bluuebunny/crossref_metadata_2025 huggingface dataset:
From Vision to Evaluation: A Metrics Framework for the ACCESS Allocations Service
Authors: Hart David L. , Deems Stephen L. , Herriott Laura T.
Published: April 2024

The Allocations Service for the Advanced Cyberinfrastructure Coordination Ecosystem: Services & Support (ACCESS) program is charged with accepting, reviewing, and processing researchers’ requests to use resources that are integrated into the ACCESS ecosystem. We present as a case study the metrics framework used to evaluate the Allocations Service project, a metrics framework that aligns with the project’s goals and identifies key performance indicators (KPIs). Several of our top-level KPIs reflect complex concepts and are composite measures built from suites of metrics compiled from two primary sources: a well-instrumented allocations and accounting system and an annual survey of the ACCESS researcher community. This approach allows us to describe and measure complex concepts such as “democratization” and “ecosystem access time” in a quantitative manner and to target improvements to project activities. The metrics framework is augmented by metrics to measure the performance of the project team, to describe general ecosystem and allocations activity, and to capture publications from the researcher community. We used this framework to gather and present data as part of the ACCESS Allocations Service first annual NSF panel review. The metrics were largely successful at communicating our progress, but we also encountered a few unexpected technical issues with the data and calculations themselves, which we are continuing to refine. Presented here as a case study, this approach to a metrics framework for the Allocations Service has proved valuable in complementing more subjective descriptions of the project, its accomplishments, and progress toward our goals.
B-BSMG: Bézier Brush Stroke Model-Based Generator for Robotic Chinese Calligraphy
Authors: Guo Dongmei , Yan Guang
Published: April 2024

In robotic Chinese calligraphy, the brush stroke training models for Chinese hairy brushes play a crucial role in stroke generation. The method of combining end-to-end techniques and physical models requires further study, however, it is difficult to obtain large amounts of brush strokes for deep learning and training. To overcome this, we propose using a simulated brush model to train a generator based on the Bézier brush stroke model generator (B-BSMG), which was formed by two symmetric cubic Bézier curves according to the physical characteristics and writing posture of the brush. The B-BSMG can generate images for deep learning and training using a dataset simulated by the Bézier brush stroke model. Our renderer is based on parameterized brush strokes, providing a better foundation for deep learning or robotic writing. The results of several experiments prove that the proposed B-BSMG can generate stroke graphics well and outperforms other advanced stroke models.
Economical Group Chain Sampling Plans for Weibull Distribution Using Bayesian Approach
Authors: Tanveer Kinza , Mughal Abdur Razzaque , Shahzadi Ishmal , Albassam Mohammed , Aslam Muhammad
Published: April 2024

The paper focuses on the economic design of group chain sampling plans (GChSP) for the Weibull distribution using Bayesian methodology. The GChSP is a technique to accept or reject a product based on a sample from a lot. The study addresses situations where destructive testing is costly and utilizes the Bayesian approach to make informed decisions. The research outlines the methodology of developing GChSP including the stages of construction, performance evaluation, and cost estimation. The study compares the proposed plans with an existing one and demonstrates that the Bayesian approach generally yields lower costs. We will provide tables, figures, and calculations related to various aspects of the proposed plans and their comparison with existing methods.
Agents of Empire
Authors: Gailmard Sean
Published: April 2024

To understand the foundations of American political institutions, it's necessary to understand the rationale for British colonial institutions that survived the empire. Political institutions in England's American colonies were neither direct imports from England, nor home-grown creations of autonomous colonists. Instead, they emerged from efforts of the English Crown to assert control over their colonies amid limited English state and military capacity. Agents of Empire explores the strategic dilemmas facing a constrained crown in its attempts to assert control. The study argues that colonial institutions emerged from the crown's management of authority delegated to agents-first companies and proprietors establishing colonies; then imperial officials governing the polities they created. The institutions remaining from these strategic dynamics form the building blocks of federalism, legislative power, separation of powers, judicial review, and other institutions that comprise the American polity today.
Domestic Service in the Soviet Union
Authors: Klots Alissa
Published: April 2024

This innovative study is the first to explore the evolution of domestic service in the Soviet Union, set against the background of changing discourses on women, labour, and socialist living. Even though domestic service conflicted with the Bolsheviks' egalitarian message, the regime embraced paid domestic labor as a temporary solution to the problem of housework. Analyzing sources ranging from court cases to oral interviews, Alissa Klots demonstrates how the regime both facilitated and thwarted domestic workers' efforts to reinvent themselves as equal members of Soviet society. Here, a desire to make maids and nannies equal participants in the building of socialism clashed with a gendered ideology where housework was women's work. This book serves not only as a window into class and gender inequality under socialism, but as a vantage point to examine the power of state initiatives to improve the lives of household workers in the modern world.
Cryoconite holes geomorphometry, spatial distribution and radiative impact over the Hells Gate Ice Shelf, East Antarctica
Authors: Traversa Giacomo , Scipinotti Riccardo , Pierattini Samuele , Bianchi Fasani Gianluca , Di Mauro Biagio
Published: April 2024

