bluuebunny/crossref_metadata_2025 huggingface dataset:
Resmetirom and Thyroid Hormone Receptor‐Targeted Treatment for Metabolic Dysfunction‐Associated Steatotic Liver Disease (MASLD)
Authors: Liu Chang‐Hai , Zeng Qing‐Min , Hu Teng‐Yue , Huang Yu , Song Yongfeng , Guan Haixia , Rockey Don C. , Tang Hong , Li Sheyu
Published: January 2025

Metabolic dysfunction‐associated steatotic liver disease (MASLD) is a rapidly increasing chronic disease worldwide, particularly among patients with type 2 diabetes. Its severe form, metabolic dysfunction‐associated steatohepatitis (MASH), is also on the rise. The treatment of MASLD and MASH poses significant challenges. Thyroid hormones and their receptors thyroid hormone receptor (TR) agonists, especially resmetirom, have shown potential in improving metabolism and reducing liver inflammation. Thyroid hormones play a crucial role in regulating metabolism and maintaining physiological balance. However, in patients with MASLD, there is a reduced conversion of 3,3′,5,5′‐tetraiodo‐l‐thyronine (T4) to biologically active 3,5,3′‐triiodo‐l‐thyronine (T3), resulting in decreased T3 levels and impaired hepatic TR signaling. This hormonal imbalance is associated with disrupted hepatic lipid metabolism. Resmetirom, an oral selective TR agonist that specifically targets hepatocytes, was approved by the Food and Drug Administration (FDA) in March 2024 for the treatment of moderate to severe liver fibrosis in non‐cirrhotic adults with MASH. This approval was based on the results of the MAESTRO clinical program, which includes multiple‐stage research designs such as the MAESTRO‐NASH, MAESTRO‐NAFLD‐1, MAESTRO‐NAFLD‐OLE, and MAESTRO‐NASH‐OUTCOMES, aims to evaluate the efficacy and safety of resmetirom in different populations of MASH patient. Although the approval of resmetirom represents a significant milestone in the treatment of MAFLD and MASH, many questions remain regarding its long‐term effectiveness and impact on clinical outcomes. Ongoing research, particularly through the MAESTRO program, holds promise for providing additional insights into the long‐term management of MASLD using resmetirom and other similar medications.
Chemical and temporal manipulation of early steps in protein assembly tunes the structure and intermolecular interactions of protein‐based materials
Authors: Italia Valeria , Jons Amanda , Kaparthi Bhavika , Faulk Britt , Maccarini Marco , Bertoncello Paolo , Meissner Ken , Martin Donald K. , Bondos Sarah E.
Published: January 2025

The Drosophila intrinsically disordered protein Ultrabithorax (Ubx) undergoes a series of phase transitions, beginning with noncovalent interactions between apparently randomly organized monomers, and evolving over time to form increasingly ordered coacervates. This assembly process ends when specific dityrosine covalent bonds lock the monomers in place, forming macroscale materials. Inspired by this hierarchical, multistep assembly process, we analyzed the impact of protein concentration, assembly time, and subphase composition on the early, noncovalent stages of Ubx assembly, which are extremely sensitive to their environment. We discovered that in low salt buffers, we can generate a new type of Ubx material from early coacervates using 5‐fold less protein, and 100‐fold less assembly time. Comparison of the new materials with standard Ubx fibers also revealed differences in the extent of wrinkling on the fiber surface. A new image analysis technique based on autocorrelation of scanning electron microscopy (SEM) images was developed to quantify these structural differences. These differences extend to the molecular level: new materials form more dityrosine covalent cross‐links per monomer, but without requiring the specific tyrosine residues necessary for crosslinking previously established materials. We conclude that varying the assembly conditions represents a facile and inexpensive process for creating new materials. Most new biopolymers are created by changing the composition of the monomers or the method used to drive assembly. In contrast, in this study we used the same monomers and assembly approach, but altered the assembly time and chemical environment to create a new material with unique properties.
α‐N‐Methyltransferase regiospecificity is mediated by proximal, redundant enzyme–substrate interactions
Authors: Crone Kathryn K. , Labonte Jason W. , Elias Mikael H. , Freeman Michael F.
Published: January 2025

N‐Methylation of the peptide backbone confers pharmacologically beneficial characteristics to peptides that include greater membrane permeability and resistance to proteolytic degradation. The borosin family of ribosomally synthesized and post‐translationally modified peptides offer a post‐translational route to install amide backbone α‐N‐methylations. Previous work has elucidated the substrate scope and engineering potential of two examples of type I borosins, which feature autocatalytic precursors that encode N‐methyltransferases that methylate their own C‐termini in trans. We recently reported the first discrete N‐methyltransferase and precursor peptide from Shewanella oneidensis MR‐1, a minimally iterative, type IV borosin that allowed the first detailed kinetic analyses of borosin N‐methyltransferases. Herein, we characterize the substrate scope and resilient regiospecificity of this discrete N‐methyltransferase by comparison of relative rates and methylation patterns of over 40 precursor peptide variants along with structure analyses of nine enzyme–substrate complexes. Sequences critical to methylation are identified and demonstrated in assaying minimal peptide substrates and non‐native peptide sequences for assessment of secondary structure requirements and engineering potential. This work grants understanding towards the mechanism of substrate recognition and iterative activity by discrete borosin N‐methyltransferases.
Loop engineering of enzymes to control their immobilization and ultimately fabricate more efficient heterogeneous biocatalysts
Authors: Zeballos Nicoll , Ginés‐Alcober Irene , Macías‐León Javier , Andrés‐Sanz Daniel , González‐Ramírez Andrés Manuel , Sánchez‐Costa Mercedes , Merino Pedro , Hurtado‐Guerrero Ramón , López‐Gallego Fernando
Published: January 2025

