bluuebunny/crossref_metadata_2025 huggingface dataset:
Benefits of controlled inclination for contactless transport by squeeze-film levitation
Authors: Ramanarayanan Sankaran , Sánchez Antonio L.
Published: August 2023

Developed in this paper is a theoretical description of the fluid flow involved in contactless transport systems that operate using squeeze-film levitation. Regular perturbation methods are employed to solve the appropriate Reynolds equation that governs the viscous, compressible flow of air in the slender film separating the oscillator and the levitated object. The resulting reduced formulation allows efficient computation of the time-averaged levitation force and moment induced by fluid pressure, as well as the accompanying quasistatic thrust force that accounts additionally for shear stresses. Investigated, in particular, is the possibility of combining two distinct methods of thrust generation that have been experimentally demonstrated in previous studies – (i) inclination of the levitated body and (ii) generation of asymmetrical flexural deformations, such as travelling waves, on the oscillator surface – the latter of which is shown to allow a transition from the typically repulsive levitation force to one that is attractive. Computations reveal that systematic control of the inclination angle can provide significant performance benefits for squeeze-film transport systems. In the case of attractive levitation, the amount of improvement that can be obtained appears to correlate closely with the degree of lateral asymmetry exhibited by the flexural oscillations.
Effects of surfactants on bubble-induced turbulence
Authors: Ma Tian , Hessenkemper Hendrik , Lucas Dirk , Bragg Andrew D.
Published: August 2023

We use experiments to explore the effect of surfactants on bubble-induced turbulence (BIT) at different scales, considering how the bubbles affect the flow kinetic energy, anisotropy and extreme events. To this end, high-resolution particle shadow velocimetry measurements are carried out in a bubble column in which the flow is generated by bubble swarms rising in water for two different bubble diameters (3 and 4 mm) and moderate gas volume fractions (0.5 %–1.3 %). We use tap water as the base liquid and add 1-Pentanol as an additional surfactant with varying bulk concentration, leading to different bubble shapes and surface boundary conditions. The results reveal that with increasing surfactant concentration, the BIT generated increases in strength, even though bubbles of a given size rise more slowly with surfactants. We also find that the level of anisotropy in the flow is enhanced with increasing surfactant concentration for bubbles of the same size, and that for the same surfactant concentration, smaller bubbles generate stronger anisotropy in the flow. Concerning the intermittency quantified by the normalized probability density functions of the fluid velocity increments, our results indicate that extreme values in the velocity increments become more probable with decreasing surfactant concentration for cases with smaller bubbles and low gas void fraction, while the effect of the surfactant is much weaker for cases with larger bubble and higher void fractions.
From Slavery to Servitude: Transformations and Continuities in Hacienda Labor, Well-Being, and Foodways in Eighteenth- and Nineteenth-Century Nasca
Authors: Weaver Brendan J. M. , Muñoz Lizette A. , Durand Karen
Published: August 2023

The nineteenth century was a dynamic period for hacienda workers on the south coast of Peru. Former Jesuit vineyards with two of the largest enslaved African-descended populations in rural coastal Peru—the haciendas of San Joseph (San José) and San Francisco Xavier (San Javier)—and their annexes in Nasca's Ingenio Valley underwent dramatic transformations with the replacement of their grapevines with cotton and the introduction of new types of workers. Cantonese indentured workers were contracted beginning in the 1830s, and the majority-enslaved workforce was legally emancipated in 1854. Seasonally, highland Andean workers joined the demographically shifting permanent hacienda population. We use evidence from excavated midden contexts at San Joseph, San Xavier, and San Joseph's annex of Hacienda La Ventilla to explore these changing agroindustrial dynamics and worker well-being in the eighteenth and nineteenth centuries. Despite the transformations at the estates, we find that culinary practices developed by enslaved Africans and their descendants during the Jesuit administration, such as the preparation of one-pot meals and stews, continued into the republican era among Cantonese indentured laborers and wage workers of Indigenous, mestizo, and Cantonese origins. We argue that such strategies centered on foodways were a crucial aspect of worker self-care regimes and broader well-being.
Is frontal pain a useful marker of chronic frontal sinusitis?
Authors: Jashek-Ahmed Farizeh , Thaj Jabin , Eweiss Ahmed
Published: August 2023

Objective

This study evaluated the relationship between frontal pain as a symptom in chronic frontal sinusitis and radiological and endoscopic findings, quality of life and disease severity. The aim was to determine its utility as a marker in chronic frontal sinusitis and in surgical decision-making.

Method

This was a prospective study of 51 consecutive patients undergoing endoscopic sinus surgery for chronic rhinosinusitis. Patients ranked their frontal pain score on a numerical rating scale from 0 to 10. Facial pain or pressure, Sino-Nasal Outcome Test-22, Nasal Obstruction Symptom Evaluation score, Lund–Mackay score and modified Lund–Kennedy score were also collated. Statistical analysis was performed using analysis of variance and Pearson correlation coefficient.

Results

Frontal pain scores were low and demonstrated no correlation with the extent of frontal sinus disease radiologically or the severity of overall sinus disease endoscopically. Higher frontal pain scores significantly correlated with poorer quality-of-life.

