bluuebunny/crossref_metadata_2025 huggingface dataset:
Tert‐butylhydroquinone attenuates LPS‐induced pyroptosis of IPEC‐J2 cells via downregulating HMGB1/TLR4/NF‐κB axis
Authors: Qiu Wenyue , Zhang Xinting , Pang Xiaoyue , Huang Jianjia , Zhou Shuilian , Wu Ruixia , Wang Rongmei , Tang Zhaoxin , Su Rongsheng
Published: September 2023

Inflammatory response induced by biological stress usually occurs in weaning piglets, it reduces the production performance of piglets and even causes death. Tert‐butylhydroquinone (TBHQ) is a food additive that has the effect of anti‐inflammation and anti‐oxidation. However, there are few reports related to the protective mechanisms of TBHQ on lipopolysaccharide (LPS) induced injury in intestinal porcine epithelial (IPEC‐J2) cells. Quantitative real‐time polymerase chain reaction and western blot analysis, respectively, detected the mRNA levels and protein expressions related to pyroptosis, tight junction (TJ) protein and high‐mobility group box 1/toll‐like receptor 4/nuclear factor kappa‐B (HMGB1/TLR4/NF‐κB) axis. Localisation and expression of NOD‐like receptor pyrin domain containing 3 (NLRP3), HMGB1 and P‐NF‐κB proteins detected by immunofluorescence. The results showed that TBHQ (12.5 and 25 μM) can increase cell activity and reduce intracellular lactate dehydrogenase (LDH) levels in a dose‐dependent manner. LPS significantly decreases cell viability and increases the LDH level. However, pretreatment with TBHQ evidently increases cell viability and decreases the LDH level of IPEC‐J2 cells. In addition, treatment with LPS decreased the mRNA level and protein expression of zonula occludens‐1, occludin and claudin‐1, and increased the mRNA level and protein expression of pyroptosis and HMGB1/TLR4/NF‐κB axis. Interestingly, pretreatment with TBHQ increased the TJ protein expressions as well as decreased the mRNA level and protein expressions of pyroptosis and HMGB1/TLR4/NF‐κB axis. Moreover, the results of immunofluorescence showed that TBHQ significantly reduced the expression of NLRP3, HMGB1 and P‐NF‐κB in LPS‐induced injury of IPEC‐J2 cells. Therefore, we come to the conclusion that TBHQ attenuates LPS‐induced pyroptosis in IPEC‐J2 cells through downregulation of the HMGB1/TLR4/NF‐κB axis, TBHQ may become a potential feed additive for preventing inflammatory diarrhoea in piglets.
The Attitude and Behavior of Japanese Managers Toward Male Employees Taking Long‐Term Parental Leave1,2
Authors: Ono Hiromi
Published: September 2023

Promoting male parental leave has become a concern for the Japanese government because of the large gender gap that exists in terms of availing parental leave. This study identified management attitudes and behaviors regarding long‐term male parental leave. Semi‐structured interviews were conducted with 14 private‐enterprise managers and supervisors whose male staff had taken at least 1 month of parental leave. The collected data were analyzed using a modified grounded theory approach, from which six groups, 19 categories, and 49 concepts were generated. It was found that (a) overcoming difficulties associated with long‐term male parental leave resulted in diverse management behaviors; (b) managers often felt that male employees were being unreasonable by taking parental leave; and (c) managers realize the need for male parental leave systems once they observe changes in employees after returning to work.
Discussion of the unique “eclogitic” clast reported from Northwest Africa 801 (CR2) and the possibility of ejection of foundered crust from deep in a molten Moon‐sized projectile
Authors: Scott Edward R. D. , Sanders Ian S. , Asphaug Erik , Tomlinson Emma L.
Published: September 2023

A unique 2 mm‐wide clast of fine‐grained garnet–omphacite peridotite with chondritic chemistry was reported from the CR2 chondrite Northwest Africa 801 by Hiyagon et al. (2016, Geochimica et Cosmochimica Acta, 186, 32–48). Those authors described the clast as eclogitic and inferred from its mineral compositions that the rock formed quickly, during perhaps 100–1000 years of burial, deep within a Moon‐sized body at about 3 GPa (30 kbar) pressure and 1000°C. Such conditions are unprecedented among meteorites and invite scrutiny. Here, we discuss the clast and its origin. The inferred conditions appear justified, but the published idea of burial during a protoplanetary merger and, soon after, exhumation in a violent collision seems improbable and contrary to the clast's low shock levels. We find that exhumation is better explained by pull‐apart of a projectile in a low velocity hit‐and‐run collision. We try inconclusively to explain near‐simultaneous burial and exhumation in a hit‐and‐run return scenario. Taking a different approach, and to conclude, we speculate that an approximately lunar‐mass body was molten beneath a thin dense chondritic crust, of which fragments foundered and sank deep into the magma ocean as an ongoing process. Fragments that were changing to garnet–omphacite peridotite were exhumed when the molten body was pulled apart in a hit‐and‐run collision with a larger body.
Updates and new reports for the flora of northern Somalia (with notes on Dicoma thuliniana and Commiphora playfairii)
Authors: Baldesi Giacomo , Baldini Riccardo Maria , Pignotti Lia
Published: September 2023

