bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring More Functions in Binders for Lithium Batteries
Authors: Zhang Lan , Wu Xiangkun , Qian Weiwei , Pan Kecheng , Zhang Xiaoyan , Li Liyuan , Jia Mengmin , Zhang Suojiang
Published: December 2023

As an indispensable part of the lithium-ion battery (LIB), a binder takes a small share of less than 3% (by weight) in the cell; however, it plays multiple roles. The binder is decisive in the slurry rheology, thus influencing the coating process and the resultant porous structures of electrodes. Usually, binders are considered to be inert in conventional LIBs. In the pursuit of higher energy density, many new binders are being developed for specific targets, such as the high-voltage (typically, $$\geqslant$$
⩾
 4.5 V) cathodes, conversion/alloy-type cathodes/anodes with large volume effect, and solid-state batteries (SSBs), in which these binders demonstrate their various functions. They may influence the solid electrolyte interface component, ensure the electrode/electrolyte interfacial stability, transport ions/electrons in the electrodes, provide adhesion and flexibility to solid-state electrolyte (SSE) films, etc. Here in this review, we try to summarize the advances on binders, among which the ones for high-voltage cathode materials, thick electrodes, micro-sized silicon particles, SSEs and SSBs are highlighted. We believe that the advanced functional binders would play decisive roles in the future development of high-energy–density LIBs and SSBs.

Graphical Abstract

Binder usually takes a small part in batteries, while recent studies prove that it has multi-functions more than just adhesive.
Biochar-based Bacillus subtilis inoculant for enhancing plants disease prevention: microbiota response and root exudates regulation
Authors: Deng Zihe , Wang Jianwen , He Yanhui , Tu Zhuo , Tian Fei , Li Haijie , Wu Zhansheng , An Xiongfang
Published: December 2023

Plants regulate root exudates to form the composition of rhizosphere microbial community and resist disease stress. Many studies advocate intervention with biochar (BC) and exogenous microbe to enhance this process and improve plant defenses. However, the mechanism by which BC mediates exogenous microorganisms to enhance root exudate-soil microbial defensive feedback remains unclear. Here, a BC-based Bacillus subtilis SL-44 inoculant (BC@SL) was prepared to investigate the defensive feedback mechanism for plants, which  enhanced plant growth and defense more than BC or SL-44 alone. BC@SL not only strengthened the direct inhibition of Rhizoctonia solani Rs by solving the problem of reduced viability of a single SL-44 inoculant but also indirectly alleviated the Rs stress by strengthening plant defensive feedback, which  was specifically manifested by the following: (1) increasing the root resistance enzyme activities (superoxide dismutase up to 3.5 FC); (2) increasing the abundance of beneficial microbe in soil (0.38–16.31% Bacillus); and (3) remodeling the composition of root exudates (palmitic acid 3.95–6.96%, stearic acid 3.56–5.93%, 2,4 tert-butylphenol 1.23–2.62%, increasing citric acid 0.94–1.81%, and benzoic acid 0.97–2.13%). The mechanism reveals that BC@SL can enhance the positive regulatory effect between root exudates and microorganisms by optimizing their composition. Overall, BC@SL is a stable and efficient new solid exogenous soil auxiliary, and this study lays the foundation for the generalization and application of green pesticides.

Graphical Abstract
Deep learning approximations for non-local nonlinear PDEs with Neumann boundary conditions
Authors: Boussange Victor , Becker Sebastian , Jentzen Arnulf , Kuckuck Benno , Pellissier Loïc
Published: December 2023

Nonlinear partial differential equations (PDEs) are used to model dynamical processes in a large number of scientific fields, ranging from finance to biology. In many applications standard local models are not sufficient to accurately account for certain non-local phenomena such as, e.g., interactions at a distance. Non-local nonlinear PDE models can accurately capture these phenomena, but traditional numerical approximation methods are infeasible when the considered non-local PDE is high-dimensional. In this article we propose two numerical methods based on machine learning and on Picard iterations, respectively, to approximately solve non-local nonlinear PDEs. The proposed machine learning-based method is an extended variant of a deep learning-based splitting-up type approximation method previously introduced in the literature and utilizes neural networks to provide approximate solutions on a subset of the spatial domain of the solution. The Picard iterations-based method is an extended variant of the so-called full history recursive multilevel Picard approximation scheme previously introduced in the literature and provides an approximate solution for a single point of the domain. Both methods are mesh-free and allow non-local nonlinear PDEs with Neumann boundary conditions to be solved in high dimensions. In the two methods, the numerical difficulties arising due to the dimensionality of the PDEs are avoided by (i) using the correspondence between the expected trajectory of reflected stochastic processes and the solution of PDEs (given by the Feynman–Kac formula) and by (ii) using a plain vanilla Monte Carlo integration to handle the non-local term. We evaluate the performance of the two methods on five different PDEs arising in physics and biology. In all cases, the methods yield good results in up to 10 dimensions with short run times. Our work extends recently developed methods to overcome the curse of dimensionality in solving PDEs.
Integrated Circuit Fabrication
Authors: Plummer James D. , Griffin Peter B.
Published: December 2023