Conclusion

This study does not support the use of frontal pain as a sensitive or specific marker of chronic frontal sinus disease.
Nudges, regulations, and behavioral public choice
Authors: Johnson Samuel G. B. , Dana Jason
Published: August 2023

Chater & Loewenstein have done a service to the field by raising the fundamental issue of how the political process distorts well-intentioned efforts at behavioral public policy. We connect this argument to broader research on government failure, particularly public choice theory in economics. We further suggest ways that behavioral research can help identify and mitigate such failures.
Why a group-level analysis is essential for effective public policy: The case for a g-frame
Authors: Bingley William J. , Haslam S. Alexander , Haslam Catherine , Hornsey Matthew J. , Mols Frank
Published: August 2023

Societal problems are not solved by individualistic interventions, but nor are systemic approaches optimal given their neglect of the social psychology underpinning group dynamics. This impasse can be addressed through agroup-level analysis (a “g-frame”) that social identity theorizing affords. Using a g-frame can make policy interventions more adaptive, inclusive, and engaging.
Community-engaged research is best positioned to catalyze systemic change
Authors: Caggiano Holly , Constantino Sara M. , Lees Jeffrey , Majumdar Rohini , Weber Elke U.
Published: August 2023

Addressing many social challenges requires both structural and behavioral change. The binary of an i- and s-frame obscures how behavioral science can help foster bottom-up collective action. Adopting a community-frame perspective moves toward a more integrative view of how social change emerges, and how it might be promoted by policymakers and publics in service of addressing challenges like climate change.
Individual-level solutions may support system-level change â if they are internalized as part of one's social identity
Authors: Koppel Lina , Robertson Claire E. , Doell Kimberly C. , Javeed Ali M. , Rasmussen Jesper , Rathje Steve , Vlasceanu Madalina , Van Bavel Jay J.
Published: August 2023

System-level change is crucial for solving society's most pressing problems. However, individual-level interventions may be useful for creating behavioral change before system-level change is in place and for increasing necessary public support for system-level solutions. Participating in individual-level solutions may increase support for system-level solutions – especially if the individual-level solutions are internalized as part of one's social identity.
It's always both: Changing individuals requires changing systems and changing systems requires changing individuals
Authors: Madva Alex , Brownstein Michael , Kelly Daniel
Published: August 2023

s-Frames and i-frames do not represent two opposed types of intervention. Rather they are interpretive lenses for focusing on specific aspects of interventions, all of which include individual and structural dimensions. There is no sense to be made of prioritizing either system change or individual change, because each requires the other.
Comprehension of indirect answers: Developmental trajectory for preschool- and early elementary school-aged children with typical development
Authors: HUANG Timothy , FINESTACK Lizbeth H.
Published: August 2023

Indirect answers are a common type of non-literal language that do not provide an explicit “yes” or “no” to a question (e.g., “I have to work late” indirectly answered “Are you going to the party?” with a negative response). In the current study, we examined the developmental trajectory of comprehension of indirect answers among 5- to 10-year-old children with typical development. Forty-eight children, 23 boys and 25 girls, between the ages of 5 years; 0 months and 10 years; 11 months (M = 8;2, SD = 19.77 months) completed an experimental task to judge whether a verbally presented indirect answer meant yes or no (Comprehension Task) and then explain their choice (Explanation Task). Responses were scored for accuracy and coded for error analysis. On the Comprehension Task, the 5- to 8-year-olds performed with approximately 85% accuracy, while the 9- and 10-year-olds achieved 95% accuracy. On the Explanation Task, the cross-sectional trajectory revealed three stages: the 5- and 6-year-olds adequately explained indirect answers 32% of the time, the 7- and 8-year-olds performed significantly higher at 55%, and the 9- and 10-year-olds made significant gains than the younger children at 66%. Error analysis revealed that when children fail to interpret speaker intentions appropriately, they repeat the speaker’s utterance or provide an insufficient explanation 80% of the time. Other responses, such as those irrelevant to the context, indicating “I don’t know” or no response, or that were made-up interpretations each accounted for 2%-10% of total inadequate explanations. Study findings indicate discrepancies between task performances and offer two separate sets of baseline data for future comparisons that investigate comprehension or explanation of indirect answers by children with different cultural and linguistic backgrounds and by those with varying cognitive and language profiles.
The Price of Isolation: Fascism, Vichy and the Holocaust in French History
Authors: Farquet Christophe
Published: August 2023

The historiographical debate about France during the Second World War has long been dominated by two foreign historians. On the one hand, the Israeli intellectual Zeev Sternhell notoriously placed the origin of fascism in France's Belle Epoque and saw Vichy France as the paradigmatic example of a fascist regime in his book,Neither Right nor Left, four decades ago. Year after year, Sternhell, who had studied in Paris, made criticisms of the Parisian intellectual milieu and denounced its egocentrism and provincialism. On the other hand, American historian Robert Paxton reigned over the history of French collaboration with Nazi Germany. Although it raised certain controversies when it was translated into French in 1973, hisVichy Francehas been since accepted as the key reference on the subject, as well as an indispensable pedagogical tool against apologetic views of Marshall Pétain's regime, which enjoy periodic revivals in the country. Despite their age – Sternhell died in 2020 and Paxton is ninety years old – these two historians have remained the unavoidable cornerstones in the discussion on French attitudes during the Second World War – the first as a competitor, the second as a paternal figure.
Discrimination Based on Personal Responsibility: Luck Egalitarianism and Healthcare Priority Setting
Authors: Albertsen Andreas
Published: August 2023