Based on collections held at herbarium FT new and noteworthy records of vascular plants from tropical Northeast Africa are provided. Five taxa – Drimia intricata, Gisekia pharnaceoides var. alata, Phyllanthus chevalieri, Vincetoxicum spirale, Vincetoxicum diplostigma – are recorded as new for the Flora of Somalia. For four species – Campylanthus parviflorus, Commiphora spinulosa, Herniaria bicolor, Pulicaria gabrielii – previously known from a single collection or only from the type locality, new records are presented. For 21 species (Amaranthus graecizans subsp. graecizans, Boswellia rivae, Coelachyrum piercei, Coleus argentifolius, Commiphora playfairii, Cornulaca ehrenbergii, Crabbea albolutea, Crepis rueppellii, Diceratella revoilii, Dicoma thuliniana, Euphorbia geldorensis, Farsetia longisiliqua, Gymnosporia arbutifolia, Gymnosporia somalensis, Iphiona pinnatifida, Marsdenia stelostigma, Pavonia burchellii, Pluchea dioscoridis, Psiadia incana, Ruttya fruticosa, Tarchonanthus camphoratus) new distributional or noteworthy records are reported.
The Influence of Compensatory Pelvic Tilt on Patient‐reported Outcome Measurements in FAI Patients Who Received Arthroscopic Treatment
Authors: You Mingke , Wang Weijia , Zhou Kai , Li Jian , Chen Gang
Published: September 2023

Objective

Pelvic compensation is common in femoroacetabular impingement (FAI) patients to reduce symptoms and increase range of motion. However, little attention was given to the postoperative clinical effect of pelvic compensation. Therefore, this study aims to compare the outcomes between pelvic compensation and normal pelvic position in femoroacetabular impingement (FAI) patients after hip arthroscopy.

Methods

The retrospective study was conducted from January 2019 to June 2022, recruited consecutive patients who were diagnosed with FAI and received subsequent arthroscopic treatment. All patients completed an X‐ray in the anterior–posterior standing position before and 4 weeks after surgery. Patients with pelvic compensation were compared with those who did not. Functional outcomes included hip disability and osteoarthritis outcome score (HOOS), modified Harris (mHHS) score, and lower‐extremity activity scale (LEAS). Secondary outcomes included the EuroQol Five Dimensions Questionnaire (EQ‐5D) and patient satisfaction. The intraclass correlation coefficient (ICC) was used to analyze interobserver and intraobserver reliability.

Results

Ninety patients with a mean age of 39.40 years were included in the study. No significant compensation changes were noted within groups after the elimination of impingement. The functional scores showed no significant difference between groups (p(HOOS) = 0.352, p(mHHS) = 0.183, p(LEAS) = 0.865). The EQ‐5D revealed statistically better performance in usual activities in the compensatory group (p = 0.044). There are no significant between‐group differences in patients' satisfaction evaluations.

Conclusion

As assessed by Patient‐Reported Outcome Measures (PROMs), patients with compensatory pelvic tilt demonstrated similar clinical outcomes without extra adverse events to patients with normal pelvic positioning in short‐term follow‐ups. Furthermore, compensatory pelvic tilt did not significantly enhance the range of motion or functional outcome at short‐term follow‐ups.
Functionally discrete fine roots differ in microbial assembly, microbial functional potential, and produced metabolites
Authors: King William L. , Yates Caylon F. , Cao Lily , O'Rourke‐Ibach Sean , Fleishman Suzanne M. , Richards Sarah C. , Centinari Michela , Hafner Benjamin D. , Goebel Marc , Bauerle Taryn , Kim Young‐Mo , Nicora Carrie D. , Anderton Christopher R. , Eissenstat David M. , Bell Terrence H.
Published: September 2023

Traditionally, fine roots were grouped using arbitrary size categories, rarely capturing the heterogeneity in physiology, morphology and functionality among different fine root orders. Fine roots with different functional roles are rarely separated in microbiome‐focused studies and may result in confounding microbial signals and host‐filtering across different root microbiome compartments. Using a 26‐year‐old common garden, we sampled fine roots from four temperate tree species that varied in root morphology and sorted them into absorptive and transportive fine roots. The rhizoplane and rhizosphere were characterized using 16S rRNA gene and internal transcribed spacer region amplicon sequencing and shotgun metagenomics for the rhizoplane to identify potential microbial functions. Fine roots were subject to metabolomics to spatially characterize resource availability. Both fungi and bacteria differed according to root functional type. We observed additional differences between the bacterial rhizoplane and rhizosphere compartments for absorptive but not transportive fine roots. Rhizoplane bacteria, as well as the root metabolome and potential microbial functions, differed between absorptive and transportive fine roots, but not the rhizosphere bacteria. Functional differences were driven by sugar transport, peptidases and urea transport. Our data highlights the importance of root function when examining root‐microbial relationships, emphasizing different host selective pressures imparted on different root microbiome compartments.
Evaluation of human skin response to solar‐simulated radiation in an ex vivo model: Effects and photoprotection of L‐Carnosine
Authors: Girardi Cristina , Benato Francesca , Massironi Marco , Vindigni Vincenzo , Stuhlmann Dominik , Massironi Michele
Published: September 2023

