bluuebunny/crossref_metadata_2025 huggingface dataset:
Positioning theory as a framework for understanding the facilitation of professional development for educational leaders
Authors: Martin Jenny , Nuttall Joce , Wood Elizabeth , Henderson Linda
Published: March 2024

The article addresses the problem of providing in-service education within government-led reform initiatives yet enhancing professionalism in the Early Childhood Education and Care sector. The study was conducted during policy-mandated reform in Australia to investigate effective ways to support educational leaders in centres rated as not meeting the national quality standard. Data were derived from a larger project designed as a formative intervention and funded by the Australian Research Council. In this article, we focus on the positioning of the educational leaders over the course of the intervention as they endeavoured to develop workplace practices. We found that the participants’ status as leaders of low-rated centres was featured in the way they positioned themselves initially. How the researchers responded has been highlighted in our analysis and, we argue, repositioning these participants as professionally capable and responsible was essential to the success of the intervention for them. This article contributes an original methodological approach to researching individual learning within the collective processes of workplace practice development and provides an understanding of the reform process from the perspective of ‘working-towards’ educational leaders.
Helicoidal minimal surfaces in the 3-sphere: an approach via spherical curves
Authors: Castro Ildefonso , Castro-Infantes Ildefonso , Castro-Infantes Jesús
Published: March 2024

We prove an existence and uniqueness theorem about spherical helicoidal (in particular, rotational) surfaces with prescribed mean or Gaussian curvature in terms of a continuous function depending on the distance to its axis. As an application in the case of vanishing mean curvature, it is shown that the well-known conjugation between the belicoid and the catenoid in Euclidean three-space extends naturally to the 3-sphere to their spherical versions and determine in a quite explicit way their associated surfaces in the sense of Lawson. As a key tool, we use the notion of spherical angular momentum of the spherical curves that play the role of profile curves of the minimal helicoidal surfaces in the 3-sphere.
A deep multi-branch attention model for histopathological breast cancer image classification
Authors: Ding Rui , Zhou Xiaoping , Tan Dayu , Su Yansen , Jiang Chao , Yu Guo , Zheng Chunhou
Published: March 2024

Since the impressive superior performance demonstrated by deep learning methods is widely used in histopathological image analysis and diagnosis, existing work cannot fully extract the information in the breast cancer images due to the limited high resolution of histopathological images. In this study, we construct a novel intermediate layer structure that fully extracts feature information and name it DMBANet, which can extract as much feature information as possible from the input image by up-dimensioning the intermediate convolutional layers to improve the performance of the network. Furthermore, we employ the depth-separable convolution method on the Spindle Structure by decoupling the intermediate convolutional layers and convolving them separately, to significantly reduce the number of parameters and computation of the Spindle Structure and improve the overall network operation speed. We also design the Spindle Structure as a multi-branch model and add different attention mechanisms to different branches. Spindle Structure can effectively improve the performance of the network, the branches with added attention can extract richer and more focused feature information, and the branch with residual connections can minimize the degradation phenomenon in our network and speed up network optimization. The comprehensive experiment shows the superior performance of DMBANet compared to the state-of-the-art method, achieving about 98% classification accuracy, which is better than existing methods. The code is available at https://github.com/Nagi-Dr/DMBANet-main.
The Optimization of Split Demand Route Planning Under Metro-Truck Collaborative Distribution
Authors: Li Jin , Wang Yaqiu , Liu Huasheng
Published: March 2024

With the evolution of people's consumption habits and the rapid growth of urban logistics, the number of trucks and delivery frequency has increased significantly, exacerbating urban traffic congestion and environmental pollution. Consequently, there is an urgent need to improve the current inefficient and highly polluted distribution mode. Currently, in most cities in China, the metro passenger flow is insufficient, and the capacity is excessive during off-peak hours, resulting in underutilized carriage capacity. The integration of surface and underground transport resources can effectively address these issues and facilitate complementary advantages and win–win cooperation between express companies and metro enterprises. This study proposes an innovative problem of split demand route planning in the cooperative distribution system involving express companies and subways. A cooperative distribution model is developed to minimize the total cost, and solved by the Cuckoo Search algorithm to obtain the optimized solution. The model is applied to the urban rail transit network in Changchun, and the results demonstrate that it is effective in reducing truck mileage and distribution costs. Compared to the single delivery pattern by trucks, the cooperative distribution approach proves to be more cost-effective and environmentally friendly.
A Test of Dublin Anti-bullying Self-Efficacy Scale for Teachers (DABSE-T)
Authors: Feijóo Sandra , Kuldas Seffetullah , Sargioti Aikaterini , Kinahan Angela , Heaney Darran , Gorman Alan , O’Higgins Norman James
Published: March 2024

