bluuebunny/crossref_metadata_2025 huggingface dataset:
Network Analysis of the Cerebrospinal Fluid Proteome Reveals Shared and Unique Differences Between Sporadic and Familial Forms of Amyotrophic Lateral Sclerosis
Authors: Trautwig Adam N. , Fox Edward J. , Dammer Eric B. , Shantaraman Anantharaman , Ping Lingyan , Duong Duc M. , Levey Allan I. , Lah James J. , Fournier Christina N. , McEachin Zachary T. , Glass Jonathan D. , Seyfried Nicholas T.
Published: March 2024

Background

Amyotrophic Lateral Sclerosis (ALS), a neurodegenerative disease involving loss of motor neurons, typically results in death within 3-5 years of disease onset. Although roughly 10 % of cases can be linked to a specific inherited mutation (e.g., C9orf72 hexanucleotide repeat expansion or SOD1 mutation), the cause of the majority of cases is unknown. Consequently, there is a critical need for biomarkers that reflect disease onset and progression across ALS subgroups.

Methods

We employed tandem mass tag mass spectrometry (TMT-MS) based proteomics on cerebrospinal fluid (CSF) to identify and quantify 2105 proteins from ALS patients with sporadic disease (n=35), C9orf72 ALS (n=10), and SOD1 ALS (n=6), as well as age-matched healthy controls (n=44) and asymptomatic C9orf72 carriers (n=6). We used differential protein abundance and network analyses to determine how protein profiles vary across disease types in ALS CSF.

Results

Integrated differential and co-expression network analysis identified proteomic differences between ALS and control, and differentially abundant proteins between sporadic, C9orf72 and SOD1 ALS. Groups of proteins also differentiated asymptomatic C9orf72 mutation carriers from those with C9orf72 ALS, marking a pre-symptomatic proteomic signature of C9orf72 ALS. Similarly, additional proteins differentiated asymptomatic from controls. Leveraging additional publicly available ALS and AD proteomic datasets, we validated our ALS CSF network and identified ALS-specific proteins within Module 5 (M5)-Extracellular matrix (e.g., IGF2, RARRES2, LGALS3, GALNT15, and LYZ) and shared biomarkers across neurodegenerative diseases linked to Module 10 (M10)-Ubiquitination/Gluconeogenesis (e.g., NEFL, NEFM, CHIT1, and CHI3L1).

Conclusions

This study represents a comprehensive analysis of the CSF proteome across sporadic and genetic causes of ALS that resolves differences among these disease subgroups and points to varying pathogenic pathways that result in disease.
Low intensity repetitive transcranial magnetic stimulation enhances remyelination by newborn and surviving oligodendrocytes in the cuprizone model of toxic demyelination
Authors: Nguyen Phuong Tram , Makowiecki Kalina , Lewis Thomas S , Fortune Alastair , Clutterbuck Mackenzie , Reale Laura , Taylor Bruce V , Rodger Jennifer , Cullen Carlie L , Young Kaylene M
Published: March 2024

In people with multiple sclerosis (MS), newborn and surviving oligodendrocytes (OLs) can contribute to remyelination, however, current therapies are unable to enhance or sustain endogenous repair. Low intensity repetitive transcranial magnetic stimulation (LI-rTMS), delivered as an intermittent theta burst stimulation (iTBS), increases the survival and maturation of newborn OLs in the healthy adult mouse cortex, but it is unclear whether LI-rTMS can promote remyelination. To examine this possibility, we fluorescently labelled oligodendrocyte progenitor cells (OPCs;Pdgfrα-CreERtransgenic mice) or mature OLs (Plp-CreERtransgenic mice) in the adult mouse brain and traced the fate of each cell population over time. Multiple consecutive daily sessions of iTBS (600 pulses; 120 mT), delivered during cuprizone (CPZ) feeding, did not alter new or pre- existing OL survival but increased the number of myelin internodes elaborated by new OLs in the primary motor cortex (M1). This resulted in each new M1 OL producing ∼471µm more myelin. When LI-rTMS was delivered after CPZ withdrawal (during remyelination), it significantly increased the length of the internodes elaborated by new M1 and callosal OLs and increased the number of surviving OLs that contributed to remyelination in the corpus callosum (CC). As LI-rTMS can non-invasively promote remyelination by modifying the behaviour of new and surviving OLs, it may be suitable as an adjunct intervention to enhance remyelination in people with MS.
ATG6 interacting with NPR1 increasesArabidopsis thalianaresistance toPstDC3000/avrRps4by increasing its nuclear accumulation and stability
Authors: Zhang Baihong , Huang Shuqin , Guo Shuyu , Meng Yixuan , Tian Yuzhen , Zhou Yue , Chen Hang , Li Xue , Zhou Jun , Chen Wenli
Published: March 2024

Autophagy-related gene 6 (ATG6) plays a crucial role in plant immunity. Nonexpressor of pathogenesis-related genes1 (NPR1) acts as a signaling hub of plant immunity. However, the relationship between ATG6 and NPR1 is unclear. Here, we find that ATG6 directly interacts with NPR1.ATG6overexpression significantly increased nuclear accumulation of NPR1. Furthermore, we demonstrate thatATG6increases NPR1 protein levels and improves its stability. Interestingly, ATG6 promotes the formation of SINCs (SA-induced NPR1 condensates)-like condensates. Additionally, ATG6 and NPR1 synergistically promote the expression ofpathogenesis-relatedgenes. Further results showed that silencingATG6inNPR1-GFPexacerbatesPstDC3000/avrRps4infection, while double overexpression ofATG6andNPR1synergistically inhibitsPstDC3000/avrRps4infection. In summary, our findings unveil an interplay of NPR1 with ATG6 and elucidate important molecular mechanisms for enhancing plant immunity.