Cryoconite holes are structures characteristic of the glacierised ablation areas, formed from dark sediment deposition which melt the glacier ice leading to their cylindrical structure formation. The present study focuses on an unstudied blue ice area of East Antarctica over the Hells Gate Ice Shelf in Northern Victoria Land. Taking advantage of neural network methodology applied on drone acquisitions, an automatic detection of cryoconite holes was carried out (88% of accuracy), mapping ~3500 m2 (0.4% fractional cover) of cryoconite holes over an area of 900 000 m2. The surveyed area showed heterogeneity in cryoconite hole distribution, with some regions showing an area fraction of holes (regions exhibiting frozen ponds and ice bands) as high as 8%. Thanks to this detection, the spatially integrated radiative forcing of cryoconite holes over blue ice surface was estimated to be almost 1 Wm−2. This estimation was based on the measured albedo difference between the two surfaces, which averages 0.31. However, the radiative forcing is strongly increased if calculated at a single cryoconite hole scale, showing an average of ~200 Wm−2. In conclusion, the present research represents a first attempt of analysing cryoconite holes as factors impacting the blue ice in Northern Victoria Land, deepening our understanding of their glaciological role at the margins of the East Antarctic Ice Sheet.
Adjoint-accelerated Bayesian inference applied to the thermoacoustic behaviour of a ducted conical flame
Authors: Yoko Matthew , Juniper Matthew P.
Published: April 2024

We use Bayesian inference, accelerated by adjoint methods, to construct a quantitatively accurate model of the thermoacoustic behaviour of a conical flame in a duct. We first perform a series of automated experiments on a ducted flame rig. Next, we propose several candidate models of the rig's components and assimilate data into each model to find the most probable parameters for that model. We rank the candidate models based on their marginal likelihood (evidence) and select the most likely model for each component. We begin this process by rigorously characterizing the acoustics of the cold rig. When the flame is introduced, we propose several candidate models for the fluctuating heat release rate. We find that the most likely flame model considers velocity perturbations in both the burner feed tube and the outer duct, even though studies in the literature typically neglect either one of these. Using the most likely model, we infer the flame transfer functions for 24 flames and quantify their uncertainties. We do this with the flames in situ, using only pressure measurements. We find that the inferred flame transfer functions render the model quantitatively accurate, and, where comparable, broadly consistent with direct measurements from several studies in the literature.
Projectively and affinely invariant PDEs on hypersurfaces
Authors: Alekseevsky Dmitri , Manno Gianni , Moreno Giovanni
Published: April 2024

In Communications in Contemporary Mathematics24 3, (2022),the authors have developed a method for constructing G-invariant partial differential equations (PDEs) imposed on hypersurfaces of an $(n+1)$-dimensional homogeneous space $G/H$, under mild assumptions on the Lie group G. In the present paper, the method is applied to the case when $G=\mathsf{PGL}(n+1)$ (respectively, $G=\mathsf{Aff}(n+1)$) and the homogeneous space $G/H$ is the $(n+1)$-dimensional projective $\mathbb{P}^{n+1}$ (respectively, affine $\mathbb{A}^{n+1}$) space, respectively. The main result of the paper is that projectively or affinely invariant PDEs with n independent and one unknown variables are in one-to-one correspondence with invariant hypersurfaces of the space of trace-free cubic forms in n variables with respect to the group $\mathsf{CO}(d,n-d)$ of conformal transformations of $\mathbb{R}^{d,n-d}$.
Executive function's structure in monolingual and bilingual adults using confirmatory factor analysis
Authors: Anjomshoae Farzaneh , Wiebe Sandra A. , Nicoladis Elena
Published: April 2024

In processing their two languages, bilinguals have to selectively attend to the target language and reduce interference from the non-target language. This experience may have specific cognitive consequences on Executive Functions (EF) through bilingual language processing. Some studies found cognitive consequences in executive functioning skills. However, other studies did not replicate these findings or found a bilingual disadvantage. The aim of this study was to test for the cognitive consequences of bilingualism in EF among a large number of young adults using a latent variable approach, to rule out non-EF task differences as an explanation for inconsistency across studies. Also, we were interested in testing the EF structure using the Confirmatory Factor Analysis (CFA) approach. The results did not support a cognitive consequence of bilingualism and also the EF structure was the same for both groups. We discuss other possible variables that might contribute to the mixed results across studies.
A pilot study to evaluate the quality of care in oral anticoagulant and antiplatelet use in patients with permanent atrial fibrillation in Irish general practice
Authors: McErlean Sarah , Broughan John , McCombe Geoff , Fawsitt Ronan , Cullen Walter , Gallagher Joe
Published: April 2024

Aim:

The aim of this pilot study is to determine the pattern of oral anticoagulant and antiplatelet use in patients with permanent atrial fibrillation (AF) in Irish general practice.

Background:

Worldwide, AF is the most common sustained cardiac arrhythmia in adults and poses a significant burden to patients, physicians and healthcare systems. There is a five-fold increased risk of stroke with AF, and AF-related strokes are associated with higher levels of both morbidity and mortality compared to other stroke subtypes. Thankfully, appropriate use of oral anticoagulation (OAC) for AF can reduce the risk of stroke by up to 64%. However, we know that patients are commonly undertreated with OAC, prescribed inappropriate doses of OAC and have prolonged use of an antiplatelet agent in addition to OAC without indication.