Emerging evidence suggests that anti-bullying programmes should have a particular focus on teacher self-efficacy for peer bullying prevention and intervention at schools. To address this suggestion, a theoretical framework and a measurement scale are needed to evaluate teacher anti-bullying self-efficacy and determine its role in the effectiveness of these anti-bullying programmes. The present research aims to adapt the Anti-Bullying Self-Efficacy Theory and test the psychometric properties of the Dublin Anti-Bullying Self-Efficacy Scale (DABSE) for teachers. A convenience sample of 221 teachers (38.9% from primary and 61.1% from post-primary schools) responded to the DABSE-T following participation in FUSE, a school anti-bullying programme in Ireland. The factorial structure of the scale was assessed using Exploratory Factor Analysis (EFA), Principal Axis Factoring with Promax Oblique rotation. Construct validity (convergent and divergent validity) was assessed using the criteria of Average Variance Extracted (AVE > .50) and the heterotrait-monotrait ratio of correlations (HTMT). Composite reliability was estimated as an indicator of internal consistency. The DABSE-T demonstrated satisfactory psychometric properties, suggesting that it is a valid and reliable measure of teacher self-efficacy beliefs, which encompass recognition of bullying behaviour, comprehension of the need for immediate intervention, acceptance of responsibility, knowledge of appropriate actions, and intervention implementation. The scale can be used to evaluate the effectiveness of anti-bullying interventions and identify teachers who may require additional support in addressing bullying incidents.
Security assessment and improvement of building ethernet KNXnet/IP protocol
Authors: Feng Tao , Zhang Bugang , Liu Chunyan , Zheng Lu
Published: March 2024

KNXnet/IP is a KNX-building automation protocol that communicates through an IP network. It is mainly used in the field of smart home and building automation control, allowing remote access to KNX devices through an IP network, so that building functions can be managed and controlled anywhere through an Internet connection. However, with the development of smart homes and building automation, such physical devices based on IP communication are more and more frequently in contact with the Internet, resulting in more and more security issues for home devices and buildings exposed to the Internet. This paper uses the formal analysis method-colored Petri net (CPN) combined with the CPN Tools to model the KNXnet/IP protocol and analyze the protocol interaction process. Based on the Dolev-Yao attacker model, the security of the KNXnet/IP protocol is evaluated and tested, and it is verified whether there are three types of attackable vulnerabilities in the protocol: replay, tampering, and spoofing. After CPN modeling analysis and verification, it is found that tampering and replay vulnerabilities in the original protocol. Therefore, we introduce timestamp and hash to strengthen the security mechanism of the protocol, which ensures the integrity, confidentiality, and freshness of the security mechanism of the protocol. After the final analysis and verification, the improvement scheme proposed in this paper can effectively improve the security performance of the protocol.
Mint species (Mentha longifolia and Mentha spicata L) growth, essential oil generation and chemical components are impacted by turmeric curcumin applications
Authors: Zaki Faten S. A. , Khalid Khalid A. , Ahmed Aisha M. A.
Published: March 2024

Mint essential oil has several applications in pharmacy and food industries. As mint species multiplied, active chemicals evolved, resulting in changes in their biological effects. Mint growth in Egypt’s sandy soils is hampered by abiotic stress. Phenols like turmeric curcumin reduce abiotic stress which plant suffers. Finding active chemicals in various aromatic plant species to substitute synthetic ones is an enticing approach to developing a new pharmaceutical regimen; these plants need to be studied to locate active components. Therefore, this study aimed to reduce the potential negative effects of abiotic stress in sand soil on horsemint (Mentha longifolia) and spearmint (Mentha spicata L) by applying turmeric curcumin (as organic elicitor), to assess if growing them in the new reclamation zones is a viable option in order to obtain essential oil naturally. Both species received 0, 30, 60, 90, and 120 mg L−1 turmeric curcumin. Horsemint exposed to 30 mg L−1 turmeric curcumin produced the maximum values of plant length (93 cm), fresh herb (114.73 g plant−1) and dry herb (33.81 g plant−1); spearmint × 30 mg L−1 turmeric curcumin resulted in the greatest amounts of chlorophyll a, chlorophyll b and carotenoids with values of 5.38, 1.83 and 1.45 mg g−1, respectively. The maximum values of eucalyptol (65.44%), camphor (23.81%), carvone (65.95%) and limonene (15.9%) were recorded under 90 mg L−1 turmeric curcumin. Horsemint plants subjected to 60 mg L−1 turmeric curcumin gave the highest essential oil yield (1.52 g plant−1), sesquiterpenes (31.4%), soluble sugars (102.19 mg g−1), free amino acids (8.73 mg g−1), phenols (3.71 mg g−1), flavonoids (5.28 mg g−1), free radical's inhibition (64.35%), protein (17.09%) and nitrogen (1.27 g plant−1); spearmint × 60 mg L−1 turmeric curcumin resulted in the greatest values of monoterpenes (98.76%), nitrogen (2.74%), phosphorous (0.54% or 0.17 g plant−1) and potassium (0.56% or 0.18 g plant−1). Control × spearmint gave the maximum value of sodium (0.17% or 0.04 g plant−1). To mitigate the detrimental effects of stress-related factors on sandy soil, turmeric curcumin can be applied to mint species; additionally, it could broaden the sources of natural products. On the other hand, this work provides as a guide for choosing mint species for usage in industries connected to essential oils based on pertinent components.
India’s Conception of Community Data and Addressing Concerns for Access to Justice
Authors: de Souza Siddharth Peter , Bhardwaj Kritika
Published: March 2024

This paper discusses the idea of community data that was introduced in the Non-Personal Data framework in India. Our interest is to engage with existing commentaries on the definitional challenges around who is a community, how it is constituted, who it represents, as well as propose a framework to be able to explore how to address concerns of access to justice. In our attempt to offer a model to operationalise community data, we argue that such community data includes three crucial aspects, that is, the identification of belonging with a community, the capacity to participate within a community, and finally opportunity to exit the community. Consequently, justice in terms of access to, and use of community data inherently includes an analysis of the individual’s standing in the community.
Signatures of Open Magnetic Flux in Jupiter's Dawnside Magnetotail
Authors: Delamere P. A. , Wilson R. J. , Wing S. , Smith A. R. , Mino B. , Spitler C. , Damiano P. , Sorathia K. , Sciola A. , Caggiano J. , Johnson J. R. , Ma X. , Bagenal F. , Zhang B. , Allegrini F. , Ebert R. , Clark G. , Brambles O.
Published: March 2024