Sunlight, and more specifically the UV component, induces several skin damages, including sunburns, erythema and photoaging. The purpose of this work is to set up an ex vivo human skin model to assess the capacity of active principles in protecting skin from the deleterious effects of solar radiation. Ex vivo human skin biopsies were cultured in an air–liquid interface and exposed to solar‐simulated radiation (SSR, 300–750 nm). L‐Carnosine (0.2% and 2%) was applied topically to be tested as photoprotective compound. The effect on oxidative stress induction, photoaging and skin transcriptional profile was assessed by evaluating reactive oxygen species, advanced glycosylation end products formation and gene expression changes. In our model, SSR increases ROS production and AGE accumulation and affects the expression of genes related to oxidative stress, pigmentation, immunity, inflammation and photoaging. Among these pathways, 11 genes were selected as biomarkers to evaluate the skin solar radiation response. Results showed that L‐Carnosine provides effective prevention against solar radiation damages reducing ROS, AGEs and mitigating the modulation of the selected biomarker genes. In conclusion, we report that our ex vivo skin model is a valuable system to assess the consequences of solar light exposure and the capacity of topically applied L‐Carnosine to counteract them.
Flower orientation and corolla length as reproductive barriers in the pollinator‐driven divergence of Erica shannonea and Erica ampullacea
Authors: McCarren S. , Johnson S. D. , Theron G. L. , Coetzee A. , Turner R. , Midgley J.
Published: September 2023

A variety of reproductive barriers can enable reproductive isolation and stable coexistence of plant species. Differing floral traits might play an important role in reproductive isolation imposed by pollinators. Such shifts in pollinator use have been hypothesized to contribute to the radiation of Erica (Ericaceae) in the Cape Floristic Region, South Africa. The sister species Erica shannonea and Erica ampullacea co‐occur and overlap in flowering phenology. Both have unscented long‐tubed flowers consistent with adaptations for pollination by long‐proboscid flies (LPFs), but differences in flower orientation and corolla tube length are indicative of a shift in pollinator species.

We conducted controlled pollination experiments and pollinator observations to determine the breeding system and pollinators of the two species.

Both species are self‐incompatible and require pollinator visits for seed production, suggesting that pollinators could strongly influence flower evolution. The horizontally orientated flowers of E. shannonea were found to be pollinated by Philoliche rostrata (Tabanidae), which has a long, fixed forward‐pointing proboscis, while the vertically upright orientated flowers of E. ampullacea were found to be pollinated by Prosoeca westermanni (Nemestrinidae), which has a shorter proboscis that can swivel downwards.

The nemestrinid fly's proboscis is too short to access the nectar in the relative long‐tubed flowers of E. shannonea and the tabanid fly's proboscis cannot swivel down to access the upright flowers of E. ampullacea. Consequently, these traits are likely to act as reproductive barriers between the two Erica species and thereby might have contributed to speciation and enable stable coexistence.
Individual differences in seated resting heart rate are associated with multisensory perceptual function in older adults
Authors: O'Dowd Alan , Hirst Rebecca J. , Setti Annalisa , Kenny Rose Anne , Newell Fiona N.
Published: September 2023

There is evidence that cardiovascular function can influence sensory processing and cognition, which are known to change with age. However, whether the precision of unisensory and multisensory temporal perception is influenced by cardiovascular activity in older adults is uncertain. We examined whether seated resting heart rate (RHR) was associated with unimodal visual and auditory temporal discrimination as well as susceptibility to the audio‐visual Sound Induced Flash Illusion (SIFI) in a large sample of older adults (N = 3232; mean age = 64.17 years, SD = 7.74, range = 50–93; 56% female) drawn from The Irish Longitudinal Study on Ageing (TILDA). Faster seated RHR was associated with better discretization of two flashes (but not two beeps) and increased SIFI susceptibility when the audio‐visual stimuli were presented close together in time but not at longer audio‐visual temporal offsets. Our findings suggest a significant relationship between cardiovascular activity and the precision of visual and audio‐visual temporal perception in older adults, thereby providing novel evidence for a link between cardiovascular function and perceptual function in aging.
Relevance of haemoglobin monitoring in apheresis plasma donors: A retrospective cohort study in Québec, Canada
Authors: Lewin Antoine , Germain Marc , Renaud Christian , Robitaille Nancy , Latour Catherine
Published: September 2023

Background and Objectives

Systematically measuring pre‐donation haemoglobin (Hb) levels might be overly cautious for apheresis plasma donation, since plasmapheresis entails a small loss of red blood cells. We explored the association between the frequency of apheresis plasma donation and capillary blood Hb levels.

Materials and Methods

This retrospective cohort study included donors who gave apheresis plasma at least twice between 24 October 2020 and 23 October 2022 in Québec, Canada. Results were stratified by sex and analysed with linear repeated‐measure mixed models with random intercepts.

Results

In total, 9535 men (mean age = 46.7 years) and 9409 women (mean age = 41.1 years) made ≥2, but no more than 16 apheresis plasma donations. Over an average of 9.2 months of observation, men maintained Hb levels well above the Hb deferral threshold, and their Hb levels decreased by only 0.17 g/dL between the 1st and 15th donation return (p < 0.0001). Over an average of 9.0 months of observation, women also maintained adequate Hb levels, and their Hb levels decreased by 0.08 g/dL between the 1st and 15th donation return.