Highlight

We unveil a novel relationship in which ATG6 positively regulates NPR1 in plant immunity.
scIDPMs: single-cell RNA-seq imputation using diffusion probabilistic models
Authors: Zhang Zhiqiang , Liu Lin
Published: March 2024

Single-cell RNA sequencing (scRNA-seq) technology is a high-throughput sequencing analysis method that enables the sequencing of mRNA in individual cells, thereby facilitating a more precise understanding of cellular gene expression and metabolic products. This approach reveals cell function and characteristics, making it widely applicable in biological research. However, scRNA-seq data often suffers from false zero values known as dropout events due to limitations in sequencing technology. These dropout events not only mask true gene expression levels but also significantly impact downstream analysis accuracy and reliability. To address this challenge, numerous computational approaches have been proposed for imputing missing gene expression values. Nevertheless, existing imputation methods struggle to fully capture the distribution of dropout values due to the high sparsity of scRNA-seq data and the complexity and randomness associated with gene expression patterns. Recently, probabilistic diffusion models have emerged as deep generative models capable of accurately restoring probability density distributions in domains such as image and audio processing. In this paper, we propose a method called scIDPMs, which utilizes conditional diffusion probabilistic models to impute scRNA-seq data. scIDPMs first identifies dropout sites based on the characteristics of cellular gene expression and then infers the dropout values by conditioning on the available gene expression values, which provide context information for the dropout values. To effectively capture the global features of gene expression profiles, scIDPMs employs a deep neural network with an attention mechanism to optimize the objective function. The performance of scIDPMs was evaluated using both simulated and real scRNA-seq datasets, and compared with eight other imputation methods. The experimental results clearly demonstrated that, in comparison to alternative approaches, scIDPMs exhibited exceptional performance in recovering biologically meaningful gene expression values and enhancing various downstream analyses.
Prediction of brain age in individuals with and at risk for alcohol use disorder using brain morphological features
Authors: Kamarajan Chella , Ardekani Babak A. , Pandey Ashwini K. , Meyers Jacquelyn L. , Chorlian David B. , Kinreich Sivan , Pandey Gayathri , Richard Christian , de Viteri Stacey Saenz , Kuang Weipeng , Porjesz Bernice
Published: March 2024

Brain age measures predicted from structural and functional brain features are increasingly being used to understand brain integrity, disorders, and health. While there is a vast literature showing aberrations in both structural and functional brain measures in individuals with and at risk for alcohol use disorder (AUD), few studies have investigated brain age in these groups. The current study examines brain age measures predicted using brain morphological features, such as cortical thickness and brain volume, in individuals with a lifetime diagnosis of AUD as well as in those at higher risk to develop AUD from families with multiple members affected with AUD (i.e., higher family history density (FHD) scores). The AUD dataset included a group of 30 adult males (mean age = 41.25 years) with a lifetime diagnosis of AUD and currently abstinent and a group of 30 male controls (mean age = 27.24 years) without any history of AUD. A second dataset of young adults who were categorized based on their FHD scores comprised a group of 40 individuals (20 males) with high FHD of AUD (mean age = 25.33 years) and a group of 31 individuals (18 males) with low FHD (mean age = 25.47 years). Brain age was predicted using 187 brain morphological features of cortical thickness and brain volume in an XGBoost regression model; a bias-correction procedure was applied to the predicted brain age. Results showed that both AUD and high FHD individuals showed an increase of 1.70 and 0.09 years (1.08 months), respectively, in their brain age relative to their chronological age, suggesting accelerated brain aging in AUD and risk for AUD. Increased brain age was associated with poor performance on neurocognitive tests of executive functioning in both AUD and high FHD individuals, indicating that brain age can also serve as a proxy for cognitive functioning and brain health. These findings on brain aging in these groups may have important implications for the prevention and treatment of AUD and ensuing cognitive decline.
The transcriptomic landscape of monosomy X (45,X) during early human fetal and placental development
Authors: Suntharalingham Jenifer P. , del Valle Ignacio , Buonocore Federica , McGlacken-Byrne Sinead M. , Brooks Tony , Ogunbiyi Olumide K. , Liptrot Danielle , Dunton Nathan , Madhan Gaganjit K , Metcalfe Kate , Nel Lydia , Marshall Abigail R. , Ishida Miho , Sebire Neil J. , Moore Gudrun E. , Crespo Berta , Solanky Nita , Conway Gerard S. , Achermann John C.
Published: March 2024