Jupiter's magnetosphere exhibits notable distinctions from the terrestrial magnetosphere. The structure and dynamics of Jupiter's dawnside magnetosphere can be characterized as a competition between internally driven sunward flow and solar wind‐driven tailward flow. During the prime mission, Juno acquired extensive data from dawn to midnight, sampling the magnetodisc and higher latitude regions. Numerical moments from the Jovian Auroral Distributions Experiment (JADE‐I) plasma (ion) instrument revealed a mid‐latitude region of anticorotational (−vϕ) flow. While the magnitude of the flow is subject to uncertainty due to low count rates in these rarefied regions, we demonstrate in the raw JADE‐I data that the sign of vϕ is a robust measurement. Global Grid Agnostic Magnetohydrodyamics for Extended Research Applications simulations show a similar region of strongly reduced flow in proximity to open field lines. Additionally, we use Jupiter Energetic‐particle Detector Instrument integral moments to determine the Hen+/H+ ratio (where n refers to He+ or He++) and show that a transition to solar wind‐like composition occurs in the same region as the anticorotational flow. We conclude that the global simulations are consistent with the Juno data, where the simulations show a crescent of open magnetic flux that is bounded by the magnetodisc and a closed high‐latitude polar region (nominally the polar cap), which is never observed in the terrestrial magnetosphere. The distinct distribution of open flux in Jupiter's dawnside magnetosphere suggests the significance of planetary rotation and may represent a characteristic feature of rotating giant magnetospheres for future exploration.
High‐ and Low‐Frequency Waveform Analysis the Marsquake of Sol 1222: Focal Mechanism, Centroid Moment Tensor Inversion and Source Time Function
Authors: Malytskyy D. , Křížová D. , Lognonné P. , Kawamura T. , Perrin C. , Plasman M. , Xu Z. , Maguire R.
Published: March 2024

The seismometer onboard InSight NASA Mars mission discovered a seismically active planet. We focused on the strongest event named S1222a (4 May 2022, Mw ∼ 4.7), which was recorded by the Very Broad Band sensors and associated channel ELYSE and is located 37.2° away from InSight. We use two different methods based on a point source approach for an elastic, horizontally layered medium to retrieve source parameters of S1222a. In the first case, the seismic moment tensor inversion of high‐frequency seismogram data is calculated using a matrix method for the direct waves. The process includes the generation of records in displacement using the frequency‐wavenumber integration technique. A method of inversion of the moment tensor of direct P‐ and S‐waves, less sensitive to path effects than reflected and transformed waves, is presented, which significantly increases the accuracy and reliability of the method. In the second case, tensors were calculated using common low‐frequency full‐waveform inversion and the tests to verify the plausibility of this solution obtained from the single station calculation were performed and the uncertainty estimations for inversions can be useful in future research.
Gas Emission Characteristics and Tectonic Implications in the Southernmost Okinawa Trough From Split‐Beam Echo Sounder Observations
Authors: Lin Yi Chin , Lin Jing‐Yi , Hsu Shu‐Kun , Chen Song‐Chuen , Lin Shiao‐Shan , Tsai Ching‐Hui
Published: March 2024

Traditionally, single‐beam echo sounder (SBES) data are used to determine the position of emission structures in the form of a two‐dimensional profile, which may not be straightforward enough to correlate the data of adjacent profiles and determine the exact discharge area. In this study, we develop semiautomatic software to remove noise and select possible flare signals to enhance the speed and precision of the data processing. The program also allows for the transformation of the data into a three‐dimensional point cloud distribution by computing the receiving angle of the data. By applying this method to investigate the distribution and mechanism of gas emission structures in the South Okinawa Trough (SOT), we determine four high flux areas and 22 isolated plumes with roots. Widespread gas flares usually occur in areas with large‐scale volcanic activity or gas‐enriched structures. Isolated gas plumes could be found for a single knoll outcrop and normal faulting structures. The energy of the flares around the knoll area is generally stronger than that observed along the normal faults. Compared with other geophysical data, we find that the widespread distribution of gas flares generally implies a larger hydrothermal potential, which may not be revealed by single‐profile acoustic image observations. We also find that the direction of flares is strongly influenced by tides, and the height of the flare represents the thermocline as a strong boundary for bubbles composited by carbon dioxide.
Spatial Inhomogeneity of Synoptic‐Induced Precipitation in a Region of Steep Topographic Relief: A Case Study
Authors: Zhang Mengke , Li Jian , Li Nina , Sun Wei , Li Puxi , Zhao Yin
Published: March 2024

