bluuebunny/crossref_metadata_2025 huggingface dataset:
The influence of ship stability in waves on naval vessel operational profiles
Authors: Petacco Nicola , Gualeni Paola
Published: August 2023

Ensuring a widely safe operational profile of naval vessels is one of the leading aspects of the design process. With reference to weather conditions, this kind of vessels often cannot avoid heavy situations to guarantee the continuity and the effectiveness of service. For this reason, an applied research investigation aimed to define guidance in operations is deemed as a worthwhile activity. In particular, the performance in waves under the perspective of intact stability has been considered in this work. The IMO second-generation intact stability criteria have been identified as a suitable tool for these investigations: as a result, there is evidence that operational guidance can be developed for a set of representative naval vessels, following the relevant guidelines. Outcomes have been represented by means of comprehensive polar diagrams addressing the intact stability failures modes. Bearing in mind the actual operational profile, results have been analysed and discussed considering how ship and operating decisions in a seaway condition may affect the performance in terms of ship stability.
Sealants and Other Management Strategies for PFAS-Contaminated Concrete and Asphalt
Authors: Douglas Grant B. , Vanderzalm Joanne L. , Kirby Jason K. , Williams Mike , Bastow Trevor P. , Bauer Mark , Bowles Karl C. , Skuse Darren , Kookana Rai S. , Davis Greg B.
Published: August 2023

Purpose of Review

The unique properties of per- and polyfluoroalkyl substances (PFASs) have seen their widespread adoption, subsequent accumulation in the environment and concern regarding potential environmental effects. Globally, airfields and paved firefighting training surfaces are hotspots for accumulation of PFAS due to extensive use of aqueous film-forming foams (AFFF). Evidence from contaminated concrete and asphalt airfield and training pavements suggests they may serve as an enduring PFAS source. This review investigates sealants as remediation technologies to minimise PFAS mobilisation from pavements drawing on current knowledge of remediation options for soils, sediments, surface and groundwaters.

Recent Findings

The review did not identify any published sealant information specific to PFAS. Our analysis showed that surface and penetrative sealants may offer an immediate solution via encapsulation of PFAS residues in concrete and asphalt. The most promising surface sealants likely to minimise water ingress and PFAS leaching are selected polymers and (modified) bitumen, owing to the relatively low cost, good adhesion, trafficability and chemical, heat and UV resistance. Potential also exists to enhance PFAS immobilisation using additives to absorb or otherwise chemically bind PFAS. Prospective penetrative sealants include silicates or siloxanes that bind to internal mineral surfaces and/or fill pores to restrict PFAS mobility. It is likely that combinations of surface and penetrative sealants will be required to meet functional, operational and management requirements with respect to new or existing contamination in concrete or asphalt pavements.

At present, few if any sealants have been evaluated for their ability to bind or mitigate PFAS mobility. This review serves as a starting point for further studies to evaluate their short or long-term effectiveness in immobilisation of PFAS residues in in situ or ex situ concrete and asphalt. Several knowledge gaps along with suggestions for future research have been made.
Evaluation of the Critical Times for the Crack Susceptibility Coefficient Calculation
Authors: Matsushita Taishi , Zamani Mohammadreza , Kump Andrej , Jarfors Anders E. W.
Published: August 2023

The objective of the present study is to evaluate the hot tearing tendency based on the Clyne and Davies model by evaluating the critical times which can be obtained using a newly developed method. A method to determine the critical times required to calculate the crack susceptibility was presented based on the measurement results with Al–Si alloys, and the method to calculate the crack susceptibility coefficient was presented. In the newly developed method named “Signal intensity method,” signals were generated by tapping the edge of a waveguide which is immersed in molten and solidifying sample and the critical solid fractions were obtained from the signal intensity change. The conventional thermal analysis was also performed simultaneously and the corresponding critical points were identified. The method shown in the present study will enable the determination of the crack susceptibility coefficient with higher accuracy.
Microencapsulated phase change material through cellulose nanofibrils stabilized Pickering emulsion templating
Authors: Liu Wei , Lin Qingyi , Chen Siyu , Yang Hongbin , Liu Kun , Pang Bo , Xu Ting , Si Chuanling
Published: August 2023

Phase change materials (PCMs) possess remarkable capability to store and release substantial amounts of energy during the processes of melting and crystallization across a wide temperature range, thus holding great promise in applications related to temperature regulation and thermal energy storage. Herein, to effectively address PCM leakage and enhance thermal conduction, PCM microcapsules with melamine–formaldehyde resin (MF) shell were prepared using in situ polymerization of Pickering emulsions stabilized by cellulose nanofibrils (CNFs). CNFs were selected as the stabilizers for the Pickering emulsions and as reinforcing nanofillers for the MF shell, owing to their excellent emulsifying capability, high mechanical strength, and sustainable nature. Paraffin wax (PW) was utilized as the PCM material. The resulting PCM microcapsules with MF resin shells and PW core had a diameter ranging from 2 to 4 µm. Results showed that microcapsule with the core–shell ratio of 2 (Micro-2.0) exhibited the highest latent heat of crystallization and latent heat of fusion, measuring approximately 128.40 J/g and 120.23 J/g, respectively. The encapsulation efficiency of Micro-2.0 was determined to be approximately 79.84%.
Mapping the integrity of rock mass with GPR: case study in decommissioning mining
Authors: Duz Beatriz Guzzo , Moreira César Augusto , Casagrande Matheus Felipe Stanfoca , Helene Livia Portes Innocenti
Published: August 2023