Enzyme immobilization is indispensable for enhancing enzyme performance in various industrial applications. Typically, enzymes require specific spatial arrangements for optimal functionality, underscoring the importance of correct orientation. Despite well‐known N‐ or C‐terminus tailoring techniques, alternatives for achieving orientation control are limited. Here, we propose a novel approach that tailors the enzyme surface with engineered His‐rich loops. To that aim, we first solve the X‐ray crystal structure of a hexameric alcohol dehydrogenase from Thermus thermophilus HB27 (TtHBDH) (PDB: 9FBD). Guided by this 3D structure, we engineer the enzyme surface with a new loop enriched with six His residues to control enzyme orientation. Molecular dynamics simulations reveal that the engineered loop's imidazole rings have greater solvent accessibility than those in native His residues, allowing for more efficient enzyme immobilization on certain metal chelate‐functionalized carriers. Using carriers functionalized with iron (III)‐catechol, the apparent Vmax of the immobilized loop variant doubles the immobilized His‐tagged one, and vice versa when both variants are immobilized on carriers functionalized with copper (II)‐imidodiacetic acid. His‐tagged and loop‐engineered TtHBDH show high operational stability reaching 100% bioconversion after 10 reaction cycles, yet the loop variant is faster than the His‐tagged one.
Allosteric modulation of NF1 GAP: Differential distributions of catalytically competent populations in loss‐of‐function and gain‐of‐function mutants
Authors: Xu Liang , Jang Hyunbum , Nussinov Ruth
Published: January 2025

Neurofibromin (NF1), a Ras GTPase‐activating protein (GAP), catalyzes Ras‐mediated GTP hydrolysis and thereby negatively regulates the Ras/MAPK pathway. NF1 mutations can cause neurofibromatosis type 1 manifesting tumors, and neurodevelopmental disorders. Exactly how the missense mutations in the GAP‐related domain of NF1 (NF1GRD) allosterically impact NF1 GAP to promote these distinct pathologies is unclear. Especially tantalizing is the question of how same‐domain, same‐residue NF1GRD variants exhibit distinct clinical phenotypes. Guided by clinical data, we take up this dilemma. We sampled the conformational ensembles of NF1GRD in complex with GTP‐bound K‐Ras4B by performing molecular dynamics simulations. Our results show that mutations in NF1GRD retain the active conformation of K‐Ras4B but with biased propensities of the catalytically competent populations of K‐Ras4B–NF1GRD complex. In agreement with clinical depiction and experimental tagging, compared to the wild type, NF1GRD E1356A and E1356V mutants effectively act through loss‐of‐function and gain‐of‐function mechanisms, leading to neurofibromatosis and developmental disorders, respectively. Allosteric modulation of NF1GRD GAP activity through biasing the conformational ensembles in the different states is further demonstrated by the diminished GAP activity by NF1GRD isoform 2, further manifesting propensities of conformational ensembles as powerful predictors of protein function. Taken together, our work identifies a NF1GRD hotspot that could allosterically tune GAP function, suggests targeting Ras oncogenic mutations by restoring NF1 catalytic activity, and offers a molecular mechanism for NF1 phenotypes determined by their distinct conformational propensities.
Combining computational modeling and experimental library screening to affinity‐mature VEEV‐neutralizing antibody F5
Authors: Sumner Christopher A. , Schwedler Jennifer L. , McCoy Katherine Maia , Holland Jack , Duva Valerie , Gelperin Daniel , Busygina Valeria , Stefan Maxwell A. , Martinez Daniella V. , Juarros Miranda A. , Phillips Ashlee M. , Weilhammer Dina R. , Grigoryan Gevorg , Kent Michael S. , Harmon Brooke N.
Published: January 2025

Engineered monoclonal antibodies have proven to be highly effective therapeutics in recent viral outbreaks. However, despite technical advancements, an ability to rapidly adapt or increase antibody affinity and by extension, therapeutic efficacy, has yet to be fully realized. We endeavored to stand‐up such a pipeline using molecular modeling combined with experimental library screening to increase the affinity of F5, a monoclonal antibody with potent neutralizing activity against Venezuelan Equine Encephalitis Virus (VEEV), to recombinant VEEV (IAB) E1E2 antigen. We modeled the F5/E1E2 binding interface and generated predictions for mutations to improve binding using a Rosetta‐based approach and dTERMen, an informatics approach. The modeling was complicated by the fact that a high‐resolution structure of F5 is not available and the H3 loop of F5 exceeds the length for which current modeling approaches can determine a unique structure. A subset of the predicted mutations from both methods were incorporated into a phage display library of scFvs. This library and a library generated by error‐prone PCR were screened for binding affinity to the recombinant antigen. Results from the screens identified favorable mutations which were incorporated into 12 human‐IgG1 variants. The best variant, containing eight mutations, improved KD from 0.63 nM (parental) to 0.01 nM. While this did not improve neutralization or therapeutic potency of F5 against IAB, it did increase cross‐reactivity to other closely related VEEV epizootic and enzootic strains, demonstrating the potential of this method to rapidly adapt existing therapeutics to emerging viral strains.
PET/CT Imaging of the Right Heart Perfusion and Glucose Metabolism Depending on a Risk Status in Patients With Idiopathic Pulmonary Arterial Hypertension
Authors: Goncharova Natalia , Ryzhkova Daria , Lapshin Kirill , Ryzhkov Anton , Malanova Aryana , Andreeva Elizaveta , Moiseeva Olga
Published: January 2025

