bluuebunny/crossref_metadata_2025 huggingface dataset:
Discretization-independent surrogate modeling of physical fields around variable geometries using coordinate-based networks
Authors: Duvall James , Duraisamy Karthik
Published: January 2025

Numerical solutions of partial differential equations require expensive simulations, limiting their application in design optimization, model-based control, and large-scale inverse problems. Surrogate modeling techniques aim to decrease computational expense while retaining dominant solution features and characteristics. Existing frameworks based on convolutional neural networks and snapshot-matrix decomposition often rely on lossy pixelization and data-preprocessing, limiting their effectiveness in realistic engineering scenarios. Recently, coordinate-based multilayer perceptron networks have been found to be effective at representing 3D objects and scenes by regressing volumetric implicit fields. These concepts are leveraged and adapted in the context of physical-field surrogate modeling. Two methods toward generalization are proposed and compared: design-variable multilayer perceptron (DV-MLP) and design-variable hypernetworks (DVH). Each method utilizes a main network which consumes pointwise spatial information to provide a continuous representation of the solution field, allowing discretization independence and a decoupling of solution and model size. DV-MLP achieves generalization through the use of a design-variable embedding vector, while DVH conditions the main network weights on the design variables using a hypernetwork. The methods are applied to predict steady-state solutions around complex, parametrically defined geometries on non-parametrically-defined meshes, with model predictions obtained in less than a second. The incorporation of random Fourier features greatly enhanced prediction and generalization accuracy for both approaches. DVH models have more trainable weights than a similar DV-MLP model, but an efficient batch-by-case training method allows DVH to be trained in a similar amount of time as DV-MLP. A vehicle aerodynamics test problem is chosen to assess the method’s feasibility. Both methods exhibit promising potential as viable options for surrogate modeling, being able to process snapshots of data that correspond to different mesh topologies.
Enhancing dynamical system modeling through interpretable machine-learning augmentations: a case study in cathodic electrophoretic deposition
Authors: Jacobsen Christian , Dong Jiayuan , Khalloufi Mehdi , Huan Xun , Duraisamy Karthik , Akram Maryam , Liu Wanjiao
Published: January 2025

We introduce a comprehensive data-driven framework aimed at enhancing the modeling of physical systems, employing inference techniques and machine-learning enhancements. As a demonstrative application, we pursue the modeling of cathodic electrophoretic deposition, commonly known as e-coating. Our approach illustrates a systematic procedure for enhancing physical models by identifying their limitations through inference on experimental data and introducing adaptable model enhancements to address these shortcomings. We begin by tackling the issue of model parameter identifiability, which reveals aspects of the model that require improvement. To address generalizability, we introduce modifications, which also enhance identifiability. However, these modifications do not fully capture essential experimental behaviors. To overcome this limitation, we incorporate interpretable yet flexible augmentations into the baseline model. These augmentations are parameterized by simple fully-connected neural networks, and we leverage machine-learning tools, particularly neural ordinary differential equations, to learn these augmentations. Our simulations demonstrate that the machine-learning-augmented model more accurately captures observed behaviors and improves predictive accuracy. Nevertheless, we contend that while the model updates offer superior performance and capture the relevant physics, we can reduce off-line computational costs by eliminating certain dynamics without compromising accuracy or interpretability in downstream predictions of quantities of interest, particularly film thickness predictions. The entire process outlined here provides a structured approach to leverage data-driven methods by helping us comprehend the root causes of model inaccuracies and by offering a principled method for enhancing model performance.
Leadership Reconfiguration in State-Acquired Privately Owned Enterprises: A Paradox between Institutional Control and Agency
Authors: Min Yijie , Lu Junyan , Wu Yunke , Zhang Yanlong
Published: January 2025

This study aims to explore the dynamics of leadership reconfiguration within emergent state-owned enterprises (SOEs), i.e., privately owned enterprises (POEs) that have been acquired by SOEs. From an institutional logic perspective, we argue that the emergence of these SOEs reflects a process in which POEs, previously dominated by market logic, incorporate state logic and transition to a hybrid form. However, this process presents a paradox for emergent SOEs: while a greater extent of reconfiguration of leadership helps them gain greater legitimacy in front of state-related institutional referents, it also results in greater conflicts between members adhering to different logics. To address this paradox, we theorize on the differences in the reconfigurations of the board and top management team (TMT) by respectively connecting their functions to institutional control and agency, two typical forms of institutional power. Our analysis reveals that emergent SOEs tend to experience reconfiguration more in the board while less in TMT. Furthermore, we find that these main effects are moderated by the industrial state-ownership density and acquirees' preacquisition political connections. Our study contributes to the SOE and M&A literature by highlighting the uniqueness of emergent SOEs arising from POE-to-SOE acquisitions. Additionally, we propose a strategy to reconcile legitimation and internal stabilizations during logic hybridizations, thereby contributing to the institutional logic literature.
Prefrontally mediated inhibition of memory systems in dissociative amnesia
Authors: Marsh Laura C. , Apšvalka Dace , Kikuchi Hirokazu , Abe Nobuhito , Kawaguchi Jun , Kopelman Michael D. , Anderson Michael C.
Published: January 2025

Background

The mechanisms underlying generalized forms of dissociative (‘psychogenic’) amnesia are poorly understood. One theory suggests that memory retrieval is inhibited via prefrontal control. Findings from cognitive neuroscience offer a candidate mechanism for this proposed retrieval inhibition. By applying predictions based on these experimental findings, we examined the putative role of retrieval suppression in dissociative amnesia.