Master fundamental technologies for modern semiconductor integrated circuits with this definitive textbook. It includes an early introduction of a state-of-the-art CMOS process flow, exposes students to big-picture thinking from the outset, and encourages a practical integration mindset. Extensive use of process and TCAD simulation, using industry tools such as Silvaco Athena and Victory Process, provides students with deeper insight into physical principles, and prepares them for applying these tools in a real-world setting. Accessible framing assumes only a basic background in chemistry, physics and mathematics, providing a gentle introduction for students from a wide range of backgrounds; and over 450 figures (many in color), and more than 280 end-of-chapter problems, will support and cement student understanding. Accompanied by lecture slides and solutions for instructors, this is the ideal introduction to semiconductor technology for senior undergraduate and graduate students in electrical engineering, materials science and physics, and for semiconductor engineering professionals seeking an authoritative introductory reference.
Combining Paleohydrology and Least-Cost Analyses to Assess the Vulnerabilities of Ancestral Pueblo Communities to Water Insecurity in the Jemez Mountains, New Mexico
Authors: Aiuvalasit Michael J. , Jorgeson Ian A.
Published: December 2023

We developed a new approach to identify vulnerabilities to water insecurity across entire archaeological culture areas by combining a paleohydrological model of the sensitivites of hydrological systems to droughts with least-cost analyses of the costs to acquire domestic water. Using a custom Python script integrated into ArcGIS Pro software, we calculated the pairwise one-way cost in time for walking between 225 water sources and 5,446 Ancestral Pueblo cultural sites across the Jemez and Pajarito Plateaus of the Jemez Mountains, New Mexico. This allowed us to identify whether periodic hydrological droughts occurring between AD 1100 and 1700 increased water acquisition costs across these regions. We found that hydrological droughts increased travel times in both regions to durations exceeding modern standards for water insecurity. Beginning in the fourteenth century, greater underlying hydrogeological sensitivities to droughts and the decline of a dual-residence pattern caused by population losses made the remaining aggregated communities of the Pajarito Plateau much more vulnerable to water insecurity than those on the Jemez Plateau. This would have upended long-standing relationships between communities and water on the Pajarito Plateau during a time when socioeconomic integration across the northern Rio Grande Valley pulled people toward valley bottoms.
Annual estimates of global and national CO2 emissions from fossil fuels: Tracking revisions to the United Nations energy statistics database input energy data
Authors: Briggs Connor , Gilfillan Dennis , Hefner Matthew , Marland Eric , Marland Gregg
Published: December 2023

Estimates of global and national emissions of carbon dioxide (CO2) are important for scientific understanding and public policy on global climate change. Estimates published annually often see revisions of estimates from previous years. Revisions of data on CO2 emissions reflect revisions of the energy data from which CO2 emissions are estimated. Learning is taking place as missing values are compiled, estimated values are revised, and data management systems are updated. Revisions are a frequent feature of the database. Revisions are widespread among countries, commodities, and transactions. We have examined 11 annual reports of the United Nations Energy Statistics Database (those published from 2010 to 2020) to see in the detailed statistics what values are being changed and what are the magnitudes and patterns of change. They are most common in recent years, among developed countries, and among data on liquid fuels. Revisions are generally small and there are no indications of systematic manipulation or bias. Revisions of specific numbers are believed to represent improvements in accuracy but lack of revisions does not point toward accuracy. This examination of revisions does not permit by itself a quantitative estimate of the data uncertainty but it does suggest that the estimates of global and national totals of CO2 emissions are generally consistent and that both absolute values and trends are reliable over time and sufficiently accurate for scientific understanding and public policy.
Complex structure of turbulence across the ASDEX Upgrade pedestal
Authors: Leppin L.A. , Görler T. , Cavedon M. , Dunne M.G. , Wolfrum E. , Jenko F. ,   the ASDEX Upgrade Team
Published: December 2023

The theoretical investigation of relevant turbulent transport mechanisms in H-mode pedestals is a great scientific and numerical challenge. In this study, we address this challenge by global, nonlinear gyrokinetic simulations of a full pedestal up to the separatrix, supported by a detailed characterisation of gyrokinetic instabilities from just inside the pedestal top to the pedestal centre and foot. We present ASDEX Upgrade pedestal simulations using an upgraded version of the gyrokinetic, Eulerian, delta-f code GENE (genecode.org) that enables stable global simulations at experimental plasma

$\beta$

values. The turbulent transport is found to exhibit a multi-channel, multi-scale character throughout the pedestal with the dominant contribution transitioning from ion-scale trapped electron modes/micro-tearing modes at the pedestal top to electron-scale electron temperature gradient modes in the steep gradient region. Consequently, the turbulent electron heat flux changes from ion to electron scales and the ion heat flux reduces to almost neoclassic values in the pedestal centre.