Conclusion

The frequency of apheresis plasma donation was not associated with clinically meaningful changes in Hb levels, neither in men nor in women. This evidence questions the relevance of systematically monitoring Hb for apheresis plasma donation, at least for donation frequencies of ≤7–8 times per year. However, an adverse impact of plasmapheresis on Hb levels cannot be ruled out for individuals donating more frequently or for longer than ~9 months.
Exploring the potential harm of varied blood storage on patients undergoing cardiovascular surgery
Authors: Ning Shuoyan , Gupta Akash , Batarfi Khalid , Liu Yang , Lucier Kayla J. , Barty Rebecca , Heddle Nancy M.
Published: September 2023

Background and Objectives

Debate exists surrounding the optimal duration of red blood cell (RBC) storage. A hypothesis emerging from previous research suggests that exposure to fresh blood may be harmful to patients undergoing cardiac surgery. This study uses a large transfusion medicine database to explore the association between in‐hospital mortality and red cell storage duration.

Materials and Methods

This is an exploratory retrospective cohort study of all adult patients at Hamilton, Canada, over a 14‐year period that received at least one allogeneic red cell transfusion during their hospitalization for cardiac surgery requiring bypass. The primary outcome for the study was in‐hospital death. Analysis was performed using multivariate Cox regression modelling with time‐dependent and time‐independent covariates and stratification variables. Five models with varying definitions for short, intermediate and prolonged duration of RBC storage were tested.

Results

From March 2004 to December 2017, 11,205 patients met the inclusion criteria and were included in the regression analyses. No significant effect of short‐duration red storage on patient mortality was observed in all statistical models, with the red cells stored for the longest duration as the reference group. When patients who received exclusively fresh (hazard ratio [HR] 1.040, 95% confidence interval [CI] 0.588–1.841, p‐value = 0.893) and older aged (HR 1.038, 95% CI 0.769–1.1.402, p‐value = 0.0801) RBCs were compared with those who received exclusively mid‐age red cells as the reference, statistical significance was similarly not reached.

Conclusion

Red cells stored for the shortest duration are not associated with increased risk of mortality among cardiac surgery patients.
The Impact of the SEADDA COST Action
Authors:   University of York, Wright Holly , Richards Julian ,   University of York, Šegan-Radonjić Marija , Tapavicki Ilic Milica , Botica Natália , Marx Amala , Salas Rossenbach Kai , Atalan Çayırezmez Nurdan , Ivanovic Dragan , Streinu Marius , Corns Antony , Uleberg Espen , Trognitz Martina , Hollander Hella , May Keith , Kilbride William , Aspöck Edeltraud , Batlle Baró Sabina , Seaton KL , Novák David
Published: September 2023

The Saving Archaeology from the Digital Dark Age (SEADDA) COST Action ran from 2019 to 2023 and produced a wide range of publications, opportunities for capacity building and knowledge transfer. This paper will discuss the less tangible forms of impact resulting from the work of the SEADDA members working within and across their own networks. These impacts include the new avenues of communication and collaboration created through the data stewardship and management focussed National Workshops held in Norway, Serbia, Portugal, Turkey, France, Romania and Ireland. Each workshop took a different form to be suit the needs of their community, but all resulted in progress towards ensuring the long- term persistence of digital archaeological data. This paper will describe the impact of each of these National Workshops. SEADDA made and strengthened connections across a range of different areas of collaboration, primarily through work with members of the European Archaeological Council, the Digital Preservation Coalition, and the ARIADNE Infrastructure for archaeological data. Each of these connections has resulted in closer ties, ongoing collaboration and other forms of impact that would not have been possible without SEADDA. SEADDA was also committed to ensuring participation of non-EU countries which participate in the COST, and supporting doctoral students and early career researchers, and the impacts of these commitments will also be highlighted in this paper.
Dual-Metric Neural Network With Attention Guidance for Surface Defect Few-Shot Detection in Smart Manufacturing
Authors: Gao Pengjie , Wang Junliang , Xia Min , Qin Zijin , Zhang Jie
Published: September 2023

As an important application of human–robot collaboration, intelligent detection of surface defects is crucial for production quality control, which also helps in relieving the workload of technical staff in human-centric smart manufacturing. To accurately detect defects with limited samples in industrial practice, a dual-metric neural network with attention-guided is proposed. First, an attention-guided recognition network with channel attention and position attention module is designed to efficiently learn representative defect features with limited samples. Second, aiming to detect defects with confusing surface images, a dual-metric function is presented to learn the classification boundary by controlling the distance of samples in feature space from intraclass and interclass. The experiment results on the fabric defect dataset demonstrate that the proposed approach outperforms state-of-the-art methods in accuracy, recall, precision, F1-score, and few-shot accuracy. Further comparative experiments reveal that the dual-metric function is superior in improving the few-shot detection accuracy.
Modeling and Design of a Five Degrees-of-Freedom Delta-Like Robot for Fast Pick-and-Place Applications
Authors: Le Mesle Valentin , Bégoc Vincent , Briot Sébastien
Published: September 2023

Delta-like architectures are widely used for fast pick-and-place applications. When rotational degrees-of-freedom are required to perform a task, one or more UPU kinematic chains are usually added to transmit the torques from motors located on the base to the platform, in order to actuate a wrist. Packaging applications usually require five degrees-of-freedom, and two UPU chains are then used to actuate two rotational degrees-of-freedom (DOFs) on the end-effector. However, the UPU chain induces significant limitations for industrial use: it significantly constrains the workspace along the vertical direction and implies a backlash in the universal joints degrading the accuracy of the robot. In this paper, we investigate an alternative to the UPU kinematic chain for designing delta-like robots with five DOFs. Indeed, the actuation of a two-DOFs wrist is performed through the use of a kinematic chain based on a succession of parallelograms associated with a delta-like leg. After a description of the kinematic models of the modified leg and an analysis of its singularities, a design optimization procedure is presented in order to define suitable geometric parameters for a given industrial application. Finally, a prototype is presented and its performances are evaluated.
What Sets Proficient and Expert Users Apart? Results of a Computer-Aided Design Experiment
Authors: Deng Yuanzhe , Chen James , Olechowski Alison
Published: September 2023

