bluuebunny/crossref_metadata_2025 huggingface dataset:
The Full‐Length Genomic Sequence of the HLA‐B*46:01:25 Allele
Authors: Li LiXin , Tian Wei
Published: November 2024

Full genomic sequence shows HLA‐B*46:01:25 differs from HLA‐B*46:01:01:01 by a thymine substitution in exon 4.
The Novel HLA‐A*02:1138 Allele, Identified by Sanger Dideoxy Nucleotide Sequencing in a Chinese Individual
Authors: Ren Juan , Xie Zhicong , Zheng Endong , Zhou Ying , Wang Xiaoning
Published: November 2024

HLA‐A*02:1138 differs from HLA‐A*02:03:01:01 by one nucleotide in exon 2.
Climate change, bodies and diplomacy: Performing watery futures in Tuvalu
Authors: Saddington Liam
Published: November 2024

Climate change is one of the key foci of critical geopolitics in the twenty‐first century, with a proliferation of scholarship considering the international conferences, imaginaries, and securitisations of the climate crisis. Since 2019, Tuvalu has been using human bodies submerged in water – including diplomats, children, and politicians ‐ within its diplomacy to draw attention to the severity of the climate crisis. By examining contemporary Tuvaluan climate diplomacy, this article advocates for a greater engagement with feminist geopolitics to interrogate the embodied practices of climate diplomacy. It draws upon fieldwork conducted in the South Pacific in 2018 and 2019 including at the 50th Pacific Island Forum in Tuvalu. Firstly, this article explores the 2019 visit of the Secretary General of the United Nations to Tuvalu ‐ arguing the photoshoot of him wearing a formal suit in the lagoon connected the imaginary of Tuvalu as a ‘sinking island’ to a wider international community. Secondly, it considers the use of Tuvaluan schoolchildren playing in the water during the 50th Pacific Island Forum. It argues this constituted a vital territorial conjuncture that drew attention to Australia's inaction on climate change and the risk to Tuvalu's future from the rise of sea level. Thirdly, it considers the body of Simon Kofe, Foreign Minister of Tuvalu, during his addresses to COP26 and COP27 from firstly the lagoon in Funafuti and then the metaverse, to examine the shifting narratives of Tuvalu's future within its climate diplomacy. This article argues that climate diplomacy is a deeply embodied practice and human geography scholarship must be more attentive to the geopolitical work that bodies do within climate diplomacy to understand the temporalities and spatialities of diplomacy better.
Sparsity of stable primes for dynamical sequences
Authors: König Joachim
Published: November 2024

We show that a dynamical sequence of polynomials over a number field whose set of stable primes is of positive density must necessarily have a very restricted, and, in particular, virtually prosolvable dynamical Galois group. Together with existing heuristics, our results suggest, moreover, that a polynomial all of whose iterates are irreducible modulo a positive density subset of the primes must necessarily be a composition of linear functions, monomials, and Dickson polynomials.
Construction of varieties of low codimension with applications to moduli spaces of varieties of general type
Authors: Bangere Purnaprajna , Gallego Francisco Javier , Mukherjee Jayan , Raychaudhury Debaditya
Published: November 2024

We develop a new way of systematically constructing infinitely many families of smooth subvarieties of any given dimension , , and any given codimension in , embedded by complete subcanonical linear series, and, in particular, in the range of Hartshorne's conjecture. We accomplish this by showing the existence of everywhere non‐reduced schemes called ropes, embedded in , and by smoothing them. In the range , we construct smooth subvarieties, embedded by complete subcanonical linear series, that are not complete intersections. We also go beyond a question of Enriques on constructing simple canonical surfaces in projective spaces, and construct simple canonical varieties in all dimensions. The canonical map of infinitely many of these simple canonical varieties is finite birational but not an embedding. Finally, we show the existence of components of moduli spaces of varieties of general type (in all dimensions , ) that are analogues of the moduli space of curves of genus with respect to the behavior of the canonical map and its deformations. In many cases, the general elements of these components are canonically embedded and their codimension is in the range of Hartshorne's conjecture.
Effective upper bounds on the number of resonances in potential scattering
Authors: Cuenin Jean‐Claude
Published: November 2024

We prove upper bounds on the number of resonances and eigenvalues of Schrödinger operators with complex‐valued potentials, where is odd. The novel feature of our upper bounds is that they are effective, in the sense that they only depend on an exponentially weighted norm of V. Our main focus is on potentials in the Lorentz space , but we also obtain new results for compactly supported or pointwise decaying potentials. The main technical innovation, possibly of independent interest, are singular value estimates for Fourier‐extension type operators. The obtained upper bounds not only recover several known results in a unified way, they also provide new bounds for potentials that are not amenable to previous methods.
Dynamic Obstacle Avoidance Strategy for High-Speed Vehicles Via Constrained Model Predictive Control and Improved Artificial Potential Field
Authors: Xu Mingyang , Yue Ming , Gu Yao , Shangguan Jinyong , Zhao Xudong
Published: November 2024