Monosomy X (45,X) is associated with Turner syndrome and pregnancy loss in humans, but the underlying mechanisms remain unclear. We therefore analyzed the transcriptomic landscape of clinically relevant human fetal 45,X tissues (including pancreas, liver, kidney, skin, placenta) with matched 46,XX and 46,XY control samples between 11-15 weeks post conception (n=78). Although most pseudoautosomal region 1 (PAR1) genes were lower in monosomy X tissues, we also found reduced expression of several key genes escaping X inactivation (e.g.,KDM5CandKDM6A), and potentially clinically important transcripts such as genes implicated in ascending aortic aneurysm. In contrast,higherexpression of an autosomal, long non-coding RNA (OVCH1-AS1) was seen in all 45,X tissues. In the placenta, lower expression ofCSF2RAwas demonstrated, likely contributing to immune dysregulation. Taken together, these findings provide novel insights into the biological consequences of a single X chromosome during early human development and potential insights in genetic mechanisms in Turner syndrome.
Molecular Signatures of Normal Pressure Hydrocephalus: A Large-scale Proteomic Analysis of Cerebrospinal Fluid
Authors: Kamalian Aida , Barough Siavash Shirzadeh , Ho Sara G. , Albert Marilyn , Luciano Mark G. , Yasar Sevil , Moghekar Abhay
Published: March 2024

Given the persistent challenge of differentiating idiopathic Normal Pressure Hydrocephalus (iNPH) from similar clinical entities, we conducted an in-depth proteomic study of cerebrospinal fluid (CSF) in 28 shunt-responsive iNPH patients, 38 Mild Cognitive Impairment (MCI) due to Alzheimer’s disease, and 49 healthy controls. Utilizing the Olink Explore 3072 panel, we identified distinct proteomic profiles in iNPH that highlight significant downregulation of synaptic markers and cell-cell adhesion proteins. Alongside vimentin and inflammatory markers upregulation, these results suggest ependymal layer and transependymal flow dysfunction. Moreover, downregulation of multiple proteins associated with congenital hydrocephalus (e.g., L1CAM, PCDH9, ISLR2, ADAMTSL2, and B4GAT1) points to a possible shared molecular foundation between congenital hydrocephalus and iNPH. Through orthogonal partial least squares discriminant analysis (OPLS-DA), a panel comprising 13 proteins has been identified as potential diagnostic biomarkers of iNPH, pending external validation. These findings offer novel insights into the pathophysiology of iNPH, with implications for improved diagnosis.
Aroma compounds profile is affected by the initial yeast ratio in wort co-fermentations
Authors: Aguiar-Cervera Jose , Visinoni Federico , Zhang Penghan , Hollywood Katherine , Vrhovsek Urska , Severn Oliver , Delneri Daniela
Published: March 2024

In recent years, the boom of the craft beer industry refocused the biotech interest from ethanol production to diversification of beer aroma profiles. This study analyses the fermentative phenotype of a collection of non-conventional yeasts and examines their role in creating new flavours, particularly through co-fermentation with industrialSaccharomyces cerevisiae. High-throughput solid and liquid media fitness screening compared the ability of eightSaccharomycesand four non-Saccharomycesyeast strains to grow in wort. We determined the volatile profile of these yeast strains and found thatHanseniaspora vineaedisplayed a particularly high production of the desirable aroma compounds ethyl acetate and 2-phenethyl acetate. Given thatH. vineaeon its own was a poor fermenter, we carried out mixed wort co-fermentations with aS. cerevisiaebrewing strain at different ratios. The two yeast strains were able to co-exist throughout the experiment, regardless of their initial inoculum, and the increase in the production of the esters observed in theH. vineaemonoculture was maintained, alongside with a high ethanol production. Moreover, different inoculum ratios yielded different aroma profiles: the 50/50S. cerevisiae/H. vineaeratio produced a more balanced profile, while the 10/90 ratio generated stronger floral aromas. Our findings show the potential of using different yeasts and different inoculum combinations to tailor the final aroma, thus offering new possibilities for a broader range of beer flavours and styles.

IMPORTANCE

Craft brewing underwent an unprecedented growth in the last years due to customer demand for more unique and complex beverages. Brewers started to explore innovative fermentation methods using new ingredients, different brewing conditions, and new yeasts to explore a larger flavour landscape. The use of non-Saccharomycesyeasts has emerged as an effective strategy to produce novel distinct flavour profiles, however, knowledge regarding their fermentation performance and volatiles production is still limited, which hinders their industrial application. In this study, we expand on the knowledge of several non-Saccharomycesyeasts in terms of their brewing application and highlight the potential ofH. vineaein co-fermentation withS. cerevisiaefor producing unique fruity beers with a standard ethanol content. Our findings provide the craft beer industry with a new strategy to produce distinctive fruity beers.
The global β-lactam resistome revealed by comprehensive sequence analysis
Authors: Gholipour Sevan , Chen John , Lee Dongkyu , Tokuriki Nobuhiko
Published: March 2024