Luck egalitarianism is a responsibility-sensitive theory of distributive justice. Its application to health and healthcare is controversial. This article addresses a novel critique of luck egalitarianism, namely, that it wrongfully discriminates against those responsible for their health disadvantage when allocating scarce healthcare resources. The philosophical literature about discrimination offers two primary reasons for what makes discrimination wrong (when it is): harm and disrespect. These two approaches are employed to analyze whether luck egalitarian healthcare prioritization should be considered wrongful discrimination. Regarding harm, it is very plausible to consider the policies harmful but much less reasonable to consider those responsible for their health disadvantages a socially salient group. Drawing on the disrespect literature, where social salience is typically not required for something to be discrimination, the policies are a form of discrimination. They are, however, not disrespectful. The upshot of this first assessment of the discrimination objection to luck egalitarianism in health is, thus, that it fails.
Canopy Leaching Rather than Desorption of PM2.5 From Leaves Is the Dominant Source of Throughfall Dissolved Organic Carbon in Forest
Authors: Cha Ji‐Yeon , Lee Seung‐Cheol , Lee Eun‐Ju , Lee Kyuyeon , Lee Hojin , Kim Hyun Seok , Ahn Jinho , Oh Neung‐Hwan
Published: August 2023

Dissolved organic carbon (DOC) in throughfall plays a vital role in providing carbon and energy to organisms in forests. We utilized carbon isotope analysis to allocate the sources of throughfall DOC, including leaching from plant tissues, PM2.5 deposition on plant foliage, and precipitation. Rainwater, PM2.5, and throughfall samples were collected from pine and oak forests between March and November 2021. The mean concentration of throughfall DOC was 7.9 mg L−1, approximately six times higher than that of rainfall. The mean Δ14C of throughfall DOC was −38.2‰, ∼200‰ higher than that of rainwater or PM2.5. Mass balance estimates revealed that canopy leaching contributed to ∼83% of throughfall DOC, while desorption of PM2.5 and rainwater accounted for only ∼3% and ∼14% of throughfall DOC, respectively. These results clearly highlight canopy leaching as the primary source of carbon input to the forest floor, with a relatively minor contribution from PM2.5 desorption on leaves.
Characterization of Icy Moon Hydrospheres Through Joint Inversion of Gravity and Magnetic Field Measurements
Authors: Petricca Flavio , Genova Antonio , Castillo‐Rogez Julie C. , Styczinski Marshall J. , Cochrane Corey J. , Vance Steven D.
Published: August 2023

Several bodies in the outer solar system are believed to host liquid water oceans underneath their icy surfaces. Knowledge of the hydrosphere properties is essential for understanding and assessing their habitability. We introduce a methodology based on Bayesian inference that enables a robust characterization of the hydrosphere through the combination of gravity and magnetic induction data. The interior models retrieved are consistent with the geophysical observations, leading to probability distributions for the relevant interior properties. We apply this joint inversion approach to constrain Europa's hydrosphere with gravity and magnetic field measurements acquired by the Galileo mission. Our results indicate that the combination of these datasets allows simultaneous constraints on the ice shell and ocean thickness, enhancing our knowledge of the hydrosphere structure. This methodology is valuable for synergistic interior science investigations of several missions in development or in planning, including Europa Clipper, JUICE and the Uranus Orbiter and Probe.
North Atlantic Tropical Cyclone Intensification: Regional Drivers and Trends
Authors: Majumdar Sharanya J. , Nebylitsa Samantha , Klotzbach Philip J. , Masiello Cameron , Michael Zachary R.
Published: August 2023

Using 42 years of reanalysis data, we investigate regional, storm‐relative characteristics of three groups of Atlantic tropical cyclone intensification: slightly, moderately, and rapidly intensifying. Probability density functions are distinct between these groups for vertical wind shear, sea surface temperature (SST), and radius of maximum winds (RMW), but less so for relative humidity (RH). In the Gulf of Mexico and southern North Atlantic, shear and RMW are good predictors. In the open Atlantic, north of 22°N, shear and SST are the best predictors. In the Caribbean, weaker relationships suggest low statistical predictability in a region where RI cases increased between 1980–2000 and 2001–2021. Of our storm‐relative variables tested, increasing SST appears to be most closely connected to the 36% increase in rapidly intensifying events between the two periods, whereas shear and RH are not significantly more favorable. The variability across regions, periods, and variables motivates further investigation.
Nonlinear Riparian Interactions Drive Changes in Headwater Streamflow
Authors: Newcomb Sarah K. , Godsey Sarah E.
Published: August 2023