$E\times B$

shear is found to strongly reduce heat flux levels in all channels (electron, ion, electrostatic, electromagnetic) and the interplay of magnetic shear and pressure gradient is found to locally stabilise ion-scale instabilities.
Generalized cross-helicity in non-ideal magnetohydrodynamics
Authors: Sharma Prachi , Yahalom Asher
Published: December 2023

The objective of the present paper is to investigate the constancy of the topological invariant, denoted the non-barotropic generalized cross-helicity in the case of non-ideal magnetohydrodynamics (MHD). Existing work considers only ideal barotropic MHD and ideal non-barotropic MHD. Here, we consider dissipative processes in the form of thermal conduction, finite electrical conductivity and viscosity and the effect of these processes on the cross-helicity conservation. An analytical approach has been adopted to obtain the mathematical expressions for the time derivative of the cross-helicity. Obtained results show that the generalized cross-helicity is not conserved in the non-ideal MHD limit and indicate which processes affect the helicity and which do not. Furthermore, we indicate the configurations in which this topological constant is conserved despite the dissipative processes. Some examples and applications are also given.
Implementing weight management during and after pregnancy to reduce diabetes and CVD risk in maternal and child populations
Authors: O'Reilly Sharleen L. , McAuliffe Fionnuala M. , Geraghty Aisling A. , Burden Christy , Davies Anna
Published: December 2023

Maintaining a healthy weight during pregnancy is critical for both women's and children's health. Excessive gestational weight gain (GWG) can lead to complications such as gestational diabetes, hypertension and caesarean delivery. Insufficient GWG can cause fetal growth restriction and increase infant mortality risk. Additionally, postpartum weight retention raises risk of obesity, type 2 diabetes and other chronic diseases for both mother and child. This review seeks to identify current obstacles in weight management research during and after pregnancy and explore evidence-based strategies to overcome them. Pregnancy offers a window of opportunity for health behaviour changes as women are more receptive to education and have regular contact with health services. Staying within Institute of Medicine's recommended GWG ranges is associated with better maternal and fetal outcomes. Systematic review evidence supports structured diet and physical activity pregnancy interventions, leading to reduced GWG and fewer complications. Health economic evaluation indicates significant returns from implementation, surpassing investment costs due to decreased perinatal morbidity and adverse events. However, the most effective way to implement interventions within routine antenatal care remains unclear. Challenges increase in the postpartum period due to competing demands on women physically, mentally and socially, hindering intervention reach and retention. Flexible, technology-supported interventions are needed, requiring frameworks such as penetration-implementation-participation-effectiveness and template-for-intervention-description-and-replication for successful implementation. Greater research efforts are necessary to inform practice and investigate fidelity aspects through pragmatic implementation trials during the pregnancy and postpartum periods. Understanding the best ways to deliver interventions will empower women to maintain a healthy weight during their reproductive years.
A steerable robot walker driven by two actuators
Authors: Li Jiaji , Liu Chenhao , Nguyen Ken , McCarthy J. Michael
Published: December 2023

This article describes a robot walker based on a new single degree-of-freedom six-bar leg mechanism that provides rectilinear, non-rotating, movement of the foot. The walker is statically stable and requires only two actuators, one for each side, to provide effective walking movement on a flat surface. We use Curvature Theory to design a four-bar linkage with a flat-sided coupler curve and then adds a translating link so that walker foot follows this coupler curve in rectilinear movement. A prototype walker was constructed that weighs 1.6 kg, is 180 mm tall, and travels at 162 mm/s. This is an innovative legged robot that has a simple reliable design.
IF YOU’RE AN EGALITARIAN … SO WHAT?
Authors: Pleasants Nigel
Published: December 2023

G. A. Cohen is justly acclaimed for his penetrating and searching critique of the commanding Rawlsian liberal paradigm in contemporary political philosophy. He is also well known for his fervent advocacy of a radical view of economic equality, namely, that “justice requires (virtually) unqualified equality itself.” This essay focuses on two issues at the heart of Cohen’s critique, namely, his argument that economic equality is a moral as well as a political responsibility, and his interrogatory question: “If you’re an egalitarian, how come you’re so rich?” I take up critics’ objection that Cohen’s arguments for what economic egalitarianism requires are overly morally demanding. I also present a puzzle about the critical reception of Cohen’s work: Given the amount and quality of engagement with his arguments on what egalitarianism would look like in a future just society, how come there’s been such scant attention to his reflections on the predicament of the “rich egalitarian” in current-day unjust society? The essay culminates in a tentative answer to this question.
EQUALITY’S DEMANDS ARE REASONABLE
Authors: Arneson Richard
Published: December 2023

There are various egalitarian moral doctrines. They differ in the requirements they impose on institutions and social practices and on individual conduct. This essay sketches two versions of egalitarian social justice and claims that the requirements they impose should strike us as reasonable, all things considered. One is welfarist egalitarianism, a cousin of classical utilitarianism. This version requires bringing about good quality lives for people and fair (equal) distribution of this good across persons. A notable feature of welfarist egalitarianism is that it accommodates the seemingly antiegalitarian claim that it does not matter in itself how one person’s condition compares to that of another, so a fortiori it does not matter in itself whether or not one person’s condition compares to that of others in the one particular way of being equal. The other version is relational or freedom-oriented egalitarianism, which holds that we should above all ensure that people are free to live as they choose and relate as equals, without social hierarchy. In the latter half of the twentieth century, John Rawls developed a powerful articulation of relational egalitarian justice. This essay sketches the two rival egalitarianisms with a view to showing their respective moral attractiveness and to suggesting that the welfarist version has greater moral attraction.
THE SOCIALISM OF THE RICH: EGALITARIANISM, WEALTH, AND PRIVILEGE IN ACADEMIC PHILOSOPHY
Authors: Meadowcroft John
Published: December 2023