Slopes are built for the purpose of extracting ore, in the case of mining, or access roads in civil works. The excavation of slopes in tropical countries is facilitated by the thick layer of soil formed from the more intense weathering when compared to other countries. However, the residence time of water in the soil is relatively longer and consequently allows the accumulation and percolation of water through rock fractures even in the dry period. These factors induce a greater probability of occurrence of ruptures. Mines in the decommissioning phase must guarantee slope stability conditions even after closure in order to comply with legislation and environmental safety. In this work, the slopes of a decommissioning mine were investigated using geophysical methods (GPR) and structural analysis of the rock mass. The results were presented in the form of radargrams that correlate distance and depth of investigation. Structural data served as the basis for the execution of kinematic analyzes for planar and wedge ruptures. The analysis of the results allowed the correlation between electromagnetic signal attenuation zones, with the presence of water and the occurrence of ruptures. Thus, the GPR results allowed the recognition of structural discontinuities, accumulation zones and water flow.
Anxiety and heart rate in a real-life class test in undergraduates choosing real-time or prerecorded oral presentations
Authors: Szabo Attila , Ábel Krisztina
Published: August 2023

Most studies on acute stress stem from works conducted under artificial laboratory conditions. Inducing stress for experimental scrutiny is problematic and can be unethical. In this study, a ‘research methods’ course’s curriculum included a demonstration study testing anxiety and heart rate responses to the midterm test. Fifty-four university students (35 males and 19 females) presented a research topic in-person (n = 14) or prerecorded while being present (n = 40). Students selected a test format they could change until the week before the midterm test. The measures were trait anxiety, test anxiety, state anxiety, heart rate (HR), the last two being measured before and after examination, and grades. All students manifested decreased state anxiety and increased HR from before to after the test. Females exhibited higher HR and state anxiety than males. Real-time presentations were associated with higher HRs but not higher state anxiety. Those who changed their planned presentation mode from in-person to prerecorded exhibited higher test anxiety but not trait anxiety than those who presented as planned. Students who presented in-person obtained lower grades than those who prerecorded their presentations. Grades were negatively correlated with state anxiety after the test, but test anxiety did not significantly mediate the grades. Pre-test state anxiety was positively associated with both trait anxiety and test anxiety. The findings suggest that test anxiety is unlikely to affect grades, but test-anxious students need more control over academic evaluation. A choice in test format could be helpful in this regard.
On the Economics of the Transition to a Circular Economy
Authors: Chennak Ahmed , Giannakas Konstantinos , Awada Tala
Published: August 2023

Humanity is facing complex challenges posed by population growth, climate change, and the need to increase food, feed, fiber, and bioenergy production while confronting the scarcity of natural resources. The transition to a circular economy, characterized by reduced resource use and waste, is being increasingly recognized in academic, business, and policy making circles as essential to meeting these challenges, with the emphasis being on the development of methods and processes that enable and facilitate the transition from a linear to a circular economy. This paper argues the need for an increased emphasis on the economics of the circular economy and presents a general framework that illustrates the transition from a linear to a circular economic system. In addition, the paper highlights the economic issues that arise during the transition to increased circularity and the policy options available to facilitate the successful transition to a more circular economic system.
A Fractional Perspective on the Dynamics of HIV, Considering the Interaction of Viruses and Immune System with the Effect of Antiretroviral Therapy
Authors: Tang Tao-Qian , Jan Rashid , Ahmad Hassan , Shah Zahir , Vrinceanu Narcisa , Racheriu Mihaela
Published: August 2023

HIV infection is a worldwide health threat, necessitating a multifaceted strategy that includes prevention, testing, treatment and care. Moreover, it is essential to address the structural and social factors that influence the spread of this viral infection. In this study, we utilize fractional calculus to clarify the dynamics of HIV infection in vivo, specifically examining the interface amid the HIV and the immune system and taking into account the impact of antiretroviral therapy. We use important results from fractional theory to analyze our proposed model of HIV infection and developed a numerical scheme to depict the system’s dynamic behavior. By varying input factors, we were able to observe the system’s chaotic nature and track its trajectory, as well as examine the effect of viruses on T-cells. Our results reveal key factors affecting the system, and demonstrate the consequence of antiretroviral therapy on our proposed model of HIV. Moreover, we observe that the system’s strong non-linearity is responsible for the oscillation phenomena and identify the most sensitive parameters of the system.
A Finger in the Game: Sport-Specific Finger Strength Training and Onset of Injury
Authors: Sjöman Anna E. , Grønhaug Gudmund , Julin Mikko V.
Published: August 2023

Introduction

Strength training has proved to be an effective way to prevent injuries, but the evidence of the impact of strength training on finger injuries is lacking. A fingerboard is a sport-specific tool used by climbers for strength training of fingers. In this study, we searched for associations between fingerboard training and finger injuries in climbers with different lengths of climbing experience and levels of performance.

Methods

A web-based survey was used to collect information on self-perceived pain or injury in fingers (SPIIF) and regular fingerboard training (RFT). The survey was administered to the Finnish climbing community. Data were analyzed using contingency tables; chi-square was used to evaluate statistical significance.

Results

No significant correlations between SPIIF and RFT were found when analyzing all the participants (n=434) together. In climbers with 6 y or more in the sport, SPIIF was not common and RFT was negatively associated with SPIIF (χ2 [1, n=200]=4.57; P=0.03). In contrast to this, in male climbers who had been climbing for less than 6 y and had advanced to 7a level or higher (French lead/Font bouldering), SPIIF was common and RFT was positively associated with SPIIF (χ2 [1, n=75]=4.61; P=0.03).