As drought and wildfire frequency increase across the western United States, our ability to predict how water resources will respond to these disturbances depends on our understanding of the feedbacks that maintain watershed function and streamflow. Previous studies of non‐perennial headwater streams have ranked drivers of low‐flow conditions; however, there is a limited understanding of the interactions between these drivers and the processes through which these interactions affect streamflow. Here, we use stream water level, soil moisture, sap flow, and vapor pressure deficit data to investigate ecohydrological interactions along a mountainous headwater stream. Correlation and cross‐correlation analyses of these variables show that ecohydrological interactions are (a) nonlinear and (b) interconnected, suggesting that analyses assuming linearity and independence of each driver are inadequate for quantifying these interactions. To account for these issues and investigate causal linkages, we use convergent cross‐mapping (CCM) to characterize the feedbacks that influence non‐perennial streamflow. CCM is a nonlinear, dynamic method that has only recently been applied to hydrologic systems. CCM results reveal that atmospheric losses associated with local sap flow and vapor pressure deficit are driving changes in soil moisture and streamflow (p < 0.01) and that atmospheric losses influence stream water more directly than shallow soil moisture. These results also demonstrate that riparian processes continue to affect subsurface flows in the channel corridor even after stream drying. This study proposes a nonlinear framework for quantifying the ecohydrologic interactions that may determine how headwater streams respond to disturbance.
Thermalization and relaxation mediated by phonon management in tin-lead perovskites
Authors: Dai Linjie , Ye Junzhi , Greenham Neil C.
Published: August 2023

Understanding and control of ultrafast non-equilibrium processes in semiconductors is key to making use of the full photon energy before relaxation, leading to new ways to break efficiency limits for solar energy conversion. In this work, we demonstrate the observation and modulation of slow relaxation in uniformly mixed tin-lead perovskites (MASnxPb1-xI3 and CsSnxPb1-xI3 nanocrystals). Transient absorption measurements reveal that slow cooling mediated by a hot phonon bottleneck effect appears at carrier densities above ~1018 cm−3 for tin-lead alloy nanocrystals, and tin addition is found to give rise to suppressed cooling. Within the alloy nanoparticles, the combination of a newly introduced high-energy band, screened Fröhlich interaction, suppressed Klemens decay and reduced thermal conductivity (acoustic phonon transport) with increased tin content contributes to the slowed relaxation. For inorganic nanocrystals where defect states couple strongly with carriers, sodium doping has been confirmed to benefit in maintaining hot carriers by decoupling them from deep defects, leading to a decreased energy-loss rate during thermalization and an enhanced hot phonon bottleneck effect. The slow cooling we observe uncovers the intrinsic photophysics of perovskite nanocrystals, with implications for photovoltaic applications where suppressed cooling could lead to hot-carrier solar cells.
High-order femtosecond vortices up to the 30th order generated from a powerful mode-locked Hermite-Gaussian laser
Authors: Liu Hongyu , Yan Lisong , Chen Hongshan , Liu Xin , Liu Heyan , Chew Soo Hoon , Gliserin Alexander , Wang Qing , Zhang Jinwei
Published: August 2023

Femtosecond vortex beams are of great scientific and practical interest because of their unique phase properties in both the longitudinal and transverse modes, enabling multi-dimensional quantum control of light fields. Until now, generating femtosecond vortex beams for applications that simultaneously require ultrashort pulse duration, high power, high vortex order, and a low cost and compact laser source has been very challenging due to the limitations of available generation methods. Here, we present a compact apparatus that generates powerful high-order femtosecond vortex pulses via astigmatic mode conversion from a mode-locked Hermite-Gaussian Yb:KGW laser oscillator in a hybrid scheme using both the translation-based off-axis pumping and the angle-based non-collinear pumping techniques. This hybrid scheme enables the generation of femtosecond vortices with a continuously tunable vortex order from the 1st up to the 30th order, which is the highest order obtained from any femtosecond vortex laser source based on a mode-locked oscillator. The average powers and pulse durations of all resulting vortex pulses are several hundred milliwatts and <650 fs, respectively. In particular, 424-fs 11th-order vortex pulses have been achieved with an average power of 1.6 W, several times more powerful than state-of-the-art oscillator-based femtosecond vortex sources.
NPM promotes hepatotoxin-induced fibrosis by inhibiting ROS-induced apoptosis of hepatic stellate cells and upregulating lncMIAT-induced TGF-β2
Authors: Ding Xue , Zhu Xin-Le , Xu Dong-Hui , Li Shuang , Yang Qiong , Feng Xian , Wei Yong-Gui , Li Huan , Yang Ling , Zhang Yu-Jun , Deng Xiao-Ling , Liu Kuan-Can , Shi Song-Lin
Published: August 2023

Liver fibrosis is caused by a variety of chronic liver injuries and has caused significant morbidity and mortality in the world with increasing tendency. Elucidation of the molecular mechanism of liver fibrosis is the basis for intervention of this pathological process and drug development. Nucleophosmin (NPM) is a widely expressed nucleolar phosphorylated protein, which is particularly important for cell proliferation, differentiation and survival. The biological role of NPM in liver fibrosis remains unknown. Here we show that NPM promotes liver fibrosis through multiple pathways. Our study found that NPM was up-regulated in cirrhosis tissues and activated in hepatic stellate cells (HSCs). NPM inhibition reduced liver fibrosis markers expression in HSCs and inhibited the HSCs proliferation and migration. In mice model, NPM knockdown in HSCs or application of specific NPM inhibitor can remarkably attenuate hepatic fibrosis. Mechanistic analysis showed that NPM promotes hepatic fibrosis by inhibiting HSCs apoptosis through Akt/ROS pathway and by upregulating TGF-β2 through Akt-induced lncMIAT. LncMIAT up-regulated TGF-β2 mRNA by competitively sponging miR-16-5p. In response to liver injury, hepatocytes, Kupffer cells and HSCs up-regulated NPM to increase TGF-β2 secretion to activate HSCs in a paracrine or autocrine manner, leading to increased liver fibrosis. Our study demonstrated that NPM regulated hepatotoxin-induced fibrosis through Akt/ROS-induced apoptosis of HSCs and via the Akt/lncMIAT-up-regulated TGF-β2. Inhibition of NPM or application of NPM inhibitor CIGB300 remarkably attenuated liver fibrosis. NPM serves a potential new drug target for liver fibrosis.
Ficolin B secreted by alveolar macrophage exosomes exacerbates bleomycin-induced lung injury via ferroptosis through the cGAS-STING signaling pathway
Authors: Wu Xu , Jiang Yixia , Li Rong , Xia Yezhou , Li Feifan , Zhao Meiyun , Li Guoqing , Tan Xiaowu
Published: August 2023