The paper proposes an automatic planning and control strategy to keep the automatic driving high-speed vehicles collision-free based on the improved artificial potential field (APF) and constrained model predictive control (MPC). First, the road potential field satisfying the constraints of vehicle safe driving is constructed according to the driving characteristics of vehicles and road boundary conditions. Focusing on the influence of the speed and direction of the obstacle vehicle on the potential field, the dynamic obstacle vehicle potential field is established. Secondly, the road potential field and the dynamic obstacle vehicle potential field are incorporated into the objective function of the path planning module to establish a real-time path planner. Thirdly, the yaw stability constraints of the vehicle are established, which are added to the QP solver and updated in real-time according to the current vehicle states, so as to establish the constrained MPC controller. In the end, the safety of this planning and control strategy for obstacle avoidance overtaking and the effectiveness of constrained MPC in improving vehicle stability are verified by comparative simulation analysis in multi-obstacle vehicles scenarios.
Data-Driven Tracking Control of a Cushion Robot With Safe Autonomous Motion Considering Human-Machine Interaction Environment
Authors: Sun Ping , Shan Rui , Chang Hongbin , Wang Shuoyu
Published: November 2024

This study proposes a data-driven safety controller with velocity constraints for a cushion robot. We constructed a mathematical description of the human-machine interaction environment by decomposing the generalized input force and coefficient matrix in the dynamic model. We established a new equivalent data model, which considered various human-machine interaction environments using a pseudo-Jacobian matrix. A stochastic configuration network (SCN) estimation method for variations in the human-machine interaction environment was proposed, with hidden layer nodes added at random. We designed a safe autonomous navigation path and proposed a data-driven control method that limited the actual velocity while stabilizing the tracking error system. In addition, the desired motion velocity of the robot was designed. This approach has the advantage of ensuring safety at a specified velocity. We also demonstrated and validated the effectiveness of the proposed data-driven algorithm using simulation-based comparative analysis and an experimental study.
Sequential Versus Concurrent Effects in Combined Stress Solder Joint Reliability
Authors: Okafor Ekene Gabriel , Ruby Collin , Norris Mathew , Leda Andrew , Huitink David Ryan
Published: November 2024

Reliability risk in solder joints has been commonly linked to various failure mechanisms, with electromigration (EM) and fatigue among the prominent drivers. Even though these failure mechanisms often occur simultaneously, typical accelerated tests are based on a single failure mechanism. Consequently, the effect of multiple interacting failure mechanisms is ignored, which may underestimate reliability risk. This common practice has the potential to reduce life prediction accuracy. To address this gap, in this paper, we present an experimental setup that is developed and used to simultaneously evaluate SAC 305 solder joint lifetime under electromigration and fatigue failure mechanisms using sequential and concurrent approaches. The sequential approach involves prestressing the solder joint using a fixed current density and temperature until the test vehicle attains a specified rise in resistance. After that, an isothermal fatigue load was applied at three prescribed temperatures. The data collected enable the estimation of parameters used for reliability prediction. On the other hand, the concurrent case involves the simultaneous application of current density, temperature, and cyclic mechanical load to the solder joint. The correlation of the experiment and complementary numerically simulated strain energy density (SED) resulted in an improved, physic-based reliability model, which has the added benefit of reduced time and cost of data collection, especially during new product development. Unlike the concurrent approach, the sequential approach shows a defect-driven failure mode. The prediction accuracy of the concurrent-based derived characteristic life model compared to that of experiment-derived characteristic life was found to be ±25%.
Nonlinear Dynamic Analysis Framework for Slender Structures Using the Modal Rotation Method
Authors: Shizuno Yoshitaka , Dong Shuonan , Kuzuno Ryo , Okada Taiki , Kawashima Shugo , Makihara Kanjuro , Otsuka Keisuke
Published: November 2024

Owing to their low induced drag, high-aspect-ratio wings are often applied to aircraft, particularly high-altitude long-endurance (HALE) aircraft. An analytical method that considers geometrical nonlinearity is necessary for the analysis of high-aspect-ratio wings as they tend to undergo large deformations. Nonlinear shell/plate or solid finite element methods are widely used for the static analysis of wing strength. However, an increase in the number of elements drastically increases the computational costs owing to the complexity of wing shapes. The modal rotation method (MRM) can avoid this additional expense by analyzing large deformations based on modes and stiffness matrices obtained from any linear or linearized model. However, MRM has only been formulated as a static analysis method. In this study, a novel modal-based dynamic analysis framework, referred to as dynamic MRM (DMRM), is developed to analyze slender cantilever structures. This paper proposes a method to discretize dynamics by capitalizing on the fact that MRM considers geometrical nonlinearity based on deformed shapes. The proposed method targets slender structures with small strains and large displacements and considers geometrical nonlinearity, but not material nonlinearity. Additionally, a formulation method for the work performed by a follower force is proposed. The energy stored in the structure agreed with the work performed by an external force in each performed simulation. DMRM achieved a 95% reduction in the calculation time compared with a nonlinear plate finite element method in a performed simulation.
Techniques for modeling ocean soundscapes: Detailed description for wind contributions
Authors: Siderius Martin , Ainslie Michael A. , Gebbie John , Schäfke Alexandra , Chapman N. Ross , Martin Bruce , Gemba Kay L.
Published: November 2024