Right ventricular heart failure (RV HF) is the leading cause of death in pulmonary arterial hypertension (PAH). Relevance of the low‐risk status assessment using available diagnostic tools requires a reliable confirmation. The study aimed to evaluate right ventricular perfusion and glucose metabolism using positron emission tomography (PET)/computed tomography (CT) with [13N]‐ammonia and [18F]‐fluorodeoxyglucose ([18F]‐FDG) in 30 IPAH patients (33.8 ± 9.4 years) according to ESC/ERS 2022 risk status. The ratio of SUVmaxRV/LV metabolism and SUVmaxRV/LV perfusion showed significant positive correlation with pulmonary artery pressure, right heart dilatation, NT‐proBNP level and negative correlation with the RV ejection fraction. The SUVmaxRV/LV perfusion and SUVmaxRV/LV metabolism ratios differed significantly according to risk status. Low risk patients had a SUVmaxRV/LV metabolism comparable to the controls without PH. The SUVmaxRV/LV perfusion ratio was elevated in low‐risk IPAH patients compared with controls. Increased SUVmaxRV/LV perfusion may be an early marker of coronary flow adaptation to RV pressure overload in low‐risk IPAH patients and requires further evaluation. Further long‐term studies are needed to determine the clinical relevance and cut‐off values for the RV/LV PET/CT with [13N]‐ammonia and [18F]‐fluorodeoxyglucose ([18F]‐FDG) uptake in different IPAH risk groups.
C‐type natriuretic peptide promotes human granulosa cell growth and estradiol production: Implications for early follicle development
Authors: Sato Yorino , Kawamura Kazuhiro
Published: January 2025

Purpose

To investigate the effects of C‐type natriuretic peptide (CNP) on human granulosa cell growth and elucidate its regulatory mechanisms.

Methods

A human non‐luteinizing granulosa cell line (HGrC) developed from small antral follicles was used to assess the impact of CNP on cell proliferation and estrogen synthesis. cGMP production via the guanylate cyclase domain of the CNP receptor, natriuretic peptide receptor 2 (NPR2), was confirmed. The regulation of CNP encoding natriuretic peptide C (NPPC) and NPR2 by estradiol and oocyte‐derived factors (ODFs) was examined.

Results

Besides detecting both NPPC and NPR2, CNP increased cellular proliferation. The specific action of CNP on cell proliferation was confirmed using siRNA transfection. CNP stimulated cGMP production, whereas a guanylate‐cyclase inhibitor suppressed CNP‐induced cell proliferation. Estradiol production was elevated by CNP treatment, accompanied by increased expression of estrogen synthetic enzymes. Furthermore, CNP upregulated NPR2 expression in cooperation with estradiol and ODFs, while estradiol increased NPPC expression.

Conclusion

This study demonstrates CNP stimulation of human granulosa cell growth and suggests potential cross‐talk between these cells and oocytes. Further research on the simultaneous administration of CNP and estradiol may offer a promising approach for promoting early‐stage follicle development in infertility treatments for patients with poor ovarian reserve.
Incorporating Deep Learning Into System Dynamics: Amortized Bayesian Inference for Scalable Likelihood‐Free Parameter Estimation
Authors: Rahmandad Hazhir , Akhavan Ali , Jalali Mohammad S.
Published: January 2025

Estimating parameters and their credible intervals for complex system dynamics models is challenging but critical to continuous model improvement and reliable communication with an increasing fraction of audiences. The purpose of this study is to integrate Amortized Bayesian Inference (ABI) methods with system dynamics. Utilizing Neural Posterior Estimation (NPE), we train neural networks using synthetic data (pairs of ground truth parameters and outcome time series) to estimate parameters of system dynamics models. We apply this method to two example models: a simple Random Walk model and a moderately complex SEIRb model. We show that the trained neural networks can output the posterior for parameters instantly given new unseen time series data. Our analysis highlights the potential of ABI to facilitate a principled, scalable, and likelihood‐free inference workflow that enhance the integration of models of complex systems with data. Accompanying code streamlines application to diverse system dynamics models.
In Situ Slow‐Release Hydrogen Sulfide Therapeutics for Advanced Disease Treatments
Authors: Chen Yiqing , Chen Zhishan , Chen Xingzhong , Zhang Shizhen , Zhang Shaoan , Kang Qiyun , Sharafudeen Kaniyarakkal , Lian Huiwang , Saravanakumar Subramanian , Zhang Xinyue , Xu Jialong , Zhu Xiaoqin , Zhang Qingbin , Han Gang , Li Yang
Published: January 2025