Pathogenesis exploration and timely intervention of lung injury is quite necessary as it has harmed human health worldwide for years. Ficolin B (Fcn B) is a recognition molecule that can recognize a variety of ligands and play an important role in mediating the cell cycle, immune response, and tissue homeostasis in the lung. However, the role of Fcn B in bleomycin (BLM)-induced lung injury is obscure. This study aims to investigate the sources of Fcn B and its mechanism in BLM-induced lung injury. WT, Fcna-/-, and Fcnb-/- mice were selected to construct the BLM-induced lung injury model. Lung epithelial cells were utilized to construct the BLM-induced cell model. Exosomes that were secreted from alveolar macrophages (AMs) were applied for intervention by transporting Fcn B. Clinical data suggested M-ficolin (homologous of Fcn B) was raised in plasma of interstitial lung disease (ILD) patients. In the mouse model, macrophage-derived Fcn B aggravated BLM-induced lung injury and fibrosis. Fcn B further promoted the development of autophagy and ferroptosis. Remarkably, cell experiment results revealed that Fcn B transported by BLM-induced AMs exosomes accelerated autophagy and ferroptosis in lung epithelial cells through the activation of the cGAS-STING pathway. In contrast, the application of 3-Methyladenine (3-MA) reversed the promotion effect of Fcn B from BLM-induced AMs exosomes on lung epithelial cell damage by inhibiting autophagy-dependent ferroptosis. Meanwhile, in the BLM-induced mice model, the intervention of Fcn B secreted from BLM-induced AMs exosomes facilitated lung injury and fibrosis via ferroptosis. In summary, this study demonstrated that Fcn B transported by exosomes from AMs exacerbated BLM-induced lung injury by promoting lung epithelial cells ferroptosis through the cGAS-STING signaling pathway.
Hardware-aware training for large-scale and diverse deep learning inference workloads using in-memory computing-based accelerators
Authors: Rasch Malte J. , Mackin Charles , Le Gallo Manuel , Chen An , Fasoli Andrea , Odermatt Frédéric , Li Ning , Nandakumar S. R. , Narayanan Pritish , Tsai Hsinyu , Burr Geoffrey W. , Sebastian Abu , Narayanan Vijay
Published: August 2023

Analog in-memory computing—a promising approach for energy-efficient acceleration of deep learning workloads—computes matrix-vector multiplications but only approximately, due to nonidealities that often are non-deterministic or nonlinear. This can adversely impact the achievable inference accuracy. Here, we develop an hardware-aware retraining approach to systematically examine the accuracy of analog in-memory computing across multiple network topologies, and investigate sensitivity and robustness to a broad set of nonidealities. By introducing a realistic crossbar model, we improve significantly on earlier retraining approaches. We show that many larger-scale deep neural networks—including convnets, recurrent networks, and transformers—can in fact be successfully retrained to show iso-accuracy with the floating point implementation. Our results further suggest that nonidealities that add noise to the inputs or outputs, not the weights, have the largest impact on accuracy, and that recurrent networks are particularly robust to all nonidealities.
Heterogeneous receptor expression underlies non-uniform peptidergic modulation of olfaction in Drosophila
Authors: Sizemore Tyler R. , Jonaitis Julius , Dacks Andrew M.
Published: August 2023

Sensory systems are dynamically adjusted according to the animal’s ongoing needs by neuromodulators, such as neuropeptides. Neuropeptides are often widely-distributed throughout sensory networks, but it is unclear whether such neuropeptides uniformly modulate network activity. Here, we leverage the Drosophila antennal lobe (AL) to resolve whether myoinhibitory peptide (MIP) uniformly modulates AL processing. Despite being uniformly distributed across the AL, MIP decreases olfactory input to some glomeruli, while increasing olfactory input to other glomeruli. We reveal that a heterogeneous ensemble of local interneurons (LNs) are the sole source of AL MIP, and show that differential expression of the inhibitory MIP receptor across glomeruli allows MIP to act on distinct intraglomerular substrates. Our findings demonstrate how even a seemingly simple case of modulation can have complex consequences on network processing by acting non-uniformly within different components of the overall network.
Reversal of cell, circuit and seizure phenotypes in a mouse model of DNM1 epileptic encephalopathy
Authors: Bonnycastle Katherine , Dobson Katharine L. , Blumrich Eva-Maria , Gajbhiye Akshada , Davenport Elizabeth C. , Pronot Marie , Steinruecke Moritz , Trost Matthias , Gonzalez-Sulser Alfredo , Cousin Michael A.
Published: August 2023