This essay explains the prevalence of egalitarian beliefs among academic philosophers, individuals who enjoy significant wealth and privilege. I argue that their egalitarianism does not present a “paradox of conviction,” as G. A. Cohen contends, but follows logically from the institutional structure of academic philosophy. This structure creates a “veil of insignificance” wherein philosophy is a moral performance that incentivizes the adoption of egalitarian beliefs. Philosophers also view the world from behind what is termed a “veil of privilege” that incentivizes a public commitment to egalitarianism as a means of distancing themselves from the role of privilege in their life and encourages the hubristic assumption that the practical problems of socialism can be easily overcome with effort or ingenuity. Identity-protective motivated reasoning means that evidence conflicting with egalitarian beliefs is avoided, ignored, or dismissed. These dynamics are reinforced by established actors who gatekeep the profession.
TWO DEMANDS UPON LUCK EGALITARIANS
Authors: Mack Eric
Published: December 2023

I offer two objections to luck egalitarianism. The no-adequate-account objection takes note of the egalitarian insistence that the disvalue of inequality is only one of a plurality of values or disvalues that needs to be considered in arriving at a judgment about the ranking of alternative distributions of welfare. This turn to pluralism places a reasonable demand upon luck egalitarianism to provide an account of how the different sorts of values or disvalues that are supposed to attach to available distributions of welfare are to be aggregated or weighed against one another in that ranking procedure. I contend that the prospects for developing such an account are dim and that some salient responses to this objection misfire. The churlishness-envy objection against luck egalitarianism is that this doctrine countenances envy directed toward the faultless good fortune of others. This objection places a reasonable demand on luck egalitarians to formulate a version of their doctrine that does not underwrite envious responses toward those who gain through brute good luck. I contend that the most auspicious path toward satisfying the demand not to underwrite churlish envy advances a luck egalitarianism that asymmetrically affirms the badness of arbitrary disadvantage rather than the badness of both arbitrary disadvantage and arbitrary advantage. Since this is the strategy pursued in Shlomi Segall’s Why Inequality Matters, I offer critiques of Segall’s initial and revised versions of asymmetrical egalitarianism in support of my conclusion that luck egalitarianism seems unable to rebut or sidestep the churlishness-envy objection. I conclude that luck egalitarianism seems unable to satisfy either of the two reasonable demands upon it that I raise.
Precise large deviations for a multidimensional risk model with regression dependence structure
Authors: Liu Yang , Fu Ke-Ang , Chen Zhenlong
Published: December 2023

In this paper, we consider a nonstandard multidimensional risk model, in which the claim sizes $\{\vec{X}_k, k\ge 1\}$ form an independent and identically distributed random vector sequence with dependent components. By assuming that there exists the regression dependence structure between inter-arrival time and the claim-size vectors, we extend the regression dependence to a more practical multidimensional risk model. For the univariate marginal distributions of claim vectors with consistently varying tails, we obtain the precise large deviation formulas for the multidimensional risk model with the regression size-dependent structure.
Crimes of Dispassion: Autonomous Weapons and the Moral Challenge of Systematic Killing
Authors: Renic Neil , Schwarz Elke
Published: December 2023

Systematic killing has long been associated with some of the darkest episodes in human history. Increasingly, however, it is framed as a desirable outcome in war, particularly in the context of military AI and lethal autonomy. Autonomous weapons systems, defenders argue, will surpass humans not only militarily but also morally, enabling a more precise and dispassionate mode of violence, free of the emotion and uncertainty that too often weaken compliance with the rules and standards of war. We contest this framing. Drawing on the history of systematic killing, we argue that lethal autonomous weapons systems reproduce, and in some cases intensify, the moral challenges of the past. Autonomous violence incentivizes a moral devaluation of those targeted and erodes the moral agency of those who kill. Both outcomes imperil essential restraints on the use of military force.
A point-free perspective on lax extensions and predicate liftings
Authors: Goncharov Sergey , Hofmann Dirk , Nora Pedro , Schröder Lutz , Wild Paul
Published: December 2023

Lax extensions of set functors play a key role in various areas, including topology, concurrent systems, and modal logic, while predicate liftings provide a generic semantics of modal operators. We take a fresh look at the connection between lax extensions and predicate liftings from the point of view of quantale-enriched relations. Using this perspective, we show in particular that various fundamental concepts and results arise naturally and their proofs become very elementary. Ultimately, we prove that every lax extension is induced by a class of predicate liftings; we discuss several implications of this result.
Cultural adaptations of group CBT for depressed clients from diverse backgrounds: A systematic review
Authors: Kunorubwe Taf
Published: December 2023

