have been determined. The classification of tax incentives is presented. The characteristic of the tax policy of the Altai Republic is given on the basis of the recommendations of the Ministry of Finance of the Russian Federation. The structure and dynamics of tax expenditures in the budget of a constituent entity of the Russian Federation are analyzed. The orientation of the tax policy of the Altai Republic towards improving regional legislation with the continuation of the course towards creating favorable conditions for development of entrepreneurship and stimulating the investment attractiveness of the region is revealed. A number of offers for improving the tax policy of the Altai Republic in terms of optimizing the system of tax incentives have been substantiated.