The topography plays an essential role in the initiation and development of precipitating clouds, therefore has a profound effect on the ultimate spatial distribution of precipitation. This study investigates the fine‐scale characteristics of a synoptic‐induced precipitation event in Southwest China, a region characterized by a sequence of steep mountains aligned roughly north‐south. The convection‐permitting simulation successfully reproduces the observed rainband induced by a synoptic‐scale shear line. The spatial distribution of accumulated precipitation over three small‐scale mountains (named M1, M2, and M3 from east to west) exhibits distinct inhomogeneity. The accumulated precipitation is significantly enhanced on the western slope of M1, the high‐altitude area of M2, and the eastern slope of M3. The low‐level vortex generated on the western slope of M1, as well as the convergence established over M2 and the eastern slope of M3, dynamically contributes to the enhanced precipitation over the various mountain locations. As the highest of the three mountains, M2 exhibits pronounced blocking effects on the mesoscale circulations. Additional sensitivity experiment demonstrates that the mesoscale circulations and corresponding precipitation are sensitive to the highest elevation in the continuous mountains. The rainfall accumulation over M2 (M3) could decrease (increase) by 54.3% (63.4%), when the terrain of M2 is reduced to the comparable height of surrounding mountains. With more upslope wind flowing over M2, the convergence over M3 is strengthened. The more intense upward motion and stronger potential instability both contribute to the notable increase of precipitation over M3. This study implies the possible mechanisms of the inhomogeneous precipitation over Southwest China and could deepen the current understanding of the topographic effects on precipitation over complex terrains.
ECMWF and UK Met Office Offshore Blowing Winds: Impact of Horizontal Resolution and Coastal Orography
Authors: Cavaleri L. , Balsamo G. , Beljaars A. , Bertotti L. , Davison S. , Edwards J. , Kanehama T. , Wedi N.
Published: March 2024

We analyze the performance of the European Centre for Medium‐Range Weather Forecasts (ECMWF) and UK Met Office (UKMO) meteorological models in predicting offshore blowing wind in coastal areas. Our attention is mainly on the Mediterranean coast, up to 200 km distance from the shore. We compare forecast neutral winds with Advanced Scatterometer measurements. The results indicate that the ECMWF forecasts systematically underestimate wind speed with respect to scatterometer data, while the UKMO model tends to overestimate. A cross‐analysis suggests that, better than fetch, model biases are a function of the model horizontal discretization, hence of the number of grid steps the wind runs over the sea. The steepness and roughness of the land orography before entering the sea, together with the related drag parameters, appear to have a strong role in determining the coastal offshore wind values. Surface drag over land tends to reduce the related wind speed, and it takes a few grid points to adjust to the smooth sea surface conditions. This is supported by a detailed study with a high resolution grid, but different orography resolutions. In these simulations, practically identical coastal wind speed distributions are found when the subgrid orography schemes are switched off. Vertical cross‐sections of potential temperature and wind in bora and mistral conditions illustrate the strong role of gravity waves, wind channeling and turbulent diffusion in coastal numerical weather prediction. Besides local wave modeling, this may be relevant for offshore wind farms, typically situated within 5–50 km from the coast.
Constraints on Southern Ocean Shortwave Cloud Feedback From the Hydrological Cycle
Authors: Tan Chuyan , McCoy Daniel T. , Elsaesser Gregory S.
Published: March 2024

Shifts in Southern Ocean (SO, 40–85°S) shortwave cloud feedback (SWFB) toward more positive values are the dominant contributor to higher effective climate sensitivity (ECS) in Coupled Model Intercomparison Project Phase 6 (CMIP6) models. To provide an observational constraint on the SO SWFB, we use a simplified physical model to connect SO SWFB with the response of column‐integrated liquid water mass (LWP) to warming and the susceptibility of albedo to LWP in 50 CMIP5 and CMIP6 GCMs. In turn, we predict the responses of SO LWP using a cloud‐controlling factor (CCF) model. The combination of the CCF model and radiative susceptibility explains about 50% of the variance in the GCM‐simulated SWFB in the SO. Observations of SW radiation fluxes, LWP, and CCFs from reanalysis are used to constrain the SO SWFB. Observations suggest a SO LWP increase in response to warming and albedo susceptibility to LWP that is on the lower end relative to GCMs. The overall constraint on the contribution of SO to global mean SWFB is −0.168 to +0.051 W m−2 K−1, relative to −0.277 to +0.270 Wm−2 K−1. In summary, observations suggest SO SWFB is less likely to be as extremely positive as predicted by some CMIP6 GCMs, but more likely to range from moderately negative to weakly positive.
Protective effect of PDE4B subtype-specific inhibition in an App knock-in mouse model for Alzheimer’s disease
Authors: Armstrong Paul , Güngör Hüseyin , Anongjanya Pariya , Tweedy Clare , Parkin Edward , Johnston Jamie , Carr Ian M. , Dawson Neil , Clapcote Steven J.
Published: March 2024

Meta-analysis of genome-wide association study data has implicated PDE4B in the pathogenesis of Alzheimer’s disease (AD), the leading cause of senile dementia. PDE4B encodes one of four subtypes of cyclic adenosine monophosphate (cAMP)-specific phosphodiesterase-4 (PDE4A–D). To interrogate the involvement of PDE4B in the manifestation of AD-related phenotypes, the effects of a hypomorphic mutation (Pde4bY358C) that decreases PDE4B’s cAMP hydrolytic activity were evaluated in the AppNL-G-F knock-in mouse model of AD using the Barnes maze test of spatial memory, 14C-2-deoxyglucose autoradiography, thioflavin-S staining of β-amyloid (Aβ) plaques, and inflammatory marker assay and transcriptomic analysis (RNA sequencing) of cerebral cortical tissue. At 12 months of age, AppNL-G-F mice exhibited spatial memory and brain metabolism deficits, which were prevented by the hypomorphic PDE4B in AppNL-G-F/Pde4bY358C mice, without a decrease in Aβ plaque burden. RNA sequencing revealed that, among the 531 transcripts differentially expressed in AppNL-G-F versus wild-type mice, only 13 transcripts from four genes – Ide, Btaf1, Padi2, and C1qb – were differentially expressed in AppNL-G-F/Pde4bY358C versus AppNL-G-F mice, identifying their potential involvement in the protective effect of hypomorphic PDE4B. Our data demonstrate that spatial memory and cerebral glucose metabolism deficits exhibited by 12-month-old AppNL-G-F mice are prevented by targeted inhibition of PDE4B. To our knowledge, this is the first demonstration of a protective effect of PDE4B subtype-specific inhibition in a preclinical model of AD. It thus identifies PDE4B as a key regulator of disease manifestation in the AppNL-G-F model and a promising therapeutic target for AD.
Long-term outcomes of physical activity counseling in in-patients with major depressive disorder: results from the PACINPAT randomized controlled trial
Authors: Kreppke Jan-Niklas , Cody Robyn , Beck Johannes , Brand Serge , Donath Lars , Eckert Anne , Faude Oliver , Hatzinger Martin , Imboden Christian , Lang Undine E. , Ludyga Sebastian , Mans Sarah , Mikoteit Thorsten , Oswald Anja , Schweinfurth-Keck Nina , Holsboer-Trachsler Edith , Zahner Lukas , Gerber Markus
Published: March 2024