Hydrogen sulfide (H2S) gas therapygarners significant attention for its potential to improve outcomes in various disease treatments. The quantitative control of H2S release is crucial for effective the rapeutic interventions; however, traditional researchon H2S therapy frequently utilizes static release models and neglects the dynamic nature of blood flow. In this study, we propose a novel slow‐release in‐situ H2S release model that leverages the dynamic hydrolysis of H2S donorswithin the bloodstream. Calcium sulfide nanoparticles (CaS NPs) withmicrosolubility characteristics exhibit continuous H2S release, surpassing 24 h at normal blood flow velocities. The extended‐release profile demonstrates superior potential in aligning with the bell‐shapedpharmacological effect of H2S, compared to NaHS. Moreover, we synthesisedrare earth‐doped CaS NPs (CaS: Eu2+, Sm3+ NPs) tha texhibit persistent luminescence, enabling visualisation of the continuous H2S release in trials. Our results demonstrate that lowdose CaS: Eu2+, Sm3+ NPs significantly reduces seizureduration to 1.2 ± 0.7 minutes, while high dose effectively suppresses colontumor growth with a tumor inhibition rate of 54%. Remarkably, these findings closely resemble endogenous H2S levels in treating epilepsy and tumors. This innovative slow‐release, in‐situ H2S the rapeutic approach via hydrolysis rejuvenates the development of H2S‐basedtherapeutics.
Toward Green and Sustainable Zinc‐Ion Batteries: The Potential of Natural Solvent‐Based Electrolytes
Authors: Yaman Uzunoglu Gulsah , Yuksel Recep
Published: January 2025

Zinc‐ion batteries (ZIBs) are emerged as a promising alternative for sustainable energy storage, offering advantages such as safety, low cost, and environmental friendliness. However, conventional aqueous electrolytes in ZIBs face significant challenges, including hydrogen evolution reaction (HER) and zinc dendrite formation, compromising their cycling stability and safety. These limitations necessitate innovative electrolyte solutions to enhance ZIB performance while maintaining sustainability. This review explores the potential of natural solvent‐based electrolytes derived from renewable and biodegradable resources. Natural deep eutectic solvents (DES), bio‐ionic liquids, and biomass‐derived organic compounds present unique advantages, including a wider electrochemical stability window, reduced HER activity, and controlled zinc deposition. Examples include DESs based on choline chloride (ChCl), glycerol‐based systems, and biomass‐derived solvents such as γ‐valerolactone (GVL) and aloe vera, demonstrating improved cycling stability and dendrite suppression. Despite their promise, challenges such as high viscosity, cost, and scalability remain critical barriers to commercialization. This review underscores the need for further research to optimize natural solvent formulations, enhance Zn anode compatibility, and integrate these systems into practical applications. By addressing these challenges, natural solvent‐based electrolytes can pave the way for safer, high‐performance, and environmentally sustainable ZIBs, particularly large‐scale energy storage systems.
Semi‐Confinement Effect Enhances CH4 and C2H4 Production in CO2 Electrocatalytic Reduction
Authors: Song Jiahao , Sun Hanlei , Yao Shuo , Liu Ziyong , Lv Ming , Li Fuli , Lv Zhihui , Hu Xinming , Wang Hongzhi , Liu Licheng
Published: January 2025

Achieving fast conversion and precise regulation of product selectivity in electrochemical CO2 reduction reaction (CO2RR) remains a challenge. The space confinement effect provides a theoretical basis for the design of catalysts of different morphology and sizes and reveals the physical phenomena caused by the confinement of electrons and other particles at the nanoscale. In this work, a semi‐confinement concept is introduced and a mesoporous silica nanosphere supported Cu catalyst (Cu‐MSN) is prepared as a typical example to realize CO2RR enhancement and product selectivity regulation (methane vs ethylene). The semi‐confined structure partially solves the mass transfer problem of classical confined catalysis. Cu‐MSN allows flexible controls aggregation form of Cu species by loading amount, which achieves a free switch from methane Faraday efficiency of 71.1% to ethylene Faraday efficiency of 66.4%. Various characterizations confirm that the fast adsorption behavior and local coordination structure transformation of Cu (from Cu─O─Si to Cu─O─Cu), which can stabilize key intermediates *CHO and *CO*COH for generating respective methane and ethylene.
Sonographic Anatomy and Imaging of the Dorsal Thumb Tendons
Authors: Fenech Michelle , Walkley Daniel , Carmody Deborah , Roots Jacqueline , Obrien Sophie , Diep Susan , Winnett Craig , Grant Andrew , Yeoh Sean , Roche Bridie
Published: January 2025

Injuries to the dorsal thumb tendons and related structures can result in impairment to thumb motion. Ultrasound imaging is useful in diagnosing structural change in the dorsal thumb tendons, branches of the superficial radial nerve, and the dorsal hood. A detailed knowledge of the anatomy, sonographic technique, and normal and abnormal sonographic appearances is required to appropriately identify pertinent findings to guide patient management.
Probabilistic model for ultimate displacement of reinforced concrete columns with flexural failure
Authors: Wang Haoyu , Zhang Pengfei , Li Shaonan , Yu Bo
Published: January 2025