Conclusions

We suggest that doing RFT may prevent SPIIF in climbers with a long background in the sport as fingerboard training can help build stronger fingers and thereby stronger tendons and ligaments. Climbers with fewer years in the sport and less adaptation to the fingers should be cautious with their training loads and RFT to avoid finger injuries and pain.
India's Communal Constitution
Authors: John Mathew
Published: August 2023

This book speaks to debates on law, constitutionalism, and the contested terrain of political identity in modern India. Set against the overwhelmingly liberal design of the Indian Constitution, the book demonstrates a tendency in the Constitution and its practice to identify the Indian people in parochial and communal terms. This tendency is identified as India's Communal Constitution and its imprint on contemporary constitutional practice is illustrated by drawing on the constitutional practice as it addresses religious freedom, personal law, minority rights and the identification of caste groups. Thus, casting the Constitution and its practice as a field of contest, the aspiration to define the Indian people as a community of individual citizens is brought face to face with its antagonists. The most significant of these antagonists is the tendency to cast the Indian people as a collection of communities which this book examines and details as India's Communal Constitution.
Annotation-Based Semantics for Space and Time in Language
Authors: Lee Kiyong
Published: August 2023

Space and time representation in language is important in linguistics and cognitive science research, as well as artificial intelligence applications like conversational robots and navigation systems. This book is the first for linguists and computer scientists that shows how to do model-theoretic semantics for temporal or spatial information in natural language, based on annotation structures. The book covers the entire cycle of developing a specification for annotation and the implementation of the model over the appropriate corpus for linguistic annotation. Its representation language is a type-theoretic, first-order logic in shallow semantics. Each interpretation model is delimited by a set of definitions of logical predicates used in semantic representations (e.g., past) or measuring expressions (e.g., counts or k). The counting function is then defined as a set and its cardinality, involving a universal quantification in a model. This definition then delineates a set of admissible models for interpretation.
Developmental changes in cerebral NAD and neuroenergetics of an antioxidant compromised mouse model of schizophrenia
Authors: Skupienski Radek , Steullet Pascal , Do Kim Q. , Xin Lijing
Published: August 2023

Defects in essential metabolic regulation for energy supply, increased oxidative stress promoting excitatory/inhibitory imbalance and phospholipid membrane dysfunction have been implicated in the pathophysiology of schizophrenia (SZ). The knowledge about the developmental trajectory of these key pathophysiological components and their interplay is important to develop new preventive and treatment strategies. However, this assertion is so far limited. To investigate the developmental regulations of these key components in the brain, we assessed, for the first time, in vivo redox state from the oxidized (NAD+) and reduced (NADH) form of Nicotinamide Adenine Dinucleotide (NAD), energy and membrane metabolites, inhibitory and excitatory neurotransmitters by 31P and 1H MRS during the neurodevelopment of an SZ animal model with genetically compromised glutathione synthesis (gclm-KO mice). When compared to age-matched wild type (WT), an increase in NAD+/NADH redox ratio was found in gclm-KO mice until early adulthood, followed by a decrease in full adults as observed in patients. Especially, in early postnatal life (P20, corresponding to childhood), levels of several metabolites were altered in gclm-KO mice, including NAD+, NAD+/NADH, ATP, and glutamine + glutamate, suggesting an interactive compensation for redox dysregulation between NAD, energy metabolism, and neurotransmission. The identified temporal neurometabolic regulations under deficits in redox regulation provide insights into preventive treatment targets for at-risk individuals, and other neurodevelopmental disorders involving oxidative stress and energetic dysfunction.
Heterogeneity in leukemia cells that escape drug-induced senescence-like state
Authors: Miller David , Kerkhofs Kyra , Abbas-Aghababazadeh Farnoosh , Madahar Sahib Singh , Minden Mark D. , Hébert Josée , Haibe-Kains Benjamin , Bayfield Mark A. , Benchimol Samuel
Published: August 2023

Erythropoietin (EPO) suppresses drug-induced apoptosis in EPO-receptor-positive leukemia cells and allows cells to persist after drug treatment by promoting cellular senescence. Importantly a small proportion of senescent cells can re-enter the cell cycle and resume proliferation after drug treatment, resulting in disease recurrence/persistence. Using a single-cell assay to track individual cells that exit a drug-induced senescence-like state, we show that cells exhibit asynchronous exit from a senescent-like state, and display different rates of proliferation. Escaped cells retain sensitivity to drug treatment, but display inter-clonal variability. We also find heterogeneity in gene expression with some of the escaped clones retaining senescence-associated gene expression. Senescent leukemia cells exhibit changes in gene expression that affect metabolism and senescence-associated secretory phenotype (SASP)-related genes. Herein, we generate a senescence gene signature and show that this signature is a prognostic marker of worse overall survival in AML and multiple other cancers. A portion of senescent leukemia cells depend on lysosome activity; chloroquine, an inhibitor of lysosome activity, promotes senolysis of some senescent leukemia cells. Our study indicates that the serious risks associated with the use of erythropoietin-stimulating agents (ESAs) in anemic cancer patients may be attributed to their ability to promote drug-tolerant cancer cells through the senescence program.
Deficiency of BAP1 inhibits neuroblastoma tumorigenesis through destabilization of MYCN
Authors: Zhang Xiaoling , Cong Xianling , Jin Xiangting , Liu Yu’e , Zhang Tong , Fan Xinyuan , Shi Xiyao , Zhang Xiaoying , Wang Xue , Yang Yong-Guang , Dai Xiangpeng
Published: August 2023