Wind over the ocean creates breaking waves that generate air-filled bubbles, which radiate underwater sound. This wind-generated sound is a significant component of the ocean soundscape, and models are essential for understanding and predicting its impact. Models for predicting sound pressure level (SPL) from wind have been studied for many years. However, the terminology and definitions behind modeling approaches have not been unified, and ambiguity has led to differences in predicted SPL. The 2022 Ambient Sound Modeling Workshop was organized to compare ambient sound modeling approaches from different researchers. The main goal of the workshop was to quantify differences in predicted SPL and related quantities for different approaches and, to the extent possible, determine the cause of the differences for a specific, well-defined scenario. Results revealed a variation of approximately 6 dB across different research groups, with differences reaching up to 10 dB in some cases compared to the benchmark results described in this paper. These variations stemmed from differing methodologies and underlying assumptions. In this paper, step-by-step guidance is given for modeling SPL due to wind. The workshop test case will be described, and results from the modeling approaches described here will be compared with those from the workshop participants.
Underwater acoustic spiral wavefront transducer with low phase directionality error
Authors: Guo Rongzhen , Lu Wei , Lan Yu
Published: November 2024

The phase and azimuth angle of acoustic spiral wavefronts are linearly related. Based on this phase directionality of spiral wavefronts, the complex azimuth determination of the positioning of unmanned underwater vehicles can be converted into simple phase acquisition processes, where the azimuth determination accuracy is influenced by the phase directionality error of a spiral wavefront transducer. This study proposes a spiral wavefront transducer that improves the underwater positioning accuracy. The transducer can emit low-frequency acoustic spiral wavefronts with low phase directionality error. Moreover, the causes of the phase directionality error of phased-spiral transducers are discussed, and optimization design principles for minimizing the error were presented. Subsequently, a transducer prototype is designed, fabricated, and tested. In the experiment, the transmitting voltage response and phase directionality of the prototype in a water tank are measured, and experimental results well agreed with the simulation results. For the prototype, the resonance frequency is 1312 Hz, the maximum transmitting voltage response is 129.7 dB, and the phase directionality error is 1.45°.
Intrasubject variability in potential early markers of sensorineural hearing damage
Authors: De Poortere Nele , Keshishzadeh Sarineh , Keppler Hannah , Dhooge Ingeborg , Verhulst Sarah
Published: November 2024

The quest for noninvasive early markers for sensorineural hearing loss (SNHL) has yielded diverse measures of interest. However, comprehensive studies evaluating the test-retest reliability of multiple measures and stimuli within a single study are scarce, and a standardized clinical protocol for robust early markers of SNHL remains elusive. To address these gaps, this study explores the intra-subject variability of various potential electroencephalogram- (EEG-) biomarkers for cochlear synaptopathy (CS) and other SNHL-markers in the same individuals. Fifteen normal-hearing young adults underwent repeated measures of (extended high-frequency) pure-tone audiometry, speech-in-noise intelligibility, distortion-product otoacoustic emissions (DPOAEs), and auditory evoked potentials; comprising envelope following responses (EFR) and auditory brainstem responses (ABR). Results confirm high reliability in pure-tone audiometry, whereas the matrix sentence-test exhibited a significant learning effect. The reliability of DPOAEs varied across three evaluation methods, each employing distinct SNR-based criteria for DPOAE-datapoints. EFRs exhibited superior test-retest reliability compared to ABR-amplitudes. Our findings emphasize the need for careful interpretation of presumed noninvasive SNHL measures. While tonal-audiometry's robustness was corroborated, we observed a confounding learning effect in longitudinal speech audiometry. The variability in DPOAEs highlights the importance of consistent ear probe replacement and meticulous measurement techniques, indicating that DPOAE test-retest reliability is significantly compromised under less-than-ideal conditions. As potential EEG-biomarkers of CS, EFRs are preferred over ABR-amplitudes based on the current study results.
Accuracy of an Activity Monitor in Assessing Physical Activity of Hospitalized Geriatric Rehabilitation Patients With Slow Walking Speed Using a Walking Aid
Authors: van Dijk Margaretha , Bijnens Wouter , Van Driessche Catoo , Van Meerbeek Toon , Allegaert Patsy , Van Cleynenbreugel Heleen , Verschueren Sabine , Verheyden Geert , Tournoy Jos , Flamaing Johan
Published: November 2024

Background/Objectives: Accurate assessment of physical activity is essential in hospital settings, but difficult for geriatric rehabilitation patients who have slow walking speed and rely on walking aids. This study conducted an external validation of the MOX activity monitor accuracy in distinguishing between sedentary (lying, sitting), standing, and dynamic activities among hospitalized geriatric rehabilitation patients. Additionally, the study assessed clinical tolerance and ease of use of the monitor. Methods: Inclusion criteria were being hospitalized on the geriatric rehabilitation ward, aged 70 years or older, and using a walking aid. The monitor was placed on the upper leg, and remained in place for 1 week. In a test-session, four activities of 4 min each (lying, sitting, standing, and walking) were filmed. Video analyses created a direct observation timeline. Daily skin irritation assessments were conducted and participants noted their discomfort level at the week’s end. Results: The study included 20 participants who relied on walking aids, with 10 requiring additional physical support while walking. The MOX activity monitor exhibited excellent accuracy in classifying the four activities, with a zero mean percentage error for sedentary activity, 2.2% for standing, and 2.7% for walking. Participants reported minimal hindrance, and the monitor proved user-friendly. Conclusion: The MOX activity monitor demonstrated remarkable accuracy in distinguishing between these four activities in a test-session and displayed strong clinical applicability. Significance: The monitor shows substantial promise as a valuable tool for assessing physical activity in hospitalized geriatric rehabilitation patients using walking aids.
It Has To Be My Way—Reducing Sedentary Time in the Transition to Retirement
Authors: Hultman Lisa , Eklund Caroline , von Heideken Wågert Petra , Söderlund Anne , Elfström Magnus L.
Published: November 2024

