bluuebunny/crossref_metadata_2025 huggingface dataset:
Intriguing magnetic and electronic behaviors in La and Ru doped Sr2IrO4
Authors: Dundi Sri Chandana B , Tiwari Jeetendra Kumar , Saranya K , Rana Arpita , Senthil Murugan G , Dhenadhayalan Namasivayam , Choi Kwang-Yong , Sekhar K C , Babu P D , Sankar Raman , Panneer Muthuselvam I
Published: December 2024

We report a detailed experimental study of the structural, magnetic and electrical properties of La and Ru doped (Sr1−x
La
x
)2Ir1−x
Ru
x
O4 (x= 0.05, 0.15). X-ray diffraction analysis reveals that both samples crystallize in a tetragonal structure with a space group I41/acd without impurities. Substitution with La and Ru leads to an increase in the lattice parameter a and a decrease in c. With increasing doping concentration, the Ir–O–Ir bond angle increases while the Ir–O bond length decreases. X-ray photoelectron spectroscopy (XPS) shows that Ir has Ir3+ (5d
6) and Ir4+ (5d
5) charge states, where the Ir4+ charge state decreases with an increase in doping concentration. The dc magnetic susceptibility χ (T) of x= 0.05 reveals a transition from paramagnetic to weak ferromagnetic (wFM) at T
C ∼ 229 K, arising from the canted antiferromagnetic (AFM) spin arrangement. The magnetic ordering temperature T
C remains unaltered for higher doping, whereas the magnetic moment is significantly reduced. The analysis of real and imaginary components of ac susceptibility data, based on conventional critical slow model, frequency shift per decade and Vogel–Fulcher law, unanimously evidences the existence of reentrant spin-glass behavior (RSG), i.e. the coexistence of weak ferromagnetism and spin glass phases for the lowest doping of x= 0.05. On the other hand, for higher doping (x = 0.15) of hole and electron, the RSG phase vanishes, leaving only the wFM phase at the same temperature as observed in x = 0.05. This suggests the higher doping of La and Ru does not affect the magnetic order, but removes the disorder between FM and AFM phases. The electrical resistivity (ρ) measurement analysis reveals that both the samples show semiconducting/insulating behavior across the temperature range. The ρ of the x= 0.05 sample is lower than that of pure sample Sr2IrO4 (Bhatti et al 2015 J. Phys.:Condens. Matter
27 016005), while ρ of x = 0.15 shows two orders of magnitude larger than the x = 0.05 sample at low temperatures. The conduction mechanism of both samples is described by the 2D Mott’s variable-range hopping model. Our results demonstrate that co-doping of two cation sites generates intriguing, competing hopping and magnetic processes.
Bearing fault signal detection based on non-negative matrix factorization and dual-feedback segmented unsaturated tristable stochastic resonance system
Authors: Zhang Gang , Cao Longmei
Published: December 2024

Stochastic resonance is widely used in bearing fault detection due to its ability to enhance weak signals. This paper proposes a fault detection method that combines noise reduction with stochastic resonance. Firstly, a segmented unsaturated potential function based on the classic potential function is constructed, and a dual-feedback structure is introduced to feed the system output back to the input, thereby enhancing system performance. Secondly, the theoretical expressions for the mean first passage time and the spectral amplification of the dual-feedback segmented unsaturated tristable stochastic resonance (DSUTSR) system are derived and analyzed. Additionally, a numerical simulation comparison using the fourth-order Runge–Kutta method is performed between the DSUTSR system and its predecessor systems to verify the improvements brought by the dual-feedback structure. Subsequently, non-negative matrix factorization (NMF) is introduced as a noise reduction method, with cross-validation used to determine the decomposition rank of NMF to guide the decomposition of the fault signal matrix. Finally, the combination of NMF and the DSUTSR system is used to detect bearing fault frequencies under white noise and Lévy noise backgrounds. Experimental results demonstrate the superiority and effectiveness of the proposed method in fault signal detection. This system holds significant potential for future weak signal detection, effectively enhancing and identifying fault signals hidden within noisy backgrounds.
On a supercritical Hardy–Sobolev type inequality with logarithmic term and related extremal problem
Authors: Francisco de Oliveira José , Silva Jeferson
Published: December 2024

Our main goal is to investigate supercritical Hardy–Sobolev type inequalities with a logarithmic term and their corresponding variational problem. We prove the existence of extremal functions for the associated variational problem, despite the loss of compactness. As an application, we show the existence of weak solution to a general class of related elliptic partial differential equations with a logarithmic term.
The effect of series stacking on fast interruption for drift step recovery diode
Authors: Yan Xiaoxue , Liang Lin , Liu Tong , Qing Zhengheng , Yan Hui
Published: December 2024