Most antibiotic-resistance genes (ARGs) evolved in environmental microbes long before humanity’s antibiotic breakthrough, and widespread antibiotic use expedited the dissemination of ARGs among clinical pathogens. While widely discussed, the investigation of environmental ARG distributions lacks the scalability and taxonomic information necessary for a comprehensive analysis. Here, we present a global distribution of all five classes of β-lactamases among microbes and environments. We generated a β-lactamase taxonomy-environment map by identifying >113,000 β-lactamases across diverse bacterial phyla and environmental ecosystems. Remarkably abundant, their occurrence is only ∼2.6-fold lower than the essentialrecAgene in various environmental ecosystems, with particularly strong enrichment in wastewater and plant samples. The enrichment in plant samples implies an environment where the arms race of β-lactam producers and resistant bacteria occurred over millions of years. We uncover the origins of clinically relevant β-lactamases (mainly in ɣ-Proteobacteria) and expand beyond the previously suggested wastewater samples in plant, terrestrial, and other aquatic settings.
The TD drive - A parametric, open-source implant for multi-area electrophysiological recordings in behaving and sleeping rats
Authors: Schröder Tim , van der Meij Jacqueline , van Heumen Paul , Samanta Anumita , Genzel Lisa
Published: March 2024

Intricate interactions between multiple brain areas underlie most functions attributed to the brain. The process of learning, as well as formation and consolidation of memories are two examples that rely heavily on functional connectivity across the brain. In addition, investigating hemispheric similarities and/or differences goes hand in hand with these multi-area interactions. Electrophysiological studies trying to further elucidate these complex processes thus depend on recording brain activity at multiple locations simultaneously and often in a bilateral fashion. Presented here is a 3D-printable implant for rats, named TD drive, capable of symmetric, bilateral wire electrode recordings, currently in up to ten distributed brain areas simultaneously. The open-source design was created employing parametric design principles, allowing prospective users to easily adapt the drive design to their needs by simply adjusting high-level parameters, such as anterior-posterior and medio-lateral coordinates of the recording electrode locations. The implant design was validated in n = 20 Lister Hooded rats that performed different tasks. The implant was compatible with tethered sleep recordings and open field recordings (Object Exploration) as well as wireless recording in a large maze (HexMaze 9×5 m) using two different commercial recording systems and headstages.

In sum, presented here is the adaptable design and assembly of a new electrophysiological implant facilitating fast preparation and implantation.
Multi-condition and multi-modal temporal profile inference during mouse embryonic development
Authors: Zhang Ran , Qiu Chengxiang , Filippova Gala , Li Gang , Shendure Jay , Vert Jean-Philippe , Deng Xinxian , Disteche Christine , Noble William Stafford
Published: March 2024

The emergence of single-cell time-series datasets enables modeling of changes in various types of cellular profiles over time. However, due to the disruptive nature of single-cell measurements, it is impossible to capture the full temporal trajectory of a particular cell. Furthermore, single-cell profiles can be collected at mismatched time points across different conditions (e.g., sex, batch, disease) and data modalities (e.g., scRNA-seq, scATAC-seq), which makes modeling challenging. Here we propose a joint modeling framework, Sunbear, for integrating multi-condition and multi-modal single-cell profiles across time. Sunbear can be used to impute single-cell temporal profile changes, align multi-dataset and multi-modal profiles across time, and extrapolate single-cell profiles in a missing modality. We applied Sunbear to reveal sex-biased transcription during mouse embryonic development and predict dynamic relationships between epigenetic priming and transcription for cells in which multi-modal profiles are unavailable. Sunbear thus enables the projection of single-cell time-series snapshots to multi-modal and multi-condition views of cellular trajectories.
A Methodology for Specific Disruption of Microtubules in Dendritic Spines
Authors: Holland Elizabeth D. , Miller Hannah L. , Millette Matthew M. , Taylor Russell J. , Drucker Gabrielle L. , Dent Erik W.
Published: March 2024

Dendritic spines, the mushroom-shaped extensions along dendritic shafts of excitatory neurons, are critical for synaptic function and are one of the first neuronal structures disrupted in neurodevelopmental and neurodegenerative diseases. Microtubule (MT) polymerization into dendritic spines is an activity-dependent process capable of affecting spine shape and function. Studies have shown that MT polymerization into spines occurs specifically in spines undergoing plastic changes. However, discerning the function of MT invasion of dendritic spines requires the specific inhibition of MT polymerization into spines, while leaving MT dynamics in the dendritic shaft, synaptically connected axons and associated glial cells intact. This is not possible with the unrestricted, bath application of pharmacological compounds. To specifically disrupt MT entry into spines we coupled a MT elimination domain (MTED) from the Efa6 protein to the actin filament-binding peptide LifeAct. LifeAct was chosen because actin filaments are highly concentrated in spines and are necessary for MT invasions. Temporally controlled expression of this LifeAct-MTED construct inhibits MT entry into dendritic spines, while preserving typical MT dynamics in the dendrite shaft. Expression of this construct will allow for the determination of the function of MT invasion of spines and more broadly, to discern how MT-actin interactions affect cellular processes.