Background: Sedentary behavior is highly prevalent in older adults transitioning to retirement. Sedentary time is all of the time spent in sedentary behavior, and prolonged sedentary time is associated with an increased risk of noncommunicable diseases. The aim of this study was to explore perceptions among older adults transitioning from working life to retirement regarding self-management strategies for reducing sedentary time and adhering to the reduced sedentary time. Methods: Twenty-eight older adults, age 60–75 years, participated in one of four focus group interviews. Qualitative content analysis was used to analyze the data. Results: The analysis resulted in the theme “It has to be my way,” and the three categories “Activities scattered with joyfulness,” “Support for changes in everyday life,” and “Health affects willingness and ability, and is affected by adherence.” Conclusions: Interpreted from the perspective of self-determination theory, self-management strategies for reducing sedentary time should be adaptable as every individual is unique, indicating a need for autonomy. Sedentary time was said to be reduced by activities that evoked joyfulness, and joyfulness was considered to increase adherence. Support for changes to one’s everyday life was considered necessary. The support that was mentioned primarily involved targeting cognitive determinants such as self-efficacy and attitudes. This new knowledge can be included when designing self-management interventions; however, more research is needed in order to evaluate whether self-management strategies targeting autonomous motivation and affective determinants, such as affective judgment and cognitive determinants, can reduce sedentary time in those who are in the transition to retirement.
A Systematic Review of the Effects of Breaking up/Interrupting Sedentary Behavior on Health Outcomes Among Community-Dwelling Adults 60+ Years
Authors: Swartz Ann M. , Steinbrink Garrett M. , Strath Scott J. , Mitra Tarini , Morelli Whitney A.
Published: November 2024

Background/Objectives: The aim of this systematic review was to evaluate the available evidence regarding the impact of breaks in sedentary time on cardiovascular, metabolic, functional, and psychosocial health of adults aged 60 years and older. Methods: A systematic search of databases was performed in May 2024. This review was registered with PROSPERO (#374311) and has been reported using the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Results: A total of seven articles (five unique studies) were included. The available evidence suggests minimal changes in health-related variables. Specifically, changes to cardio-metabolic and psychosocial variables were limited. Changes to physical function appear to show the most promise. While only one of the studies included focused solely on reducing sedentary behavior, all others focused on reducing sedentary behavior by increasing physical activity. Two of the seven articles showed significant changes compared with the control group to sedentary time ranging from 32 to 58 min. Mean sedentary bout time and number of sedentary bouts longer than 30 min were reduced in two of the seven articles. No changes in sit-to-stand transitions were reported. Conclusion: There is limited evidence focusing on the impact of breaks or interruptions to sedentary time on the physical and mental health of community-dwelling adults 60+ years. Significance/Implications: This systematic review examines recent research aimed to disrupt sedentary behavior and positively impact health in community-dwelling older adults. Results show the difficulty of increasing sit-to-stand transitions/breaks in sedentary behavior, and highlight the challenge of disentangling the effects of sedentary behavior, and physical activity on health.
Radioisotopic chronology of Ocean Anoxic Event 1a: Framework for analysis of driving mechanisms
Authors: Li Youjuan , Singer Brad S. , Takashima Reishi , Schmitz Mark D. , Podrecca Luca G. , Sageman Bradley B. , Selby David , Yamanaka Toshiro , Mohr Michael T. , Hayashi Keiichi , Tomaru Taiga , Savatic Katarina
Published: November 2024

The timing, tempo, and causative mechanisms of Ocean Anoxic Event 1a (OAE1a), one of several such abrupt perturbations of the Mesozoic global carbon cycle, remain uncertain. Mudstones interbedded with tuffs in Hokkaido, Japan preserve carbon and osmium isotope shifts recording OAE1a. U-Pb zircon ages of tuffs constrain the OAE1a onset to 119.55 +0.072/−0.079 million years ago (Ma) and its duration to 1116 +87/−93 thousand years (kyr). Isotopic excursions of osmium followed by carbon that mark the rapid onset of OAE1a each lasted ~115 kyr. Critically, the occurrence of index fossil
Leupoldina cabri
in the Hokkaido OAE1a section, which also caps and thus postdate Ontong Java Plateau (OJP) basalts, has a U-Pb zircon age of ~118.7 to 118.4 Ma. Therefore, OJP volcanism remains a probable source of unradiogenic osmium and light carbon and a causative mechanism of OAE1a.
Bioinspired catalytic pocket promotes CO
2
-to-ethanol photoconversion on colloidal quantum wells
Authors: Pan Rongrong , Wang Qi , Zhao Yan , Feng Zhendong , Xu Yanjun , Wang Zhuan , Li Yapeng , Zhang Xiuming , Zhang Haoqing , Liu Jia , Gu Xiang-Kui , Zhang Jiangwei , Weng Yuxiang , Zhang Jiatao
Published: November 2024