The excellent working consistency of drift step recovery diode (DSRD) contributes to the formation of high-voltage devices by means of connecting in series. In addition to the voltage, there are still other important parameters of DSRD when connecting in series waiting to be discussed. In this paper, the effect of series stacking on the fast interruption process of DSRD is systematically and comprehensively investigated from theory, simulation, and experiment. The pulse voltage output characteristics of DSRD based on silicon (Si) and silicon carbide (SiC) with the number of chips in the stack ranging from 1 to 8 and 1–10 are studied using transformer circuits and dual power supply circuits, respectively. The results of Si and SiC two materials exhibit good consistency, both showing that the rising time (t
r) of the output voltage gradual decreases and then stabilizes with increase in the number of chips. By establishing a simplified equivalent circuit for stacked DSRDs in series, the calculation formula for t
r is given. It turns out that the series connection can reduce the device’s capacitance and thus reduce t
r, provided that the voltage obtained on each single chip does not change with the increasing stacking quantity. In addition, taking the ∼16 kV DSRD as an example, the effect of seven different stacking schemes on the fast interruption of the device is analyzed. Based on the standards of high V
peak, high dv/dt, and small t
r, the output characteristics of the schemes with stacking quantities 1 and 14 are the worst, while the schemes with stacking quantities 2–5 have better characteristics. The main reason for the phenomena depends on the relative impact of the drift layer structure and number of chips in the stacking scheme on t
r.
Electrostatic discharge failure and protection of single-walled carbon nanotube field-effect transistors
Authors: Chen Yipeng , Zhang Ling , Zhu Xinyu , Jiang Yunhao , Xu Zhencheng , Gao Zhiliang , Cheng Qianding , Zhou Li , Dong Shurong
Published: December 2024

Carbon nanotube-based field-effect transistors (CNT-FETs) have been considered as an alternative to traditional Si-based metal–oxide–semiconductor FETs. Here we investigate the electrostatic discharge (ESD) failure characteristics of single-walled CNT (SWCNT) FETs. In an ESD event, the instantaneous high current will generate a certain amount of heat in the CNT-FET channel, resulting in its thermal failure owing to its randomly aligned SWCNT networks. The CNT-FET failure mechanism and its ESD characteristics with various key parameters are studied in detail. These insights provide new ideas and guidance for research into and application of CNT-FETs. In order to achieve a full chip ESD protection network for CNT chips, we refer to commonly used ESD devices in silicon-based processes and designed CNT-based ESD devices, including GD-CNT-FETs (gated-VDD CNT-FET) and RC-CNT-FET (RC-trigger CNT-FET). CNT-FETs with randomly aligned SWCNT networks, whose failure current level is only about 50 µA µm−1, need a larger area to achieve effective ESD protection.
A light-emitting-diodes-integrated silicon carbide insulated gate bipolar transistor
Authors: Zhang Guoliang , Shen Zhanwei , Wang Zhijie , Chen Yujian , Qiu Yufeng , Zhang Feng , Zhang Rong
Published: December 2024

A light-emitting-diodes (LEDs)-integrated silicon carbide (SiC) insulated gate bipolar transistors (LI-IGBT) is proposed in this paper. The novelty of the LI-IGBT depends on the photogeneration effect of III-nitride LEDs embedded in the poly-Si regions of IGBT. Then, the photogenerated carriers are formed in the JFET region and the drift layer, indicating the increase of the conductivity in LI-IGBT as compared with the SiC IGBT with hole-barrier layer (H-IGBT) and the SiC IGBT with charge storage layer (CSL-IGBT). The static simulation results show that the electron density of the LI-IGBT at the middle of the drift layer is separately 17.44 times and 15.81 times higher than those of the H-IGBT and CSL-IGBT, yielding 40.91% and 37.38% reduction of forward voltage drop, respectively, and also, the LI-IGBT shows 304.59% and 263.67% improvements in BFOM as compared with CSL-IGBT and H-IGBT, respectively. For the dynamic simulation in one cycle, the loss of LI-IGBT is separately reduced by 6.57% and 8.57% compared to H-IGBT and CSL-IGBT. Meanwhile, the relationship between VC(sat) and Eturn-off can be optimized by adjusting collector doping and minority carrier lifetime. These results reveal that the proposed SiC IGBT will be more suitable for ultra-high voltage application.
A novel approximation method for two dimensional phase transfer problem in a moving domain with heat generation parameter
Authors: Joshi Jaya , Rajeev  , Gómez-Aguilar J F , Lavín-Delgado J E
Published: December 2024

This study presents a two dimensional mathematical model of heat transfer process, describing the melting process in a moving domain, which deals with the effect of temperature dependent heat generation and absorption. In many physical processes, as materials undergo phase change, they experience heat generation or heat loss as a result of various internal mechanisms including chemical transformations and Joule heating. Therefore, it is necessary to incorporate the effect of internal heat variations for ensuring the accuracy of phase transfer process. This study also addresses the consequences of time dependent boundary temperature. Another major finding of this study includes the development of a hybrid numerical technique based on the operational matrix of Vieta-Fibonacci polynomials with heat balance integral method (HBIM) to determine the solution of the considered two dimensional heat transfer process in a moving domain. Since, the exact solution of this complex problem is not yet possible. Therefore, a comparison between the obtained results and exact solution for a specific one- dimensional case is presented, which reveals that both results are nearly identical. The consequences of heat generation and heat absorption on the temperature profile and melting curve are shown graphically.
Quantum synchronization in an asymmetric coupled optomechanical system
Authors: Sun J T , Yi X X , Liu H D
Published: December 2024