The transcription factor MYCN is frequently amplified and overexpressed in a variety of cancers including high-risk neuroblastoma (NB) and promotes tumor cell proliferation, survival, and migration. Therefore, MYCN is being pursued as an attractive therapeutic target for selective inhibition of its upstream regulators because MYCN is considered a “undruggable” target. Thus, it is important to explore the upstream regulators for the transcription and post-translational modification of MYCN. Here, we report that BRCA1-associated protein-1 (BAP1) promotes deubiquitination and subsequent stabilization of MYCN by directly binding to MYCN protein. Furthermore,BAP1knockdown inhibits NB tumor cells growth and migration in vitro and in vivo, which can be rescued partially by ectopic expression of MYCN. Importantly, depletion ofBAP1confers cellular resistance to bromodomain and extraterminal (BET) protein inhibitor JQ1 and Aurora A kinase inhibitor Alisertib. Furthermore, IHC results of NB tissue array confirmed the positive correlation between BAP1 and MYCN protein. Altogether, our work not only uncovers an oncogenic function of BAP1 by stabilizing MYCN, but also reveals a critical mechanism for the post-translational regulation of MYCN in NB. Our findings further indicate that BAP1 could be a potential therapeutic target for MYCN-amplified neuroblastoma.
The long transcript of lncRNA TMPO-AS1 promotes bone metastases of prostate cancer by regulating the CSNK2A1/DDX3X complex in Wnt/β-catenin signaling
Authors: Wang Min , Yin Chi , Wu Zhengquan , Wang Xinwen , Lin Qijun , Jiang Xingyu , Du Hong , Lang Chuandong , Peng Xinsheng , Dai Yuhu
Published: August 2023

The second most common male cancer is prostate cancer (PCa), which has a high tendency for bone metastasis. Long non-coding RNAs, including TMPO-AS1, play a crucial role in PCa progression. However, TMPO-AS1’s function in PCa bone metastasis (BM) and its underlying molecular mechanisms are unclear. Herein, we found that the long transcript of TMPO-AS1 (TMPO-AS1L) was upregulated in PCa tissues with bone metastasis, and overexpression of TMPO-AS1L correlated with advanced clinicopathological features and reduced BM-free survival in patients with PCa. Upregulated TMPO-AS1L promoted, whereas downregulated TMPO-AS1L inhibited, the PCa cell bone metastatic capacity in vitro and in vivo. Mechanistically, TMPO-AS1L was demonstrated to act as a scaffold, that strengthened the interaction of casein kinase 2 alpha 1 (CSNK2A1) and DEAD-box helicase 3 X-linked (DDX3X), and activated the Wnt/β-catenin signaling pathway, thus promoting BM of PCa. Moreover, upregulation of TMPO-AS1L in PCa resulted from transcription elongation modulated by general transcription factor IIF subunit 2 (GTF2F2). Collectively, our study provides critical insights into the role of TMPO-AS1L in PCa BM via Wnt/β-catenin signaling, identifying TMPO-AS1L as a candidate marker of PCa bone metastasis prognosis and therapeutic target.
Cardiomyocyte proliferation is suppressed by ARID1A-mediated YAP inhibition during cardiac maturation
Authors: Boogerd Cornelis J. , Perini Ilaria , Kyriakopoulou Eirini , Han Su Ji , La Phit , van der Swaan Britt , Berkhout Jari B. , Versteeg Danielle , Monshouwer-Kloots Jantine , van Rooij Eva
Published: August 2023

The inability of adult human cardiomyocytes to proliferate is an obstacle to efficient cardiac regeneration after injury. Understanding the mechanisms that drive postnatal cardiomyocytes to switch to a non-regenerative state is therefore of great significance. Here we show that Arid1a, a subunit of the switching defective/sucrose non-fermenting (SWI/SNF) chromatin remodeling complex, suppresses postnatal cardiomyocyte proliferation while enhancing maturation. Genome-wide transcriptome and epigenome analyses revealed that Arid1a is required for the activation of a cardiomyocyte maturation gene program by promoting DNA access to transcription factors that drive cardiomyocyte maturation. Furthermore, we show that ARID1A directly binds and inhibits the proliferation-promoting transcriptional coactivators YAP and TAZ, indicating ARID1A sequesters YAP/TAZ from their DNA-binding partner TEAD. In ischemic heart disease, Arid1a expression is enhanced in cardiomyocytes of the border zone region. Inactivation of Arid1a after ischemic injury enhanced proliferation of border zone cardiomyocytes. Our study illuminates the pivotal role of Arid1a in cardiomyocyte maturation, and uncovers Arid1a as a crucial suppressor of cardiomyocyte proliferation.
Modulatory dynamics of periodic and aperiodic activity in respiration-brain coupling
Authors: Kluger Daniel S. , Forster Carina , Abbasi Omid , Chalas Nikos , Villringer Arno , Gross Joachim
Published: August 2023

Bodily rhythms such as respiration are increasingly acknowledged to modulate neural oscillations underlying human action, perception, and cognition. Conversely, the link between respiration and aperiodic brain activity – a non-oscillatory reflection of excitation-inhibition (E:I) balance – has remained unstudied. Aiming to disentangle potential respiration-related dynamics of periodic and aperiodic activity, we applied recently developed algorithms of time-resolved parameter estimation to resting-state MEG and EEG data from two labs (total N = 78 participants). We provide evidence that fluctuations of aperiodic brain activity (1/f slope) are phase-locked to the respiratory cycle, which suggests that spontaneous state shifts of excitation-inhibition balance are at least partly influenced by peripheral bodily signals. Moreover, differential temporal dynamics in their coupling to non-oscillatory and oscillatory activity raise the possibility of a functional distinction in the way each component is related to respiration. Our findings highlight the role of respiration as a physiological influence on brain signalling.
A stretchable, mechanically robust polymer exhibiting shape-memory-assisted self-healing and clustering-triggered emission
Authors: Wang Xiaoyue , Xu Jing , Zhang Yaoming , Wang Tingmei , Wang Qihua , Li Song , Yang Zenghui , Zhang Xinrui
Published: August 2023