Cognitive behavioural therapy (CBT) is considered a frontline treatment for major depressive disorder (MDD) and is recommended as a preferred option in many Western healthcare settings. CBT has proven effective for clients from the majority population in Western countries, but to meet the needs of diverse clients it may require adaptation. The benefits of culturally adapted group CBT (CA-GCBT) for clients from diverse backgrounds remains uncertain. The objective of this review is to systematically identify, evaluate, and integrate the existing empirical literature on CA-GCBT for depressed clients from diverse backgrounds. A comprehensive search was conducted in April 2021 across various databases, including, MEDLINE, PsycINFO, Cinahl, Academic Search, and APA PsycArticle. Quantitative studies meeting the inclusion criteria resulted in a total of ten articles being included in the review. Results from the analysis revealed a statistically significant reduction in depressive symptoms following CA–GCBT in nine out of the ten studies, with one study providing descriptive results. Additionally, improvements were observed in dysfunctional beliefs, functioning, and quality of life ratings. These findings suggest promising outcomes for racially minoritised clients in Western countries and racial majority clients in non-Western countries. Adaptations in CA-GCBT primarily focus on modifying the group delivery, therapy content, staffing, processes, and client-specific factors. Overall, CA-GCBT shows promise as a treatment for depressed clients from diverse backgrounds. However, further evaluation is necessary to establish its efficacy in clinical practice more robustly, to identify which adaptations are most effective for specific populations and to explore the experiences of implementing or attending such group interventions.

Key learning aims

(1)

To explore the benefits of CA-GCBT for depressed clients from diverse backgrounds. Although CBT is a frontline treatment for MDD and often delivered in group format, it remains unclear whether CA-GCBT is beneficial.

(2)

To summarise findings about the benefits of CA-GCBT for racially minoritised clients in Western countries and racial majority clients in non-Western countries.

(3)

To outline the modifications made to common CBT group approaches to enhance cultural responsiveness for clients from diverse backgrounds.

(4)

To provide support to therapists, healthcare services, and broader healthcare structures seeking to implement evidence-based knowledge when adapting group CBT for diverse cultural groups. This enables them to modify existing group CBT protocols or consider specific CA-GCBT interventions.
Aortic aneurysms: current pathogenesis and therapeutic targets
Authors: Cho Min Ji , Lee Mi-Ran , Park Jong-Gil
Published: December 2023

Aortic aneurysm is a chronic disease characterized by localized expansion of the aorta, including the ascending aorta, arch, descending aorta, and abdominal aorta. Although aortic aneurysms are generally asymptomatic, they can threaten human health by sudden death due to aortic rupture. Aortic aneurysms are estimated to lead to 150,000 ~ 200,000 deaths per year worldwide. Currently, there are no effective drugs to prevent the growth or rupture of aortic aneurysms; surgical repair or endovascular repair is the only option for treating this condition. The pathogenic mechanisms and therapeutic targets for aortic aneurysms have been examined over the past decade; however, there are unknown pathogenic mechanisms involved in cellular heterogeneity and plasticity, the complexity of the transforming growth factor-β signaling pathway, inflammation, cell death, intramural neovascularization, and intercellular communication. This review summarizes the latest research findings and current pathogenic mechanisms of aortic aneurysms, which may enhance our understanding of aortic aneurysms.
Metallothionein 3 promotes osteoclast differentiation and survival by regulating the intracellular Zn2+ concentration and NRF2 pathway
Authors: Arisumi Shinkichi , Fujiwara Toshifumi , Yasumoto Keitaro , Tsutsui Tomoko , Saiwai Hirokazu , Kobayakawa Kazu , Okada Seiji , Zhao Haibo , Nakashima Yasuharu
Published: December 2023

In osteoclastogenesis, the metabolism of metal ions plays an essential role in controlling reactive oxygen species (ROS) production, mitochondrial biogenesis, and survival, and differentiation. However, the mechanism regulating metal ions during osteoclast differentiation remains unclear. The metal-binding protein metallothionein (MT) detoxifies heavy metals, maintains metal ion homeostasis, especially zinc, and manages cellular redox levels. We carried out tests using murine osteoclast precursors to examine the function of MT in osteoclastogenesis and evaluated their potential as targets for future osteoporosis treatments. MT genes were significantly upregulated upon differentiation from osteoclast precursors to mature osteoclasts in response to receptor activators of nuclear factor-κB (NF-κB) ligand (RANKL) stimulation, and MT3 expression was particularly pronounced in mature osteoclasts among MT genes. The knockdown of MT3 in osteoclast precursors demonstrated a remarkable inhibition of differentiation into mature osteoclasts. In preosteoclasts, MT3 knockdown suppressed the activity of mitogen-activated protein kinase (MAPK) and NF-κB signaling pathways upon RANKL stimulation, leading to affect cell survival through elevated cleaved Caspase 3 and poly (ADP-ribose) polymerase (PARP) levels. Additionally, ROS levels were decreased, and nuclear factor erythroid 2-related factor 2 (NRF2) (a suppressor of ROS) and the downstream antioxidant proteins, such as catalase (CAT) and heme oxygenase 1 (HO-1), were more highly expressed in the MT3 preosteoclast knockdowns. mitochondrial ROS, which is involved in mitochondrial biogenesis and the production of reactive oxygen species, were similarly decreased because cAMP response element-binding (CREB) and peroxisome proliferator-activated receptor γ coactivator 1β (PGC-1β) were less activated due to MT3 depletion. Thus, by modulating ROS through the NRF2 pathway, MT3 plays a crucial role in regulating osteoclast differentiation and survival, acting as a metabolic modulator of intracellular zinc ions.
Decoding metabolic signatures in Alzheimer’s disease: a mitochondrial perspective
Authors: Bano Daniele , Ehninger Dan , Bagetta Giacinto
Published: December 2023