Significance Statement

The LifeAct-MTED construct provides spatial and temporal control of microtubule depolymerization within individual cells

Targeting this construct directly to spines allows for the specific inhibition of microtubule dynamics into dendritic spines, without affecting microtubule dynamics in the dendritic shaft

Implementation of the construct will allow for the testing of microtubule contributions to specific biological processes, without global disruption of microtubule dynamics
Revisiting leptonic nonunitarity
Authors: Aloni Daniel , Dery Avital
Published: March 2024

In the presence of extra neutrino states at high scales, the low-energy effective 3×3 leptonic mixing matrix (LMM) is in general nonunitary. We revisit the question of what is our current knowledge of individual LMM matrix elements without assuming unitarity. We first demonstrate that a minimal set of experimental constraints suffices in bounding LMM nonunitarity parameters to the level of O(10−3), without the use of neutrino oscillation data. We then revisit oscillation results as a complementary cross-check, using different physics and different experimental techniques to probe a similar parameter space. We correct some common misconceptions in the neutrino nonunitarity literature resulting from an incautious treatment of input parameters. We find that neutrino oscillation experiments can constrain LMM nonclosure, but, contrary to claims in the literature, are completely insensitive to the overall normalization of the LMM. Thus, we conclude that oscillation experiments, including the future DUNE experiment, have no power in excluding nonunitarity altogether.

Published by the American Physical Society
2024
Does Lorentz-symmetric design boost network performance in jet physics?
Authors: Li Congqiao , Qu Huilin , Qian Sitian , Meng Qi , Gong Shiqi , Zhang Jue , Liu Tie-Yan , Li Qiang
Published: March 2024

In the deep learning era, improving the neural network performance in jet physics is a rewarding task, as it directly contributes to more accurate physics measurements at the LHC. Recent research has proposed various network designs in consideration of the full Lorentz symmetry, but its benefit is still not systematically asserted, given that there remain many successful networks without taking it into account. We conduct a detailed study on the Lorentz-symmetric design. We propose two generalized approaches for modifying a network—these methods are experimented on Particle Flow Network, ParticleNet, and LorentzNet and exhibit a general performance gain. We also reveal that the notable improvement attributed to the “pairwise mass” feature in the network is due to its introduction of a structure that fully complies with Lorentz symmetry. We confirm that Lorentz-symmetry preservation serves as a strong inductive bias of jet physics, hence calling for attention to such general recipes in future network designs.

Published by the American Physical Society
2024
GALILEO: Galactic Axion Laser Interferometer Leveraging Electro-Optics
Authors: Ebadi Reza , Kaplan David E. , Rajendran Surjeet , Walsworth Ronald L.
Published: March 2024

We propose a novel experimental method for probing light dark matter candidates. We show that an electro-optical material’s refractive index is modified in the presence of a coherently oscillating dark matter background. A high-precision resonant Michelson interferometer can be used to read out this signal. The proposed detection scheme allows for the exploration of an uncharted parameter space of dark matter candidates over a wide range of masses—including masses exceeding a few tens of microelectronvolts, which is a challenging parameter space for microwave cavity haloscopes.

Published by the American Physical Society
2024
Turbulence in Magnetic Reconnection Jets from Injection to Sub-Ion Scales
Authors: Richard Louis , Sorriso-Valvo Luca , Yordanova Emiliya , Graham Daniel B. , Khotyaintsev Yuri V.
Published: March 2024

We investigate turbulence in magnetic reconnection jets in the Earth’s magnetotail using data from the Magnetospheric Multiscale spacecraft. We show that signatures of a limited inertial range are observed in many reconnection jets. The observed turbulence develops on the timescale of a few ion gyroperiods, resulting in intermittent multifractal energy cascade from the characteristic scale of the jet down to the ion scales. We show that at sub-ion scales, the fluctuations are close to monofractal and predominantly kinetic Alfvén waves. The observed energy transfer rate across the inertial range is ∼108  J kg−1 s−1, which is the largest reported for space plasmas so far.

Published by the American Physical Society
2024
Partial molecular orbitals in face-sharing
3d
manganese trimer: Comparative studies on
Ba4TaMn3O12
and
Ba4NbMn3O12
Authors: Ali Anzar , Kim Heung-Sik , Yadav Poonam , Lee Suheon , Yoon Duhee , Choi Sungkyun
Published: March 2024

We present a molecular orbital candidate Ba4TaMn3O12 with a face-sharing octahedra trimer, by comparing it with a related compound Ba4NbMn3O12. The synthesis of the polycrystalline powder is optimized by suppressing the secondary impurity phase via x-ray diffraction. Magnetic susceptibility measurements on the optimized samples reveal a weak magnetic hysteresis with magnetic transitions consistent with heat capacity results. The effective magnetic moments from susceptibility indicate a strongly coupled S=2 antiferromagnetic trimer at around room temperature, whereas the estimated magnetic entropy from heat capacity suggests the localized S=3/2 timer. These results can be explainable by a partial molecular orbital state, in which three t2g electrons are localized in each Mn ion and one eg electron is delocalized over two-end Mn ions of the trimer based on density functional theory calculations. This unconventional 3d orbital state is comprehended as a consequence of competition between the hybrid interatomic orbitals within the Mn trimer and the local moment formation by on-site Coulomb correlations.