Methods:

A descriptive, cross-sectional observational study was undertaken. Proportionate sampling was used across 11 practices from the Ireland East practice-based research network. The general practitioners completed a report form on each patient provided by the research team by undertaking a retrospective chart review.

Findings:

Eleven practices participated with a total number of 1855 patients with AF. We received data on 153 patients.

The main findings from this pilot project are that:

1.

11% of patients were undertreated with OAC

2.

20 % of patients were on an incorrect non-vitamin K antagonist oral anticoagulant dose

3.

28 patients (18%) were inappropriately prescribed combination antithrombotic therapy

Undertreatment and underdosing of OAC expose patients to higher risk of thromboembolic events, bleeding and all-cause mortality. Prolonged combination antithrombotic therapy is associated with serious increased risk of bleeding with no additional stroke protection. This pilot project highlights several gaps between guidelines and clinical practice. By identifying these areas, we hope to develop a targeted quality improvement intervention using the electronic health records in general practice to improve the care that those with AF receive.
VOTAT in Action
Authors: Stadler Matthias , Pickal Amadeus J. , Brandl Laura , Krieger Florian
Published: April 2024

Abstract: In our study, we integrated the vary-one-thing-at-a-time (VOTAT) strategy within epistemic activities in knowledge-lean problem-solving. VOTAT, altering a single variable while keeping others constant, was examined through a dual approach: an empirical analysis with MicroDYN tasks and a theoretical discussion. Empirically, we identified differences among participants who fully engaged in the VOTAT loop, those with incomplete loops, and nonusers. These distinctions were evident in their problem-solving approaches, hypothesis formulation, and decision-making efficiency. Theoretically, we contextualized VOTAT's role within epistemic activities, extending its application beyond the specific tasks in our study. Our findings reveal that VOTAT's use markedly impacts problem-solving processes, demonstrating varied cognitive strategies among different participant groups. This has implications for understanding problem-solving cognition and designing tasks that better capture the nuances of epistemic activities.
Emergent Trends Complicate the Interpretation of the United States Drought Monitor (USDM)
Authors: Li Zhiying , Smerdon Jason E. , Seager Richard , Siegert Noel , Mankin Justin S.
Published: April 2024

Effective drought management must be informed by an understanding of whether and how current drought monitoring and assessment practices represent underlying nonstationary climate conditions, either naturally occurring or forced by climate change. Here we investigate the emerging climatology and associated trends in drought classes defined by the United States Drought Monitor (USDM), a weekly product that, since 2000, has been used to inform drought management in the United States. The USDM classifies drought intensity based in part on threshold percentiles in key hydroclimate quantities. Here we assess how those USDM‐defined drought threshold percentiles have changed over the last 23 years, examining precipitation, runoff, soil moisture (SM), terrestrial water storage (TWS), vapor pressure deficit (VPD), and near‐surface air temperature. We also assess underlying trends in the frequency of drought classifications across the U.S. Our analysis suggests that the frequency of drought class occurrence is exceeding the threshold percentiles defined by the USDM in a number of regions in the United States, particularly in the American West, where the last 23 years have emerged as a prolonged dry period. These trends are also reflected in percentile‐based thresholds in precipitation, runoff, SM, TWS, VPD, and temperature. Our results emphasize that while the USDM appears to be accurately reflecting observed nonstationarity in the physical climate, such trends raise critical questions about whether and how drought diagnosis, classification, and monitoring should address long‐term intervals of wet and dry periods or trends.
What Is the Contribution of Convergence Zones to Global Precipitation? Assessing Observations and Climate Models Biases
Authors: Perez Gabriel M. P. , Vidale Pier Luigi , Dacre Helen , Martin Thomas C. M.
Published: April 2024

Convergence zones (CZs) are known drivers of precipitation regimes from regional to planetary scales. However, there is a scarcity of accounts of the contribution of CZs to the global precipitation. In this study, we build upon a recently developed Lagrangian diagnostic to attribute precipitation to CZ events in observations and simulations submitted to the Coupled Model Intercomparison Project 6 (CMIP6). Observed CZs are identified using ERA5 reanalysis wind and attributed precipitation from observational products based on satellite estimates and rain gauges. We estimate that approximately 54% (51%–59%, depending on the precipitation product) of global precipitation falls over CZs; in some regions, such as the Intertropical Convergence Zone (ITCZ) and subtropical monsoon regions, this proportion is greater than 60%. All CMIP6 simulations analyzed here attribute about 10% more precipitation to CZ events than what the observations suggest. To investigate this overestimation, we decompose the precipitation error in terms of frequency and intensity of CZ precipitation and find that all models present a substantial positive bias in the frequency of CZ precipitation, suggesting that climate models trigger precipitation too easily in regions of airmass confluence; such positive frequency biases in CZ precipitation help explaining well‐known biases in climate models, such as the double‐ITCZ in the Pacific. We also find that models with better mass conservation present an apportionment of CZ precipitation closest to the observational estimates, demonstrating the relevance of mass conservation in advection schemes.
Causes for Decadal Trends in Surface Solar Radiation in the Alpine Region in the 1981–2020 Period
Authors: Correa Lucas Ferreira , Folini Doris , Chtirkova Boriana , Wild Martin
Published: April 2024