Self-healing and recyclable polymer materials are being developed through extensive investigations on noncovalent bond interactions. However, they typically exhibit inferior mechanical properties. Therefore, the present study is aimed at synthesizing a polyurethane–urea elastomer with excellent mechanical properties and shape-memory-assisted self-healing behavior. In particular, the introduction of coordination and hydrogen bonds into elastomer leads to the optimal elastomer exhibiting good mechanical properties (strength, 76.37 MPa; elongation at break, 839.10%; toughness, 308.63 MJ m−3) owing to the phased energy dissipation mechanism involving various supramolecular interactions. The elastomer also demonstrates shape-memory properties, whereby the shape recovery force that brings damaged surfaces closer and facilitates self-healing. Surprisingly, all specimens exhibite clustering-triggered emission, with cyan fluorescence is observed under ultraviolet light. The strategy reported herein for developing multifunctional materials with good mechanical properties can be leveraged to yield stimulus-responsive polymers and smart seals.
Atmospheric turbulence strength distribution along a propagation path probed by longitudinally structured optical beams
Authors: Zhou Huibin , Su Xinzhou , Duan Yuxiang , Song Hao , Zou Kaiheng , Zhang Runzhou , Song Haoqian , Hu Nanzhe , Tur Moshe , Willner Alan E.
Published: August 2023

Atmospheric turbulence can cause critical problems in many applications. To effectively avoid or mitigate turbulence, knowledge of turbulence strength at various distances could be of immense value. Due to light-matter interaction, optical beams can probe longitudinal turbulence changes. Unfortunately, previous approaches tended to be limited to relatively short distances or large transceivers. Here, we explore turbulence probing utilizing multiple sequentially transmitted longitudinally structured beams. Each beam is composed of Bessel-Gaussian ($${{{{{{\rm{BG}}}}}}}_{{{{{{\mathcal{l}}}}}}{{=}}0,{k}_{z}}$$

BG

l
=
0
,

k

z

) modes with different $${k}_{z}$$

k

z

values such that a distance-varying beam width is produced, which results in a distance- and turbulence-dependent modal coupling to $${{{{{\mathcal{l}}}}}}{{{{{\mathscr{\ne }}}}}}0$$
l
{{\relax \special {t4ht̂3)}\o:mathrel: {\unhbox \voidb@x \special {t4ht@+{38}{35}x2260;}x}}}
0
orders. Our simulation shows that this approach has relatively uniform and low errors (<0.3 dB) over a 10-km path with up to 30-dB turbulence-structure-constant variation. We experimentally demonstrate this approach for two emulated turbulence regions (~15-dB variation) with <0.8-dB errors. Compared to previous techniques, our approach can potentially probe longer distances or require smaller transceivers.
Electro-assisted methane oxidation to formic acid via in-situ cathodically generated H2O2 under ambient conditions
Authors: Kim Jiwon , Kim Jae Hyung , Oh Cheoulwoo , Yun Hyewon , Lee Eunchong , Oh Hyung-Suk , Park Jong Hyeok , Hwang Yun Jeong
Published: August 2023

Direct partial oxidation of methane to liquid oxygenates has been regarded as a potential route to valorize methane. However, CH4 activation usually requires a high temperature and pressure, which lowers the feasibility of the reaction. Here, we propose an electro-assisted approach for the partial oxidation of methane, using in-situ cathodically generated reactive oxygen species, at ambient temperature and pressure. Upon using acid-treated carbon as the electrocatalyst, the electro-assisted system enables the partial oxidation of methane in an acidic electrolyte to produce oxygenated liquid products. We also demonstrate a high production rate of oxygenates (18.9 μmol h−1) with selective HCOOH production. Mechanistic analysis reveals that reactive oxygen species such as ∙OH and ∙OOH radicals are produced and activate CH4 and CH3OH. In addition, unstable CH3OOH generated from methane partial oxidation can be additionally reduced to CH3OH on the cathode, and so-produced CH3OH is further oxidized to HCOOH, allowing selective methane partial oxidation.
Control of motor landing and processivity by the CAP-Gly domain in the KIF13B tail
Authors: Fan Xiangyu , McKenney Richard J.
Published: August 2023

Microtubules are major components of the eukaryotic cytoskeleton. Posttranslational modifications (PTMs) of tubulin regulates interactions with microtubule-associated proteins (MAPs). One unique PTM is the cyclical removal and re-addition of the C-terminal tyrosine of α-tubulin and MAPs containing CAP-Gly domains specifically recognize tyrosinated microtubules. KIF13B, a long-distance transport kinesin, contains a conserved CAP-Gly domain, but the role of the CAP-Gly domain in KIF13B’s motility along microtubules remains unknown. To address this, we investigate the interaction between KIF13B’s CAP-Gly domain, and tyrosinated microtubules. We find that KIF13B’s CAP-Gly domain influences the initial motor-microtubule interaction, as well as processive motility along microtubules. The effect of the CAP-Gly domain is enhanced when the motor domain is in the ADP state, suggesting an interplay between the N-terminal motor domain and C-terminal CAP-Gly domain. These results reveal that specialized kinesin tail domains play active roles in the initiation and continuation of motor movement.
BtuB TonB-dependent transporters and BtuG surface lipoproteins form stable complexes for vitamin B12 uptake in gut Bacteroides
Authors: Abellon-Ruiz Javier , Jana Kalyanashis , Silale Augustinas , Frey Andrew M. , Baslé Arnaud , Trost Matthias , Kleinekathöfer Ulrich , van den Berg Bert
Published: August 2023