Major depressive disorder (MDD) is an increasingly common psychiatric illness associated with a high risk of insufficient physical activity, which in turn is associated with negative mental and physical health outcomes. Theory-based, individually tailored, in-person and remote physical activity counseling has the potential to increase physical activity levels in various populations. Given this, the present study investigated the effect of such a physical activity intervention on the physical activity behavior of in-patients with MDD. This was a multi-center, two-arm randomized controlled trial including initially insufficiently physically active adult in-patients with MDD from four study sites in Switzerland. The sample consisted of 220 participants (Mage = 41 ± 12.6 years, 52% women), 113 of whom were randomized to the intervention group and 107 to the control group. The main outcome, moderate-to-vigorous physical activity (MVPA), was assessed at three time points via hip-worn accelerometer. According to accelerometer measures, there was no significant difference in minutes spent in MVPA over a 12-month intervention period when comparing the intervention with the control group (β = −1.02, 95% CI = −10.68 to 8.64). Higher baseline physical activity significantly predicted physical activity at post and follow-up. This study showed that it is feasible to deliver an individually tailored, theory-based physical activity counseling intervention to in-patients with MDD, however yielding no significant effects on accelerometer-based MVPA levels. Further efforts are warranted to identify efficacious approaches.

Trial registration: ISRCTN, ISRCTN10469580, registered on 3rd September 2018, https://www.isrctn.com/ISRCTN10469580.
FBXO22 promotes glioblastoma malignant progression by mediating VHL ubiquitination and degradation
Authors: Shen Zhigang , Dong Tao , Yong Hongmei , Deng Chuyin , Chen Changxiu , Chen Xintian , Chen Miaolei , Chu Sufang , Zheng Junnian , Li Zhongwei , Bai Jin
Published: March 2024

Glioblastoma (GBM) is the most common malignant primary brain tumor. Despite comprehensive treatment with traditional surgery, radiotherapy, and chemotherapy, the median survival rate is <14.6% and the 5-year survival rate is only 5%. FBXO22, a substrate receptor of the SCF ubiquitin ligases, has been reported to play a promoting role in melanoma, liver cancer, cervical cancer, and other cancers. However, the function of FBXO22 in GBM has not been reported. In the present study, we demonstrate that FBXO22 is highly expressed in glioma and is positively correlated with worse pathological features and shorter survival of GBM patients. We revealed that FBXO22 promotes GBM cell proliferation, angiogenesis, migration, and tumorigenesis in vitro and in vivo. In terms of mechanism, we reveal that FBXO22 decreases VHL expression by directly mediating VHL ubiquitination degradation, which ultimately increases HIF-1α and VEGFA expression. In addition, our data confirm that there are positive correlations among FBXO22, HIF-1α, and VEGFA expression, and there is a negative correlation between FBXO22 and VHL protein expression in glioma patients. Our study strongly indicates that FBXO22 is a promising diagnostic marker and therapeutic target for glioma patients.
Plasmid-mediated phenotypic noise leads to transient antibiotic resistance in bacteria
Authors: Hernandez-Beltran J. Carlos R. , Rodríguez-Beltrán Jerónimo , Aguilar-Luviano Oscar Bruno , Velez-Santiago Jesús , Mondragón-Palomino Octavio , MacLean R. Craig , Fuentes-Hernández Ayari , San Millán Alvaro , Peña-Miller Rafael
Published: March 2024

The rise of antibiotic resistance is a critical public health concern, requiring an understanding of mechanisms that enable bacteria to tolerate antimicrobial agents. Bacteria use diverse strategies, including the amplification of drug-resistance genes. In this paper, we showed that multicopy plasmids, often carrying antibiotic resistance genes in clinical bacteria, can rapidly amplify genes, leading to plasmid-mediated phenotypic noise and transient antibiotic resistance. By combining stochastic simulations of a computational model with high-throughput single-cell measurements of blaTEM-1 expression in Escherichia coli MG1655, we showed that plasmid copy number variability stably maintains populations composed of cells with both low and high plasmid copy numbers. This diversity in plasmid copy number enhances the probability of bacterial survival in the presence of antibiotics, while also rapidly reducing the burden of carrying multiple plasmids in drug-free environments. Our results further support the tenet that multicopy plasmids not only act as vehicles for the horizontal transfer of genetic information between cells but also as drivers of bacterial adaptation, enabling rapid modulation of gene copy numbers. Understanding the role of multicopy plasmids in antibiotic resistance is critical, and our study provides insights into how bacteria can transiently survive lethal concentrations of antibiotics.
Expression of USP25 associates with fibrosis, inflammation and metabolism changes in IgG4-related disease
Authors: Jiang Panpan , Jing Yukai , Zhao Siyu , Lan Caini , Yang Lu , Dai Xin , Luo Li , Cai Shaozhe , Zhu Yingzi , Miller Heather , Lai Juan , Zhang Xin , Zhao Xiaochao , Wu Yonggui , Yang Jingzhi , Zhang Wen , Guan Fei , Zhong Bo , Umehara Hisanori , Lei Jiahui , Dong Lingli , Liu Chaohong
Published: March 2024