As computer-aided design (CAD) tools have become an essential aspect of modern mechanical engineering design, the demand for CAD experts has increased significantly. The development from novice, to proficient, to expert user is of particular interest to the industrial and academic design communities. Yet little is known about the development of modeling choices, strategies, and patterns that characterize expert CAD skills; much of the past work that reports user action data is based on student or novice data. We compared the CAD modeling process across nine proficient and ten expert designers as they were tested to complete the same design task. Under identical conditions—the same time constraints in the same CAD platform and with the same task—the expert users were able to complete a larger proportion of the task with higher dimensional accuracy. While the experts were able to dissect and retrieve geometries from manufacturing drawings more efficiently than proficient users, they were also able to plan a modeling strategy that required less effort and revisions. With our experimental findings, we identify the demand for procedural knowledge-building for young engineers, with the ultimate goal of more effectively developing experts in engineering design with CAD.
Three-Dimensional Material Mask Overlay Topology Optimization Approach With Truncated Octahedron Elements
Authors: Singh Nikhil , Kumar Prabhat , Saxena Anupam
Published: September 2023

This paper presents a 3D material mask overlay topology optimization approach using truncated octahedron elements and spheroidal masks. Truncated octahedron elements provide face connectivity between two juxtaposed elements, thus eliminating singular solutions inherently. A novel meshing scheme with Tetra-Kai-Decaheral or TKD (generic case of truncated octahedron) elements is proposed. The scheme is extended to parameterized generic-shaped domains. Various benefits of implementing the elements are also highlighted, and the corresponding finite element is introduced. Spheroidal negative masks are employed to determine the material within the elements. Seven design variables define each mask. A material density formulation is proposed, and sensitivity analysis for gradient-based optimization is developed. fminconmatlab function is used for the optimization. The efficacy and success of the approach are demonstrated by solving structures and compliant mechanism design problems. Compliance is minimized for the former, whereas a multi-criteria arising due to flexibility and stiffness measures is extremized for optimizing the mechanisms. Convergence of the optimization is smooth. The volume constraint is satisfied and remains active at the end of the optimization.
Cluster-induced desorption/ionization mass spectrometry of Ir(ppy)3
Authors: Keller Philip , Aoyagi Satoka , Dürr Michael
Published: September 2023

fac-Tris(2-phenylpyridine) iridium [Ir(ppy)3] has been investigated by means of soft desorption/ionization induced by neutral SO2 clusters in combination with mass spectrometry. Desorption of intact Ir(ppy)3 was observed. Further analysis of the isotopic pattern revealed two forms of ionization, either by uptake of a proton or by electron abstraction. The relative contribution of the two processes depends on measurement time and H2O partial pressure, as well as preparation scheme and surface morphology of the samples.
Muscle Fiber Conduction Velocity During Electrically Stimulated Contraction at Various Joint Angles, During Joint Movements, and During Voluntary Contractions
Authors: Hirono Tetsuya , Watanabe Kohei
Published: September 2023

Muscle fiber conduction velocity (MFCV) can be affected by muscle fiber geometry at different joint angles and during joint movements. This study aimed to investigate MFCV during electrically evoked contraction at different joint angles, during joint movements, and during voluntary contractions. Sixteen healthy young men participated. A stimulation electrode was attached on the innervation zone of the vastus lateralis, and a linear electrode array was attached on the vastus lateralis. Under a static condition, electrically evoked electromyography signals were recorded at knee joint angles set every 15° between 0° and 105°. Under a passive movement condition, signals were recorded during knee extension and flexion passively. Under a voluntary contraction condition, signals were recorded while performing 30% or 60% of maximum voluntary contraction. MFCV was calculated using cross-correlation coefficients. Under the static condition, there were no differences in MFCV among various joint angles. Under the passive movement condition, MFCV was significantly greater during high velocity or shortening. Under the voluntary contraction condition, MFCV was significantly greater during high-intensity voluntary contraction and with a shortened muscle length. Joint angles do not influence MFCV markedly during relaxation, but it is possible to overestimate MFCV during movement or voluntary contraction.
Reducing single-use cutlery with green nudges: Evidence from China’s food-delivery industry
Authors: He Guojun , Pan Yuhang , Park Albert , Sawada Yasuyuki , Tan Elaine S.
Published: September 2023

Rising consumer demand for online food delivery has increased the consumption of disposable cutlery, leading to plastic pollution worldwide. In this work, we investigate the impact of green nudges on single-use cutlery consumption in China. In collaboration with Alibaba’s food-delivery platform, Eleme (which is similar to Uber Eats and DoorDash), we analyzed detailed customer-level data and found that the green nudges—changing the default to “no cutlery” and rewarding consumers with “green points”—increased the share of no-cutlery orders by 648%. The environmental benefits are sizable: If green nudges were applied to all of China, more than 21.75 billion sets of single-use cutlery could be saved annually, equivalent to preventing the generation of 3.26 million metric tons of plastic waste and saving 5.44 million trees.
Hold big business to task on ecosystem restoration
Authors: Lamont Timothy A. C. , Barlow Jos , Bebbington Jan , Cuckston Thomas , Djohani Rili , Garrett Rachael , Jones Holly P. , Razak Tries B. , Graham Nicholas A. J.
Published: September 2023