Vitamin B12 (cobalamin) is required for most human gut microbes, many of which are dependent on scavenging to obtain this vitamin. Since bacterial densities in the gut are extremely high, competition for this keystone micronutrient is severe. Contrasting with Enterobacteria, members of the dominant genus Bacteroides often encode several BtuB vitamin B12 outer membrane transporters together with a conserved array of surface-exposed B12-binding lipoproteins. Here we show that the BtuB transporters from Bacteroides thetaiotaomicron form stable, pedal bin-like complexes with surface-exposed BtuG lipoprotein lids, which bind B12 with high affinities. Closing of the BtuG lid following B12 capture causes destabilisation of the bound B12 by a conserved BtuB extracellular loop, causing translocation of the vitamin to BtuB and subsequent transport. We propose that TonB-dependent, lipoprotein-assisted small molecule uptake is a general feature of Bacteroides spp. that is important for the success of this genus in colonising the human gut.
Neural manifolds for odor-driven innate and acquired appetitive preferences
Authors: Chandak Rishabh , Raman Baranidharan
Published: August 2023

Sensory stimuli evoke spiking neural responses that innately or after learning drive suitable behavioral outputs. How are these spiking activities intrinsically patterned to encode for innate preferences, and could the neural response organization impose constraints on learning? We examined this issue in the locust olfactory system. Using a diverse odor panel, we found that ensemble activities both during (‘ON response’) and after stimulus presentations (‘OFF response’) could be linearly mapped onto overall appetitive preference indices. Although diverse, ON and OFF response patterns generated by innately appetitive odorants (higher palp-opening responses) were still limited to a low-dimensional subspace (a ‘neural manifold’). Similarly, innately non-appetitive odorants evoked responses that were separable yet confined to another neural manifold. Notably, only odorants that evoked neural response excursions in the appetitive manifold could be associated with gustatory reward. In sum, these results provide insights into how encoding for innate preferences can also impact associative learning.
Bilateral human laryngeal motor cortex in perceptual decision of lexical tone and voicing of consonant
Authors: Liang Baishen , Li Yanchang , Zhao Wanying , Du Yi
Published: August 2023

Speech perception is believed to recruit the left motor cortex. However, the exact role of the laryngeal subregion and its right counterpart in speech perception, as well as their temporal patterns of involvement remain unclear. To address these questions, we conducted a hypothesis-driven study, utilizing transcranial magnetic stimulation on the left or right dorsal laryngeal motor cortex (dLMC) when participants performed perceptual decision on Mandarin lexical tone or consonant (voicing contrast) presented with or without noise. We used psychometric function and hierarchical drift-diffusion model to disentangle perceptual sensitivity and dynamic decision-making parameters. Results showed that bilateral dLMCs were engaged with effector specificity, and this engagement was left-lateralized with right upregulation in noise. Furthermore, the dLMC contributed to various decision stages depending on the hemisphere and task difficulty. These findings substantially advance our understanding of the hemispherical lateralization and temporal dynamics of bilateral dLMC in sensorimotor integration during speech perceptual decision-making.
A common neuronal ensemble in nucleus accumbens regulates pain-like behaviour and sleep
Authors: Sun Haiyan , Li Zhilin , Qiu Zhentong , Shen Yu , Guo Qingchen , Hu Su-Wan , Ding Hai-Lei , An Shuming , Cao Jun-Li
Published: August 2023

A comorbidity of chronic pain is sleep disturbance. Here, we identify a dual-functional ensemble that regulates both pain-like behaviour induced by chronic constrictive injury or complete Freund’s adjuvant, and sleep wakefulness, in the nucleus accumbens (NAc) in mice. Specifically, a select population of NAc neurons exhibits increased activity either upon nociceptive stimulation or during wakefulness. Experimental activation of the ensemble neurons exacerbates pain-like (nociceptive) responses and reduces NREM sleep, while inactivation of these neurons produces the opposite effects. Furthermore, NAc ensemble primarily consists of D1 neurons and projects divergently to the ventral tegmental area (VTA) and preoptic area (POA). Silencing an ensemble innervating VTA neurons selectively increases nociceptive responses without affecting sleep, whereas inhibiting ensemble-innervating POA neurons decreases NREM sleep without affecting nociception. These results suggest a common NAc ensemble that encodes chronic pain and controls sleep, and achieves the modality specificity through its divergent downstream circuit targets.
Holocene climate change in southern Oman deciphered by speleothem records and climate model simulations
Authors: Tian Ye , Fleitmann Dominik , Zhang Qiong , Sha Lijuan , Wassenburg Jasper. A. , Axelsson Josefine , Zhang Haiwei , Li Xianglei , Hu Jun , Li Hanying , Zhao Liang , Cai Yanjun , Ning Youfeng , Cheng Hai
Published: August 2023