Extending across seven countries, the Alps represent an important element for climate and atmospheric circulation in Central Europe. Its complex topography affects processes on different scales within the atmospheric system. This is of major relevance for the decadal trends in surface solar radiation (SSR), also known as periods of global dimming and brightening (GDB). In this study we analyzed data from 38 stations in and around the Swiss and Austrian Alps, over a period ranging from the 1980s up to the 2020s, with the aim of characterizing the spatio‐temporal variations of the GDB and understanding the causes for such trends in this region. Our results show a different behavior in the SSR decadal trends in the western part of the Alps in comparison to the eastern part. Our results also suggest a remarkable difference between the causes of such trends at the stations at low altitudes in comparison to the stations at higher altitudes. Significant contributions from changes in cloud optical depth and surface albedo to the SSR decadal trends at high elevation sites were also found, in contrast to a substantial clear‐sky forcing that strongly dominates at low elevations. Results from previous literature and available data suggest that cloud optical depth changes at high altitudes and clear‐sky forcing at low altitudes could be associated with the indirect and direct aerosol effects, respectively, due to differing pollution levels at low and high elevation sites.
Risk‐Constrained Optimal Scheduling in Water Distribution Systems Toward Real‐Time Pricing Electricity Market
Authors: Zhou Xinhong , Chu Shipeng , Zhang Tuqiao , Yu Tingchao , Shao Yu
Published: April 2024

In recent years, as a result of emerging renewable energy markets, several developed regions have already launched Real‐Time Pricing (RTP) strategies for electricity markets. Establishing optimal pump operation for water companies in RTP electricity markets presents a challenging problem. In a RTP market, both positive and negative electricity prices are possible. These negative prices create economically attractive opportunities for Water Distribution System (WDS) to dispatch their energy consumption. On the other hand, excessively high prices may put WDS at risk of supply disruptions and reduced service levels. However, the continuous development of wind power and photovoltaics results in more volatile and unpredictable fluctuations in the price of renewable energy. The risk arising from uncertainty in electricity prices can lead to a significant increase in actual costs. To address this issue, this paper develops an a posteriori random forest (AP‐RF) approach to forecast the probability density function of electricity prices for the next day and provide a risk‐constrained pump scheduling method toward RTP electricity market. The experimental results demonstrate that the developed method effectively addresses the issue of increased costs caused by inaccurate electricity price forecasting.
A Better Way to Predict Arctic Riverbank Erosion
Authors: Fritts Rachel
Published: April 2024

Permafrost thaw might cause Arctic riverbanks to erode more quickly. But a new study shows why these erosion rates aren’t as dramatic as some scientists feared.
Emerging insights into transcriptional condensates
Authors: Ryu Kwangmin , Park Gunhee , Cho Won-Ki
Published: April 2024

Eukaryotic transcription, a fundamental process that governs cell-specific gene expression, has long been the subject of extensive investigations in the fields of molecular biology, biochemistry, and structural biology. Recent advances in microscopy techniques have led to a fascinating concept known as “transcriptional condensates.” These dynamic assemblies are the result of a phenomenon called liquid‒liquid phase separation, which is driven by multivalent interactions between the constituent proteins in cells. The essential proteins associated with transcription are concentrated in transcriptional condensates. Recent studies have shed light on the temporal dynamics of transcriptional condensates and their potential role in enhancing the efficiency of transcription. In this article, we explore the properties of transcriptional condensates, investigate how they evolve over time, and evaluate the significant impact they have on the process of transcription. Furthermore, we highlight innovative techniques that allow us to manipulate these condensates, thus demonstrating their responsiveness to cellular signals and their connection to transcriptional bursting. As our understanding of transcriptional condensates continues to grow, they are poised to revolutionize our understanding of eukaryotic gene regulation.
Enhancer–promoter specificity in gene transcription: molecular mechanisms and disease associations
Authors: Friedman Meyer J. , Wagner Tobias , Lee Haram , Rosenfeld Michael G. , Oh Soohwan
Published: April 2024

Although often located at a distance from their target gene promoters, enhancers are the primary genomic determinants of temporal and spatial transcriptional specificity in metazoans. Since the discovery of the first enhancer element in simian virus 40, there has been substantial interest in unraveling the mechanism(s) by which enhancers communicate with their partner promoters to ensure proper gene expression. These research efforts have benefited considerably from the application of increasingly sophisticated sequencing- and imaging-based approaches in conjunction with innovative (epi)genome-editing technologies; however, despite various proposed models, the principles of enhancer–promoter interaction have still not been fully elucidated. In this review, we provide an overview of recent progress in the eukaryotic gene transcription field pertaining to enhancer–promoter specificity. A better understanding of the mechanistic basis of lineage- and context-dependent enhancer–promoter engagement, along with the continued identification of functional enhancers, will provide key insights into the spatiotemporal control of gene expression that can reveal therapeutic opportunities for a range of enhancer-related diseases.
Incoherent non-Hermitian skin effect in photonic quantum walks
Authors: Longhi Stefano
Published: April 2024