Methods

We analyzed fMRI data from two previously reported cases of dissociative amnesia. Patients had been shown reminders from forgotten and remembered time periods (colleagues and school friends). We examined the neuroanatomical overlap between regions engaged in the unrecognized compared to the recognized condition, and the regions engaged during retrieval suppression in laboratory-based tasks. Effective connectivity analyses were performed to test the hypothesized modulatory relationship between the right anterior dorsolateral prefrontal cortex (raDLPFC) and the hippocampus. Both patients were scanned again following treatment, and analyses were repeated.

Results

We observed substantial functional alignment between the inhibitory regions engaged during laboratory-based retrieval suppression tasks, and those engaged when patients failed to recognize their current colleagues. This included significant activation in the raDLPFC and right ventrolateral prefrontal cortex, and a corresponding deactivation across autobiographical memory regions (hippocampus, medial PFC). Dynamic causal modeling confirmed the hypothesized modulatory relationship between the raDLPFC and the hippocampus. This pattern was no longer evident following memory recovery in the first patient, but persisted in the second patient who remained amnesic.

Conclusions

Findings are consistent with an inhibitory mechanism driving down activity across core memory regions to prevent the recognition of personally relevant stimuli.
Association between auditory mismatch negativity and visual working memory in school-age children with attention deficit/hyperactivity disorder
Authors: Yang Han , Guo Jialiang , Yin Weizhen , Deng Yangyang , Fu Tong , Huang Shitao , Huang Jipeng , Hong Danping , Zhu Zhihang , Yang Chanjuan , Zhou Yanling , Song Yan , Dang Cai-Ping
Published: January 2025

Background

Attention-deficit/hyperactivity disorder (ADHD) patients exhibit characteristics of impaired working memory (WM) and diminished sensory processing function. This study aimed to identify the neurophysiologic basis underlying the association between visual WM and auditory processing function in children with ADHD.

Methods

The participants included 86 children with ADHD (aged 6–15 years, mean age 9.66 years, 70 boys, and 16 girls) and 90 typically developing (TD) children (aged 7–16 years, mean age 10.30 years, 66 boys, and 24 girls). Electroencephalograms were recorded from all participants while they performed an auditory discrimination task (oddball task). The visual WM capacity and ADHD symptom severity were measured for all participants.

Results

Compared with TD children, children with ADHD presented a poorer visual WM capacity and a smaller mismatch negativity (MMN) amplitude. Notably, the smaller MMN amplitude in children with ADHD predicted a less impaired WM capacity and milder inattention symptom severity. In contrast, the larger MMN amplitude in TD children predicted a better visual WM capacity.

Conclusions

Our results suggest an intimate relationship and potential shared mechanism between visual WM and auditory processing function. We liken this shared mechanism to a total cognitive resource limit that varies between groups of children, which could drive correlated individual differences in auditory processing function and visual WM. Our findings provide a neurophysiological correlate for reports of WM deficits in ADHD patients and indicate potential effective markers for clinical intervention.
Characterizing of dropouts in the mental health of refugees and asylum seekers (MEHIRA) study examining the effects of a stepped and collaborative care model – a multicentered rater-blinded randomized controlled trial
Authors: Kemna Solveig , Bringmann Max , Karnouk Carine , Hoell Andreas , Tschorn Mira , Kamp-Becker Inge , Padberg Frank , Übleis Aline , Hasan Alkomiet , Falkai Peter , Salize Hans-Joachim , Meyer-Lindenberg Andreas , Banaschewski Tobias , Schneider Frank , Habel Ute , Plener Paul , Hahn Eric , Wiechers Maren , Strupf Michael , Jobst Andrea , Millenet Sabina , Hoehne Edgar , Sukale Thorsten , Schuster Martin , Dinauer Raphael , Mehran Nassim , Kaiser Franziska , Lieb Klaus , Heinz Andreas , Rapp Michael , Bajbouj Malek , Böge Kerem
Published: January 2025

Background

Dropout from healthcare interventions can negatively affect patients and healthcare providers through impaired trust in the healthcare system and ineffective use of resources. Research on this topic is still largely missing on refugees and asylum seekers. The current study aimed to characterize predictors for dropout in the Mental Health in Refugees and Asylum Seekers (MEHIRA) study, one of the largest multicentered controlled trials investigating the effectiveness and cost-effectiveness of a nationwide stepped and collaborative care model.

Methods

Predictors were multiply imputed and selected for descriptive modelling using backward elimination. The final variable set was entered into logistic regression.

Results

The overall dropout rate was 41,7%. Dropout was higher in participants in group therapy (p = 0.001; OR = 10.7), with larger satisfaction with social relationships (p = 0.017; OR = 1.87), with difficulties in maintaining personal relationships (p = 0.005; OR = 4.27), and with higher depressive symptoms (p = 0.029; OR = 1.05). Participants living in refugee accommodation (p = 0.040; OR = 0.45), with a change in social status (p = 0.008; OR = 0.67) and with conduct (p = 0.020; OR = 0.24) and emotional problems (p = 0.013; OR = 0.31) were significantly less likely to drop out of treatment.