Dynamin-1 is a large GTPase with an obligatory role in synaptic vesicle endocytosis at mammalian nerve terminals. Heterozygous missense mutations in the dynamin-1 gene (DNM1) cause a novel form of epileptic encephalopathy, with pathogenic mutations clustering within regions required for its essential GTPase activity. We reveal the most prevalent pathogenic DNM1 mutation, R237W, disrupts dynamin-1 enzyme activity and endocytosis when overexpressed in central neurons. To determine how this mutation impacted cell, circuit and behavioural function, we generated a mouse carrying the R237W mutation. Neurons from heterozygous mice display dysfunctional endocytosis, in addition to altered excitatory neurotransmission and seizure-like phenotypes. Importantly, these phenotypes are corrected at the cell, circuit and in vivo level by the drug, BMS-204352, which accelerates endocytosis. Here, we demonstrate a credible link between dysfunctional endocytosis and epileptic encephalopathy, and importantly reveal that synaptic vesicle recycling may be a viable therapeutic target for monogenic intractable epilepsies.
Deep learning model improves tumor-infiltrating lymphocyte evaluation and therapeutic response prediction in breast cancer
Authors: Choi Sangjoon , Cho Soo Ick , Jung Wonkyung , Lee Taebum , Choi Su Jin , Song Sanghoon , Park Gahee , Park Seonwook , Ma Minuk , Pereira Sérgio , Yoo Donggeun , Shin Seunghwan , Ock Chan-Young , Kim Seokhwi
Published: August 2023

Tumor-infiltrating lymphocytes (TILs) have been recognized as key players in the tumor microenvironment of breast cancer, but substantial interobserver variability among pathologists has impeded its utility as a biomarker. We developed a deep learning (DL)-based TIL analyzer to evaluate stromal TILs (sTILs) in breast cancer. Three pathologists evaluated 402 whole slide images of breast cancer and interpreted the sTIL scores. A standalone performance of the DL model was evaluated in the 210 cases (52.2%) exhibiting sTIL score differences of less than 10 percentage points, yielding a concordance correlation coefficient of 0.755 (95% confidence interval [CI], 0.693–0.805) in comparison to the pathologists’ scores. For the 226 slides (56.2%) showing a 10 percentage points or greater variance between pathologists and the DL model, revisions were made. The number of discordant cases was reduced to 116 (28.9%) with the DL assistance (p < 0.001). The DL assistance also increased the concordance correlation coefficient of the sTIL score among every two pathologists. In triple-negative and human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients who underwent the neoadjuvant chemotherapy, the DL-assisted revision notably accentuated higher sTIL scores in responders (26.8 ± 19.6 vs. 19.0 ± 16.4, p = 0.003). Furthermore, the DL-assistant revision disclosed the correlation of sTIL-high tumors (sTIL ≥ 50) with the chemotherapeutic response (odd ratio 1.28 [95% confidence interval, 1.01–1.63], p = 0.039). Through enhancing inter-pathologist concordance in sTIL interpretation and predicting neoadjuvant chemotherapy response, here we report the utility of the DL-based tool as a reference for sTIL scoring in breast cancer assessment.
Egyptian mandarin peel oil's anti-scabies potential via downregulation-of-inflammatory/immune-cross-talk: GC–MS and PPI network studies
Authors: Elmaidomy Abeer H. , Abdel-Maqsoud Nehad M. Reda , Tammam Omar. Y. , Abdel-Rahman Islam M. , Elrehany Mahmoud A. , Bakhsh Hussain T. , Altemani Faisal H. , Algehainy Naseh A. , Alzubaidi Mubarak A. , Alsenani Faisal , Sayed Ahmed M. , Abdelmohsen Usama Ramadan , Zahran Eman Maher
Published: August 2023

The current study investigated the scabicidal potential of Egyptian mandarin peel oil (Citrus reticulata Blanco, F. Rutaceae) against sarcoptic mange-in-rabbits. Analysis of the oil's GC–MS identified a total of 20 compounds, accounting for 98.91% of all compounds found. Mandarin peel oil topical application improved all signs of infection, causing a scabicidal effect three days later, whereas in vitro application caused complete mite mortality one day later. In comparison to ivermectin, histopathological analysis showed that the epidermis' inflammatory-infiltration/hyperkeratosis-had disappeared. In addition to TIMP-1, the results of the mRNA gene expression analysis showed upregulation of I-CAM-1-and-KGF and downregulation of ILs-1, 6, 10, VEGF, MMP-9, and MCP-1. The scabies network was constructed and subjected to a comprehensive bioinformatic evaluation. TNF-, IL-1B, and IL-6, the top three hub protein-coding genes, have been identified as key therapeutic targets for scabies. From molecular docking data, compounds 15 and 16 acquired sufficient affinity towards the three screened proteins, particularly both possessing higher affinity towards the IL-6 receptor. Interestingly, it achieved a higher binding energy score than the ligand of the docked protein rather than displaying proper binding interactions like those of the ligand. Meanwhile, geraniol (15) showed the highest affinity towards the GST protein, suggesting its contribution to the acaricidal effect of the extract. The subsequent, MD simulations revealed that geraniol can achieve stable binding inside the binding site of both GST and IL-6. Our findings collectively revealed the scabicidal ability of mandarin peel extract for the first time, paving the way for an efficient, economical, and environmentally friendly herbal alternative for treating rabbits with Sarcoptes mange.
High gravity material extrusion system and extruded polylactic acid performance enhancement
Authors: Jiang Xin , Koike Ryo
Published: August 2023