Published by the American Physical Society
2024
Experimental evidence for a current-biased Josephson junction acting as either a macroscopic boson or fermion
Authors: Ouyang P. H. , He S. R. , Wang Y. Z. , Chai Y. Q. , He J. X. , Chang H. , Wei L. F.
Published: March 2024

It is well known that elementary particles in the real 3+1-dimensional world are either bosons or fermions, without exception, and not both. Here, we show that a quantized current-biased Josephson junction (CBJJ), as an artificial macroscopic “particle,” can serve as either a boson or a fermion or the combination, depending on the amplitude of the biased dc current. By using high vacuum two-angle electron beam evaporations, we fabricated CBJJ devices and calibrated their physical parameters by applying low-frequency signal drivings. At 50mK temperature environment, the microwave transmission characteristics of the fabricated CBJJ devices were measured at the low power limit. The experimental results verify the relevant theoretical predictions, i.e., when the bias current is significantly lower than the critical ones of the junctions, the device works in a very linear regime and thus behaves as a harmonic oscillator “boson”; while if the biased current is sufficiently large (especially approaching the junctions' critical currents), the device works manifestly in the nonlinear regime and thus behaves as a two-level artificial atom “fermion.” Therefore, by adjusting the biased dc current, the CBJJ device can be effectively switched from a Bose-type macroscopic particle to a Fermi-type one and thus might open an approach for quantum technology applications at a macroscopic scale.

Published by the American Physical Society
2024
Building an organizational legacy: four key principles for responsible leadership
Authors: Welch James
Published: March 2024

Purpose

In response to the prevalent emphasis on short-term leadership, this article introduces a leadership framework that emphasizes four essential principles. These principles are aimed at promoting long-term effectiveness and sustainability in organizations centered on responsible leadership. These principles include developing long-term orientation, embracing organizational diversity, demonstrating emotional intelligence, and prioritizing ethical decision-making. These responsible leadership principles play a critical role in fostering long-term organizational success.

Design/methodology/approach

This article presents a conceptual framework that organizes and structures the key concepts, ideas, and theories regarding organizational effectiveness and long term viability.

Findings

For a responsible leader to establish a lasting social legacy and foster sustainable development, it is crucial for them to cultivate a robust and viable corporate culture, built around these four leadership principles. These principles bear witness to the fact that true evidence of sustainable leadership achievement emerges only after the leader's departure. Responsible leaders, through their track record, leave behind a social legacy by nurturing long-term organizational viability. To ensure a positive and enduring legacy beyond their leadership tenure, leaders can adopt these five principles that provide a foundation for the organization to thrive well into the future.

Originality/value

In the modern context, many leaders hesitate to make tough decisions due to the prevailing focus on immediate results. Followers, stakeholders, and investors prioritize quick responses, often at the expense of long-term considerations. However, by prioritizing the implementation of these four principles, leaders can overcome the allure of immediate gratification and instead, shift their focus toward long-term success measured in years, not just months. In leadership, the legacy left behind holds greater significance than we often realize, and recognizing this importance is crucial for the future prosperity of our organizations.
Literature analysis on material selection and evaluation for firefighter gloves
Authors: Purandare Saloni , Xiang Chunhui
Published: March 2024

Purpose

Firefighter Personal Protective Equipment (PPE) is the only barrier between the firefighter and hazardous environment. Gloves are a crucial component of the multi-component PPE. Over time the gloves have reduced the intensity of hand injuries, yet further improvement in terms of material selection and glove design is required to strike the balance between protection and comfort. Focusing on the material aspect, the purpose of this study is to present literature analysis on material selection and testing for firefighter gloves.

Design/methodology/approach

The study conducted a literature analysis on material selection and characterization of firefighter PPE. The review summarizes and evaluates past work addressing the characterization of firefighter gloves in accordance with NFPA 1971 requirements and points out found research gaps to aid with foundation of future research.

Findings

The study summarizes several research works to inform readers about the material selection and characterization of firefighter gloves. Based on the analyzed literature, the study resulted in material specification sheets for firefighter gloves. The developed material specification sheets provide information in terms of crucial material properties to be incorporated for accurate functioning of firefighter gloves, testing methods to validate those material properties and materials from analyzed literature exhibiting desired properties.

Originality/value

With large research addressing firefighter PPE, only limited studies focus specifically on gloves. Thus, this study provides a literature analysis covering material selection and testing for gloves. A consolidated firefighter gloves material specification document, which does not appear to be available in the literature, will provide a foundation for the development and characterization of firefighter gloves to better serve the functions along with ensuring user comfort.
Adoption of digital marketing in tourism SMEs: a review and research agenda
Authors: Sharma Ankita , Sharma Swati
Published: March 2024

Purpose

This paper aims to present a review of small and medium-sized enterprise (SME) literature on the adoption of technology for marketing with the objective the knowledge trajectory from SMEs to tourism SMEs (TSMEs) and presents a research agenda for the adoption of digital marketing among TSMEs.

Design/methodology/approach

The quantitative literature review method is adopted to analyze 50 articles published in high-ranking journals from 2011–2021. The selected papers were reviewed to quantitatively present the popular theoretical frameworks, constructs and research methods used for the adoption of digital marketing among SMEs and to present a future research agenda in the context of TSMEs.

Findings

The findings present a review of theoretical approaches, research design, methods, and models used by researchers, and identify new directions for future research in the context of the adoption of digital marketing among TSMEs. The paper presents a theoretical critique of the technology adoption theories and builds on diffusion of innovation theory, technology–organization–environment (TOE), and institutional theory to propose an expanded model to study digital marketing adoption among TSMEs.