Conclusion

Overall, the outcomes of this study suggest that predictors assessing social relationships, social status, and living conditions should be considered as topics of psychological treatment to increase adherence and as predictors for future research studies (including treatment type).
Mammals lost and at risk of extinction in Jordan: historical analysis of constitutions and hunting laws
Authors: Eid Ehab , Abu Azam Sadam
Published: January 2025

Jordan’s mammalian fauna has experienced significant declines due to intensified hunting since the early twentieth century, leading to the extinction of six species and threatening 39% of the remaining species. This research evaluates the evolution of Jordan’s hunting laws across three historical stages – the Ottoman period, the establishment of Jordan and the modern era – highlighting their impacts on mammalian diversity and identifying legislative gaps contributing to species declines. Using Arabic-based legal databases and historical archives, we found that inadequate legal frameworks, political instability, economic pressures and weak enforcement often accelerated species depletion. Notably, the 1957 Hunting Law permitted hunting of vulnerable species with a licence and of predators without a licence, worsening species decline. Although the 1962 Defense Law aimed to protect nature, its expiration hindered progress. The 1966 Hunting Law largely duplicated the 1957 law, perpetuating these problems, and then hunting regulations were absorbed into agricultural law, undermining conservation efforts. Despite these legal shortcomings, Jordan’s modernization vision provides hope for reform, including the potential restoration of the Hunting Law under the Ministry of Environment and incorporating the right to a healthy environment into Jordan’s constitution to help prevent a mass extinction of mammals.
Metaphysical permanencies and variations on Medieval and Renaissance minor beauty
Authors: Salvestrini Amalia
Published: January 2025

This article aims to explore a theme of the metaphysica paupera from the reflections of the Friar Minor Luca Pacioli, highlighting their roots in the Neo-Platonic and Augustinian tradition, but also in some aspects of the Franciscan one. I will show, firstly, how in the early Franciscan environment the idea of minor beauty was progressively developed in relation to the form of life that places poverty at its centre. Secondly, I will outline how, in Bonaventure’s reflections, this idea, initially associated with a practical and moral dimension, is reframed in a theological sense, in terms of evangelical perfection, and in a metaphysical sense, finding its full foundation in the idea of a proportional beauty that establishes a metaphysics of relationship. Finally, I will highlight how both ideas – that of a metaphysics of relationship and a Franciscan matrix – persist in Pacioli, in his mathematization of knowledge, capable of including minor beauty as the metaphysical principle of the world, as well as of all human activities and forms of knowledge.
Proinflammatory gene expression is associated with prospective risk for adolescent suicidal thoughts and behaviors over twelve months
Authors: Clayton Matthew G. , Cole Steve W. , Giletta Matteo , Hastings Paul D. , Nock Matthew K. , Rudolph Karen D. , Slavich George M. , Prinstein Mitchell J.
Published: January 2025

Objective:

Recent theories have implicated inflammatory biology in the development of psychopathology and maladaptive behaviors in adolescence, including suicidal thoughts and behaviors (STB). Examining specific biological markers related to inflammation is thus warranted to better understand risk for STB in adolescents, for whom suicide is a leading cause of death.

Method:

Participants were 211 adolescent females (ages 9–14 years; Mage = 11.8 years, SD = 1.8 years) at increased risk for STB. This study examined the prospective association between basal levels of inflammatory gene expression (average of 15 proinflammatory mRNA transcripts) and subsequent risk for suicidal ideation and suicidal behavior over a 12-month follow-up period.

Results:

Controlling for past levels of STB, greater proinflammatory gene expression was associated with prospective risk for STB in these youth. Similar effects were observed for CD14 mRNA level, a marker of monocyte abundance within the blood sample. Sensitivity analyses controlling for other relevant covariates, including history of trauma, depressive symptoms, and STB prior to data collection, yielded similar patterns of results.

Conclusions:

Upregulated inflammatory signaling in the immune system is prospectively associated with STB among at-risk adolescent females, even after controlling for history of trauma, depressive symptoms, and STB prior to data collection. Additional research is needed to identify the sources of inflammatory up-regulation in adolescents (e.g., stress psychobiology, physiological development, microbial exposures) and strategies for mitigating such effects to reduce STB.
Age and anxiety symptoms jointly moderated the curvilinear changes in trial-level ERN following repeated errors on a Go/No-Go task during early adolescence
Authors: Tan Jaron X.Y. , Hamm Jeremy M. , Liu Pan
Published: January 2025