The non-Hermitian skin effect describes the concentration of an extensive number of eigenstates near the boundaries of certain dissipative systems. This phenomenon has raised a huge interest in different areas of physics, including photonics, deeply expanding our understanding of non-Hermitian systems and opening up new avenues in both fundamental and applied aspects of topological phenomena. The skin effect has been associated to a nontrivial point-gap spectral topology and has been experimentally demonstrated in a variety of synthetic matter systems, including photonic lattices. In most of physical models exhibiting the non-Hermitian skin effect full or partial wave coherence is generally assumed. Here we push the concept of skin effect into the fully incoherent regime and show that rather generally (but not universally) the non-Hermitian skin effect persists under dephasing dynamics. The results are illustrated by considering incoherent light dynamics in non-Hermitian photonic quantum walks.
TMEM9 promotes lung adenocarcinoma progression via activating the MEK/ERK/STAT3 pathway to induce VEGF expression
Authors: Wang Zhiqian , Zhao Peng , Tian Kaihua , Qiao Zhongshi , Dong Hao , Li Jie , Guan Zitong , Su Hui , Song Yang , Ma Xuezhen
Published: April 2024

Abnormal Transmembrane protein 9 (TMEM9) expression has been identified in various human tumors. However, the prognostic potential and mechanistic role of TMEM9 in lung adenocarcinoma (LUAD) remain unclear. Here, we first found a significant upregulation of TMEM9 in LUAD tissues, and TMEM9 expression was positively correlated with microvessel density (MVD), T stage, and clinical stage. Survival analysis demonstrated TMEM9 was an independent indicator of poor prognosis in LUAD patients. In addition, downregulation of TMEM9 suppressed tumor growth and metastasis in vitro and in vivo models, and reduced HUVEC proliferation, migration, and tube formation in a cancer cell/HUVEC coculture model. Furthermore, TMEM9 upregulated VEGF expression, and VEGF-neutralizing antibodies reversed HUVEC angiogenesis and cancer cell migration ability caused by overexpression of TMEM9. In contrast, recombinant VEGF (rVEGF) abolished the inhibitory effect of TMEM9-knockdown LUAD cells on HUVEC angiogenesis and tumor cell migration. Moreover, we showed that TMEM9 upregulated VEGF expression by activating the mitogen-activated protein kinase/extracellular signal-regulated kinase/STAT3 (MEK/ERK/STAT3) pathway. Together, our study provides mechanistic insights into the role of TMEM9 in LUAD and highlights the potential of targeting the TMEM9/MEK/ERK/STAT3/VEGF pathway as a novel therapy for preventing LUAD progression.
PICK1 inhibits the malignancy of nasopharyngeal carcinoma and serves as a novel prognostic marker
Authors: Ou Xiaomin , Zhang Yingzi , Xu Yiqing , Liu Yi , Tu Wenzhi , Hu Chaosu , Liu Yong
Published: April 2024

Although many important advances have been made in the treatment of nasopharyngeal carcinoma (NPC) in recent years, local recurrence and distant metastasis remain the main factors affecting NPC prognosis. Biomarkers for predicting the prognosis of NPC need to be urgently identified. Here, we used whole-exon sequencing (WES) to determine whether PICK1 mutations are associated with the prognosis of NPC. Functionally, PICK1 inhibits the proliferation and metastasis of NPC cells both in vivo and in vitro. Mechanistically, PICK1 inhibited the expression of proteins related to the Wnt/β-catenin signaling pathway. PICK1 restrained the nuclear accumulation of β-catenin and accelerated the degradation of β-catenin through the ubiquitin-proteasome pathway. The reduced PICK1 levels were significantly associated with poor patient prognosis. Hence, our study findings reveal the mechanism by which PICK1 inactivates the Wnt/β-catenin signaling pathway, thereby inhibiting the progression of NPC. They support PICK1 as a potential tumor suppressor and prognostic marker for NPC.
Untethered soft actuators for soft standalone robotics
Authors: Jung Yeongju , Kwon Kangkyu , Lee Jinwoo , Ko Seung Hwan
Published: April 2024

Soft actuators produce the mechanical force needed for the functional movements of soft robots, but they suffer from critical drawbacks since previously reported soft actuators often rely on electrical wires or pneumatic tubes for the power supply, which would limit the potential usage of soft robots in various practical applications. In this article, we review the new types of untethered soft actuators that represent breakthroughs and discuss the future perspective of soft actuators. We discuss the functional materials and innovative strategies that gave rise to untethered soft actuators and deliver our perspective on challenges and opportunities for future-generation soft actuators.
Disordered clock protein interactions and charge blocks turn an hourglass into a persistent circadian oscillator
Authors: Jankowski Meaghan S. , Griffith Daniel , Shastry Divya G. , Pelham Jacqueline F. , Ginell Garrett M. , Thomas Joshua , Karande Pankaj , Holehouse Alex S. , Hurley Jennifer M.
Published: April 2024