Research limitations/implications

The article presents a significant advancement in the theoretical understanding of the adoption of digital marketing by offering the application of the TOE framework with moderating role of mimetic and normative pressures. Thus, the study contributes to the scarce research on institutional theory in the context of services (tourism) and offers an alternative and holistic perception to study digital marketing. The research model serves as an organizing tool for future researchers and practitioners to probe and further augment knowledge development in tourism and TSMEs.

Originality/value

Negligible published work on TSMEs makes this study valuable and the proposed model gives strategic information in the given context.
Modelling in Support of Better Agricultural and Food Policies: the JRC's Integrated Agro‐economic Modelling platform (iMAP)
Authors: Barreiro‐Hurle Jesus , Fellmann Thomas , M'barek Robert
Published: March 2024

Research in the area of agro‐economic modelling has been one of the key contributions of the Joint Research Centre (JRC) to the development of better agri‐food policies in the EU. This article provides an overview of the development of the JRC's integrated agro‐economic modelling platform since its establishment in 2005. We highlight the main contributions to policy analysis and describe in detail two key areas, namely the provision of medium‐term projections for agricultural markets and the analysis of various CAP proposals. Furthermore, we describe the gradual shift to expand the capabilities of individual models within the platform to encompass aspects beyond traditional agro‐economic aspects and incorporate environmental considerations. Model integration remains a focus both within the platform at different levels and scales, and in conjunction with biophysical models. This, together with incorporating knowledge from other fields of economic analysis is fundamental to capture changing policy objectives.
A cost outcome study of varicocoele embolisation and future pregnancy in an Australian public hospital setting
Authors: Clements Warren , Chenoweth Abigail , Morphett Laura , Billington Eliza , Nandurkar Rohan , Phan Tuan , Venn Georgina A , Lukies Matthew W
Published: March 2024

Introduction

Varicocoele is commonly encountered in males with infertility. Studies have shown that varicocoele repair (surgery or embolisation) can improve the rate of subsequent pregnancy. In Australia, there have been no studies assessing the cost of varicocoele embolisation and current practice is based on international data. This study aimed to assess the cost of varicocoele embolisation and estimate the treatment cost per pregnancy.

Methods

Retrospective cost‐outcome study of patients treated by embolisation between January 2018 and 2023. A bottom‐up approach was used to calculate procedure costs whereas a top‐down approach was used to calculate costs for all other patient services, including direct and indirect costs. To calculate cost per pregnancy, costs were adjusted according to existing published data on the rate of pregnancy after embolisation.

Results

Costing data from 18 patients were included, of median age 33.5 years (range 26–60) and median varicocoele grade 2.5 (range 1–3). All patients had unilateral treatment, most commonly via right internal jugular (16 patients, 89%) and using a 0.035″ system (17 patients, 94%). The median cost for the entire treatment including procedural, non‐procedural, ward and peri‐procedural costs was AUD$2208.10 (USD$1405 or EUR€1314), range AUD$1691–7051. The projected cost to the healthcare system per pregnancy was AUD$5387 (USD$3429 or EUR€3207).

Conclusion

Total varicocoele embolisation cost and the cost per‐pregnancy were lower than for both embolisation and surgical repair in existing international studies. Patients undergoing varicocoele treatment should have the option to access an interventional radiologist to realise the benefits of this low‐cost pinhole procedure.
Younger Dryas and Early Holocene ice‐margin dynamics in northwest Russia
Authors: Boyes Benjamin M. , Pearce Danni M. , Linch Lorna D. , Nash David J.
Published: March 2024

The dynamics of the last Fennoscandian Ice Sheet (FIS) are relatively well constrained in the Nordic countries. Ice‐sheet dynamics in NW Russia, however, are comparatively less well understood owing to the scale and resolution of existing studies. New large‐scale glacial geomorphological datasets from NW Russia based on high‐resolution remotely sensed imagery allow for an independent reassessment of the extent and dynamics of the FIS during the Younger Dryas and Early Holocene (c. 12.9–10 ka) in NW Russia. The reconstruction provides a more detailed link between geomorphological expressions of palaeoglaciation than previous proposals. Rather than a continuous Younger Dryas ice marginal zone (IMZ) stretching from Finland to northern Norway, the geomorphological signature of NW Russia reveals 14 IMZs that document discrete stationary ice‐margin positions (possibly standstill and/or readvance events) during the overall retreat. The relative age sequence of the IMZs, supported by an updated numerical age database, suggests that they formed time‐transgressively during the Younger Dryas and Early Holocene rather than contemporaneously. Moreover, specific landform assemblages reveal contrasting glacial landsystems in NW Russia: (i) a northern subpolar glacial landsystem; and (ii) a southern temperate glacial landsystem. The model presented herein provides robust empirical constraints for testing and validating numerical ice‐sheet models and understanding ice‐sheet responses to rapid climate change.
Factors Influencing the Outcomes of Discharge of Care Order Proceedings: An Examination of National Data, Children's E‐Records and Professional Interviews
Authors: Staines Jo , Stone Beth , Roy Jessica , Macdonald Gillian
Published: March 2024