Corporate reporting must embrace holistic, scientific principles
Neurodegeneration enters the era of functional genomics
Authors: Aguzzi Adriano , Kampmann Martin
Published: September 2023

There are no cures for the most common neurodegenerative diseases. None of the currently approved treatments cure or halt these conditions; rather, they address symptoms or slow disease progression. A focus on protein deposits in the brain—a hallmark of Alzheimer’s disease (AD) and Parkinson’s disease (PD)—has led to the development of immunotherapy drugs. Other promising avenues of investigation include the roles of neuroinflammation in neurodegeneration. However, the clinical impact of these approaches is still uncertain. What about exploiting our knowledge of the human genome and the ability to modify it with surgically precise tools? Can functional genomics approaches in neurodegenerative disease research provide the breakthroughs we need?
The HPV8 E6 protein targets the Hippo and Wnt signaling pathways as part of its arsenal to restrain keratinocyte differentiation
Authors: Wu Sharon C. , Grace Miranda , Munger Karl
Published: September 2023

Infections with β-genus human papillomaviruses (HPVs) cause hyperplastic cutaneous lesions. In individuals with the rare hereditary skin disease, epidermodysplasia verruciformis, such lesions can progress to cutaneous squamous cell carcinomas (cSCCs). β-HPV infections may also underlie cSCC development in chronically immunosuppressed individuals. Despite their prevalence and disease association, these viruses are not as well studied as the cancer-associated high-risk α-genus HPVs. HPV-associated lesions are characterized by a marked expansion of dividing, basal-like, poorly differentiated viral cells that contain viral genomes. This reflects the ability of HPVs to inhibit epithelial cell differentiation which is likely driven by the need to establish and maintain long-term viral infections in basal-like epithelial cells. Remarkably, the β-HPVs accomplish this by targeting different cellular effectors than the α-genus HPVs. It was previously reported that the HPV8 E6 protein restrains epithelial cell differentiation by inhibiting Notch and transforming growth factor β signaling. Here, we report that the HPV8 E6 protein can subvert Hippo signaling by activating Transcriptional Enhanced Associate Domain (TEAD) transcriptional programs that inhibit the expression of keratinocyte differentiation markers. Moreover, we determined that HPV8 E6 can interfere with gene expression programs triggered by Wnt signaling by binding to the β-catenin-associated transcriptional co-activator B-cell CLL/lymphoma 9-like(BCL9L) and that this also serves to restrain the expression of epithelial differentiation markers. Hence, the HPV8 E6 protein has evolved a remarkably large array of mechanisms to subvert the differentiation program of the infected epithelial cells.

IMPORTANCE

Human papillomaviruses (HPVs) infect basal epithelial cells and cause a dramatic expansion of basal-like, proliferative cells. This reflects the ability of papillomaviruses to delay keratinocyte differentiation, thereby maintaining aspects of the basal cell identity of persistently infected cells. This may enable papillomaviruses to establish and maintain long-term infections in squamous epithelial tissues. Previous work has revealed that the ability of β-HPV8 E6 protein to inhibit Notch and transforming growth factor β signaling importantly contributes to this activity. Here, we present evidence that HPV8 E6 also subverts Hippo and Wnt signaling and that these activities also aid in restraining keratinocyte differentiation.
mSphere of Influence: If virulence is energetically costly, how can it be maintained?
Authors: Davis Kimberly Michele
Published: September 2023

Kimberly Davis works in the field of bacterial pathogenesis and studies heterogeneity in bacterial populations within host tissues. In this mSphere of Influence article, she reflects on how the paper “Stabilization of cooperative virulence by the expression of an avirulent phenotype” by M. Diard et al. (M. Diard et al.,
Nature
494:353–6, 2013, DOI:
10.1038/nature11913
) impacted the way she thinks about bacterial population dynamics and the costs and benefits of producing virulence factors during infection.
Analysis of SARS-CoV-2 isolates, namely the Wuhan strain, Delta variant, and Omicron variant, identifies differential immune profiles
Authors: Shahbaz Shima , Bozorgmehr Najmeh , Lu Julia , Osman Mohammed , Sligl Wendy , Tyrrell D. Lorne , Elahi Shokrollah
Published: September 2023

There is an urgent need to better understand the impact of different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on immune response and disease dynamics to facilitate better intervention strategies. Here, we show that SARS-CoV-2 variants differentially affect host immune responses. The magnitude and quantity of cytokines and chemokines were comparable in those infected with the Wuhan strain and the Delta variant. However, individuals infected with the Omicron variant had significantly lower levels of these mediators. We also found an elevation of plasma galectins (Gal-3, Gal-8, and Gal-9) in infected individuals, in particular, in those with the original strain. Soluble galectins exert a proinflammatory role in COVID-19 pathogenesis. This was illustrated by their correlation with the plasma levels of sCD14, sCD163, enhanced TNF-α/IL-6 secretion, and increased SARS-CoV-2 infectivity
in vitro
. Moreover, we observed enhanced CD4
+
and CD8
+
T cell activation in Wuhan strain-infected individuals. Surprisingly, there was a more pronounced T cell activation in those infected with the Omicron in comparison to the Delta variant. In line with T cell activation status, we observed a more pronounced expansion of T cells expressing different co-inhibitory receptors in patients infected with the Wuhan strain, followed by the Omicron and Delta variants. Individuals infected with the Wuhan strain or the Omicron variant had a similar pattern of plasma soluble immune checkpoints. Our results imply that a milder innate immune response might be beneficial and protective in those infected with the Omicron variant. Our results provide a novel insight into the differential impact of SARS-CoV-2 variants on host immunity.