Organismal physiology is widely regulated by the molecular circadian clock, a feedback loop composed of protein complexes whose members are enriched in intrinsically disordered regions. These regions can mediate protein-protein interactions via SLiMs, but the contribution of these disordered regions to clock protein interactions had not been elucidated. To determine the functionality of these disordered regions, we applied a synthetic peptide microarray approach to the disordered clock protein FRQ in Neurospora crassa. We identified residues required for FRQ’s interaction with its partner protein FRH, the mutation of which demonstrated FRH is necessary for persistent clock oscillations but not repression of transcriptional activity. Additionally, the microarray demonstrated an enrichment of FRH binding to FRQ peptides with a net positive charge. We found that positively charged residues occurred in significant “blocks” within the amino acid sequence of FRQ and that ablation of one of these blocks affected both core clock timing and physiological clock output. Finally, we found positive charge clusters were a commonly shared molecular feature in repressive circadian clock proteins. Overall, our study suggests a mechanistic purpose for positive charge blocks and yielded insights into repressive arm protein roles in clock function.
Establishing superfine nanofibrils for robust polyelectrolyte artificial spider silk and powerful artificial muscles
Authors: He Wenqian , Wang Meilin , Mei Guangkai , Liu Shiyong , Khan Abdul Qadeer , Li Chao , Feng Danyang , Su Zihao , Bao Lili , Wang Ge , Liu Enzhao , Zhu Yutian , Bai Jie , Zhu Meifang , Zhou Xiang , Liu Zunfeng
Published: April 2024

Spider silk exhibits an excellent combination of high strength and toughness, which originates from the hierarchical self-assembled structure of spidroin during fiber spinning. In this work, superfine nanofibrils are established in polyelectrolyte artificial spider silk by optimizing the flexibility of polymer chains, which exhibits combination of breaking strength and toughness ranging from 1.83 GPa and 238 MJ m−3 to 0.53 GPa and 700 MJ m−3, respectively. This is achieved by introducing ions to control the dissociation of polymer chains and evaporation-induced self-assembly under external stress. In addition, the artificial spider silk possesses thermally-driven supercontraction ability. This work provides inspiration for the design of high-performance fiber materials.
Magnetically propagating Hund’s exciton in van der Waals antiferromagnet NiPS3
Authors: He W. , Shen Y. , Wohlfeld K. , Sears J. , Li J. , Pelliciari J. , Walicki M. , Johnston S. , Baldini E. , Bisogni V. , Mitrano M. , Dean M. P. M.
Published: April 2024

Magnetic van der Waals (vdW) materials have opened new frontiers for realizing novel many-body phenomena. Recently NiPS3has received intense interest since it hosts an excitonic quasiparticle whose properties appear to be intimately linked to the magnetic state of the lattice. Despite extensive studies, the electronic character, mobility, and magnetic interactions of the exciton remain unresolved. Here we address these issues by measuring NiPS3with ultra-high energy resolution resonant inelastic x-ray scattering (RIXS). We find that Hund’s exchange interactions are primarily responsible for the energy of formation of the exciton. Measuring the dispersion of the Hund’s exciton reveals that it propagates in a way that is analogous to a double-magnon. We trace this unique behavior to fundamental similarities between the NiPS3exciton hopping and spin exchange processes, underlining the unique magnetic characteristics of this novel quasiparticle.
Multiple hydrogen-bonding induced nonconventional red fluorescence emission in hydrogels
Authors: Wu Jiayu , Wang Yuhuan , Jiang Pan , Wang Xiaolong , Jia Xin , Zhou Feng
Published: April 2024

The development of unconventional long-wavelength fluorescent polymer hydrogels without using polycyclic aromatic hydrocarbons or extended π-conjugation is a fundamental challenge in luminescent materials owing to a lack of understanding regarding the spatial interactions induced inherent clustering-triggered emission under water-rich conditions. Inspired by the color change of protein astaxanthin as a result of heat-induced denaturation, we propose a thermodynamically driven strategy to develop red fluorescence (~610 nm) by boiling multiple hydrogen-bonded poly(N-acryloylsemicarbazide) hydrogels in a water bath. We reveal that thermodynamically driven conformational changes of polymer chains from isolated hydrogen bonding donor-acceptor structures to through-space interaction structures induce intrinsic fluorescence shifts from blue to red during clustering-triggered emission. The proposed multiple hydrogen-bonding supramolecular hydrogel shows good fluorescence stability, mechanical robustness, and 3D printability for customizable shaping. We provide a viable method to prepare nonconventional long-wavelength fluorescent hydrogels towards soft fluorescent devices without initially introducing any fluorescent components.
Persistent TFIIH binding to non-excised DNA damage causes cell and developmental failure
Authors: Muniesa-Vargas Alba , Davó-Martínez Carlota , Ribeiro-Silva Cristina , van der Woude Melanie , Thijssen Karen L. , Haspels Ben , Häckes David , Kaynak Ülkem U. , Kanaar Roland , Marteijn Jurgen A. , Theil Arjan F. , Kuijten Maayke M. P. , Vermeulen Wim , Lans Hannes
Published: April 2024