Qunf Cave oxygen isotope (δ18Oc) record from southern Oman is one of the most significant of few Holocene Indian summer monsoon cave records. However, the interpretation of the Qunf δ18Oc remains in dispute. Here we provide a multi-proxy record from Qunf Cave and climate model simulations to reconstruct the Holocene local and regional hydroclimate changes. The results indicate that besides the Indian summer monsoon, the North African summer monsoon also contributes water vapor to southern Oman during the early to middle Holocene. In principle, Qunf δ18Oc values reflect integrated oxygen-isotope fractionations over a broad moisture transport swath from moisture sources to the cave site, rather than local precipitation amount alone, and thus the Qunf δ18Oc record characterizes primary changes in the Afro-Asian monsoon regime across the Holocene. In contrast, local climate proxies appear to suggest an overall slightly increased or unchanged wetness over the Holocene at the cave site.
Hydrogenation versus hydrogenolysis during alkaline electrochemical valorization of 5-hydroxymethylfurfural over oxide-derived Cu-bimetallics
Authors: Hauke Philipp , Merzdorf Thomas , Klingenhof Malte , Strasser Peter
Published: August 2023

The electrochemical conversion of 5-Hydroxymethylfurfural, especially its reduction, is an attractive green production pathway for carbonaceous e-chemicals. We demonstrate the reduction of 5-Hydroxymethylfurfural to 5-Methylfurfurylalcohol under strongly alkaline reaction environments over oxide-derived Cu bimetallic electrocatalysts. We investigate whether and how the surface catalysis of the MOx phases tune the catalytic selectivity of oxide-derived Cu with respect to the 2-electron hydrogenation to 2.5-Bishydroxymethylfuran and the (2 + 2)-electron hydrogenation/hydrogenolysis to 5-Methylfurfurylalcohol. We provide evidence for a kinetic competition between the evolution of H2 and the 2-electron hydrogenolysis of 2.5-Bishydroxymethylfuran to 5-Methylfurfurylalcohol and discuss its mechanistic implications. Finally, we demonstrate that the ability to conduct 5-Hydroxymethylfurfural reduction to 5-Methylfurfurylalcohol in alkaline conditions over oxide-derived Cu/MOx Cu foam electrodes enable an efficiently operating alkaline exchange membranes electrolyzer, in which the cathodic 5-Hydroxymethylfurfural valorization is coupled to either alkaline oxygen evolution anode or to oxidative 5-Hydroxymethylfurfural valorization.
Prussian blue analog with separated active sites to catalyze water driven enhanced catalytic treatments
Authors: Wang Liu-Chun , Chiou Pei-Yu , Hsu Ya-Ping , Lee Chin-Lai , Hung Chih-Hsuan , Wu Yi-Hsuan , Wang Wen-Jyun , Hsieh Gia-Ling , Chen Ying-Chi , Chang Li-Chan , Su Wen-Pin , Manoharan Divinah , Liao Min-Chiao , Thangudu Suresh , Li Wei-Peng , Su Chia-Hao , Tian Hong-Kang , Yeh Chen-Sheng
Published: August 2023

Chemodynamic therapy (CDT) uses the Fenton or Fenton-like reaction to yield toxic ‧OH following H2O2 → ‧OH for tumoral therapy. Unfortunately, H2O2 is often taken from the limited endogenous supply of H2O2 in cancer cells. A water oxidation CoFe Prussian blue (CFPB) nanoframes is presented to provide sustained, external energy-free self-supply of ‧OH from H2O to process CDT and/or photothermal therapy (PTT). Unexpectedly, the as-prepared CFPB nanocubes with no near-infrared (NIR) absorption is transformed into CFPB nanoframes with NIR absorption due to the increased Fe3+-N ≡ C-Fe2+ composition through the proposed proton-induced metal replacement reactions. Surprisingly, both the CFPB nanocubes and nanoframes provide for the self-supply of O2, H2O2, and ‧OH from H2O, with the nanoframe outperforming in the production of ‧OH. Simulation analysis indicates separated active sites in catalyzation of water oxidation, oxygen reduction, and Fenton-like reactions from CFPB. The liposome-covered CFPB nanoframes prepared for controllable water-driven CDT for male tumoral mice treatments.
Vacancy-mediated anomalous phononic and electronic transport in defective half-Heusler ZrNiBi
Authors: Ren Wuyang , Xue Wenhua , Guo Shuping , He Ran , Deng Liangzi , Song Shaowei , Sotnikov Andrei , Nielsch Kornelius , van den Brink Jeroen , Gao Guanhui , Chen Shuo , Han Yimo , Wu Jiang , Chu Ching-Wu , Wang Zhiming , Wang Yumei , Ren Zhifeng
Published: August 2023

Studies of vacancy-mediated anomalous transport properties have flourished in diverse fields since these properties endow solid materials with fascinating photoelectric, ferroelectric, and spin-electric behaviors. Although phononic and electronic transport underpin the physical origin of thermoelectrics, vacancy has only played a stereotyped role as a scattering center. Here we reveal the multifunctionality of vacancy in tailoring the transport properties of an emerging thermoelectric material, defective n-type ZrNiBi. The phonon kinetic process is mediated in both propagating velocity and relaxation time: vacancy-induced local soft bonds lower the phonon velocity while acoustic-optical phonon coupling, anisotropic vibrations, and point-defect scattering induced by vacancy shorten the relaxation time. Consequently, defective ZrNiBi exhibits the lowest lattice thermal conductivity among the half-Heusler family. In addition, a vacancy-induced flat band features prominently in its electronic band structure, which is not only desirable for electron-sufficient thermoelectric materials but also interesting for driving other novel physical phenomena. Finally, better thermoelectric performance is established in a ZrNiBi-based compound. Our findings not only demonstrate a promising thermoelectric material but also promote the fascinating vacancy-mediated anomalous transport properties for multidisciplinary explorations.
Molecular basis of Mg2+ permeation through the human mitochondrial Mrs2 channel
Authors: Li Ming , Li Yang , Lu Yue , Li Jianhui , Lu Xuhang , Ren Yue , Wen Tianlei , Wang Yaojie , Chang Shenghai , Zhang Xing , Yang Xue , Shen Yuequan
Published: August 2023