The ability to detect and monitor errors enables us to maintain optimal performance across tasks. One neurophysiological index of error monitoring is the error-related negativity (ERN), a fronto-central negative deflection peaking between 0 and 150 ms following an erroneous response. While the developmental literature has illustrated age-related differences in the ERN and its association with anxiety, the literature has mainly focused on the between-person differences of the ERN. Our study examined the within-person variations of the ERN in 115 community-dwelling 9- to 12-year-olds (66 girls; mean age/SD = 11.00/1.16 years). Participants completed an EEG Go/No-Go task and reported their anxiety symptoms. Multilevel growth analyses yielded significant within-person, curvilinear changes in the ERN throughout the task. Youths’ trial-level ERN increased (i.e., became more negative) with early errors, but decreased with subsequent errors. This curvilinear pattern was evident in older, but not younger, youths. Age also interacted with anxiety symptoms: younger youths with higher anxiety showed a continuous increase in the ERN throughout the task, whereas older youths with higher anxiety showed an initial increase followed by a decline in the ERN. Our study contributed novel evidence for the development of the ERN and the underlying mechanisms of the ERN-anxiety relationship that cannot be captured by between-person approaches.
Concurrent Heat Extremes in Relation to Global Warming, High Atmospheric Pressure and Low Soil Moisture in the Northern Hemisphere
Authors: Nasong Dalai , Zhou Sha , Kornhuber Kai , Yu Bofu
Published: January 2025

Summer heat extremes increasingly co‐occur worldwide, posing disastrous impacts on our society and the environment. However, the spatial pattern and underlying mechanisms of concurrent heat extremes remain unclear. We used a statistical framework to estimate the spatial concurrence strength of heat extremes in the Northern Hemisphere and identified their relationships to global warming, atmospheric circulation, and land‐atmosphere feedbacks. Concurrent heat extremes over different regions have significantly increased in the Northern Hemisphere from 1950 to 2023. Moreover, heat extremes show strong spatial concurrence strength, and the driving factors vary geographically. Global warming is responsible for long‐term increases in the frequency and strength of concurrent heat extremes, with most pronounced impact in tropical regions. In the absence of warming trends, the temporal and spatial variations in concurrent heat extremes are mainly caused by simultaneous high atmospheric pressure controlled by large‐scale circulations, particularly in mid‐latitude regions. While low soil moisture enhances regional heat extremes through land‐atmosphere feedbacks, it plays a minor role in driving concurrent heat extremes alone but can contribute in combination with high‐pressure anomalies. Given the ever‐increasing risks of heat extremes, our study underscores the importance of identifying the mechanisms of spatially concurrent heat extremes to improve prediction and mitigation of widespread heatwaves and their adverse impacts on socio‐economic sustainability and human well‐being.
Relationship Between Rupture Length and Magnitude of Oceanic Transform Fault Earthquakes
Authors: de Melo Guilherme W. S. , Grevemeyer Ingo , Lange Dietrich , Metz Dirk , Kopp Heidrun
Published: January 2025

The rupture behavior of large oceanic strike‐slip earthquakes remains largely unresolved using seismic signals recorded thousands of kilometers away from the source area. Large submarine earthquakes, however, generate hydroacoustic T‐waves propagating through the ocean over long distances. Here, we show that these T‐waves recorded at regional distances on the Ascension hydrophone array of the International Monitoring System can provide critical information on the earthquake location and rupture behavior. We use recordings from 47 events in oceanic transform faults, ranging in magnitude from 5.6 ≤ Mw ≤ 7.1, to investigate the rupture processes. We find that most strike‐slip earthquakes show unilateral rupture behavior, while a few larger events were more complex. Furthermore, earthquakes in oceanic transforms have longer ruptures than events of the same magnitude in continental faults. We argue that differences in the scaling relation of oceanic and continental strike‐slip earthquakes support a lower rigidity in the oceanic lithosphere caused by hydration.
Enhancing Hectare‐Scale Groundwater Recharge Estimation by Integrating Data From Cosmic‐Ray Neutron Sensing Into Soil Hydrological Modeling
Authors: Scheiffele Lena M. , Munz Matthias , Francke Till , Baroni Gabriele , Oswald Sascha E.
Published: January 2025

Vadose zone models, calibrated with state variables, may offer a robust approach for deriving groundwater recharge. Cosmic‐ray neutron sensing (CRNS) provides soil moisture over a large support volume (horizontal extent of hectares) and offers the opportunity to estimate water fluxes at this scale. However, the horizontal and vertical sensitivity of the method results in an inherently weighted water content, which poses a challenge for its application in soil hydrologic modeling. We systematically assess calibrating a soil hydraulic model in HYDRUS 1D at a cropped field site. Calibration was performed using different field‐scale soil moisture time series and the ability of the model to represent root zone soil moisture and derive groundwater recharge was assessed. As our benchmark, we used a distributed point sensor network from within the footprint of the CRNS. Models calibrated on CRNS data or combinations of CRNS with deeper point measurements resulted in cumulative groundwater recharge comparable to the benchmark. While models based exclusively on CRNS data do not represent the root zone soil moisture dynamics adequately, combining CRNS with profile soil moisture overcomes this limitation. Models calibrated on CRNS data also perform well in timing the downward flux compared to an independent estimate based on soil water tension measurements. However, the latter provides quantitative groundwater recharge estimates spanning a wide range of values, including unrealistic highs exceeding local annual precipitation. Conversely, modeled groundwater recharge based on the distributed sensor network or on CRNS resulted in estimates ranging between 30% and 40% of annual precipitation.
Observing non-Hermiticity induced chirality breaking in a synthetic Hall ladder
Authors: Ye Rui , He Yanyan , Li Guangzhen , Wang Luojia , Wu Xiaoxiong , Qiao Xin , Zheng Yuanlin , Jin Liang , Wang Da-Wei , Yuan Luqi , Chen Xianfeng
Published: January 2025