Congenital nucleotide excision repair (NER) deficiency gives rise to several cancer-prone and/or progeroid disorders. It is not understood how defects in the same DNA repair pathway cause different disease features and severity. Here, we show that the absence of functional ERCC1-XPF or XPG endonucleases leads to stable and prolonged binding of the transcription/DNA repair factor TFIIH to DNA damage, which correlates with disease severity and induces senescence features in human cells. In vivo, in C. elegans, this prolonged TFIIH binding to non-excised DNA damage causes developmental arrest and neuronal dysfunction, in a manner dependent on transcription-coupled NER. NER factors XPA and TTDA both promote stable TFIIH DNA binding and their depletion therefore suppresses these severe phenotypical consequences. These results identify stalled NER intermediates as pathogenic to cell functionality and organismal development, which can in part explain why mutations in XPF or XPG cause different disease features than mutations in XPA or TTDA.
Ultrastructural localization of Porphyromonas gingivalis gingipains in the substantia nigra of Parkinson’s disease brains
Authors: Ermini Florian , Low Victoria F. , Song Jennifer J. , Tan Adelie Y. S. , Faull Richard L. M. , Dragunow Michael , Curtis Maurice A. , Dominy Stephen S.
Published: April 2024

Gingipains are protease virulence factors produced by Porphyromonas gingivalis, a Gram-negative bacterium best known for its role in chronic periodontitis. Gingipains were recently identified in the middle temporal gyrus of postmortem Alzheimer’s disease (AD) brains, where gingipain load correlated with AD diagnosis and tau and ubiquitin pathology. Since AD and Parkinson’s disease (PD) share some overlapping pathologic features, including nigral pathology and Lewy bodies, the current study explored whether gingipains are present in the substantia nigra pars compacta of PD brains. In immunohistochemical techniques and multi-channel fluorescence studies, gingipain antigens were abundant in dopaminergic neurons in the substantia nigra of both PD and neurologically normal control brains. 3-dimensional reconstructions of Lewy body containing neurons revealed that gingipains associated with the periphery of alpha-synuclein aggregates but were occasionally observed inside aggregates. In vitro proteomic analysis demonstrated that recombinant alpha-synuclein is cleaved by lysine-gingipain, generating multiple alpha-synuclein fragments including the non-amyloid component fragments. Immunogold electron microscopy with co-labeling of gingipains and alpha-synuclein confirmed the occasional colocalization of gingipains with phosphorylated (pSER129) alpha-synuclein. In dopaminergic neurons, gingipains localized to the perinuclear cytoplasm, neuromelanin, mitochondria, and nucleus. These data suggest that gingipains localize in dopaminergic neurons in the substantia nigra and interact with alpha-synuclein.
The relationship between prescription rates of oral corticosteroids for respiratory diseases and deprivation in England
Authors: Barker Erin , Pocock Jessica , Moss Joe , Hex Nick , Rankin Jordan , Hudson Richard
Published: April 2024

Respiratory diseases, including asthma and chronic obstructive pulmonary disease (COPD), are common in England with the worst respiratory outcomes observed in the most deprived areas. There is limited published research to establish whether the rate of oral corticosteroid (OCS) prescribing for asthma and COPD is linked to levels of deprivation. This study carried out a multivariable regression analysis of publicly available data and found that deprivation is associated with a statistically significant increase in the proportion of patients receiving an OCS prescription for asthma or COPD at a GP practice level (p < 0.001). The model estimated that the proportion of prescriptions is 1.88% (95% CI 1.83% to 1.92%) and 2.84% (95% CI 2.70% to 2.98%) for the least deprived GP practice and the most deprived GP practice, respectively. This study lays the groundwork for future research using individual patient level data to consider the impact of variation in OCS prescribing rates.
Normative volumes and relaxation times at 3T during brain development
Authors: Romascano David , Piredda Gian Franco , Caneschi Samuele , Hilbert Tom , Corredor Ricardo , Maréchal Bénédicte , Kober Tobias , Ledoux Jean-Baptiste , Fornari Eleonora , Hagmann Patric , Denervaud Solange
Published: April 2024

While research has unveiled and quantified brain markers of abnormal neurodevelopment, clinicians still work with qualitative metrics for MRI brain investigation. The purpose of the current article is to bridge the knowledge gap between case-control cohort studies and individual patient care. Here, we provide a unique dataset of seventy-three 3-to-17 years-old healthy subjects acquired with a 6-minute MRI protocol encompassing T1 and T2 relaxation quantitative sequence that can be readily implemented in the clinical setting; MP2RAGE for T1 mapping and the prototype sequence GRAPPATINI for T2 mapping. White matter and grey matter volumes were automatically quantified. We further provide normative developmental curves based on these two imaging sequences; T1, T2 and volume normative ranges with respect to age were computed, for each ROI of a pediatric brain atlas. This open-source dataset provides normative values allowing to position individual patients acquired with the same protocol on the brain maturation curve and as such provides potentially useful quantitative biomarkers facilitating precise and personalized care.
Development and validation of a smartwatch algorithm for differentiating physical activity intensity in health monitoring
Authors: Chen Daixi , Du Yuchen , Liu Yuan , Hong Jun , Yin Xiaojian , Zhu Zhuoting , Wang Jingjing , Zhang Junyao , Chen Jun , Zhang Bo , Du Linlin , Yang Jinliuxing , He Xiangui , Xu Xun
Published: April 2024