Alzheimer’s disease (AD) is one of the most prevalent age-related neurodegenerative diseases and accounts for the majority of dementia cases worldwide. Tremendous ongoing efforts of basic and clinical research have expanded our knowledge on AD and its complex multifactorial pathogenesis. For sporadic AD, it is widely assumed that silent and early symptomatic stages initiate decades before the irreversible decline in cognitive abilities that ultimately lead to debilitating conditions. In addition to amyloid plaques and tau-containing neurofibrillary tangles as the most prominent hallmarks of AD lesions within the affected brain areas, we now possess a broader collection of pathological signatures that are associated with AD development and progression. In this regard, there is a substantial body of evidence suggesting that hypometabolism occurs in the brains of individuals at the prodromal stage before dementia is diagnosed, which may reflect an early role of metabolic dysfunction in AD. This perspective surveys the vast literature and critically assesses the current evidence demonstrating a mitochondrial contribution to AD. Additionally, we discuss our interpretations of the reported mitochondrial signatures and consider how altered mitochondrial bioenergetics may be an additional risk factor for AD pathogenesis.
Safety and tolerability of intravitreal umedaptanib pegol (anti-FGF2) for neovascular age-related macular degeneration (nAMD): a phase 1, open-label study
Authors: Pereira Daniel S. , Akita Kazumasa , Bhisitkul Robert B. , Nishihata Toshiaki , Ali Yusuf , Nakamura Emiko , Nakamura Yoshikazu
Published: December 2023

Objective

To evaluate the efficacy and safety of a single-dose intravitreal umedaptanib pegol (anti-FGF2, investigational new drug) for the treatment of neovascular age-related macular degeneration (nAMD).

Methods

Nine participants who had a diagnosis of refractory nAMD were enrolled and received a single intravitreal injection of umedaptanib pegol at increasing doses of 0.2, 1.0 or 2.0 mg in the study eye.

Results

All three doses of umedaptanib pegol evaluated in the study were safe and well tolerated. No severe adverse event (AE) was observed in the study. There was an improvement in retinal fluid measured by central subfield thickness (CST) in most subjects. Remarkably, all three subjects who received 2.0 mg/eye showed improvement of more than 150 μm.

Conclusions

Intravitreal umedaptanib pegol was safe, well tolerated, and demonstrated an indication of bioactivity in participants that have persistent subretinal fluid refractory to the treatment with anti-VEGFs.
A simple method for developing lysine targeted covalent protein reagents
Authors: Gabizon Ronen , Tivon Barr , Reddi Rambabu N. , van den Oetelaar Maxime C. M. , Amartely Hadar , Cossar Peter J. , Ottmann Christian , London Nir
Published: December 2023

Peptide-based covalent probes can target shallow protein surfaces not typically addressable using small molecules, yet there is a need for versatile approaches to convert native peptide sequences into covalent binders that can target a broad range of residues. Here we report protein-based thio-methacrylate esters—electrophiles that can be installed easily on unprotected peptides and proteins via cysteine side chains, and react efficiently and selectively with cysteine and lysine side chains on the target. Methacrylate phosphopeptides derived from 14-3-3-binding proteins irreversibly label 14-3-3σ via either lysine or cysteine residues, depending on the position of the electrophile. Methacrylate peptides targeting a conserved lysine residue exhibit pan-isoform binding of 14-3-3 proteins both in lysates and in extracellular media. Finally, we apply this approach to develop protein-based covalent binders. A methacrylate-modified variant of the colicin E9 immunity protein irreversibly binds to the E9 DNAse, resulting in significantly higher thermal stability relative to the non-covalent complex. Our approach offers a simple and versatile route to convert peptides and proteins into potent covalent binders.
Soybean reduced internode 1 determines internode length and improves grain yield at dense planting
Authors: Li Shichen , Sun Zhihui , Sang Qing , Qin Chao , Kong Lingping , Huang Xin , Liu Huan , Su Tong , Li Haiyang , He Milan , Fang Chao , Wang Lingshuang , Liu Shuangrong , Liu Bin , Liu Baohui , Fu Xiangdong , Kong Fanjiang , Lu Sijia
Published: December 2023

Major cereal crops have benefitted from Green Revolution traits such as shorter and more compact plants that permit high-density planting, but soybean has remained relatively overlooked. To balance ideal soybean yield with plant height under dense planting, shortening of internodes without reducing the number of nodes and pods is desired. Here, we characterized a short-internode soybean mutant, reduced internode 1 (rin1). Partial loss of SUPPRESSOR OF PHYA 105 3a (SPA3a) underlies rin1. RIN1 physically interacts with two homologs of ELONGATED HYPOCOTYL 5 (HY5), STF1 and STF2, to promote their degradation. RIN1 regulates gibberellin metabolism to control internode development through a STF1/STF2–GA2ox7 regulatory module. In field trials, rin1 significantly enhances grain yield under high-density planting conditions comparing to its wild type of elite cultivar. rin1 mutants therefore could serve as valuable resources for improving grain yield under high-density cultivation and in soybean–maize intercropping systems.
Selective ring expansion and C−H functionalization of azulenes
Authors: Park Sangjune , Kim Cheol-Eui , Jeong Jinhoon , Ryu Ho , Maeng Chanyoung , Kim Dongwook , Baik Mu-Hyun , Lee Phil Ho
Published: December 2023