In order to describe the probabilistic characteristics of the ultimate displacement, a probabilistic model for ultimate displacement of reinforced concrete columns with flexural failure was proposed based on the Bayesian theory and the Markov Chain Monte Carlo (MCMC) method. An analytical model for probabilistic ultimate displacement was established first according to the plane cross‐section assumption and the equivalent plastic hinge theory. Then probabilistic model parameters were determined based on the Bayesian theory and the MCMC method. Finally, the proposed model was verified by comparison with 252 sets of experimental data and existing ultimate displacement models. Comparisons show that the proposed model not only provides reasonable prediction accuracy but also describes the probability distribution of ultimate displacement realistically. Furthermore, the proposed model is useful for the validation of the accuracy and applicability of available deterministic ultimate displacement models, which provide probabilistic validation methods based on the confidence interval and probability density function.
Natural Flood Risk Management in Tropical Southeast Asia: Prospects in the Biodiverse Archipelagic Nation of the Philippines
Authors: Tolentino Pamela Louise M. , Williams Richard D. , Hurst Martin D.
Published: January 2025

Natural flood management (NFM) has gained prominence as a flood risk management approach in temperate settings but lacks extensive applied examples and evidence in tropical settings, despite significant ecosystem degradation and high flood risk exposure. Tropical river catchments often experience highly variable hydrographs (i.e., prone to flash floods) and intense rainfall from monsoon and typhoon‐dominated weather systems that can cause landslides and sediment‐transporting river flows. These conditions provide a backdrop to the prospects for NFM in tropical Southeast Asia, of which the Philippines is representative. Catchments in the country are typically small and thus associated with short hydrological response times. They are also characterized by diversity of river types, high rates of lateral mobility, extensive downstream urbanization, and complex land use mosaics at the coast. Consideration of NFM as a conceptual framework in the Philippines may enable conversations about adapting existing flood risk management approaches. To explore these NFM alternatives, we conceptualize opportunities in a typical catchment that we divide into four nested, connected parts: managing headwaters as sponges; conserving and restoring river and floodplain width; blue‐green infrastructure in urban areas; and maintaining and creating space for water in fluvial‐coastal settings. There is potential in countries such as the Philippines to adopt NFM strategies that have shown promise in temperate regions and select Southeast Asian countries, where emerging evidence supports their effectiveness. Monitoring tropical NFM interventions remains crucial to gather evidence supporting broader application of nature‐based solutions for flood risk mitigation and biodiversity loss in tropical Southeast Asia.
Identification of scat samples from three terrestrial mustelids in Taiwan: a simple method
Authors: Jang‐Liaw Nian‐Hong , Huang Hao-Ming , Chen Yen-Jean , Yim Li-Min , Yeh Nai-Cheng , Chung Chia-Heng , Chiang Po-Jen
Published: January 2025

Among the five species of the Mustelidae found in Taiwan, four terrestrial species are potentially sympatric. These species include yellow‐throated marten Martes flavigula, Siberian weasel Mustela sibirica, Taiwan least weasel Mustela nivalis formosana, and Chinese ferret‐badger Melogale moschata. Scat from the first three mustelids are similar in morphology. Therefore, differentiating the scats of these three species is challenging, and without accurate species identification, scatology‐related techniques such as dietary analysis are problematic. Here, we developed a novel set of primers capable of effectively identifying scat samples of these three species through a simple PCR amplification process. This allows for collection of more accurate field data on these species, enabling a better understanding of their ecological niche and basic biological information for future conservation strategies.
Monitoring American woodcock abundance in Tennessee using automated recording units
Authors: Buck Evan J. , Buehler David A.
Published: January 2025

Although American woodcock (Scolopax minor) have been declining for the past 50 years, their breeding activity is not regularly monitored across much of the southeastern United States. Due to predictable crepuscular display behaviors, woodcock are a good candidate for monitoring with automated recording units (ARUs). Here, we test the efficacy of ARUs for monitoring woodcock against human observers. We also evaluate the use of automated detection software for 2 woodcock display sounds, the peent call and twitter display, and estimate whether abundance estimates can be derived from the acoustic data. We find that human observers detected more woodcock and counted more twitter displays than ARUs with manual human review but counted similar numbers of peent calls. The automated detection program monitoR successfully classified 52% of peent calls captured in recordings but was unable to consistently classify twitter displays. We were unable to successfully predict the number of woodcock in a given area based on the total number of peents or twitters recorded per survey by human observers in the field. Automated recording units can be effectively used to monitor woodcock presence but have limitations compared to human observers for estimating abundance.
Investigation of heat transfer in the geometry of helical screw rheometer having couple stress fluid
Authors: Zeb Muhammad , Awais Muhammad , Farooq Muhammad , Khalil Salma , Alqahtani Ali Saeed , Malik Muhammad Yousaf
Published: January 2025