Non-Hermitian topological photonics plays a key role in bridging topological matter with gain and loss engineering in optics. Here we report the experimental observation of the break of chiral currents in a Hall ladder from the non-Hermiticity by constructing synthetic frequency dimension in two rings, where currents on both legs of the ladder co-propagate in the same direction. The origin of such phenomena is resulted from the interplay between the effective magnetic flux and the on-site gain and loss. Such non-Hermitian co-propagating currents exhibit characteristics of unidirectional frequency conversion in both rings, and moreover, different from the counterpart in Hermitian systems, can provide a method to probe the signatures of the non-Hermitian skin effect from steady-state bulk dynamics. Our model is further extended to models including next-nearest-neighbor couplings, pointing to a way for observing the non-Hermitian signature with higher winding number, and provides a new control knob for light manipulation with the topological dissipation engineering.
Experimental demonstration of 8190-km long-haul semiconductor-laser chaos synchronization induced by digital optical communication signal
Authors: Wang Anbang , Wang Junli , Jiang Lin , Wang Longsheng , Wang Yuncai , Yan Lianshan , Qin Yuwen
Published: January 2025

Common-signal-induced synchronization of semiconductor lasers have promising applications in physical-layer secure transmission with high speed and compatibility with the current fiber communication. Here, we propose an ultra-long-distance laser synchronization scheme by utilizing random digital optical communication signal as the common drive signal. By utilizing the long-haul optical coherent communication techniques, high-fidelity fiber transmission of the digital drive can be achieved and thus ultra-long-distance synchronization is expected. Experiments were implemented with distributed feedback lasers injected by a random-digital phase-modulated drive light. Results show that high-quality synchronization can be achieved as the drive signal rate is larger than the laser relaxation frequency and the transmission bit error ratio is below a critical value. Chaos synchronization over 8191-km fiber transmission was experimentally achieved. Compared to traditional common-signal-induced synchronization using analog drive signal such as chaos, the distance is increased by 8 times, and complicated hardware devices for channel impairment compensation are no longer required. In addition, the proposed method does not sacrifice communication capacity like traditional methods which need a channel to transmit analog drive signal. It is therefore believed that this common-digital-signal induced laser synchronization paves a way for secure backbone and submarine transmission.
Transverse optical gradient force in untethered rotating metaspinners
Authors: Engay Einstom , Shanei Mahdi , Mylnikov Vasilii , Wang Gan , Johansson Peter , Volpe Giovanni , Käll Mikael
Published: January 2025

Nanostructured dielectric metasurfaces offer unprecedented opportunities to control light-matter momentum exchange, and thereby the forces and torques that light can exert on matter. Here we introduce optical metasurfaces as components of ultracompact untethered microscopic metaspinners capable of efficient light-induced rotation in a liquid environment. Illuminated by weakly focused light, a metaspinner generates torque via photon recoil through the metasurfaces’ ability to bend light towards high angles despite their sub-wavelength thickness, thereby creating orbital angular momentum. We find that a metaspinner is subject to an anomalous transverse lateral optical gradient force that acts in concert with the classical gradient force. Consequently, when two or more metaspinners are trapped together in a laser beam, they collectively orbit the optical axis in the opposite direction to their spinning motion, in stark contrast to rotors coupled through hydrodynamic or mechanical interactions. The metaspinners delineated herein not only serve to illustrate the vast possibilities of utilizing optical metasurfaces for fundamental exploration of optical torques, but they also represent potential building-blocks of artificial active matter systems, light-driven micromachinery, and general-purpose optomechanical devices.
A light-driven device for neuromorphic computing
Authors: Nath Shimul Kanti
Published: January 2025

A unique optoelectronic synaptic device has been developed, leveraging the negative photoconductance property of a single-crystal material system called Cs2CoCl4. This device exhibits a simultaneous volatile resistive switching response and sensitivity to optical stimuli, positioning Cs2CoCl4 as a promising candidate for optically enhanced neuromorphic applications.
Micro-vibration assisted dual-layer spiral microneedles to rapidly extract dermal interstitial fluid for minimally invasive detection of glucose
Authors: Saifullah Khaled Mohammed , Mushtaq Asim , Azarikhah Pouria , Prewett Philip D. , Davies Graham J. , Faraji Rad Zahra
Published: January 2025

Various hydrogels have been explored to create minimally invasive microneedles (MNs) to extract interstitial fluid (ISF). However, current methods are time-consuming and typically require 10–15 min to extract 3–5 mg of ISF. This study introduces two spiral-shaped swellable MN arrays: one made of gelatin methacryloyl (GelMA) and polyvinyl alcohol (PVA), and the other incorporating a combination of PVA, polyvinylpyrrolidone (PVP), and hyaluronic acid (HA) for fast ISF extraction. These MN arrays demonstrated a rapid swelling ratio of 560 ± 79.6% and 370 ± 34.1% in artificial ISF within 10 min, respectively. Additionally, this study proposes a novel method that combines MNs with a custom-designed Arduino-based applicator vibrating at frequency ranges (50–100 Hz) to improve skin penetration efficiency, thereby enhancing the uptake of ISF in ex vivo. This dynamic combination enables GelMA/PVA MNs to rapidly uptake 6.41 ± 1.01 mg of ISF in just 5 min, while PVA/PVP/HA MNs extract 5.38 ± 0.77 mg of ISF within the same timeframe. To validate the capability of the MNs to recover glucose as the target biomarker, a mild heating procedure is used, followed by determining glucose concentration using a d-glucose content assay kit. The efficient extraction of ISF and glucose detection capabilities of the spiral MNs suggest their potential for rapid and minimally invasive biomarker sensing.
Auditory evoked-potential abnormalities in a mouse model of 22q11.2 Deletion Syndrome and their interactions with hearing impairment
Authors: Lu Chen , Linden Jennifer F.
Published: January 2025