In this work, we investigate the quantum synchronization and ϕ synchronization of two mechanical oscillators of different frequencies in two optomechanical systems with asymmetric coupling interaction. The whole system can be modulated by cavity detuning or driving amplitudes. Under certain parameters, quantum ϕ synchronization can be enhanced by asymmetric coupling in optomechanical systems, and the phase difference ϕ has an inversion. Moreover, we show that with the introduction of Kerr nonlinear medium, nonlinearity is dominated in achieving synchronization within asymmetric coupled cavities and ϕ can be corrected. Apart from achieving quantum synchronization, quantum anti-synchronization can be observed depending on the asymmetric coupling and the asymmetric external driving field. Our findings could offer insights into other quantum effects and pave the way for studying quantum correlations in asymmetric coupled optomechanical systems.
Polarization of the x-rays from Fe ions following K-shell electron-impact excitation and dielectronic recombination
Authors: Rui Jinglin , Xie Luyou , Zhang Junming , He Wenliang , Ma Yulong , Dong Chenzhong
Published: December 2024

The total and magnetic sublevels cross sections both for the electron impact excitation (EIE) of C-like Fe
20+ ion from the ground state to the K-shell excited states

(
1
s
2

s

2

2

p

3

)

J
=
0
,
1
,
2

and for the dielectronic recombination (DR) of B-like Fe
21+ ion to the same K-shell excited states have been calculated using a fully relativistic distorted-wave approach. Based on these results, the degrees of linear polarization for the same x-ray lines associated with strong 2p → 1s transitions have been obtained. Significant differences are observed in the polarizations of radiative x-rays from these two atomic processes, which can be employed to distinguish the formation mechanism of the corresponding x-ray lines.
Stability and Physical Aspects of Viable Wormhole Solution in $f(R,\mathcal{L}_m)$-gravity: An Embedding Approach
Authors: Khatri Mohan , Lallawmzuali Marina
Published: December 2024

In this paper, we analyze the properties of wormhole (WH) solutions within the framework of modified \(f(R,\mathcal{L}_m)\) gravity. The shape function and redshift function are essential components in the modeling of wormholes, as they dictate the wormhole's metrics and characteristics. Our study sheds light on how the features of \(f(R,\mathcal{L}_m)\) gravity interact with gravitational effects, offering insights into possible wormhole configurations. We also investigate the behavior of energy conditions, the fundamental properties of wormholes, and their embedding diagrams. The stability of the WH solutions is further assessed using the Tolman–Oppenheimer–Volkoff (TOV) equation, which confirms that the solutions meet the equilibrium criteria. Additionally, the volume integral quantifier (VIQ) is discussed to understand the amount of exotic matter required around the wormhole throat. The increasing nature of the active gravitational mass supports the physical viability of the WH solutions. We also explore the complexity factor and sound speed associated with the WH solutions. Overall, our findings contribute to the broader discussion on alternative theories of gravity and the nature of exotic spacetime geometries.
Two-dimensional photothermally induced grating
Authors: Khan Tauqeer , Rahman Muneeb ur , Riaz Nusrat , Asad Ahsan Bin , Khan Muhammad Imtiaz , Ziauddin
Published: December 2024

The phenomenon of photothermally induced transparency (PTIT) arises from the nonlinear behavior of an optical cavity, resulting from the heating of mirrors. By introducing a coupling field in the form of a standing wave, PTIT can be transitioned into photothermally induced grating (PTIG). A two-dimensional (2D) diffraction pattern is achieved through the adjustment of key parameters such as coupling strength and effective detuning. Notably, we observe first, second, and third-order intensity distributions, with the ability to transfer probe energy predominantly to the third order by fine-tuning the coupling strength. The intensity distribution is characterized by (±m, ±n), where m, n = 1, 2, 3. This proposed 2D grating system offers a novel platform for manipulating PTIG, presenting unique possibilities for enhanced functionality and control.
Signal estimation bias in x-ray dark-field imaging using dual phase grating interferometer
Authors: Wang 王 Zhi-Li 志立 , Zhang 张 Zun 尊 , Chen 陈 Heng 恒 , Ge 葛 Xin 昕
Published: December 2024

In x-ray dark-field imaging using dual phase grating interferometer, multi-contrast signals are extracted from a set of acquired phase-stepping data by using the least-squares fitting algorithm. The extracted mean intensity, amplitude and visibility signals may be intrinsically biased. However, it is still unclear how large these biases are and how the data acquisition parameters influence the biases in the extracted signals. This work set out to address these questions. Analytical expressions of the biases of the extracted signals were theoretically derived by using a second-order Taylor series expansion. Extensive numerical simulations were performed to validate the theoretical results. It is illustrated that while the estimated mean intensity signal is always unbiased, the estimated amplitude and visibility signals are both positively biased. While the biases of the estimated amplitude signals are proportional to the inverse of the total number of phase steps, the biases of the estimated visibility signals are inversely proportional to the product of the total number of phase steps and the mean number of photons counted per phase step. Meanwhile, it is demonstrated that the dependence of the biases on the mean visibility is quite different from that of Talbot–Lau interferometer due to the difference in the intensity model. We expect that these results can be useful for data acquisition optimizations and interpretation of x-ray dark-field images.
Zinc-doped hydroxyapatite loaded chitosan gelatin nanocomposite scaffolds as a promising platform for bone regeneration
Authors: Bhushan Sakchi , Singh Sandhya , Maiti Tushar Kanti , Das Ankita , Barui Ananya , Chaudhari Leena R , Joshi Meghnad G , Dutt Dharm
Published: December 2024