Understanding more about the discharge of care orders is vital—whether a care order remains in place has significant implications for children and their families and for local authorities. While there has been comprehensive research about the process and outcomes of care proceedings, much less is known about the discharge of care orders—particularly how, why and when care orders are ended and the differences between applications that are granted and those that are not. The present study combined data from an anonymized administrative data on discharge applications, a detailed analysis of children's e‐records and qualitative interviews with family justice professionals to create the first detailed profile of discharge applications across England and Wales. This paper reports, for the first time, the number of discharge applications and outcomes across England and Wales, highlighting regional as well as between‐country variation. Drawing on data from children's e‐records and interviews with professionals, highlighting how and why local authorities are more likely to submit discharge applications, and to have applications granted, than parents. Recommendations are made for how to adapt professional practice and policy around discharge applications to better meet the needs of children and families.
Human umbilical cord mesenchymal stem cells reverse depression in rats induced by chronic unpredictable mild stress combined with lipopolysaccharide
Authors: Wang Pengxiang , Li Yunxia , Song Yongli , Gao Yuan , Hao Chunxia , Zhou Yang , Bao Siqin , Guo Jitong , Li Xihe
Published: March 2024

Background

Inflammation and oxidative stress are considered crucial to the pathogenesis of depression. Rat models of depression can be created by combined treatments of chronic unpredictable mild stress (CUMS) and lipopolysaccharide (LPS). Behaviors associated with depression could be improved by treatment with mesenchymal stem cells (MSCs) owing to immunomodulatory functions of the cells. Therapeutic potentials of the MSCs to reverse pro‐inflammatory cytokines, proteins, and metabolites were identified by transcriptomic, proteomic, and metabolomic analysis, respectively.

Methods

A depression model was established in male SD rats by 2 weeks of CUMS combined with LPS. The models were verified by behavioral tests, namely SPT, OFT, EPM, and qRT‐PCR for pro‐inflammatory cytokines. Such depressed rats were administered human umbilical cord MSCs (hUC‐MSCs) via the tail vein once a week for 2 and 4 weeks. The homing capacity was confirmed by detection of the fluorescent dye on day 7 after the hUC‐MSCs were labeled with CM‐Dil and administered. The expression of GFAP in astrocytes serves as a biomarker of CNS disorders and IBA1 in microglia serves as a marker of microglia activation were detected by immunohistochemistry at 2 and 4 weeks after final administration of hUC‐MSCs. At the same time, transcriptomics of rat hippocampal tissue, proteomic and metabolomic analysis of the serum from the normal, depressed, and treated rats were also compared.

Results

Reliable models of rat depression were successfully induced by treatments of CUMS combined with LPS. Rat depression behaviors, pro‐inflammatory cytokines, and morphological disorders of the hippocampus associated with depression were reversed in 4 weeks by hUC‐MSC treatment. hUC‐MSCs could reach the hippocampus CA1 region through the blood circulation on day 7 after administration owing to the disruption of blood brain barrier (BBB) by microglial activation from depression. Differentiations of whole‐genome expression, protein, and metabolite profiles between the normal and depression‐modeled rats, which were analyzed by transcriptomic, proteomics, and metabolomics, further verified the high association with depression behaviors.

Conclusions

Rat depression can be reversed or recovered by treatment with hUC‐MSCs.
Predictors for early‐onset psychotic symptoms in patients newly diagnosed with Parkinson's disease without psychosis at baseline: A 5‐year cohort study
Authors: Chen Jing , Chen Baoyu , Zhao Danhua , Feng Xiaotong , Wang Qi , Li Yuan , Chen Junyi , Bai Chaobo , Guo Xintong , He Xiaoyu , Zhang Lin , Yuan Junliang
Published: March 2024

Aims

To investigate the risk factors for early‐onset psychosis in Parkinson's disease (PD) in a cohort of patients from the Parkinson's Progression Markers Initiative.

Methods

Longitudinal data on motor and non‐motor features, dopamine transporter (DAT) imaging, and cerebrospinal fluid (CSF) measurements were collected. The survival probability of psychotic symptoms, potential risk factors for psychosis development over a 5‐year follow‐up period, and the performance of the prediction model were evaluated.

Results

Among the 338 newly diagnosed patients with PD, 83 developed psychotic symptoms. Gastrointestinal autonomic dysfunction, presence of probable rapid‐eye‐movement sleep behavior disorder, and the ratio Aβ42: total‐tau could independently predict onset of psychosis in PD (hazard ratio (HR) = 1.157, 95% confidence interval (CI) 1.022–1.309, p = 0.021, HR = 2.596, 95% CI 1.287–5.237, p = 0.008, and HR = 0.842, 95% CI 0.723–0.980, p = 0.027, respectively). The combined model integrating baseline clinical predictors, DAT imaging, and CSF measurements achieved better sensitivity than the clinical predictors alone (area under the curve = 0.770 [95% CI 0.672–0.868] vs. 0.714 [95% CI 0.625–0.802], p = 0.098).

Conclusion

We identified clinical and CSF predictors of early‐onset psychosis in patients with PD. Our study provides evidence and implications for prognostic stratification and therapeutic approaches for PD psychosis.