Additive manufacturing (AM) has gained significant attention in recent years owing to its ability to quickly and easily fabricate complex shapes and geometries that are difficult or impossible to achieve with traditional manufacturing methods. This study presents the development of a high-gravity material extrusion (HG-MEX) system, which generates a high-gravity field through centrifugal acceleration. In this process, the material is dissolved by heating the nozzle and subsequently deposited on the construction platform. The primary objective of this research is to evaluate the positive effects of gravity on material extrusion (MEX), which is a key aspect of AM. To accomplish this, a combined machine comprising a MEX unit and centrifuge is constructed. This HG-MEX system is used to analyze and reflect the influence of gravity on the material extrusion. The experimental evaluations demonstrate that the application of high gravity is a promising approach to improve the shape accuracy and performance of the parts fabricated through MEX. Notably, our results confirm the feasibility of utilizing MEX under high gravity to enhance performance in AM processes.
Trajectory of hiPSCs derived neural progenitor cells differentiation into dermal papilla-like cells and their characteristics
Authors: Riabinin Andrei , Kalabusheva Ekaterina , Khrustaleva Anastasia , Akulinin Mikhail , Tyakht Alexander , Osidak Egor , Chermnykh Elina , Vasiliev Andrey , Vorotelyak Ekaterina
Published: August 2023

Dermal papilla cells (DPCs) play roles in key functions of the epidermis such as hair generation. The use of human induced pluripotent cells (hiPSCs) makes it possible to obtain DP-like cells and study the molecular mechanisms of DPC development during embryogenesis. In this work, we studied the phenotypic trajectory of hiPSCs during their differentiation into DP-like cells and evaluated the epithelial-mesenchymal interaction potential of the resulting cell line. Specifically, we differentiated hiPSCs into neural progenitor cells (NPCs) and subsequently into DP-like cells. Analysis of bulk RNA-seq data during this process enabled us to observe gene expression dynamics during five stages of dermal differentiation. Furthermore, functional assays (organoids in both collagen gels and hanging drop cultures and tubulogenesis assays) revealed that the dermal cell lines we generated could interact with epidermal cells.
A comparative assessment between Globorisk and WHO cardiovascular disease risk scores: a population-based study
Authors: Dehghan Azizallah , Rezaei Fatemeh , Aune Dagfinn
Published: August 2023

The Globorisk and WHO cardiovascular risk prediction models are country-specific and region-specific, respectively. The goal of this study was to assess the agreement and correlation between the WHO and Globorisk 10-year cardiovascular disease risk prediction models. The baseline data of 6796 individuals aged 40–74 years who participated in the Fasa cohort study without a history of cardiovascular disease or stroke at baseline were included. In the WHO and Globorisk models scores were calculated using age, sex, systolic blood pressure (SBP), current smoking, diabetes, and total cholesterol for laboratory-based risk and age, sex, SBP, current smoking, and body mass index (BMI) for non-laboratory-based risk (office-based or BMI-based). In Globorisk and WHO risk agreement across risk categories (low, moderate, and high) was examined using the kappa statistic. Also, Pearson correlation coefficients and scatter plots were used to assess the correlation between Globorisk and WHO models. Bland–Altman plots were presented for determination agreement between Globorisk and WHO risk scores in individual’s level. In laboratory-based models, agreement across categories was substantial in the overall population (kappa values: 0.75) and also for females (kappa values: 0.74) and males (kappa values: 0.76), when evaluated separately. In non-laboratory-based models, agreement across categories was substantial for the whole population (kappa values: 0.78), and almost perfect for among males (kappa values: 0.82) and substantial for females (kappa values: 0.73). The results showed a very strong positive correlation (r ≥ 0.95) between WHO and Globorisk laboratory-based scores for the whole population, males, and females and also a very strong positive correlation (r > 0.95) between WHO and Globorisk non-laboratory-based scores for the whole population, males, and females. In the laboratory-based models, the limit of agreements was better in males (95%CI 2.1 to − 4.2%) than females (95%CI 4.3 to − 7.3%). Also, in the non-laboratory-based models, the limit of agreements was better in males (95%CI 2.9 to − 4.0%) than females (95%CI 3.2 to − 6.1%). There was a good agreement between both the laboratory-based and the non-laboratory-based WHO models and the Globorisk models. The correlation between two models was very strongly positive. However, in the Globorisk models, more people were in high-risk group than in the WHO models. The scatter plots and Bland–Altman plots showed systematic differences between the two scores that vary according to the level of risk. So, for these models may be necessary to modify the cut points of risk groups. The validity of these models must be determined for this population.
Dauciform roots affect functional traits of Carex filispica under nitrogen and phosphorus fertilization in alpine meadow
Authors: Fan Rong , Hua Jinguo , Jiang Songlin , Wang Xiaoqi , Liu Wanting , Ji Wenli
Published: August 2023