IgG4-related disease (IgG4-RD) has complex clinical manifestations ranging from fibrosis and inflammation to deregulated metabolism. The molecular mechanisms underpinning these phenotypes are unclear. In this study, by using IgG4-RD patient peripheral blood mononuclear cells (PBMCs), IgG4-RD cell lines and Usp25 knockout mice, we show that ubiquitin-specific protease 25 (USP25) engages in multiple pathways to regulate fibrotic and inflammatory pathways that are characteristic to IgG4-RD. Reduced USP25 expression in IgG4-RD leads to increased SMAD3 activation, which contributes to fibrosis and induces inflammation through the IL-1β inflammatory axis. Mechanistically, USP25 prevents ubiquitination of RAC1, thus, downregulation of USP25 leads to ubiquitination and degradation of RAC1. Decreased RAC1 levels result in reduced aldolase A release from the actin cytoskeleton, which then lowers glycolysis. The expression of LYN, a component of the B cell receptor signalosome is also reduced in USP25-deficient B cells, which might result in B cell activation deficiency. Altogether, our results indicate a potential anti-inflammatory and anti-fibrotic role for USP25 and make USP25 a promising diagnostic marker and potential therapeutic target in IgG4-RD.
Programming mechanics in knitted materials, stitch by stitch
Authors: Singal Krishma , Dimitriyev Michael S. , Gonzalez Sarah E. , Cachine A. Patrick , Quinn Sam , Matsumoto Elisabetta A.
Published: March 2024

Knitting turns yarn, a 1D material, into a 2D fabric that is flexible, durable, and can be patterned to adopt a wide range of 3D geometries. Like other mechanical metamaterials, the elasticity of knitted fabrics is an emergent property of the local stitch topology and pattern that cannot solely be attributed to the yarn itself. Thus, knitting can be viewed as an additive manufacturing technique that allows for stitch-by-stitch programming of elastic properties and has applications in many fields ranging from soft robotics and wearable electronics to engineered tissue and architected materials. However, predicting these mechanical properties based on the stitch type remains elusive. Here we untangle the relationship between changes in stitch topology and emergent elasticity in several types of knitted fabrics. We combine experiment and simulation to construct a constitutive model for the nonlinear bulk response of these fabrics. This model serves as a basis for composite fabrics with bespoke mechanical properties, which crucially do not depend on the constituent yarn.
Velocities of transmission eigenchannels and diffusion
Authors: Genack Azriel Z. , Huang Yiming , Maor Asher , Shi Zhou
Published: March 2024

The diffusion model is used to calculate both the time-averaged flow of particles in stochastic media and the propagation of waves averaged over ensembles of disordered static configurations. For classical waves exciting static disordered samples, such as a layer of paint or a tissue sample, the flux transmitted through the sample may be dramatically enhanced or suppressed relative to predictions of diffusion theory when the sample is excited by a waveform corresponding to a transmission eigenchannel. Even so, it is widely assumed that the velocity of waves is irretrievably randomized in scattering media. Here we demonstrate in microwave measurements and numerical simulations that the statistics of velocity of different transmission eigenchannels are distinct and remains so on all length scales and are identical on the incident and output surfaces. The interplay between eigenchannel velocities and transmission eigenvalues determines the energy density within the medium, the diffusion coefficient, and the dynamics of propagation. The diffusion coefficient and all scattering parameters, including the scattering mean free path, oscillate with the width of the sample as the number and shape of the propagating channels in the medium change.
Functional screening in human HSPCs identifies optimized protein-based enhancers of Homology Directed Repair
Authors: Perez-Bermejo Juan A. , Efagene Oghene , Matern William M. , Holden Jeffrey K. , Kabir Shaheen , Chew Glen M. , Andreoletti Gaia , Catton Eniola , Ennis Craig L. , Garcia Angelica , Gerstenberg Trevor L. , Hill Kaisle A. , Jain Aayami , Krassovsky Kristina , Lalisan Cassandra D. , Lord Daniel , Quejarro B. Joy , Sales-Lee Jade , Shah Meet , Silva Brian J. , Skowronski Jason , Strukov Yuri G. , Thomas Joshua , Veraz Michael , Vijay Twaritha , Wallace Kirby A. , Yuan Yue , Grogan Jane L. , Wienert Beeke , Lahiri Premanjali , Treusch Sebastian , Dever Daniel P. , Soros Vanessa B. , Partridge James R. , Seim Kristen L.
Published: March 2024