Sluggish surface reaction is a critical factor that strongly governs the efficiency of photocatalytic solar fuel production, particularly in CO
2
-to-ethanol photoconversion. Here, inspired by the principles underlying enzyme catalytic proficiency and specificity, we report a biomimetic photocatalyst that affords superior CO
2
-to-ethanol photoreduction efficiency (5.5 millimoles gram
−1
hour
−1
in average with 98.2% selectivity) distinctly surpassing the state of the art. The key is to create a class of catalytic pocket, which contains spatially organized NH
2
…Cu-Se(-Zn) multiple functionalities at close range, over ZnSe colloidal quantum wells. Such structure offers a platform to mimic the concerted cooperation between the active site and surrounding secondary/outer coordination spheres in enzyme catalysis. This is manifested by the chemical adsorption and activation of CO
2
via a bent geometry, favorable stabilization toward a variety of important intermediates, promotion of multielectron/proton transfer processes, etc. These results highlight the potential of incorporating enzyme-like features into the design of photocatalysts to overcome the challenges in CO
2
reduction.
MEMS-metasurface–enabled mode-switchable vortex lasers
Authors: Wang Chuanshuo , Meng Chao , Mei Xianglong , Gui Lili , Thrane Paul C. V. , Chen Hao , Ding Fei , Xu Kun , Bozhevolnyi Sergey I.
Published: November 2024

Compared to conventional lasers limited to generating static modes, mode-switchable lasers equipped with adjustable optics significantly enhance the flexibility and versatility of coherent light sources. However, most current approaches to achieving mode-switchable lasers depend on conventional, i.e., inherently bulky and slow, optical components. Here, we demonstrate fiber lasers empowered by electrically actuated intracavity microelectromechanical system (MEMS)–based optical metasurface (MEMS-OMS) enabling mode switching between fundamental Gaussian and vortex modes at ~1030 nm. By finely adjusting the voltage applied to the MEMS mirror, high-contrast switching between Gaussian (
l
= 0) and vortex (
l
= 1, 2, 3, and 5, depending on the OMS arrangement) laser modes is achieved, featuring high mode purities (>95%) and fast responses (~100 microseconds). The proposed intracavity MEMS-OMS–enabled laser configuration provides an at-source solution for generating high-purity fast-switchable laser modes, with potential applications ranging from advanced optical imaging to optical tweezers, optical machining, and intelligent photonics.
Imaging dendrite growth in solid-state sodium batteries using fluorescence tomography technology
Authors: Yang Shuaishuai , Li Na , Zhao Enyue , Wang Chengzhi , He Jingxin , Xiao Xiong , Fang Debao , Ni Qing , Han Xile , Xue Xiaobin , Chen Lai , Li Ning , Li Jingbo , Guo Tuan , Su Yuefeng , Jin Haibo
Published: November 2024

Dendrite growth in solid-state sodium batteries (SSBs) is one of the most concerned issues that critically affect the battery efficiency and cycling performance. Here, by designing a fluorescent Eu
3+
-doped Na
3
Zr
2
Si
2
PO
12
solid electrolyte (SE) to facilitate three-dimensional (3D) optical imaging on a confocal laser scanning microscopy, a fluorescence tomography (FT) method is developed for observing the sodium dendrite growth during charge/discharge cycles of the SSBs in a 3D view. It is quantitatively revealed that small-size sodium islands appear after several cycles, and with the cycles increasing, large-size dendrites in tens of micrometers gradually form until a critical sodium dendrite volume arrives where a short circuit or severe performance deterioration occurs. Furthermore, by regulating the Eu
3+
doping ratio, a record-high sodium plating/stripping cycling stability for more than 1 year (487.5 days) is achieved at 25°C. This work demonstrates an FT method observing sodium dendrite growth in SSBs and will promote the functional design of high-performance SEs.
Electron confinement–induced plasmonic breakdown in metals
Authors: Das Prasanna , Rudra Sourav , Rao Dheemahi , Banerjee Souvik , Indiradevi Ashalatha , Garbrecht Magnus , Boltasseva Alexandra , Bondarev Igor V. , Shalaev Vladimir M. , Saha Bivas
Published: November 2024

Plasmon resonance represents the collective oscillation of free electron gas density and enables enhanced light-matter interactions in nanoscale dimensions. Traditionally, the classical Drude model describes plasmonic excitation, wherein plasma frequency exhibits no spatial dispersion. Here, we show conclusive experimental evidence of the breakdown of plasmon resonance and a consequent metal-insulator transition in an ultrathin refractory plasmonic material, hafnium nitride (HfN). Epitaxial HfN thick films exhibit a low-loss and high-quality Drude-like plasmon resonance in the visible spectral range. However, as the film thickness is reduced to nanoscale dimensions, Coulomb interaction among electrons increases because of electron confinement, leading to the spatial dispersion of plasma frequency. With a further decrease in thickness, electrons lose their ability to shield the incident electric field, turning the medium into a dielectric. The observed metal-insulator transition might carry some signatures of Wigner crystallization and indicates that such transdimensional, between 2D and 3D, films can serve as a promising playground to study strongly correlated electron systems.
Entangled and non-modular enhancer sequences producing independent spatial activities
Authors: Museridze Mariam , Ceolin Stefano , Mühling Bettina , Ramanathan Srishti , Barmina Olga , Sekhar Pallavi Santhi , Gompel Nicolas
Published: November 2024