The 22q11.2 deletion is a risk factor for multiple psychiatric disorders including schizophrenia and also increases vulnerability to middle-ear problems that can cause hearing impairment. Up to 60% of deletion carriers experience hearing impairment and ~30% develop schizophrenia in adulthood. It is not known if these risks interact. Here we used the Df1/+ mouse model of the 22q11.2 deletion to investigate how hearing impairment might interact with increased genetic vulnerability to psychiatric disease to affect brain function. We measured brain function using cortical auditory evoked potentials (AEPs), which are commonly measured non-invasively in humans. After identifying one of the simplest and best-validated methods for AEP measurement in mice from the diversity of previous approaches, we measured peripheral hearing sensitivity and cortical AEPs in Df1/+ mice and their WT littermates. We exploited large inter-individual variation in hearing ability among Df1/+ mice to distinguish effects of genetic background from effects of hearing impairment. Central auditory gain and adaptation were quantified by comparing brainstem activity and cortical AEPs and by analyzing the growth of cortical AEPs with increasing sound level or inter-tone interval duration. We found that level-dependent AEP growth was abnormally large in Df1/+ mice regardless of hearing impairment, but other AEP measures of central auditory gain and adaptation depended on both genotype and hearing phenotype. Our results demonstrate the relevance of comorbid hearing loss to auditory brain dysfunction in 22q11.2DS and also identify potential biomarkers for psychiatric disease that are robust to hearing impairment.
High-coverage whole-genome sequencing of a Jakun individual from the “Orang Asli” Proto-Malay subtribe from Peninsular Malaysia
Authors: Yap Wai-Sum , Cengnata Alvin , Saw Woei-Yuh , Abdul Rahman Thuhairah , Teo Yik-Ying , Lim Renee Lay-Hong , Hoh Boon-Peng
Published: January 2025

Jakun, a Proto-Malay subtribe from Peninsular Malaysia, is believed to have inhabited the Malay Archipelago during the period of agricultural expansion approximately 4 thousand years ago (kya). However, their genetic structure and population history remain inconclusive. In this study, we report the genome structure of a Jakun female, based on whole-genome sequencing, which yielded an average coverage of 35.97-fold. We identified approximately 3.6 million single-nucleotide variations (SNVs) and 517,784 small insertions/deletions (indels). Of these, 39,916 SNVs were novel (referencing dbSNP151), and 10,167 were nonsynonymous (nsSNVs), spanning 5674 genes. Principal Component Analysis (PCA) revealed that the Jakun genome sequence closely clustered with the genomes of the Cambodians (CAM) and the Metropolitan Malays from Singapore (SG_MAS). The ADMIXTURE analysis further revealed potential admixture from the EA and North Borneo populations, as corroborated by the results from the F3, F4, and TreeMix analyses. Mitochondrial DNA analysis revealed that the Jakun genome carried the N21a haplogroup (estimated to have occurred ~19 kya), which is commonly found among Malays from Malaysia and Indonesia. From the whole-genome sequence data, we identified 825 damaging and deleterious nonsynonymous single-nucleotide polymorphisms (nsSNVs) affecting 720 genes. Some of these variants are associated with age-related macular degeneration, atrial fibrillation, and HDL cholesterol level. Additionally, we located a total of 3310 variants on 32 core adsorption, distribution, metabolism, and elimination (ADME) genes. Of these, 193 variants are listed in PharmGKB, and 21 are nsSNVs. In summary, the genetic structure identified in the Jakun individual could enhance the mapping of genetic variants for disease-based population studies and further our understanding of the human migration history in Southeast Asia.
Small variant benchmark from a complete assembly of X and Y chromosomes
Authors: Wagner Justin , Olson Nathan D. , McDaniel Jennifer , Harris Lindsay , Pinto Brendan J. , Jáspez David , Muñoz-Barrera Adrián , Rubio-Rodríguez Luis A. , Lorenzo-Salazar José M. , Flores Carlos , Sahraeian Sayed Mohammad Ebrahim , Narzisi Giuseppe , Byrska-Bishop Marta , Evani Uday S. , Xiao Chunlin , Lake Juniper A. , Fontana Peter , Greenberg Craig , Freed Donald , Mootor Mohammed Faizal Eeman , Boutros Paul C. , Murray Lisa , Shafin Kishwar , Carroll Andrew , Sedlazeck Fritz J. , Wilson Melissa , Zook Justin M.
Published: January 2025