IMPORTANCE

There is a need to better understand how different SARS-CoV-2 variants influence the immune system and disease dynamics to facilitate the development of better vaccines and therapies. We compared immune responses in 140 SARS-CoV-2-infected individuals with the Wuhan strain, the Delta variant, or the Omicron variant. All these patients were admitted to the intensive care unit and were SARS-CoV-2 vaccination naïve. We found that SARS-CoV-2 variants differentially affect the host immune response. This was done by measuring soluble biomarkers in their plasma and examining different immune cells. Overall, we found that the magnitude of cytokine storm in individuals infected with the Wuhan strain or the Delta variant was greater than in those infected with the Omicron variant. In light of enhanced cytokine release syndrome in individuals infected with the Wuhan strain or the Delta variant, we believe that a milder innate immune response might be beneficial and protective in those infected with the Omicron variant.
Dynamical modeling of proliferative-invasive plasticity and IFNγ signaling in melanoma reveals mechanisms of PD-L1 expression heterogeneity
Authors: Subhadarshini Seemadri , Sahoo Sarthak , Debnath Shibjyoti , Somarelli Jason A , Jolly Mohit Kumar
Published: September 2023

Background

Phenotypic heterogeneity of melanoma cells contributes to drug tolerance, increased metastasis, and immune evasion in patients with progressive disease. Diverse mechanisms have been individually reported to shape extensive intra-tumor and inter-tumor phenotypic heterogeneity, such as IFNγ signaling and proliferative to invasive transition, but how their crosstalk impacts tumor progression remains largely elusive.

Methods

Here, we integrate dynamical systems modeling with transcriptomic data analysis at bulk and single-cell levels to investigate underlying mechanisms behind phenotypic heterogeneity in melanoma and its impact on adaptation to targeted therapy and immune checkpoint inhibitors. We construct a minimal core regulatory network involving transcription factors implicated in this process and identify the multiple ‘attractors’ in the phenotypic landscape enabled by this network. Our model predictions about synergistic control of PD-L1 by IFNγ signaling and proliferative to invasive transition were validated experimentally in three melanoma cell lines—MALME3, SK-MEL-5 and A375.

Results

We demonstrate that the emergent dynamics of our regulatory network comprising MITF, SOX10, SOX9, JUN and ZEB1 can recapitulate experimental observations about the co-existence of diverse phenotypes (proliferative, neural crest-like, invasive) and reversible cell-state transitions among them, including in response to targeted therapy and immune checkpoint inhibitors. These phenotypes have varied levels of PD-L1, driving heterogeneity in immunosuppression. This heterogeneity in PD-L1 can be aggravated by combinatorial dynamics of these regulators with IFNγ signaling. Our model predictions about changes in proliferative to invasive transition and PD-L1 levels as melanoma cells evade targeted therapy and immune checkpoint inhibitors were validated in multiple RNA-seq data sets from in vitro and in vivo experiments.

Conclusion

Our calibrated dynamical model offers a platform to test combinatorial therapies and provide rational avenues for the treatment of metastatic melanoma. This improved understanding of crosstalk among PD-L1 expression, proliferative to invasive transition and IFNγ signaling can be leveraged to improve the clinical management of therapy-resistant and metastatic melanoma.
Targeting T-cell malignancies using allogeneic double-negative CD4-CAR-T cells
Authors: Fang Karen Kai-Lin , Lee Jongbok , Khatri Ismat , Na Yoosu , Zhang Li
Published: September 2023

Background

Patients with relapsed/refractory T-cell malignancies have limited treatment options. The use of chimeric antigen receptor (CAR)-T cell therapy for T-cell malignancies is challenging due to possible blast contamination of autologous T-cell products and fratricide of CAR-T cells targeting T-lineage antigens. Recently, allogeneic double-negative T cells (DNTs) have been shown to be safe as an off-the-shelf adoptive cell therapy and to be amendable for CAR transduction. Here, we explore the antitumor activity of allogeneic DNTs against T-cell malignancies and the potential of using anti-CD4-CAR (CAR4)-DNTs as adoptive cell therapy for T-cell malignancies.

Methods

Healthy donor-derived allogeneic DNTs were ex vivo expanded with or without CAR4 transduction. The antitumor activity of DNTs and CAR4-DNTs against T-cell acute lymphoblastic leukemia (T-ALL) and peripheral T-cell lymphoma (PTCL) were examined using flow cytometry-based cytotoxicity assays and xenograft models. Mechanisms of action were investigated using transwell assays and blocking assays.