The advancement in the arena of bone tissue engineering persuades us to develop novel nanocomposite scaffolds in order to improve antibacterial, osteogenic, and angiogenic properties that show resemblance to natural bone extracellular matrix. Here, we focused on the development of novel zinc-doped hydroxyapatite (ZnHAP) nanoparticles (1, 2 and 3 wt%; size: 50–60 nm) incorporated chitosan–gelatin (CG) nanocomposite scaffold, with an interconnected porous structure. The addition of ZnHAP nanoparticles decreases the pore size (∼30 µm) of the CG scaffolds. It was observed that with the increase in the concentration of ZnHAP nanoparticles (3 wt%) in CG scaffolds, the swelling ratio (1760% ± 2.0%), porosity (71% ± 0.98%) and degradation rate (35%) decreased, whereas mechanical property (1 MPa) increased, which was better as compared to control (CG) samples. Similarly, the high deposition of apatite crystals especially CG-ZnHAP3 nanocomposite scaffold revealed the excellent osteoconductive potential among all other scaffolds. MC3T3-E1 osteoblastic cells seeded with CG-ZnHAP nanocomposite scaffolds depicted better cell adhesion, proliferation and differentiation to osteogenic lineages. Finally, the chorioallantoic membrane (CAM) assay revealed better angiogenesis of ZnHAP nanoparticles (3 wt%) loaded CG scaffolds supporting vascularization after 7th day incubation in the CAM area. Overall, the results showed that the CG-ZnHAP3 nanocomposite scaffold could be a potential candidate for bone defect repair.
Current and future adaptation potential of heat-tolerant maize in Cameroon: a combined attribution and adaptation study
Authors: Jansen Lennart , Undorf Sabine , Gornott Christoph
Published: December 2024

Sub-Saharan Africa is projected to be exposed to substantial climate change hazards, especially in its agricultural sector, so adaptation will be necessary to safeguard crop yields. Tropical and subtropical maize production regions approach critical temperature thresholds in the growing season already in today’s climate, and climate change might already be contributing to this. In this study we analyse the impact of anthropogenic climate change on maize yields and the potential for adaptation in Cameroon. We innovate by introducing a counterfactual climate as baseline to a definition for adaptation potential proposed in the literature to assess the relative benefit heat-tolerant crop varieties have already under current and under projected climate change. Spatially detailed simulations of maize yields are performed using the process-based crop model APSIM with W5E5 reanalysis data and bias-corrected and downscaled climate model data from CMIP6/ISIMIP3b for counterfactual, historical and projected future climate scenarios SSP1-2.6 and SSP3-7.0. It is found that unadapted maize yields experience significant losses under all climate change scenarios, with mean losses of 0.3 t ha−1 for the current period compared to the counterfactual climate without anthropogenic climate forcings and that yields are significantly higher for the heat-tolerant varieties across all scenarios simulated. Yield impacts of heat tolerance are highest under projected climate change, making it effective climate change adaptation. This result is robust to the exact value of parameterised heat tolerance. Breeding heat-tolerant varieties as parameterised in this study can be an effective adaptation but is still not enough to mitigate simulated losses under a high-emissions scenario.
Mineralogy as a potential driver of irregular radiocarbon patterns among Icelandic fluvial carbon pools
Authors: Gallarotti Nora , Bröder Lisa , Lattaud Julie , Wartenweiler Stephan , Haghipour Negar , Eglinton Timothy I
Published: December 2024

Fluvial export of organic carbon (OC) from the terrestrial biosphere to the ocean forms a key component of the global carbon cycle. Carbon sources and transformations along the land–ocean aquatic continuum are dynamic with a complex interplay between particulate and dissolved organic and inorganic carbon pools (POC, DOC, DIC). Radiocarbon dating serves as a valuable tool, providing crucial insights into turnover and residence times within these pools. However, the myriad of carbon sources, including ancient ‘petrogenic’ OC from sedimentary rocks or freshly assimilated OC derived from aquatic in-situ production, makes it challenging to interpret 14C signatures in the context of terrestrial biospheric OC turnover and residence times. Icelandic rivers and streams offer an opportunity to examine biospheric carbon dynamics due to the virtual absence of petrogenic OC (e.g., shales, carbonates) in underlying bedrock. Our study of 43 rivers and streams, collectively draining approximately 42% of Iceland’s surface, revealed that radiocarbon signatures of POC largely align with global river patterns but lacked the presence of significantly old (14C-depleted) carbon likely reflecting the absence of ancient petrogenic OC. In contrast, DOC tended to be older compared to global rivers and the corresponding POC and DIC pools in Icelandic rivers. These observations challenge the paradigm that riverine POC generally exhibits longer turnover and residence times than DOC. After excluding other potential factors, we argue that this apparent age inversion among carbon pools in Icelandic rivers may reflect retention of DOC prior to its release to the aquatic continuum through interactions with high surface area minerals prevalent in the volcanic soils of Iceland. This finding may be relevant for other fluvial systems draining volcanic bedrock and have broader implications regarding biospheric OC dynamics in rivers and streams globally.
Particle-in-cell simulations of electron beam-plasma discharge in a narrow gap with varying transverse boundary conditions
Authors: Chen Jiahong , Chen Jian , Cao Qinchuang , Wang Zhibin
Published: December 2024