The modularity of transcriptional enhancers is central to our understanding of morphological evolution, allowing specific changes to a gene expression pattern component, without affecting others. Enhancer modularity refers to physically separated stretches of regulatory sequence producing discrete spatiotemporal transcriptional activity. This concept stems from assays that test the sufficiency of a DNA segment to drive spatial reporter expression resembling that of the corresponding gene. Focusing on spatial patterns, it overlooks quantitative aspects of gene expression, underestimating the regulatory sequence actually required to reach full endogenous expression levels. Here, we show that five regulatory activities of the gene
yellow
in
Drosophila
, classically described as modular, result from extensively overlapping sequences, with broadly distributed regulatory information. Nevertheless, the independent regulatory activities of these entangled enhancers appear to be nucleated by specific segments that we called enhancer cores. Our work calls for a reappraisal of enhancer definition and properties, as well as of the consequences on regulatory evolution.
LDC000067, a CDK9 inhibitor, unveils promising results in suppressing influenza virus infections
in vitro
and
in vivo
Authors: Zhang Mingxin , Lian Xiaoqin , Gao Yarou , Jiang Lefang , Li Zhuogang , Zhang Haonan , Su Yue , Peng Qun , Chen Xulin
Published: November 2024

Influenza virus infections continue to pose a significant threat to public health. Current anti-influenza drugs target viral proteins; however, the emergence of resistant strains has hampered their effectiveness. Fortunately, as with most viruses, influenza virus depends on various host factors during its replication cycle and in pathogenicity. Therefore, the manipulation of key host factors for viral replication to combat influenza has garnered increased attention due to its lesser tendency to induce viral mutation. Cyclin-dependent kinases (CDKs) are a family of protein kinases that regulate various cellular processes, including the cell cycle and transcription. While the specific involvement of CDKs in the transcription of influenza virus genes is less extensively studied than their roles in the cell cycle, some evidence suggests their potential contributions as anti-influenza drugs. Here, we report that LDC000067 (LDC), a highly specific CDK9 inhibitor, not only strongly suppressed influenza virus replication
in vitro
and
in vivo
but also emerged as a potential candidate for anti-influenza virus agents. Further investigation revealed that inhibition of CDK9 by LDC treatment and CDK9 silencing disrupts viral RNA transcription and the nuclear import of vRNPs, significantly suppressing influenza virus replication. Mechanistically, we showed that LDC treatment and CDK9 silencing reduce Pol II expressions, a requisite host protein for viral RNA transcription. Altogether, our findings indicate that CDK9 could be a promising target for developing antivirals against influenza virus infections, and LDC, with its strong anti-influenza properties, instills confidence in its potential as an effective anti-influenza agent.
Microbial communities associated with marine sponges from diverse geographic locations harbor biosynthetic novelty
Authors: Nowak Vincent V. , Hou Peng , Owen Jeremy G.
Published: November 2024

Marine sponges are a prolific source of biologically active small molecules, many of which originate from sponge-associated bacteria. Identifying the producing bacteria is a key step in developing sustainable routes for the production of these metabolites. To facilitate the required computational analyses, we developed MetaSing, a reproducible singularity-based pipeline for assembly, identification of high-quality metagenome-assembled genomes (MAGs), and analysis of biosynthetic gene clusters (BGCs) from metagenomic short-read data. We applied this pipeline to metagenomic sequencing data from 16 marine sponges collected from New Zealand, Tonga, and the Mediterranean Sea. This analysis yielded 643 MAGs representing 510 species. Of the 2,670 BGCs identified across all samples, 70.8% were linked to a MAG. Comparison of BGCs to those identified from previously sequenced bacteria revealed high biosynthetic novelty in variety of underexplored phyla, including Poribacteria, Acidobacteriota, and Dadabacteria. Alongside the observation that each sample contains unique biosynthetic potential, this holds great promise for natural product discovery and for furthering the understanding of different sponge holobionts.

IMPORTANCE

Discovery of new chemical compounds such as natural products is a crucial endeavor to combat the increasing resistance to antibiotics and other drugs. This manuscript demonstrates that microbial communities associated with marine sponges investigated in this work encode the potential to produce novel chemistry. Lesser studied bacterial taxa that are often difficult to cultivate are particularly rich in potential.
Minute virus of mice NS1 redirects casein kinase 2 specificity to suppress the ATR DNA damage response pathway during infection
Authors: Etingov Igor , Pintel David J.
Published: November 2024