Results

Allogeneic DNTs induced endogenous antitumor cytotoxicity against T-ALL and PTCL in vitro, but high doses of DNTs were required to attain therapeutic effects in vivo. The potency of DNTs against T-cell malignancies was significantly enhanced by transducing DNTs with a third-generation CAR4. CAR4-DNTs were manufactured without fratricide and showed superior cytotoxicity against CD4+T-ALL and PTCL in vitro and in vivo relative to empty-vector transduced-DNTs. CAR4-DNTs eliminated T-ALL and PTCL cell lines and primary T-ALL blasts in vitro. CAR4-DNTs effectively infiltrated tumors, delayed tumor progression, and prolonged the survival of T-ALL and PTCL xenografts. Further, pretreatment of CAR4-DNTs with PI3Kδ inhibitor idelalisib promoted memory phenotype of CAR4-DNTs and enhanced their persistence and antileukemic efficacy in vivo. Mechanistically, LFA-1, NKG2D, and perforin/granzyme B degranulation pathways were involved in the DNT-mediated and CAR4-DNT-mediated killing of T-ALL and PTCL.

Conclusions

These results demonstrate that CAR4-DNTs can effectively target T-ALL and PTCL and support allogeneic CAR4-DNTs as adoptive cell therapy for T-cell malignancies.
A description of classical and quantum cosmology for a single scalar field torsion gravity
Authors: Laya Dipankar , Bhaumik Roshni , Dutta Sourav , Chakraborty Subenoy
Published: September 2023

In the background of homogeneous and isotropic flat FLRW spacetime, both classical and quantum cosmologies have been studied for teleparallel dark energy (DE) model. Using Noether symmetry analysis, not only the symmetry vector but also the coupling function in the Lagrangian and the potential of the scalar field have been determined. Also symmetry analysis identifies a cyclic variable in the Lagrangian along the symmetry vector and as a result the Lagrangian simplifies to a great extent so that classical solution is obtained. Subsequently, in quantum cosmology Wheeler–DeWitt (WD) equation has been constructed and the quantum version of the conserved momenta corresponding to Noether symmetry identifies the periodic part of the wave function of the universe and as a result the WD equation becomes solvable. Finally, quantum description shows finite nonzero probability at the classical big bang singularity.
Quantum phases of two-component bosons in a non-Hermitian optical lattice system
Authors: Zhang Xiao-ru , Yang Shi-Jie
Published: September 2023

In this paper, we investigate the quantum phases of two-component bosons in a non-Hermitian optical lattice system featuring a nonreciprocal hopping phase factor. Our analysis focuses on the Bose–Hubbard model in a two-dimensional (2D) square lattice, utilizing the inhomogeneous dynamical Gutzwiller mean-field theory (DGMFT) to examine the ground state. The impact on quantum phases of the inter component interaction varies in the weak-interaction (the inter-component interactions are smaller than intra-component interactions, i.e., [Formula: see text]) and in the strong-interaction (the inter-component interactions are bigger than intra-component interactions, i.e., [Formula: see text]) regime. In the weak regime, we observe a diverse range of quantum phases, including vortex-like liquid, MI islands (the Mott insulator (MI) islands periodically distributed in the superfluid (SF) background) and SF islands (the SF islands periodically distributed in the MI background), and the inter-component counterflow superfluid (CFSF) phases. In the strong regime, we observe phase separation of the two-component bosons.
Taxonomy of Abstractive Dialogue Summarization: Scenarios, Approaches, and Future Directions
Authors: Jia Qi , Liu Yizhu , Ren Siyu , Zhu Kenny Q.
Published: September 2023

Abstractive dialogue summarization generates a concise and fluent summary covering the salient information in a dialogue among two or more interlocutors. It has attracted significant attention in recent years based on the massive emergence of social communication platforms and an urgent requirement for efficient dialogue information understanding and digestion. Different from news or articles in traditional document summarization, dialogues bring unique characteristics and additional challenges, including different language styles and formats, scattered information, flexible discourse structures, and unclear topic boundaries. This survey provides a comprehensive investigation of existing work for abstractive dialogue summarization from scenarios, approaches to evaluations. It categorizes the task into two broad categories according to the type of input dialogues, i.e., open-domain and task-oriented, and presents a taxonomy of existing techniques in three directions, namely, injecting dialogue features, designing auxiliary training tasks, and using additional data. A list of datasets under different scenarios and widely accepted evaluation metrics are summarized for completeness. After that, the trends of scenarios and techniques are summarized, together with deep insights into correlations between extensively exploited features and different scenarios. Based on these analyses, we recommend future directions, including more controlled and complicated scenarios, technical innovations and comparisons, publicly available datasets in special domains, and so on.
The Topological Mu-Calculus: Completeness and Decidability
Authors: Baltag Alexandru , Bezhanishvili Nick , Fernández-Duque David
Published: September 2023

We study the topological μ-calculus, based on both Cantor derivative and closure modalities, proving completeness, decidability, and finite model property over general topological spaces, as well as overT0andTDspaces. We also investigate the relational μ-calculus, providing general completeness results for all natural fragments of the μ-calculus over many different classes of relational frames. Unlike most other such proofs for μ-calculi, ours is model theoretic, making an innovative use of a known method from modal logic (the ‘final’ submodel of the canonical model), which has the twin advantages of great generality and essential simplicity.
Hardware VM Isolation in the Cloud
Authors: Kaplan David
Published: September 2023

Confidential computing is a security model that fits well with the public cloud. It enables customers to rent VMs while enjoying hardware-based isolation that ensures that a cloud provider cannot purposefully or accidentally see or corrupt their data. SEV-SNP was the first commercially available x86 technology to offer VM isolation for the cloud and is deployed in Microsoft Azure, AWS, and Google Cloud. As confidential computing technologies such as SEV-SNP develop, confidential computing is likely to simply become the default trust model for the cloud.