The sex chromosomes contain complex, important genes impacting medical phenotypes, but differ from the autosomes in their ploidy and large repetitive regions. To enable technology developers along with research and clinical laboratories to evaluate variant detection on male sex chromosomes X and Y, we create a small variant benchmark set with 111,725 variants for the Genome in a Bottle HG002 reference material. We develop an active evaluation approach to demonstrate the benchmark set reliably identifies errors in challenging genomic regions and across short and long read callsets. We show how complete assemblies can expand benchmarks to difficult regions, but highlight remaining challenges benchmarking variants in long homopolymers and tandem repeats, complex gene conversions, copy number variable gene arrays, and human satellites.
Reconstitution of human DNA licensing and the structural and functional analysis of key intermediates
Authors: Wells Jennifer N. , Edwardes Lucy V. , Leber Vera , Allyjaun Shenaz , Peach Matthew , Tomkins Joshua , Kefala-Stavridi Antonia , Faull Sarah V. , Aramayo Ricardo , Pestana Carolina M. , Ranjha Lepakshi , Speck Christian
Published: January 2025

Human DNA licensing initiates replication fork assembly and DNA replication. This reaction promotes the loading of the hMCM2-7 complex on DNA, which represents the core of the replicative helicase that unwinds DNA during S-phase. Here, we report the reconstitution of human DNA licensing using purified proteins. We showed that the in vitro reaction is specific and results in the assembly of high-salt resistant hMCM2-7 double-hexamers. With ATPγS, an hORC1-5-hCDC6-hCDT1-hMCM2-7 (hOCCM) assembles independent of hORC6, but hORC6 enhances double-hexamer formation. We determined the hOCCM structure, which showed that hORC-hCDC6 recruits hMCM2-7 via five hMCM winged-helix domains. The structure highlights how hORC1 activates the hCDC6 ATPase and uncovered an unexpected role for hCDC6 ATPase in complex disassembly. We identified that hCDC6 binding to hORC1-5 stabilises hORC2-DNA interactions and supports hMCM3-dependent recruitment of hMCM2-7. Finally, the structure allowed us to locate cancer-associated mutations at the hCDC6-hMCM3 interface, which showed specific helicase loading defects.
Site-saturation mutagenesis of 500 human protein domains
Authors: Beltran Antoni , Jiang Xiang’er , Shen Yue , Lehner Ben
Published: January 2025

Missense variants that change the amino acid sequences of proteins cause one-third of human genetic diseases1. Tens of millions of missense variants exist in the current human population, and the vast majority of these have unknown functional consequences. Here we present a large-scale experimental analysis of human missense variants across many different proteins. Using DNA synthesis and cellular selection experiments we quantify the effect of more than 500,000 variants on the abundance of more than 500 human protein domains. This dataset reveals that 60% of pathogenic missense variants reduce protein stability. The contribution of stability to protein fitness varies across proteins and diseases and is particularly important in recessive disorders. We combine stability measurements with protein language models to annotate functional sites across proteins. Mutational effects on stability are largely conserved in homologous domains, enabling accurate stability prediction across entire protein families using energy models. Our data demonstrate the feasibility of assaying human protein variants at scale and provides a large consistent reference dataset for clinical variant interpretation and training and benchmarking of computational methods.
Influence of selected dosages of plastic microparticles on the porcine fecal microbiome
Authors: Gałęcka Ismena , Rychlik Andrzej , Całka Jarosław
Published: January 2025

Studies conducted so far have shown that nano- and microplastic may disturb the intestinal microenvironment by interacting with the intestinal epithelium and the gut microbiota. Depending on the research model used, the effect on the microbiome is different—an increase or decrease in selected taxa resulting in the development of dysbiosis. Dysbiosis may be associated with intestinal inflammation, development of mental disorders or diabetes. The aim of the study was to analyze the intestinal microbiome in 15 gilts divided into 3 research groups (n = 5; control group, receiving micropartices at a dose 0.1 g/day (LD) and 1 g/day (HD)). Feaces were collected before and after 28 days of exposure to PET microplastics. The analysis of the intestinal microbiome was performed using next-generation sequencing. Alpha and beta diversity indices were compared, showing, that repetition affected only the abundance indices in the control and LD groups, but not in the HD group. The relationships between the number of reads at the phylum, genus and species level and the microplastic dose were calculated using statistical methods (r-Pearson correlation, generalized regression model, analysis of variance). The statistical analysis revealed, that populations of Family XIII AD3011 group, Coprococcus, V9D2013 group, UCG-010 and Sphaerochaeta increased with increasing MP-PET dose. The above-mentioned taxa are mainly responsible for the production of short-chain fatty acids (SCFA). It may be assumed, that SCFA are one of the mechanisms involved in the response to oral exposure to MP-PET.
Ten-year outcomes after DMEK, DSAEK, and PK: insights on graft survival, endothelial cell density loss, rejection and visual acuity
Authors: Wilhelm Theresa Isabelle , Gauché Laura , Böhringer Daniel , Maier Philip , Heinzelmann Sonja , Glegola Mateusz , Kammrath Betancor Paola , Reinhard Thomas
Published: January 2025