Homology Directed Repair (HDR) enables precise genome editing, but the implementation of HDR-based therapies is hindered by limited efficiency in comparison to methods that exploit alternative DNA repair routes, such as Non-Homologous End Joining (NHEJ). In this study, we develop a functional, pooled screening platform to identify protein-based reagents that improve HDR in human hematopoietic stem and progenitor cells (HSPCs). We leverage this screening platform to explore sequence diversity at the binding interface of the NHEJ inhibitor i53 and its target, 53BP1, identifying optimized variants that enable new intermolecular bonds and robustly increase HDR. We show that these variants specifically reduce insertion-deletion outcomes without increasing off-target editing, synergize with a DNAPK inhibitor molecule, and can be applied at manufacturing scale to increase the fraction of cells bearing repaired alleles. This screening platform can enable the discovery of future gene editing reagents that improve HDR outcomes.
Defect-induced helicity dependent terahertz emission in Dirac semimetal PtTe2 thin films
Authors: Chen Zhongqiang , Qiu Hongsong , Cheng Xinjuan , Cui Jizhe , Jin Zuanming , Tian Da , Zhang Xu , Xu Kankan , Liu Ruxin , Niu Wei , Zhou Liqi , Qiu Tianyu , Chen Yequan , Zhang Caihong , Xi Xiaoxiang , Song Fengqi , Yu Rong , Zhai Xuechao , Jin Biaobing , Zhang Rong , Wang Xuefeng
Published: March 2024

Nonlinear transport enabled by symmetry breaking in quantum materials has aroused considerable interest in condensed matter physics and interdisciplinary electronics. However, achieving a nonlinear optical response in centrosymmetric Dirac semimetals via defect engineering has remained a challenge. Here, we observe the helicity dependent terahertz emission in Dirac semimetal PtTe2 thin films via the circular photogalvanic effect under normal incidence. This is activated by a controllable out-of-plane Te-vacancy defect gradient, which we unambiguously evidence with electron ptychography. The defect gradient lowers the symmetry, which not only induces the band spin splitting but also generates the giant Berry curvature dipole responsible for the circular photogalvanic effect. We demonstrate that the THz emission can be manipulated by the Te-vacancy defect concentration. Furthermore, the temperature evolution of the THz emission features a minimum in the THz amplitude due to carrier compensation. Our work provides a universal strategy for symmetry breaking in centrosymmetric Dirac materials for efficient nonlinear transport.
Prior infection with unrelated neurotropic virus exacerbates influenza disease and impairs lung T cell responses
Authors: Foo Isabelle Jia-Hui , Chua Brendon Y. , Clemens E. Bridie , Chang So Young , Jia Xiaoxiao , McQuilten Hayley A. , Yap Ashley Huey Yiing , Cabug Aira F. , Ashayeripanah Mitra , McWilliam Hamish E. G. , Villadangos Jose A. , Evrard Maximilien , Mackay Laura K. , Wakim Linda M. , Fazakerley John K. , Kedzierska Katherine , Kedzierski Lukasz
Published: March 2024

Immunity to infectious diseases is predominantly studied by measuring immune responses towards a single pathogen, although co-infections are common. In-depth mechanisms on how co-infections impact anti-viral immunity are lacking, but are highly relevant to treatment and prevention. We established a mouse model of co-infection with unrelated viruses, influenza A (IAV) and Semliki Forest virus (SFV), causing disease in different organ systems. SFV infection eight days before IAV infection results in prolonged IAV replication, elevated cytokine/chemokine levels and exacerbated lung pathology. This is associated with impaired lung IAV-specific CD8+ T cell responses, stemming from suboptimal CD8+ T cell activation and proliferation in draining lymph nodes, and dendritic cell paralysis. Prior SFV infection leads to increased blood brain barrier permeability and presence of IAV RNA in brain, associated with increased trafficking of IAV-specific CD8+ T cells and establishment of long-term tissue-resident memory. Relative to lung IAV-specific CD8+ T cells, brain memory IAV-specific CD8+ T cells have increased TCR repertoire diversity within immunodominant DbNP366+CD8+ and DbPA224+CD8+ responses, featuring suboptimal TCR clonotypes. Overall, our study demonstrates that infection with an unrelated neurotropic virus perturbs IAV-specific immune responses and exacerbates IAV disease. Our work provides key insights into therapy and vaccine regimens directed against unrelated pathogens.
Demonstration of hypergraph-state quantum information processing
Authors: Huang Jieshan , Li Xudong , Chen Xiaojiong , Zhai Chonghao , Zheng Yun , Chi Yulin , Li Yan , He Qiongyi , Gong Qihuang , Wang Jianwei
Published: March 2024

Complex entangled states are the key resources for measurement-based quantum computations, which is realised by performing a sequence of measurements on initially entangled qubits. Executable quantum algorithms in the graph-state quantum computing model are determined by the entanglement structure and the connectivity of entangled qubits. By generalisation from graph-type entanglement in which only the nearest qubits interact to a new type of hypergraph entanglement in which any subset of qubits can be arbitrarily entangled via hyperedges, hypergraph states represent more general resource states that allow arbitrary quantum computation with Pauli universality. Here we report experimental preparation, certification and processing of complete categories of four-qubit hypergraph states under the principle of local unitary equivalence, on a fully reprogrammable silicon-photonic quantum chip. Genuine multipartite entanglement for hypergraph states is certificated by the characterisation of entanglement witness, and the observation of violations of Mermin inequalities without any closure of distance or detection loopholes. A basic measurement-based protocol and an efficient resource state verification by color-encoding stabilizers are implemented with local Pauli measurement to benchmark the building blocks for hypergraph-state quantum computation. Our work prototypes hypergraph entanglement as a general resource for quantum information processing.
Non-catalytic role of phosphoinositide 3-kinase in mesenchymal cell migration through non-canonical induction of p85β/AP2-mediated endocytosis
Authors: Matsubayashi Hideaki T. , Mountain Jack , Takahashi Nozomi , Deb Roy Abhijit , Yao Tony , Peterson Amy F. , Saez Gonzalez Cristian , Kawamata Ibuki , Inoue Takanari
Published: March 2024