In this paper, the effects of transverse boundary conditions, specifically the bias voltage on the transverse wall and the gap width, on electron beam-generated plasmas (EBPs) confined in a narrow gap, are investigated using the particle-in-cell/Monte Carlo collision (PIC/MCC) simulations. Simulation results reveal that the application of bias voltage causes beam deflections, leading to the formation of band structures in the beam electron velocity space. Three branches of electrostatic waves, including electron beam mode, Langmuir wave, and electron acoustic mode, are identified. Increasing the bias voltage and reducing gap width intensify beam deflections, resulting in the suppression of waves. Both wave excitation and beam deflection significantly modify beam electron transport, leading to the plasma non-uniformity. These findings enhance the understanding of beam transport and plasma behavior in discharges confined in a narrow gap.
Effectiveness of behavior change techniques to address barriers to follow-up colonoscopy: results from an online survey and randomized factorial experiment
Authors: Kerrison Robert S , Gil Natalie , Stoffel Sandro , Hirst Yasemin , Whitaker Katriina L , Rees Colin , Duffy Stephen , von Wagner Christian
Published: December 2024

Background

Nonattendance at colonoscopy is associated with reduced colorectal cancer (CRC) survival.

Purpose

The aim of this research was to quantify barriers to colonoscopy and test the effectiveness of behavior change techniques (BCTs) to address them.

Methods

Two studies were conducted. In the first study, participants were asked to imagine their next CRC screening result was abnormal, and were presented with the standard abnormal result letter used in the English CRC Screening Programme. Participants then completed a short survey. Multivariate regression tested associations between perceived barriers and intentions. In the second study, participants were randomly presented with a modified version of the abnormal results letter, which incorporated one or more BCTs, designed to target barriers identified in study 1, using a 28 factorial design. Participants then completed the same survey used in study 1. Multivariate regression tested the effectiveness of the BCTs to modify target barriers and intentions.

Results

In study 1, 5 items were associated with intentions, namely “Lack of understanding that CRC can be asymptomatic,” “Perceived importance of screening,” “Transport/travel,” “Shared decision making and family influenced participation,” and “Fear of pain and discomfort” (all P’s < .05). In study 2, the inclusion of a social support message, targeting “shared decision-making and family influenced participation,” facilitated independent decision making and increased intentions (both P’s < .05). There was no evidence to support the remaining 7 BCTs to modify barriers or intentions (all P’s < .05).

Conclusions

Inclusion of a social support message facilitated independent decision-making and improved intentions.
The iPhylo suite: an interactive platform for building and annotating biological and chemical taxonomic trees
Authors: Li Yueer , Peng Chen , Chi Fei , Huang Zinuo , Yuan Mengyi , Zhou Xin , Jiang Chao
Published: December 2024

Accurate and rapid taxonomic classifications are essential for systematically exploring organisms and metabolites in diverse environments. Many tools have been developed for biological taxonomic trees, but limitations apply, and a streamlined method for constructing chemical taxonomic trees is notably absent. We present the iPhylo suite (https://www.iphylo.net/), a comprehensive, automated, and interactive platform for biological and chemical taxonomic analysis. The iPhylo suite features web-based modules for the interactive construction and annotation of taxonomic trees and a stand-alone command-line interface (CLI) for local operation or deployment on high-performance computing (HPC) clusters. iPhylo supports National Center for Biotechnology Information (NCBI) taxonomy for biologicals and ChemOnt and NPClassifier for chemical classifications. The iPhylo visualization module, fully implemented in R, allows users to save progress locally and customize the underlying R code. Finally, the CLI module facilitates analysis across all hierarchical relational databases. We showcase the iPhylo suite’s capabilities for visualizing environmental microbiomes, analyzing gut microbial metabolite synthesis preferences, and discovering novel correlations between microbiome and metabolome in humans and environment. Overall, the iPhylo suite is distinguished by its unified and interactive framework for in-depth taxonomic and integrative analyses of biological and chemical features and beyond.
R3Design: deep tertiary structure-based RNA sequence design and beyond
Authors: Tan Cheng , Zhang Yijie , Gao Zhangyang , Cao Hanqun , Li Siyuan , Ma Siqi , Blanchette Mathieu , Li Stan Z
Published: December 2024

The rational design of Ribonucleic acid (RNA) molecules is crucial for advancing therapeutic applications, synthetic biology, and understanding the fundamental principles of life. Traditional RNA design methods have predominantly focused on secondary structure-based sequence design, often neglecting the intricate and essential tertiary interactions. We introduce R3Design, a tertiary structure-based RNA sequence design method that shifts the paradigm to prioritize tertiary structure in the RNA sequence design. R3Design significantly enhances sequence design on native RNA backbones, achieving high sequence recovery and Macro-F1 score, and outperforming traditional secondary structure-based approaches by substantial margins. We demonstrate that R3Design can design RNA sequences that fold into the desired tertiary structures by validating these predictions using advanced structure prediction models. This method, which is available through standalone software, provides a comprehensive toolkit for designing, folding, and evaluating RNA at the tertiary level. Our findings demonstrate R3Design’s superior capability in designing RNA sequences, which achieves around $44\%$ in terms of both recovery score and Macro-F1 score in multiple datasets. This not only denotes the accuracy and fairness of the model but also underscores its potential to drive forward the development of innovative RNA-based therapeutics and to deepen our understanding of RNA biology.
Machine learning–enabled virtual screening indicates the anti-tuberculosis activity of aldoxorubicin and quarfloxin with verification by molecular docking, molecular dynamics simulations, and biological evaluations
Authors: Zheng Si , Gu Yaowen , Gu Yuzhen , Zhao Yelin , Li Liang , Wang Min , Jiang Rui , Yu Xia , Chen Ting , Li Jiao
Published: December 2024