Fuchs Endothelial Corneal Dystrophy (FECD) is the most frequent indication for corneal transplantation, with Descemet membrane endothelial keratoplasty (DMEK), Descemet stripping automated endothelial keratoplasty (DSAEK), and penetrating keratoplasty (PK) being viable options. This retrospective study compared 10-year outcomes of these techniques in a large cohort of 2956 first-time keratoplasty eyes treated for FECD at a high-volume corneal transplant center in Germany. While DMEK and DSAEK provided faster visual recovery (median time to BSCVA ≥ 6/12 Snellen: DMEK 7.8 months, DSAEK 12.4 months, PK 37.9 months; cumulative probability of BSCVA ≥ 6/12 Snellen within 5 years: DMEK 93%, DSAEK 83%, PK 63%), PK surprisingly exhibited superior long-term graft survival (92% vs. 75% for DMEK and 73% for DSAEK at 10 years). Endothelial cell density (ECD) decreased significantly faster after DMEK and DSAEK, potentially contributing to their lower graft survival (10-year ECD > 1000 cells/mm2 probability: DMEK 3%, DSAEK 8%, PK 18%). DMEK demonstrated the lowest rejection rate (10% at 10 years vs. 13% for PK and 19% for DSAEK). These findings challenge the perceived superiority of endothelial keratoplasty and highlight the need for further investigation into the long-term implications of accelerated endothelial cell loss after DMEK and DSAEK.
Evaluation of fatigue performance of asphalt materials based on their relaxation behavior
Authors: Zhang Beibei , Jing Mengqi
Published: January 2025

Although the fatigue properties of asphalt materials have been extensively studied, the relationship between the rheological properties and road performance of asphalt mixtures remains underexplored. In this study, we have examined the relaxation properties of asphalt binders through relaxation tests conducted on asphalt and its mastic under different conditions. A repeated stress relaxation-recovery test is designed for assessing both the relaxation and elastic properties, and a set of reasonable test parameters is recommended, thereby establishing a novel test method for measuring the relaxation and elastic behaviors of asphalt. In addition, we have proposed evaluation indexes, such as relaxation time, relaxation rate, and strain recovery rate, to assess the stress relaxation performance and strain recovery ability. It is observed that the relaxation rate and strain recovery rate of the material can be used to characterize the material’s relaxation and elasticity properties, respectively. Thus, the proposed indexes can be used to comprehensively evaluate the viscoelastic performance of the material. The fatigue performance of the selected materials is further examined using the linear amplitude sweep (LAS) test, and the correlation between the relaxation properties and fatigue performance (as indicated by fatigue parameters) is explored. Furthermore, a fatigue performance prediction equation based on the repetitive stress relaxation-recovery test is established. The findings reveal a strong correlation between the relaxation properties and fatigue performance, suggesting that the stress relaxation test can accurately assess the fatigue performance of asphalt materials.
Classifying synoptic patterns driving tornadic storms and associated spatial trends in the United States
Authors: Jiang Qin , Dawson II Daniel T. , Li Funing , Chavas Daniel R.
Published: January 2025

Severe convective storms and tornadoes rank among nature’s most hazardous phenomena, inflicting significant property damage and casualties. Near-surface weather conditions are closely governed by large-scale synoptic patterns. It is crucial to delve into the involved multiscale associations to understand tornado potential in response to climate change. Using clustering analysis, this study unveils that leading synoptic patterns driving tornadic storms and associated spatial trends are distinguishable across geographic regions in the U.S. Synoptic patterns with intense forcing featured by intense upper-level eddy kinetic energy and a dense distribution of Z500 fields dominate the increasing trend in tornado frequency in the southeast U.S., generating more tornadoes per event. Conversely, the decreasing trend noted in certain regions of the central Great Plains is associated with weak upper-level synoptic forcing. These findings offer an explanation of observational changes in tornado occurrences, suggesting that the physical mechanisms driving those changes differ across regions.
Endothelial tip-cell position, filopodia formation and biomechanics require BMPR2 expression and signaling
Authors: Hiepen Christian , Benamar Mounir , Barrasa-Fano Jorge , Condor Mar , Ilhan Mustafa , Münch Juliane , Hastar Nurcan , Kerkhoff Yannic , Harms Gregory S. , Mielke Thorsten , Koenig Benjamin , Block Stephan , Rocks Oliver , Abdelilah-Seyfried Salim , Van Oosterwyck Hans , Knaus Petra
Published: January 2025

Blood vessel formation relies on biochemical and mechanical signals, particularly during sprouting angiogenesis when endothelial tip cells (TCs) guide sprouting through filopodia formation. The contribution of BMP receptors in defining tip-cell characteristics is poorly understood. Our study combines genetic, biochemical, and molecular methods together with 3D traction force microscopy, which reveals an essential role of BMPR2 for actin-driven filopodia formation and mechanical properties of endothelial cells (ECs). Targeting of Bmpr2 reduced sprouting angiogenesis in zebrafish and BMPR2-deficient human ECs formed fewer filopodia, affecting cell migration and actomyosin localization. Spheroid assays revealed a reduced sprouting of BMPR2-deficient ECs in fibrin gels. Even more strikingly, in mosaic spheroids, BMPR2-deficient ECs failed to acquire tip-cell positions. Yet, 3D traction force microscopy revealed that these distinct cell behaviors of BMPR2-deficient tip cells cannot be explained by differences in force-induced matrix deformations, even though these cells adopted distinct cone-shaped morphologies. Notably, BMPR2 positively regulates local CDC42 activity at the plasma membrane to promote filopodia formation. Our findings reveal that BMPR2 functions as a nexus integrating biochemical and biomechanical processes crucial for TCs during angiogenesis.