We report a transition metal-catalyzed ring expansion of azulene that can be contrasted with C–H functionalization. This study represents the first example of the successful ring expansion of azulene using Cu(hfacac)2 (hfacac: hexafluoroacetylacetonate) with a diazo reagent. This result is notable for extending the Buchner reaction, previously limited to benzenoid aromatics, to nonbenzenoid compounds. The chemoselectivity of the reaction can be directed towards C–H functionalization by substituting the Cu catalyst with AgOTf. This approach does not require the addition of phosphine, NHC, or related ligands, and prefunctionalization of azulenes is unnecessary. Furthermore, the method exhibits excellent functional group tolerance, allowing for the synthesis of a wide range of 6,7-bicyclic compounds and C–H functionalized azulenes. We also present a theoretical study that explains the experimental observations, explaining why copper afford the ring expansion product while silver forms the C–H alkylation product.
SMARCB1 loss activates patient-specific distal oncogenic enhancers in malignant rhabdoid tumors
Authors: Liu Ning Qing , Paassen Irene , Custers Lars , Zeller Peter , Teunissen Hans , Ayyildiz Dilara , He Jiayou , Buhl Juliane Laura , Hoving Eelco Wieger , van Oudenaarden Alexander , de Wit Elzo , Drost Jarno
Published: December 2023

Malignant rhabdoid tumor (MRT) is a highly malignant and often lethal childhood cancer. MRTs are genetically defined by bi-allelic inactivating mutations in SMARCB1, a member of the BRG1/BRM-associated factors (BAF) chromatin remodeling complex. Mutations in BAF complex members are common in human cancer, yet their contribution to tumorigenesis remains in many cases poorly understood. Here, we study derailed regulatory landscapes as a consequence of SMARCB1 loss in the context of MRT. Our multi-omics approach on patient-derived MRT organoids reveals a dramatic reshaping of the regulatory landscape upon SMARCB1 reconstitution. Chromosome conformation capture experiments subsequently reveal patient-specific looping of distal enhancer regions with the promoter of the MYC oncogene. This intertumoral heterogeneity in MYC enhancer utilization is also present in patient MRT tissues as shown by combined single-cell RNA-seq and ATAC-seq. We show that loss of SMARCB1 activates patient-specific epigenetic reprogramming underlying MRT tumorigenesis.
Higher Antarctic ice sheet accumulation and surface melt rates revealed at 2 km resolution
Authors: Noël Brice , van Wessem J. Melchior , Wouters Bert , Trusel Luke , Lhermitte Stef , van den Broeke Michiel R.
Published: December 2023

Antarctic ice sheet (AIS) mass loss is predominantly driven by increased solid ice discharge, but its variability is governed by surface processes. Snowfall fluctuations control the surface mass balance (SMB) of the grounded AIS, while meltwater ponding can trigger ice shelf collapse potentially accelerating discharge. Surface processes are essential to quantify AIS mass change, but remain poorly represented in climate models typically running at 25-100 km resolution. Here we present SMB and surface melt products statistically downscaled to 2 km resolution for the contemporary climate (1979-2021) and low, moderate and high-end warming scenarios until 2100. We show that statistical downscaling modestly enhances contemporary SMB (3%), which is sufficient to reconcile modelled and satellite mass change. Furthermore, melt strongly increases (46%), notably near the grounding line, in better agreement with in-situ and satellite records. The melt increase persists by 2100 in all warming scenarios, revealing higher surface melt rates than previously estimated.
Bolometric detection of Josephson inductance in a highly resistive environment
Authors: Subero Diego , Maillet Olivier , Golubev Dmitry S. , Thomas George , Peltonen Joonas T. , Karimi Bayan , Marín-Suárez Marco , Yeyati Alfredo Levy , Sánchez Rafael , Park Sunghun , Pekola Jukka P.
Published: December 2023

The Josephson junction is a building block of quantum circuits. Its behavior, well understood when treated as an isolated entity, is strongly affected by coupling to an electromagnetic environment. In 1983, Schmid predicted that a Josephson junction shunted by a resistance exceeding the resistance quantum RQ = h/4e2 ≈ 6.45 kΩ for Cooper pairs would become insulating since the phase fluctuations would destroy the coherent Josephson coupling. However, recent microwave measurements have questioned this interpretation. Here, we insert a small Josephson junction in a Johnson-Nyquist-type setup where it is driven by weak current noise arising from thermal fluctuations. Our heat probe minimally perturbs the junction’s equilibrium, shedding light on features not visible in charge transport. We find that the Josephson critical current completely vanishes in DC charge transport measurement, and the junction demonstrates Coulomb blockade in agreement with the theory. Surprisingly, thermal transport measurements show that the Josephson junction acts as an inductor at high frequencies, unambiguously demonstrating that a supercurrent survives despite the Coulomb blockade observed in DC measurements.
Pyroptosis inhibiting nanobodies block Gasdermin D pore formation
Authors: Kopp Anja , Hagelueken Gregor , Jamitzky Isabell , Moecking Jonas , Schiffelers Lisa D. J. , Schmidt Florian I. , Geyer Matthias
Published: December 2023