Mitochondrial RNA splicing 2 (Mrs2), a eukaryotic CorA ortholog, enables Mg2+ to permeate the inner mitochondrial membrane and plays an important role in mitochondrial metabolic function. However, the mechanism by which Mrs2 permeates Mg2+ remains unclear. Here, we report four cryo-electron microscopy (cryo-EM) reconstructions of Homo sapiens Mrs2 (hMrs2) under various conditions. All of these hMrs2 structures form symmetrical pentamers with very similar pentamer and protomer conformations. A special structural feature of Cl−-bound R-ring, which consists of five Arg332 residues, was found in the hMrs2 structure. Molecular dynamics simulations and mitochondrial Mg2+ uptake assays show that the R-ring may function as a charge repulsion barrier, and Cl− may function as a ferry to jointly gate Mg2+ permeation in hMrs2. In addition, the membrane potential is likely to be the driving force for Mg2+ permeation. Our results provide insights into the channel assembly and Mg2+ permeation of hMrs2.
CBD-oil as a potential solution in case of severe tamoxifen-related side effects
Authors: Buijs Sanne M. , Braal C. Louwrens , Buck Stefan A. J. , van Maanen Noud F. , van der Meijden-Erkelens Lonneke M. , Kuijper-Tissot van Patot Heleen A. , Hoop Esther Oomen-de , Saes Lotte , van den Boogerd Sophia J. , Struik Liesbeth E. M. , van Rossum-Schornagel Quirine C. , Mathijssen Ron H. J. , Koolen Stijn L. W. , Jager Agnes
Published: August 2023

Tamoxifen may lead to bothersome side effects contributing to non-compliance and decreased quality of life. Patients searching for relief are increasingly turning to cannabinoids such as CBD-oil. However, CBD-oil might affect tamoxifen pharmacokinetics (PK) through CYP2D6 inhibition. The aims of this open-label, single-arm study were (1) to determine the PK profile of tamoxifen when using CBD-oil, and (2) to subsequently investigate whether CBD-oil has a beneficial influence on side effects. Study patients had to have steady-state endoxifen concentrations ≥16 nM (conservative threshold). PK sampling and side effect assessment was done at initiation of CBD-oil and 28 days thereafter. Bio-equivalence could be concluded if the 90% confidence interval (CI) for the difference in endoxifen AUC fell within the [−20%; +25%] interval. The effect of CBD-oil on side effects was evaluated using the FACT-ES questionnaire. Endoxifen AUC decreased after CBD-oil by 12.6% (n = 15, 90% CI −18.7%, −6.1%) but remained within bio-equivalence boundaries. The endocrine sub-scale of the FACT-ES improved clinically relevant with 6.7 points (n = 26, p < 0.001) and health-related quality of life improved with 4.7 points after using CBD (95% CI + 1.8, +7.6). We conclude that CBD-oil, if of good quality and with a dosage below 50 mg, does not have to be discouraged in patients using it for tamoxifen-related side effects. Clinical trial registration: International Clinical Trial Registry Platform (NL8786; https://www.who.int/clinical-trials-registry-platform).
Combining the AKT inhibitor capivasertib and SERD fulvestrant is effective in palbociclib-resistant ER+ breast cancer preclinical models
Authors: Hopcroft Lorna , Wigmore Eleanor M. , Williamson Stuart C. , Ros Susana , Eberlein Cath , Moss Jennifer I. , Urosevic Jelena , Carnevalli Larissa S. , Talbot Sara , Bradshaw Lauren , Blaker Catherine , Gunda Sreeharsha , Owenson Venetia , Hoffmann Scott , Sutton Daniel , Jones Stewart , Goodwin Richard J. A. , Willis Brandon S. , Rooney Claire , de Bruin Elza C. , Barry Simon T.
Published: August 2023

Combining the selective AKT inhibitor, capivasertib, and SERD, fulvestrant improved PFS in a Phase III clinical trial (CAPItello-291), treating HR+ breast cancer patients following aromatase inhibitors, with or without CDK4/6 inhibitors. However, clinical data suggests CDK4/6 treatment may reduce response to subsequent monotherapy endocrine treatment. To support understanding of trials such as CAPItello-291 and gain insight into this emerging population of patients, we explored how CDK4/6 inhibitor treatment influences ER+ breast tumour cell function and response to fulvestrant and capivasertib after CDK4/6 inhibitor treatment. In RB+, RB− T47D and MCF7 palbociclib-resistant cells ER pathway ER and Greb-1 expression were reduced versus naïve cells. PI3K-AKT pathway activation was also modified in RB+ cells, with capivasertib less effective at reducing pS6 in RB+ cells compared to parental cells. Expression profiling of parental versus palbociclib-resistant cells confirmed capivasertib, fulvestrant and the combination differentially impacted gene expression modulation in resistant cells, with different responses seen in T47D and MCF7 cells. Fulvestrant inhibition of ER-dependent genes was reduced. In resistant cells, the combination was less effective at reducing cell cycle genes, but a consistent reduction in cell fraction in S-phase was observed in naïve and resistant cells. Despite modified signalling responses, both RB+ and RB− resistant cells responded to combination treatment despite some reduction in relative efficacy and was effective in vivo in palbociclib-resistant PDX models. Collectively these findings demonstrate that simultaneous inhibition of AKT and ER signalling can be effective in models representing palbociclib resistance despite changes in pathway dependency.