Drug resistance in Mycobacterium tuberculosis (Mtb) is a significant challenge in the control and treatment of tuberculosis, making efforts to combat the spread of this global health burden more difficult. To accelerate anti-tuberculosis drug discovery, repurposing clinically approved or investigational drugs for the treatment of tuberculosis by computational methods has become an attractive strategy. In this study, we developed a virtual screening workflow that combines multiple machine learning and deep learning models, and 11 576 compounds extracted from the DrugBank database were screened against Mtb. Our screening method produced satisfactory predictions on three data-splitting settings, with the top predicted bioactive compounds all known antibacterial or anti-TB drugs. To further identify and evaluate drugs with repurposing potential in TB therapy, 15 screened potential compounds were selected for subsequent computational and experimental evaluations, out of which aldoxorubicin and quarfloxin showed potent inhibition of Mtb strain H37Rv, with minimal inhibitory concentrations of 4.16 and 20.67 μM/mL, respectively. More inspiringly, these two compounds also showed antibacterial activity against multidrug-resistant TB isolates and exhibited strong antimicrobial activity against Mtb. Furthermore, molecular docking, molecular dynamics simulation, and the surface plasmon resonance experiments validated the direct binding of the two compounds to Mtb DNA gyrase. In summary, our effective comprehensive virtual screening workflow successfully repurposed two novel drugs (aldoxorubicin and quarfloxin) as promising anti-Mtb candidates. The verification results provide useful information for the further development and clinical verification of anti-TB drugs.
Introduction: Motherhood, Mobility, Migration in Twenty-First-Century Women’s Writing
Authors: Kačkutė Eglė , Heffernan Valerie
Published: December 2024

Despite the centrality of experiences of migration, exile, and displacement in our globalized world, there are surprisingly few literary narratives that tell the stories of mothers who mother on the move, who mother in or through several languages, across linguistic and cultural barriers, or who negotiate non-motherhood in transnational settings. This special issue seeks to right this imbalance by drawing attention to matrifocal and maternal narratives of migration, displacement, exile, expatriation, transnationality, and nomadism since they shed light on ways in which motherhood is negotiated in this relatively new reality. It explores the diversity of literary representations of migrant motherhood in contemporary women’s writing and reflects on the poetics of motherhood and mothering across literature in different cultures and languages. In this way, the special issue contributes to the understanding of motherhood in a contemporary globalized world by shedding light on what often falls outside of the Western discourses of motherhood and mothering, thus offering fresh ways of imagining and living motherhood that is agential, empowered, and relational.
A Drosophila model of mucopolysaccharidosis IIIB
Authors: Simkhada Bibhu , Nazario-Yepiz Nestor O , Freymuth Patrick S , Lyman Rachel A , Shankar Vijay , Wiggins Kali , Flanagan-Steet Heather , Basu Amrita , Weiss Ryan J , Anholt Robert R H , Mackay Trudy F C
Published: December 2024

Mucopolysaccharidosis type IIIB is a rare lysosomal storage disorder caused by defects in alpha-N-acetylglucosaminidase (NAGLU) and characterized by severe effects in the central nervous system. Mutations in NAGLU cause accumulation of partially degraded heparan sulfate in lysosomes. The consequences of these mutations on whole-genome gene expression and their causal relationships to neural degeneration remain unknown. Here, we used the functional Drosophila melanogaster ortholog of NAGLU, Naglu, to develop a fly model for MPS IIIB induced by gene deletion (NagluKO), missense (NagluY160C), and nonsense (NagluW422X) mutations. We used the Drosophila activity monitoring system to analyze activity and sleep and found sex- and age-dependent hyperactivity and sleep defects in mutant flies. Fluorescence microscopy on mutant fly brains using Lysotracker dye revealed a significant increase in acidic compartments. Differentially expressed genes determined from RNA sequencing of fly brains are involved in biological processes that affect nervous system development. A genetic interaction network constructed using known interacting partners of these genes consists of 2 major subnetworks, one of which is enriched in genes associated with synaptic function and the other with neurodevelopmental processes. Our data indicate that lysosomal dysfunction arising from disruption of heparan sulfate breakdown has widespread effects on the steady state of intracellular vesicle transport, including vesicles associated with synaptic transmission. Evolutionary conservation of fundamental biological processes predicts that the Drosophila model of mucopolysaccharidosis type IIIB can serve as an in vivo system for the future development of therapies for mucopolysaccharidosis type IIIB and related disorders.
The ATP-dependent DEAD-box RNA helicase Dbp2 regulates the glucose/nitrogen stress response in baker’s yeast by modulating reversible nuclear retention and decay of SKS1 mRNA
Authors: Paul Soumita , Das Subhadeep , Banerjea Mayukh , Chaudhuri Shouvik , Das Biswadip
Published: December 2024