Class IA phosphoinositide 3-kinase (PI3K) galvanizes fundamental cellular processes such as migration, proliferation, and differentiation. To enable these multifaceted roles, the catalytic subunit p110 utilizes the multi-domain, regulatory subunit p85 through its inter SH2 domain (iSH2). In cell migration, its product PI(3,4,5)P3 generates locomotive activity. While non-catalytic roles are also implicated, underlying mechanisms and their relationship to PI(3,4,5)P3 signaling remain elusive. Here, we report that a disordered region of iSH2 contains AP2 binding motifs which can trigger clathrin and dynamin-mediated endocytosis independent of PI3K catalytic activity. The AP2 binding motif mutants of p85 aberrantly accumulate at focal adhesions and increase both velocity and persistency in fibroblast migration. We thus propose the dual functionality of PI3K in the control of cell motility, catalytic and non-catalytic, arising distinctly from juxtaposed regions within iSH2.
Developing a machine learning model for accurate nucleoside hydrogels prediction based on descriptors
Authors: Li Weiqi , Wen Yinghui , Wang Kaichao , Ding Zihan , Wang Lingfeng , Chen Qianming , Xie Liang , Xu Hao , Zhao Hang
Published: March 2024

Supramolecular hydrogels derived from nucleosides have been gaining significant attention in the biomedical field due to their unique properties and excellent biocompatibility. However, a major challenge in this field is that there is no model for predicting whether nucleoside derivative will form a hydrogel. Here, we successfully develop a machine learning model to predict the hydrogel-forming ability of nucleoside derivatives. The optimal model with a 71% (95% Confidence Interval, 0.69−0.73) accuracy is established based on a dataset of 71 reported nucleoside derivatives. 24 molecules are selected via the optimal model external application and the hydrogel-forming ability is experimentally verified. Among these, two rarely reported cation-independent nucleoside hydrogels are found. Based on their self-assemble mechanisms, the cation-independent hydrogel is found to have potential applications in rapid visual detection of Ag+ and cysteine. Here, we show the machine learning model may provide a tool to predict nucleoside derivatives with hydrogel-forming ability.
Multi-omic integration of microbiome data for identifying disease-associated modules
Authors: Muller Efrat , Shiryan Itamar , Borenstein Elhanan
Published: March 2024

Multi-omic studies of the human gut microbiome are crucial for understanding its role in disease across multiple functional layers. Nevertheless, integrating and analyzing such complex datasets poses significant challenges. Most notably, current analysis methods often yield extensive lists of disease-associated features (e.g., species, pathways, or metabolites), without capturing the multi-layered structure of the data. Here, we address this challenge by introducing “MintTea”, an intermediate integration-based approach combining canonical correlation analysis extensions, consensus analysis, and an evaluation protocol. MintTea identifies “disease-associated multi-omic modules”, comprising features from multiple omics that shift in concord and that collectively associate with the disease. Applied to diverse cohorts, MintTea captures modules with high predictive power, significant cross-omic correlations, and alignment with known microbiome-disease associations. For example, analyzing samples from a metabolic syndrome study, MintTea identifies a module with serum glutamate- and TCA cycle-related metabolites, along with bacterial species linked to insulin resistance. In another dataset, MintTea identifies a module associated with late-stage colorectal cancer, including Peptostreptococcus and Gemella species and fecal amino acids, in line with these species’ metabolic activity and their coordinated gradual increase with cancer development. This work demonstrates the potential of advanced integration methods in generating systems-level, multifaceted hypotheses underlying microbiome-disease interactions.
Vacancies tailoring lattice anharmonicity of Zintl-type thermoelectrics
Authors: Zhu Jinfeng , Ren Qingyong , Chen Chen , Wang Chen , Shu Mingfang , He Miao , Zhang Cuiping , Le Manh Duc , Torri Shuki , Wang Chin-Wei , Wang Jianli , Cheng Zhenxiang , Li Lisi , Wang Guohua , Jiang Yuxuan , Wu Mingzai , Qu Zhe , Tong Xin , Chen Yue , Zhang Qian , Ma Jie
Published: March 2024

While phonon anharmonicity affects lattice thermal conductivity intrinsically and is difficult to be modified, controllable lattice defects routinely function only by scattering phonons extrinsically. Here, through a comprehensive study of crystal structure and lattice dynamics of Zintl-type Sr(Cu,Ag,Zn)Sb thermoelectric compounds using neutron scattering techniques and theoretical simulations, we show that the role of vacancies in suppressing lattice thermal conductivity could extend beyond defect scattering. The vacancies in Sr2ZnSb2 significantly enhance lattice anharmonicity, causing a giant softening and broadening of the entire phonon spectrum and, together with defect scattering, leading to a ~ 86% decrease in the maximum lattice thermal conductivity compared to SrCuSb. We show that this huge lattice change arises from charge density reconstruction, which undermines both interlayer and intralayer atomic bonding strength in the hierarchical structure. These microscopic insights demonstrate a promise of artificially tailoring phonon anharmonicity through lattice defect engineering to manipulate lattice thermal conductivity in the design of energy conversion materials.