To develop and validate a machine learning based algorithm to estimate physical activity (PA) intensity using the smartwatch with the capacity to record PA and determine outdoor state. Two groups of participants, including 24 adults (13 males) and 18 children (9 boys), completed a sequential activity trial. During each trial, participants wore a smartwatch, and energy expenditure was measured using indirect calorimetry as gold standard. The support vector machine algorithm and the least squares regression model were applied for the metabolic equivalent (MET) estimation using raw data derived from the smartwatch. Exercise intensity was categorized based on MET values into sedentary activity (SED), light activity (LPA), moderate activity (MPA), and vigorous activity (VPA). The classification accuracy was evaluated using area under the ROC curve (AUC). The METs estimation accuracy were assessed via the mean absolute error (MAE), the correlation coefficient, Bland–Altman plots, and intraclass correlation (ICC). A total of 24 adults aged 21–34 years and 18 children aged 9–13 years participated in the study, yielding 1790 and 1246 data points for adults and children respectively for model building and validation. For adults, the AUC for classifying SED, MVPA, and VPA were 0.96, 0.88, and 0.86, respectively. The MAE between true METs and estimated METs was 0.75 METs. The correlation coefficient and ICC were 0.87 (p < 0.001) and 0.89, respectively. For children, comparable levels of accuracy were demonstrated, with the AUC for SED, MVPA, and VPA being 0.98, 0.89, and 0.85, respectively. The MAE between true METs and estimated METs was 0.80 METs. The correlation coefficient and ICC were 0.79 (p < 0.001) and 0.84, respectively. The developed model successfully estimated PA intensity with high accuracy in both adults and children. The application of this model enables independent investigation of PA intensity, facilitating research in health monitoring and potentially in areas such as myopia prevention and control.
PHOTH-graphene: a new 2D carbon allotrope with low barriers for Li-ion mobility
Authors: Santos E. A. J. , Lima K. A. L. , Mendonça F. L. L. , Silva D. A. da , Giozza W. F. , Junior L. A. Ribeiro
Published: April 2024

The continued interest in 2D carbon allotropes stems from their unique structural and electronic characteristics, which are crucial for diverse applications. This work theoretically introduces PHOTH-Graphene (PHOTH-G), a novel 2D planar carbon allotrope formed by 4-5-6-7-8 carbon rings. PHOTH-G emerges as a narrow band gap semiconducting material with low formation energy, demonstrating good stability under thermal and mechanical conditions. This material has slight mechanical anisotropy with Young modulus and Poisson ratios varying between 7.08-167.8 GPa and 0.21-0.96. PHOTH-G presents optical activity restricted to the visible range. Li atoms adsorbed on its surface have a migration barrier averaging 0.38 eV.
Sex ratio shift after frozen single blastocyst transfer in relation to blastocyst morphology parameters
Authors: Wang Tiantian , Zhu Lixia , Yin Mingru , Yu Weina , Dong Jing , Jin Wei , Lyu Qifeng , Jin Lei , Long Hui
Published: April 2024

The sex ratio shift was observed in peoples who underwent ART treatment. Moreover, there is limited evidence on differences in sex ratio between single frozen-thawed blastocyst morphology, insemination type and transfer days. So further research is needed in this area with regard to factors possibly affecting the sex ratio. Retrospective study based on multicenter including two large assisted reproduction centers in Shanghai and Wuhan in China. A total of 6361 singleton delivery offspring after frozen-thawed blastocyst transfer. Propensity score weighting and logistic regression models were used to estimate the associations between blastocyst morphology grading and child sex ratio. The main outcome measures is singleton sex ratio. In our study, the primary outcome measure was sex ratio which was calculated as the proportion of male newborns among all live births. Higher quality blastocysts resulted in a higher sex ratio than single poor-quality frozen-thawed blastocyst transfer. Among the three blastocyst morphological parameters of trophectoderm (TE), Grade A and B were significantly associated with a higher sex ratio than Grade C. The similar trend was observed in both IVF and ICSI treated subgroups. As compared with expansion (4 + 3), expansion degree 6 achieved a higher sex ratio in overall populations and IVF treated subgroup. Transferring blastocysts of day 6 had the highest sex ratio both in IVF group and ICSI group. A 6.95% higher sex ratio in transferring blastocysts of day 5 in IVF group than those in ICSI group. No significant association between inner cell mass degree and sex ratio was observed. However, as compared with IVF treatment, all morphology parameters achieved the similar or the biased sex ratio favoring female in ICSI treated subgroup. Quality of blastocysts was positively associated with sex ratio. TE score and expansion degree rather than ICM were significantly associated with sex ratio at birth. ICSI treatment promotes the biased sex ratio favoring female.