During infection the autonomous parvovirus minute virus of mice (MVM) generates extensive DNA damage which facilitates virus replication and induces a cellular DNA damage response (DDR) driven by the ataxia telangiectasia mutated (ATM) kinase. Atypically, the ataxia telangiectasia and Rad-3-related (ATR) DDR pathway remains inactive. Upon DNA damage ATR is normally recruited to single-stranded DNA sequences formed at genomic DNA damage sites, and while within a multiprotein complex activates, via phosphorylation, the key DDR regulator checkpoint kinase 1 (Chk1). Inactivation of ATR during MVM infection leads to the accumulation of damaged DNA and enhancement of virus replication. Although ATR is inactivated, we show that during infection, the Chk1 activation pathway downstream of the initial ATR activating events remained functional. Activation of ATR, and consequently of Chk1, requires interaction with TopBP1, which itself is maintained in proximity to ATR by interaction with the phosphorylated S387 residue of Rad9, part of the Rad9-Hus1-Rad1 (911) complex. Both MVM infection and MVM NS1 overexpression inhibited Rad9 S387 phosphorylation and subsequent ATR activation. ATR inactivation during infection was suppressed by expression of Rad9 bearing a phosphomimetic 387 residue, indicating that this site, and the function it served, was the target of NS1 inhibition. NS1 interaction with CK2α and CK2α enzymatic activity was both required to prevent ATR activation, indicating MVM retargeted this kinase’s activity during infection. Inhibition of the protein phosphatase 2C (PP2C) prevented Rad9 S387 dephosphorylation and Chk1 inactivation during MVM infection and NS1 overexpression revealing its role in the pathway’s suppression.

IMPORTANCE

Infection by the parvovirus minute virus of mice (MVM) causes significant DNA damage and induces a potent DNA damage response (DDR) which the virus exploits to further its replication. The cell responds to infection with an ATM-regulated DDR; however, atypically, the ATR-regulated DDR pathway is disabled during infection. This prevents Chk1 activation, thus allowing the accumulation of damaged DNA which facilitates virus replication. We describe here how MVM, and specifically the main viral replication protein NS1, inhibits ATR activation. Activation of ATR, and consequently Chk1, requires TopBP1 localization into the activating complex via its interaction with a phosphorylated residue of Rad9. We show that NS1 redirects casein kinase 2 to activate a phosphatase in the PP2C family which causes dephosphorylation of this critical residue, thus inhibiting ATR activation. This work provides mechanistic insight into one of the ways by which parvoviruses modify the host DDR response to facilitate their replication.
Acarbose impairs gut
Bacteroides
growth by targeting intracellular glucosidases
Authors: Brown Haley A. , Morris Adeline L. , Pudlo Nicholas A. , Hopkins Ashley E. , Martens Eric C. , Golob Jonathan L. , Koropatkin Nicole M.
Published: November 2024

Acarbose is a type 2 diabetes medicine that prevents dietary starch breakdown into glucose by inhibiting host amylase and glucosidase enzymes. Numerous gut species in the
Bacteroides
genus enzymatically break down starch and change in relative abundance within the gut microbiome in acarbose-treated individuals. To mechanistically explain this observation, we used two model starch-degrading
Bacteroides
,
Bacteroides ovatus
(Bo), and
Bacteroides thetaiotaomicron
(Bt). Bt growth on starch polysaccharides is severely impaired by acarbose, whereas Bo growth is much less affected by the drug. The
Bacteroides
use a starch utilization system (Sus) to grow on starch. We hypothesized that Bo and Bt Sus enzymes are differentially inhibited by acarbose. Instead, we discovered that although acarbose primarily targets the Sus periplasmic GH97 enzymes in both organisms, the drug affects starch processing at multiple other points. Acarbose competes for transport through the TonB-dependent SusC proteins and binds to the Sus transcriptional regulators. Furthermore, Bo expresses a non-Sus GH97 (BoGH97D) when grown in starch with acarbose. The Bt homolog, BtGH97H, is not expressed in the same conditions, nor can overexpression of BoGH97D complement the Bt growth inhibition in the presence of acarbose. This work informs us about unexpected complexities of Sus function and regulation in
Bacteroides
, including variation between related species. Furthermore, this indicates that the gut microbiome may be a source of variable response to acarbose treatment for diabetes.

IMPORTANCE

Acarbose is a type 2 diabetes medication that works primarily by stopping starch breakdown into glucose in the small intestine. This is accomplished by the inhibition of host enzymes, leading to better blood sugar control via reduced ability to derive glucose from dietary starches. The drug and undigested starch travel to the large intestine where acarbose interferes with the ability of some bacteria to grow on starch. However, little is known about how gut bacteria interact with acarbose, including microbes that can use starch as a carbon source. Here, we show that two gut species,
Bacteroides ovatus
(Bo) and
Bacteroides thetaiotaomicron
(Bt), respond differently to acarbose: Bt growth is inhibited by acarbose, while Bo growth is less affected. We reveal a complex set of mechanisms involving differences in starch import and sensing behind the different Bo and Bt responses. This indicates the gut microbiome may be a source of variable response to acarbose treatment for diabetes via complex mechanisms in common gut microbes.
Beyond boundaries: Depositional environment controls on erodibility, process, and form in rivers incising sedimentary bedrock
Authors: Colaianne Nicholas J. , Shobe Charles M. , Moler Joseph , Benison Kathleen C. , Chilton Kristin D.
Published: November 2024