This study examines the generalized Couette flow of couple stress fluid within the geometry of a helical screw rheometer (HSR). The geometry of the HSR is simplified by modeling the screw as an exposed rectangular channel and flattening the barrel surface. The screw and barrel are maintained at constant temperatures, and , respectively. The viscosity of the fluid is assumed to vary with temperature, and the Reynolds model is applied to describe this temperature‐viscosity relationship. The resulting mathematical formulation leads to nonlinearly coupled ordinary differential equations, with velocity and temperature as unknown functions. To solve for the velocity profiles and temperature distribution, an analytical technique known as the perturbation method is utilized. The expressions for volume flow rates are also derived. A graphical analysis is performed to examine the effects of various dimensionless parameters, such as the couple stress parameter , flight angle , constant number , Brinkman number , and pressure gradients in and ‐directions. It is observed that , and enhance the flow profiles and temperature distribution, while variations in reduce the velocity profile in the ‐direction but increase the net velocity and temperature distribution. The pressure gradient in ‐direction promotes the velocity component in ‐direction with no effects on the velocity component in ‐direction. Similarly, the pressure gradient in ‐direction increases the velocity component in ‐direction with no effects on the velocity component in ‐direction. These findings offer insights into optimizing flow behavior and heat transfer in HSR systems and provide a deeper understanding of the interactions between velocity, temperature, and material properties.
7 Fingers Back and Forth Across the Border: A Tale of Two Countries and Their Circus Collaborations
Authors: Leroux Louis Patrick
Published: January 2025

This chapter explores some of the implicit and explicit cross-border collaborations and circulations that characterize the contemporary North American circus scene, notably focusing on Les 7 doigts de la main (7 Fingers), a collective based in Montreal made up of artists from Québec, France and America. There is a long history of cross-border circus activity between Québec and the U.S., from Rickett’s early modern circus touring Québec in the late 1700s and Ringling Brothers’ attracting Canadian talent to the U.S., to Québec exporting and imposing its artistic, acrobatics-based “new” circus through the success of Cirque du Soleil and other touring companies. This chapter concentrates on some lesser-known stories and connections bridging Montreal, San Francisco, and New York, as experienced by the 7 Fingers. Having deep roots in both Montreal and San Francisco, the collective has constantly been juggling multiple affiliations, affection, and cultural codes. The artistic directors are more than ever aware of their generative role with the next generations of North American circus performers on both sides of the border.
Living on the Margins of the Empire: Political Relations Between Québec and the United States: 1940–2000
Authors: Paquin Stéphane , Kirkey Christopher
Published: January 2025

The United States has had a diplomatic presence in Québec for some 200 years, and now has two consulates, one in Québec City and one in Montréal. Québec opened its first delegation to the U.S. nearly 85 years ago, during the Second World War. Despite Québec's strong commercial and security interests in the United States, it is almost impossible for a Québec premier to secure a bilateral meeting with an American president. In fact, there are very few precedents. In the United States, Québec does not enjoy direct and privileged ties with the president or members of the executive branch of the U.S. federal government, as it does with France. Despite this, Québec has nonetheless sought to increase its leverage in the United States since the 1960s. This chapter chronicles the efforts of Québec to advance its interests by examining efforts of successive provincial governments to institutionalize and deepen its political relationship with the United States through direct engagement with the American executive and legislative branches of government. In particular, a range of paradiplomatic efforts constructed and pursued by Québec between 1940 and 2000, are identified and closely evaluated.
Party Realignment in Québec: Lessons from the United States
Authors: Godbout Jean-François , Bélanger Éric
Published: January 2025

This chapter investigates party realignment in the province of Québec. Drawing from the insights of the cleavage theory crafted by Lipset and Rokkan (1967) and the American experience, the study identifies three main conflict dimensions that have structured the party system over time. These overarching issues are economic redistribution, sovereignty, and diversity. The positions of parties on these cleavages are measured using the 2012, 2014, and 2018 Québec elections. The results confirm that the management of diversity is the most influential dimension of the new party system. The study concludes by drawing parallels between Québec’s experience and partisan polarization in the United States.
Sitting time at work and cardiovascular disease risk—a longitudinal analysis of the Study on Mental Health at Work (S-MGA)
Authors: Schmidt Nicole , Romero Starke Karla , Sauter Martha , Burr Hermann , Seidler Andreas , Hegewald Janice
Published: January 2025

Purpose

This study analyzed longitudinal data to examine whether occupational sitting time is associated with increases in body mass index (BMI) and five-year cardiovascular disease (CVD) risk.

Methods

We included 2,000 employed men and women (aged 31–60) from the German Study on Mental Health at Work (S-MGA) for a BMI analysis and 1,635 participants free of CVD at baseline (2011/2012) for a CVD analysis. Occupational sitting time was categorized into five groups (< 5, 5 to < 15, 15 to < 25, 25 to < 35, and ≥ 35 h per week). BMI change was measured from baseline (2011/2012) to follow-up (2017). Incident CVD included hypertension, heart disease, myocardial infarction, and stroke (all self-reported). Multiple linear regression examined the association between sitting time and BMI change, while modified Poisson regression analyzed CVD incidence, adjusting for age, sex, occupation, shift work, leisure activity, and smoking by sex. Covariates were self-reported.

Results

Over five years, the average BMI change was 0.49 (SD 1.9). We found no association between baseline occupational sitting time and BMI changes, with consistent results in sensitivity analyses. During this period, 245 participants developed cardiovascular disease. There was no increased risk of CVD among those with more sitting time compared to less. No differences in risk were found between women and men.