In Saccharomyces cerevisiae, SKS1 mRNA encoding a glucose-sensing serine/threonine kinase belongs to “nucleus-retained” (NR) mRNAs representing a subset of otherwise normal transcripts, which exhibits slow nuclear export and excessively long nuclear dwell time. Nuclear retention of the SKS1 mRNA triggered by a 202 nt “export-retarding” nuclear zip code element promotes its rapid degradation in the nucleus by the nuclear exosome/CTEXT. In this investigation, we demonstrate that Dbp2p, an ATP-dependent DEAD-box RNA helicase binds to SKS1 and other NR-mRNAs and thereby inhibits their export by antagonizing with the binding of the export factors Mex67p/Yra1p. Consistent with this observation, a significant portion of these NR-mRNAs was found to localize into the cytoplasm in a yeast strain carrying a deletion in the DBP2 gene with the concomitant enhancement of its steady-state level and stability. This observation supports the view that Dbp2p promotes the nuclear retention of NR-mRNAs to trigger their subsequent nuclear degradation. Further analysis revealed that Dbp2p-dependent nuclear retention of SKS1 mRNA is reversible, which plays a crucial role in the adaptability and viability of the yeast cells in low concentrations of glucose/nitrogen in the growth medium. At high nutrient levels when the function of Sks1p is not necessary, SKS1 mRNA is retained in the nucleus and degraded. In contrast, during low glucose/nitrogen levels when Sks1p is vital to respond to such situations, the nuclear retention of SKS1 mRNA is relieved to permit its increased nuclear export and translation leading to a huge burst of cytoplasmic Sks1p.
A single-cell transcriptomic atlas reveals the cell differentiation trajectory and the response to virus invasion in swelling clove of garlic
Authors: Gao Song , Li Fu , Zeng Zheng , He Qiaoyun , Mostafa Hassan H A , Zhang Suling , Wang Taotao , Wang Yanzhou , Liu Touming
Published: December 2024

The garlic bulb comprises several cloves, the swelling growth of which is significantly hindered by the accumulation of viruses. Herein, we describe a single-cell transcriptomic atlas of swelling cloves with virus accumulation, which comprised 19 681 high-quality cells representing 11 distinct cell clusters. Cells of two clusters, clusters 7 (C7) and 11 (C11), were inferred to be from the meristem. Cell trajectory analysis suggested the differentiation of clove cells to start from the meristem cells, along two pseudo-time paths. Investigation into the cell-specific activity of invasive viruses demonstrated that garlic virus genes showed relatively low expression activity in cells of the clove meristem. There were 2060 garlic genes co-expressed with virus genes, many of which showed an association with the defense response. Five glutathione synthase/reductase genes co-expressed with virus genes displayed up-regulated expression, and the glutathione and related metabolites level showed an alteration in virus-invasive garlic clove, implying the role of glutathione in viral immunity of garlic. Our study offers valuable insights into the clove organogenesis and interaction between garlic and virus at single-cell resolution.
The antibacterial and antibiofilm role of cannabidiol against periodontopathogenic bacteria
Authors: Santos Anna Livia Oliveira , Santiago Mariana Brentini , Silva Nagela Bernadelli Sousa , Souza Sara Lemes , Almeida Joaquim Maurício Duarte , Martins Carlos Henrique Gomes
Published: December 2024

Aims

Bacterial resistance and systemic risks associated with periodontitis underscore the need for novel antimicrobial agents. Cannabis sativa is a promising source of antimicrobial molecules, and cannabidiol (CBD) attracts significant interest. This study evaluated the antibacterial and antibiofilm activity of CBD against periodontopathogens, and assessed its toxicity in vivo model.

Methods and results

Antibacterial activity was determined by the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Biofilm inhibition was determined the minimum inhibitory concentration of biofilm (MICB50). Toxicity was assessed using Caeonorhabditis elegans. The periodontopathogens tested were Actinomyces naeslundii (ATCC 19039), Peptostreptococcus anaerobius (ATCC 27337), Veillonella parvula (ATCC 17745), Fusobacterium nucleatum (ATCC 10953), and Aggregatibacter actinomycetemcomitans (ATCC 43717). CBD exhibited antibacterial effects with MICs of 0.39 to 3.12 µg ml−1 and MICB50 of 0.39 µg ml−1 to 1.56 µg ml−1 against biofilms, without toxicity below 375 µg ml−1.

Conclusion

The results suggest that CBD is a non-toxic product with antibacterial and antibiofilm potential, exhibiting promise as a therapeutic alternative for oral diseases.
Hybrid exons evolved by coupling transcription initiation and splicing at the nucleotide level
Authors: Mick Steven T , Carroll Christine L , Uriostegui-Arcos Maritere , Fiszbein Ana
Published: December 2024

Exons within transcripts are traditionally classified as first, internal or last exons, each governed by different regulatory mechanisms. We recently described the widespread usage of ‘hybrid’ exons that serve as terminal or internal exons in different transcripts. Here, we employ an interpretable deep learning pipeline to dissect the sequence features governing the co-regulation of transcription initiation and splicing in hybrid exons. Using ENCODE data from human tissues, we identified 80 000 hybrid first-internal exons. These exons often possess a relaxed chromatin state, allowing transcription initiation within the gene body. Interestingly, transcription start sites of hybrid exons are typically centered at the 3′ splice site, suggesting tight coupling between splicing and transcription initiation. We identified two subcategories of hybrid exons: the majority resemble internal exons, maintaining strong 3′ splice sites, while a minority show enrichment in promoter elements, resembling first exons. Diving into the evolution of their sequences, we found that human hybrid exons with orthologous first exons in other species usually gained 3′ splice sites or whole exons upstream, while those with orthologous internal exons often gained promoter elements. Overall, our findings unveil the intricate regulatory landscape of hybrid exons and reveal stronger connections between transcription initiation and RNA splicing than previously acknowledged.
Broad repression of DNA repair genes in senescent cells identified by integration of transcriptomic data
Authors: Frey Yann , Haj Majd , Ziv Yael , Elkon Ran , Shiloh Yosef
Published: December 2024