Over recent decades, there has been a severe nitrogen-deposition in alpine meadows which often leads to phosphorus limitation of plant productivity. In these high-altitude localities, Cyperaceae have an increasing biomass while other functional groups decrease. Meanwhile, Cyperaceae are known to have the ability of producing dauciform roots, which are formed under phosphorus limitation, but in China, are only described in these high-altitude places. So, is the superiority of Cyperaceae and the formation of dauciform roots in high-altitude localities related to the accumulation of nitrogen? And is there a link between them? A Carex filispica dominated community in Baima Snow Mountain was selected and quantitative fertilization with four levels of nitrogen and three levels of phosphorus was performed. After 2 weeks, Carex filispica individuals with and without dauciform roots were separated and analyzed for their regular root properties, dauciform root properties, biomass and chemical traits of above- and belowground parts. The total cover of the community declined under phosphorus limitation with increasing nitrogen supply, while the relative cover difference of Carex filispica increased with increasing nitrogen supply and decreased with increasing phosphorus supply. Dauciform roots had a more significant response to nitrogen supply than to phosphorus supply and they were formed the most at a low supply of nitrogen. The biomass and root properties of individuals with dauciform roots were enhanced by nitrogen supply and inhibited by phosphorus supply, while those of individuals without dauciform roots were often enhanced by phosphorus supply. Individuals with and without dauciform roots showed two different mechanisms, and were limited by significantly different factors, which can explain the opposite performance of Cyperaceae after nitrogen and phosphorus supply in previous studies.
Birth size and the serum level of biological age markers in men
Authors: Żelaźniewicz Agnieszka , Nowak-Kornicka Judyta , Pawłowski Bogusław
Published: August 2023

Previous studies showed that intrauterine growth restrictions, resulting in smaller body size at birth, are associated with altered development and the risk of age-related diseases in adult life. Thus, prenatal development may predict aging trajectories in humans. The study aimed to verify if body size at birth is related to biological age in adult men. The study sample consisted of 159 healthy, non-smoking men with a mean age of 35.24 (SD 3.44) years. Birth weight and length were taken from medical records. The ponderal index at birth was calculated. Biological age was evaluated based on serum levels of s-Klotho, hsCRP, DHEA/S, and oxidative stress markers. Pregnancy age at birth, lifestyle, weight, cortisol, and testosterone levels were controlled. The results showed no relationship between birth size and s-Klotho, DHEA/S level, inflammation, or oxidative stress. Also, men born as small-for-gestational-age (N = 49) and men born as appropriate-for-gestational-age (N = 110) did not differ in terms of biological age markers levels. The results were similar when controlled for pregnancy week at birth, chronological age, BMI, testosterone, or cortisol level. The results suggest that there is no relationship between intrauterine growth and biomarkers of aging in men aged 30–45 years from the affluent population.
Pre-exposure prophylaxis service among men who have sex with men in Malaysia: findings from a discrete choice experiment
Authors: Dubov Alex , Altice Frederick L. , Gutierrez José I. , Wickersham Jeffrey A. , Azwa Iskandar , Kamarulzaman Adeeba , Gautam Kamal , Shrestha Roman
Published: August 2023

Men who have sex with men (MSM) in Malaysia are disproportionately affected by HIV. As pre-exposure prophylaxis (PrEP) is being introduced, we assessed population-based PrEP delivery preferences among MSM in Malaysia. We conducted a discrete choice experiment through an online survey among 718 MSM. The survey included 14 choice tasks presenting experimentally varied combinations of five attributes related to PrEP delivery (i.e., cost, dosing strategy, clinician interaction strategy, dispensing venue, and burden of visits to start PrEP). We used latent class analysis and Hierarchical Bayesian modeling to generate the relative importance of each attribute and preference across six possible PrEP delivery programs. PrEP dosing, followed by cost, was the most important attribute. The participants were clustered into five preference groups. Two groups (n = 290) most commonly preferred on-demand, while the other three preferred injectable PrEP. One group (n = 188) almost exclusively considered cost in their decision-making, and the smallest group (n = 86) was substantially less interested in PrEP for reasons unrelated to access. In simulated scenarios, PrEP initiation rates varied by the type of program available to 55·0% of MSM. Successful PrEP uptake among Malaysian MSM requires expanding beyond daily oral PrEP to on-demand and long-acting injectable PrEP, especially at affordable cost.
Influence of different skew angles of the submerged vane on pressure flushing performance
Authors: Beiramipour Sepideh , Kantoush Sameh A. , Haghjouei Hadi , Qaderi Kourosh , Rahimpour Majid
Published: August 2023

Siltation significantly threatens a reservoir’s original storage capacity and lifespan. Pressure flushing is an effective measure against siltation through the partial drawdown of the reservoir water level with limited flushed cone volumes in front of the bottom outlet. In this study, a novel configuration with submerged vanes has been proposed and tested experimentally to increase the flushed sediment volume during pressure flushing. In the new configuration, submerged vanes aligned with ten skew angles (θ) of 10°, 20°, 30°, 45°, 70°, 110°, 135°, 150°, 160°, and 170° to the flow direction in noncohesive sediment bed materials were used. The results showed that increasing the skew angle at 45° ≤ θ ≤ 160° increased the flushing cone geometry. The minimum and maximum flushing cone dimensions and volume occurred at skew angles of θ = 45° and 135° ≤ θ ≤ 160° around the bottom outlet. The sediment flushing volume in the presence of submerged vanes at 135° ≤ θ ≤ 160° increased 25 times compared to tests without submerged vanes. Eventually, nonlinear regression analysis yielded an equation for estimating flushing cone volumes. The developed equation was tested in real case studies of a target reservoir, and an acceptable correlation between the calculated and experimental results was obtained.