Conclusion

There was no association between occupational sitting time and five-year changes in BMI or incident CVD.
The influence of anorexia nervosa on oral health and related parameters potentially relevant to orthodontic treatment: a systematic review and meta-analysis
Authors: Niederau Christian , Alman Eda , Rizk Marta , Becker Kathrin , Marx Nikolaus , Coenen Franziska A. , Knaup Isabel , Wolf Michael , Craveiro Rogerio Bastos
Published: January 2025

Objectives

Information on the oral health of patients with anorexia nervosa remains not satisfactory. The aim of this systematic review is to evaluate oral health parameters in anorexic patients compared to healthy individuals. Furthermore, potential clinical implications for orthodontic treatment are discussed from an orthodontic perspective.

Materials and methods

Electronic databases were searched for case-control and controlled clinical trial studies on dentofacial manifestations in anorexic patients up to 2/2024. Study selection, data extraction and risk of bias assessment was done independently by two authors. Random-effects meta-analyses of mean differences (MDs) or relative risks (RRs) with their 95% confidence intervals (CIs) were conducted, followed by sensitivity analyses.

Results

Eleven out of 573 initially identified studies were included. They involved oral health analyses of general anorexic patients ≥ 12 years (mean age 18.4). The meta-analysis showed that anorexia nervosa was associated with a significantly increased caries experience (DMFT), plaque accumulation and gingival inflammation (BOP). PH and salivary flow rate were significantly altered in patients with anorexia nervosa, although no significant relationship between α-amylase levels and anorexia nervosa was demonstrated.

Conclusions

These data enabled us to formulate modalities for anorexia-specific orthodontic treatments. Based on the results, patients with anorexia nervosa exhibit an increased risk of caries and gingival inflammatory signs.

Clinical relevance

The systematic information on dentofacial manifestations obtained in this study should be considered to better manage the oral health of anorexia patients.
Projected marine heatwaves over the Mediterranean Sea and the network of marine protected areas: a three-dimensional assessment
Authors: Konsta Katerina , Doxa Aggeliki , Katsanevakis Stelios , Mazaris Antonios D.
Published: January 2025

Marine heatwaves (MHWs) are periods of abnormally warm ocean temperatures that exert significant impacts on marine ecosystems. MHWs are commonly identified as periods when temperature conditions surpass predetermined thermal thresholds. Although they can propagate beneath the ocean’s surface, MHWs are typically assessed using sea surface temperatures. In this study, we investigate the future progression and depth penetration of MHWs across the Mediterranean Sea and the existing network of Marine Protected Areas (MPAs). We utilize daily three-dimensional seawater temperature projections from the POLCOMS-ERSEM model for the period 2006–2100 from surface to 2000 m depth under the RCP8.5 forcing scenario, to explore the future spatio-temporal properties of MHWs. We employ two different baseline climatological periods for establishing thresholds based on which MHWs are identified: one remains constant, while the other is adjusted in time to reflect the evolving adaptive capacities of ecosystems in response to long-term warming trends. Our analysis reveals that, regardless of the threshold applied, the Mediterranean MPAs will experience long-lasting and intense MHWs in the future across the ocean’s depths. While the utilization of a shifting baseline period results in shorter and milder shallow MHWs within the Mediterranean MPAs (i.e. annual duration: 45 days per year and mean annual intensity: 1.63 °C) compared to the fixed baseline approach (i.e. annual duration: 195 days per year and mean annual intensity: 1.89 °C), deeper ocean zones exhibit a saturation of MHWs, with year-round events, particularly below 1000 m, under both baseline approaches. Our findings highlight the profound penetration of MHWs into the ocean's depths, posing a serious threat to the protected ecosystems of the Mediterranean, especially in marine subsurface environments. Notably, our findings suggest that MHWs are expected to demonstrate similar spatio-temporal patterns to those observed within the MPAs across the entire Mediterranean basin. MPAs are, thus, anticipated to face equivalent challenges from MHW impacts, affecting their protected ecosystems and biodiversity across various depths.
Effective Thermal Conductivity of Nanofluids Containing Silicon Dioxide, Titanium Dioxide, Copper Oxide, Polystyrene, or Polymethylmethacrylate Nanoparticles Dispersed in Water, Ethylene Glycol, or Glycerol
Authors: Berger Bioucas Francisco E. , Koller Thomas M. , Fröba Andreas P.
Published: January 2025