Bedrock rivers adjust to the properties of the rock into which they incise, imprinting the geologic past on Earth's surface. We compared rock properties and channel form along the Dry Fork in the Allegheny Mountains, West Virginia, as it crosses between Mississippian sandstone and carbonate rock units, to investigate how the depositional history of channel-margin bedrock influences modern channel form. We used thin-section petrography to interpret site-specific depositional environments. We quantified rock strength with point-load testing, discontinuity spacing by measuring bed and fracture spacing, and channel form through cross-section surveys. Petrography indicates that the sandstone was likely deposited in an alluvial fan, while the carbonate formed in a shallow-marine environment. The sandstone has modestly higher point-load strength than the carbonate, but the units differ more dramatically in their discontinuity spacing. The sandstone is thinly (3–10 cm) bedded and densely (50–100 cm) fractured; the carbonate has thicker (45 cm) beds and sparser (180–300 cm) fractures. Sandstone channel cross sections are wider, shallower, and rougher, whereas carbonate cross sections are narrower, deeper, and smoother. Results suggest that a transition from plucking-dominated erosion in the discontinuity-rich sandstone to abrasion- and/or dissolution-dominated erosion in the discontinuity-poor carbonate, rather than differences in rock strength, drives observed morphologic differences. Differences in discontinuity spacing might arise from differential bed thickness between the two units, both because bed boundaries are discontinuities and because thinner beds lead to more densely spaced fractures. We hypothesize that depositional dynamics—the unsteady deposition of an alluvial fan resulting in thin beds versus steady, shallow-marine deposition that deposited thicker beds—explain the observed differences in bed thickness, discontinuity spacing, and modern erosion process dominance and channel form, emphasizing how modern Earth-surface processes are contingent on the geologic past.
Recognising uncertainty: an integrated framework for palliative care in perinatal medicine
Authors: Wilkinson Dominic , Bertaud Sophie , Mancini Alexandra , Murdoch Edile
Published: November 2024

In perinatal medicine, the number of babies with life-limiting or life-threatening conditions is increasing and the benefits of providing palliative care with a holistic, interdisciplinary approach are well documented. It can be particularly challenging, however, to integrate palliative care into routine care where there exists uncertainty about a baby’s diagnosis or potential outcome.

This framework, developed collaboratively by the British Association of Perinatal Medicine (BAPM) and the Association of Paediatric Palliative Medicine (APPM), offers supportive guidance for all healthcare professionals working in perinatal medicine across antenatal and neonatal services. It explicitly acknowledges that palliative care is not just for babies who are dying or who will certainly die in early life; incorporating a palliative approach into antenatal and neonatal care for all babies with an uncertain outcome can be particularly valuable. The framework provides guidance on recognising babies who may benefit from palliative care and outlines the key elements of perinatal palliative care: holistic family support, empowering parents to be parents, parallel planning, symptom management and loss and bereavement care. It provides recommendations for the delivery of palliative care services, advocating for a unified approach that involves all members of the perinatal team, supported by specialist services as needed.

This framework calls for a shift in the philosophy and practice of perinatal care to integrate palliative care into the everyday and to recognise and embrace the challenge of uncertain prognosis.
Young adult reflections on life experiences following preterm birth: a cross-sectional descriptive study
Authors: Mackay Cheryl Anne , Gray Caitlin , Campbell Catherine , Sharp Mary
Published: November 2024

Background

Increasingly, preterm-born children are entering adulthood as survival at earlier gestational ages improves. However, there is little understanding of the lived experience in preterm-born adults.

Methods

A cross-sectional descriptive study was conducted including young adults from a regional birth cohort of infants born <33 weeks in Western Australia. Participants provided written reflections of their experiences growing up and included messages for future families experiencing preterm birth. Content analysis was conducted according to SRQR (Standards for Reporting Qualitative Research) guidelines. Ethics approval was granted by the Women and Newborn Health Service Ethics Committee.

Results

Forty-one adults reflected on their life experiences, and 31 included messages for future families. Two predominant themes were (1) neonatal experiences and (2) experiences from childhood and adulthood which were divided into ‘positive’ and ‘negative’ subthemes. Participants made 44 references to the neonatal period: 31 (70.5%) ‘challenging’ including sickness (17, 54.8%), uncertainty (10, 32.3%), family separation (4, 12.9%); and 13 (29.5%) ‘positive’ including survival (6, 46.2%), support (5, 38.5%), strength (2, 15.4%). Childhood and adulthood was described as ‘positive’ in 119 (73.5%) references including a good life (41, 33.3%), supportive family (20, 16.3%), success (18, 14.6%), strength (18, 14.6%), gratitude (15, 12.2%), positive self-talk (7, 5.7%); and ‘negative’ in 43 (26.5%) including health challenges (19, 44.2%), school difficulties (10, 23.3%), family difficulties (9, 20.9%). Messages for future families included what to expect (56, 75.7%) and helpful advice (18, 24.3%).

Conclusion

Our preterm-born young adults predominantly describe positive life experiences of childhood and adulthood balanced with an awareness of particular challenges.
Atypical anti-GBM disease in pregnancy
Authors: Chandler Shaun , Palamuthusingam Dharmenaan
Published: November 2024

A woman in her 20s presented with nephrotic syndrome and hyperemesis in early pregnancy. Pertinent initial investigations revealed a severe acute kidney injury, a serum albumin of 19 g/L, a random protein creatinine ratio of 800 g/mol and microscopic haematuria. All immunological and infection serology testing including anti-glomerular basement membrane (anti-GBM; ELISA) were negative. Kidney biopsy demonstrated diffuse crescentic glomerulonephritis with cellular crescents involving >90% of glomeruli, with immunofluorescence demonstrating intense linear reactivity for IgG consistent with atypical anti-GBM glomerular nephritis. Early pregnancy termination and treatment with immunosuppression were chosen after shared decision-making between the patient and physician. The patient had a poor response to treatment and remained dialysis dependent 12 months later.