Cellular senescence plays a significant role in tissue aging. Senescent cells, which resist apoptosis while remaining metabolically active, generate endogenous DNA-damaging agents, primarily reactive oxygen species. Efficient DNA repair is therefore crucial in these cells, especially when they undergo senescence escape, resuming DNA replication and cellular proliferation. To investigate whether senescent cell transcriptomes reflect adequate DNA repair capacity, we conducted a comprehensive meta-analysis of 60 transcriptomic datasets comparing senescent to proliferating cells. Our analysis revealed a striking downregulation of genes encoding essential components across DNA repair pathways in senescent cells. This includes pathways active in different cell cycle phases such as nucleotide excision repair, base excision repair, nonhomologous end joining and homologous recombination repair of double-strand breaks, mismatch repair and interstrand crosslink repair. The downregulation observed suggests a significant accumulation of DNA lesions. Experimental monitoring of DNA repair readouts in cells that underwent radiation-induced senescence supported this conclusion. This phenomenon was consistent across various senescence triggers and was also observed in primary cell lines from aging individuals. These findings highlight the potential of senescent cells as ‘ticking bombs’ in aging-related diseases and tumors recurring following therapy-induced senescence.
Neutrophil extracellular traps have active DNAzymes that promote bactericidal activity
Authors: Ku Ti-Hsuan , Ram-Mohan Nikhil , Zudock Elizabeth J , Abe Ryuichiro , Yang Samuel
Published: December 2024

The mechanisms of bacterial killing by neutrophil extracellular traps (NETs) are unclear. DNA, the largest component of NETs was believed to merely be a scaffold with antimicrobial activity only through the charge of the backbone. Here, we demonstrate for the first time that NETs DNA is beyond a mere scaffold to trap bacteria and it produces hydroxyl free radicals through the spatially concentrated G-quadruplex/hemin DNAzyme complexes, driving bactericidal effects. Immunofluorescence staining showed potential colocalization of G-quadruplex and hemin in extruded NETs DNA, and Amplex UltraRed assay portrayed its peroxidase activity. Proximity labeling of bacteria revealed localized concentration of radicals resulting from NETs bacterial trapping. Ex vivo bactericidal assays revealed that G-quadruplex/hemin DNAzyme is the primary driver of bactericidal activity in NETs. NETs are DNAzymes that may have important biological consequences.
Generative design-enabled exploration of wireframe DNA origami nanostructures
Authors: Vetturini Anthony J , Cagan Jonathan , Taylor Rebecca E
Published: December 2024

Recent advances in computer-aided design tools have helped rapidly advance the development of wireframe DNA origami nanostructures. Specifically, automated tools now exist that can convert an input polyhedral mesh into a DNA origami nanostructure, greatly reducing the design difficulty for wireframe DNA origami nanostructures. However, one limitation of these automated tools is that they require a designer to fully conceptualize their intended nanostructure, which may be limited by their own preconceptions. Here, a generative design framework is introduced capable of generating many wireframe DNA origami nanostructures without the need for a predefined mesh. User-defined objectives that guide the generative process are input as either single- or multi-objective optimization problems. A graph grammar is used to both contextualize physical properties of the DNA nanostructure and control the types of generated design features. This framework allows a designer to explore upon and ideate among many generated nanostructures that comply with their own unique constraints. A web-based graphical user interface is provided, allowing users to compare various generated solutions side by side in an interactive environment. Overall, this work illustrates how a constrained generative design framework can be implemented as an assistive tool in exploring design-feature trade-offs of wireframe DNA nanostructures, resulting in novel wireframe nanostructures.
A scaleable inducible knockout system for studying essential gene function in the malaria parasite
Authors: Ramaprasad Abhinay , Blackman Michael J
Published: December 2024

The malaria parasite needs nearly half of its genes to propagate normally within red blood cells. Inducible ways to interfere with gene expression like the DiCre-lox system are necessary to study the function of these essential genes. However, existing DiCre-lox strategies are not well-suited to be deployed at scale to study several genes simultaneously. To overcome this, we have developed SHIFTiKO (frameshift-based trackable inducible knockout), a novel scaleable strategy that uses short, easy-to-construct, barcoded repair templates to insert loxP sites around short regions in target genes. Induced DiCre-mediated excision of the flanked region causes a frameshift mutation resulting in genetic ablation of gene function. Dual DNA barcodes inserted into each mutant enables verification of successful modification and induced excision at each locus and collective phenotyping of the mutants, not only across multiple replication cycles to assess growth fitness but also within a single cycle to identify specific phenotypic impairments. As a proof of concept, we have applied SHIFTiKO to screen the functions of malarial rhomboid proteases, successfully identifying their blood stage-specific essentiality. SHIFTiKO thus offers a powerful platform to conduct inducible phenotypic screens to study essential gene function at scale in the malaria parasite.