The present study represents a continuation of our investigations on the effective thermal conductivity λ
eff of nanofluids by systematically varying the types of base fluids and particles. For the spherical nanoparticles with mean diameters between (20 and 175) nm, the metal oxides silicon dioxide (SiO2), titanium dioxide (TiO2), and copper oxide (CuO) as well as the polymers polystyrene (PS) and polymethylmethacrylate (PMMA) were selected to cover a broad range for the particle thermal conductivity λ
p from about (0.1 to 30) W⋅m–1⋅K–1. The corresponding polar base fluids water, ethylene glycol, and glycerol allow to not only vary their thermal conductivity λ
bf by a factor of more than two, but also their dynamic viscosity by about three orders of magnitude. For the measurement of λ
eff of the twelve different particle–fluid combinations, i.e., TiO2 or CuO with all three liquids as well as SiO2, PS, or PMMA with water or ethylene glycol, a steady-state guarded parallel-plate instrument (GPPI) associated with an expanded (k = 2) relative uncertainty between 0.022 and 0.032 was used at atmospheric pressure over a temperature range from (283 to 358) K at varying particle volume fractions up to 0.31. The results for the thermal-conductivity ratio λ
eff·λ
bf
–1 are independent of temperature and show a moderate and relatively linear change as a function of the particle volume fraction. For similar ratios λ
p·λ
bf
–1, the experimental data for λ
eff·λ
bf
–1 are also very similar, which are above, close to, or below 1 if λ
p is larger than, comparable to, or smaller than λ
bf, respectively. For all nanofluids investigated, the Hamilton–Crosser model can describe the present measurement results and reliable experimental data reported in the literature for λ
eff·λ
bf
–1 typically within ± 5 %. Overall, the measurement results from this work contribute to an extension of the database for λ
eff of nanofluids with respect to the investigated wide ranges of systems, temperature, and particle volume fraction.
Exposure of Sn-Wetted W CPS Targets to Simultaneous NBI Beam and High-Power CW Laser Pulses at the High-Heat Flux OLMAT Facility
Authors: Oyarzabal E. , De Castro A. , Alegre D. , Fernandez-Mayo P. , Tafalla D. , McCarthy K. J. ,   The OLMAT Team, Honrubia F. Miguel , Carrasco R. , Sebastián J. A. , Diaz F. Martin , Manchon J. Gomez , Jimenez-Denche A. , Navarro M. , Bueno L. A. , de la Peña A. , Portas A.
Published: January 2025

First experiments are reported of the simultaneous exposure of a number of Sn-wetted W CPSs and a reference W CPS to 100 ms NBI pulses (divertor steady-state loading conditions) and 2 ms long high-energy laser pulses (divertor ELM like loading conditions) at the High-Heat Flux OLMAT facility. The use of a fast-frame imaging camera allows monitoring the onset of particle ejection from the targets during laser pulses and obtaining the corresponding laser heat fluxes as a measure of the resilience of these targets. Fast camera images are used also to determine ejected particle numbers and to estimate their maximum velocities as laser power is increased in order to compare the influence of W CPS structure on these parameters. In addition, the craters resulting from particle ejection are studied for each target with an optical microscope and a scanning electron microscope. Moreover, in-situ W and Sn particle ejection is followed using visible emission spectroscopy and post-exposure W melting after particle ejection is observed using the energy dispersive X-ray method EDX for all the studied targets. This shows that Sn is unable to protect the underlying W substrate from high-energy laser damage, albeit a subsequent refilling of the formed craters with Sn is visible during NBI-only pulses after laser damage. Thus, it is considered that optimization of surface refilling/replenishment with Sn is needed to improve the W substrate protection. From this work, it is also found that the W CPS reference material has a higher laser heat flux threshold for particle ejection than the Sn-wetted targets. Nevertheless, it is important to take into account that in these experiments with laser pulses, the possible beneficial effects of vapor shielding that can take place during particle irradiation at ELMs or disruptions are not present, thus these experiments represent a worst-case scenario.
An Efficient Implementation of Interior-Point Methods for a Class of Nonsymmetric Cones
Authors: Chen Yuwen , Goulart Paul
Published: January 2025

We present an implementation of interior-point methods for generalized power cones, power mean cones and relative entropy cones, by exploiting underlying low-rank and sparsity properties of the Hessians of their logarithmically homogeneous self-concordant barrier functions. We prove that the augmented linear system in our interior-point method can be sparse and quasidefinite after adding a static regularization term, enabling the use of sparse LDL factorization for nonsymmetric cones. Numerical results show that our implementation can exploit sparsity in our test examples.
Optimization of the poloxamer 407-conjugated gelatin to synthesize pH-sensitive nanocarriers for controlled paclitaxel delivery
Authors: Ly Huy Q. , Chen Yin-Ju , Nguyen Van Toan , Tseng Ching-Li
Published: January 2025

Chemotherapy is one of the most prevalent and efficacious treatments for a wide variety of cancers; however, chemotherapeutic agents have clinically limited applications due to their low water solubility and risk of side effects. Nanomedicine can help to easily deliver hydrophobic and hydrophilic agents for cancer treatment. Here, we describe a nanocarrier system that enables the sustainable and controllable release of hydrophobic anticancer drugs, Paclitaxel, based on poloxamer 407-conjugated gelatin (GeP) copolymers. The particle size, zeta potential, morphology, and thermal stability of the nanogels were characterized. The successful synthesis of nanogels was confirmed by analyzing their chemical components. Among the GePs at different amounts of poloxamer 407, a ratio of gelatin and poloxamer (Ge:P) at 1:15 for preparation resulted in the nanogels being positive in charge, spherical in shape, and 97.84 ± 2.94 nm in hydrodynamic diameter (Dh), with optimal drug-carrying efficacy. The in vitro drug release from nanogels was accelerated in the tumor microenvironment at pH 5.5 in comparison to pH 7.4, and the drug release kinetics from nanogels were due to Fickian diffusion. Finally, the cytotoxicity assays indicated that GePs were biocompatible nanocarriers without toxicity on both normal (VERO) and breast cancer cell (MCF-7) lines, which could improve the pharmacokinetics and pharmacodynamics of paclitaxel. Overall, these results revealed an optimal ratio (1:15) of Ge:P for the synthesis of pH-responsive hybrid nanogels for sufficient paclitaxel releasement to kill MCF-7 for effective cancer treatment.