Human Gasdermin D (GSDMD) is a key mediator of pyroptosis, a pro-inflammatory form of cell death occurring downstream of inflammasome activation as part of the innate immune defence. Upon cleavage by inflammatory caspases in the cytosol, the N-terminal domain of GSDMD forms pores in the plasma membrane resulting in cytokine release and eventually cell death. Targeting GSDMD is an attractive way to dampen inflammation. In this study, six GSDMD targeting nanobodies are characterized in terms of their binding affinity, stability, and effect on GSDMD pore formation. Three of the nanobodies inhibit GSDMD pore formation in a liposome leakage assay, although caspase cleavage was not perturbed. We determine the crystal structure of human GSDMD in complex with two nanobodies at 1.9 Å resolution, providing detailed insights into the GSDMD–nanobody interactions and epitope binding. The pore formation is sterically blocked by one of the nanobodies that binds to the oligomerization interface of the N-terminal domain in the multi-subunit pore assembly. Our biochemical and structural findings provide tools for studying inflammasome biology and build a framework for the design of GSDMD targeting drugs.
Enabling direct-growth route for highly efficient ethanol upgrading to long-chain alcohols in aqueous phase
Authors: Gu Juwen , Gong Wanbing , Zhang Qian , Long Ran , Ma Jun , Wang Xinyu , Li Jiawei , Li Jiayi , Fan Yujian , Zheng Xinqi , Qiu Songbai , Wang Tiejun , Xiong Yujie
Published: December 2023

Upgrading ethanol to long-chain alcohols (LAS, C6+OH) offers an attractive and sustainable approach to carbon neutrality. Yet it remains a grand challenge to achieve efficient carbon chain propagation, particularly with noble metal-free catalysts in aqueous phase, toward LAS production. Here we report an unconventional but effective strategy for designing highly efficient catalysts for ethanol upgrading to LAS, in which Ni catalytic sites are controllably exposed on surface through sulfur modification. The optimal catalyst exhibits the performance well exceeding previous reports, achieving ultrahigh LAS selectivity (15.2% C6OH and 59.0% C8+OH) at nearly complete ethanol conversion (99.1%). Our in situ characterizations, together with theoretical simulation, reveal that the selectively exposed Ni sites which offer strong adsorption for aldehydes but are inert for side reactions can effectively stabilize and enrich aldehyde intermediates, dramatically improving direct-growth probability toward LAS production. This work opens a new paradigm for designing high-performance non-noble metal catalysts for upgrading aqueous EtOH to LAS.
Gate-tunable anomalous Hall effect in Bernal tetralayer graphene
Authors: Chen Hao , Arora Arpit , Song Justin C. W. , Loh Kian Ping
Published: December 2023

Large spin-orbit coupling is often thought to be critical in realizing magnetic order-locked charge transport such as the anomalous Hall effect (AHE). Recently, artificial stacks of two-dimensional materials, e.g., magic-angle twisted bilayer graphene on hexagonal boron-nitride heterostructures and dual-gated rhombohedral trilayer graphene, have become platforms for realizing AHE without spin-orbit coupling. However, these stacking arrangements are not energetically favorable, impeding experiments and further device engineering. Here we report an anomalous Hall effect in Bernal-stacked tetralayer graphene devices (BTG), the most stable configuration of four-layer graphene. BTG AHE is switched on by a displacement field and is most pronounced at low carrier densities. The onset of AHE occurs in tandem with a full metal to a broken isospin transition indicating an orbital origin of the itinerant ferromagnetism. At lowest densities, BTG exhibits an unconventional hysteresis with step-like anomalous Hall plateaus. Persisting to several tens of kelvin, AHE in BTG demonstrates the ubiquity and robustness of magnetic order in readily available and stable multilayer Bernal graphene stacks—a new venue for intrinsic non-reciprocal responses.
A multi-omics dataset for the analysis of frontotemporal dementia genetic subtypes
Authors: Menden Kevin , Francescatto Margherita , Nyima Tenzin , Blauwendraat Cornelis , Dhingra Ashutosh , Castillo-Lizardo Melissa , Fernandes Noémia , Kaurani Lalit , Kronenberg-Versteeg Deborah , Atasu Burcu , Sadikoglou Eldem , Borroni Barbara , Rodriguez-Nieto Salvador , Simon-Sanchez Javier , Fischer Andre , Craig David Wesley , Neumann Manuela , Bonn Stefan , Rizzu Patrizia , Heutink Peter
Published: December 2023

Understanding the molecular mechanisms underlying frontotemporal dementia (FTD) is essential for the development of successful therapies. Systematic studies on human post-mortem brain tissue of patients with genetic subtypes of FTD are currently lacking. The Risk and Modyfing Factors of Frontotemporal Dementia (RiMod-FTD) consortium therefore has generated a multi-omics dataset for genetic subtypes of FTD to identify common and distinct molecular mechanisms disturbed in disease. Here, we present multi-omics datasets generated from the frontal lobe of post-mortem human brain tissue from patients with mutations in MAPT, GRN and C9orf72 and healthy controls. This data resource consists of four datasets generated with different technologies to capture the transcriptome by RNA-seq, small RNA-seq, CAGE-seq, and methylation profiling. We show concrete examples on how to use the resulting data and confirm current knowledge about FTD and identify new processes for further investigation. This extensive multi-omics dataset holds great value to reveal new research avenues for this devastating disease.