bluuebunny/crossref_metadata_2025 huggingface dataset:
School-based research centres: one school’s exploration
Authors: Loch Sarah
Published: September 2023

School-based research centres are growing in number and have potential to amplify school students’ voices in research through activities within the school. This paper explores how one research centre in an independent school in Australia, in a financially and socially privileged context, is using tertiary-type structures (namely, an ethics committee, research journal and conference) to engage students in research activities and give them voice about research in their school. Writing as centre director and practitioner researcher in the school, I explore these activities which position research as a skill with potential to further students’ academic capital, as well as their ability to challenge their understanding of privilege in the world. A core motivation for this paper is consideration of the transposition of structures designed for adults into the school context and exploring how students engage with these structures in order to have a voice as researchers and in research.
Stratified reduction of singularities of generalized analytic functions
Authors: Molina-Samper B. , Palma-Márquez J. , Sanz Sánchez F.
Published: September 2023

Generalized analytic functions are naturally defined in manifolds with boundary and are built from sums of convergent real power series with non-negative real exponents. In this paper we deal with the problem of reduction of singularities of these functions. Namely, we prove that a germ of generalized analytic function can be transformed by a finite sequence of blowing-ups into a function which is locally of monomial type with respect to the coordinates defining the boundary of the manifold where it is defined.
Environmental drawbacks of lightweight design algorithms in material extrusion additive manufacturing: a case study
Authors: Mele Mattia , Pisaneschi Gregorio , Ciotti Michele , Campana Giampaolo , Zucchelli Andrea , Fiorini Maurizio
Published: September 2023

Lightweight design is often assumed to be the leading strategy to improve the sustainability of parts produced by additive manufacturing. The present study confutes such an assumption by a cradle-to-gate life cycle assessment of different lightweight strategies applied to a specific case study in the medical field. In particular, a patient-specific finger splint made of polyamide is redesigned by means of generative design, topology optimization and lattice structures. The analysis investigates two markedly different deposition processes, namely Arburg plastic freeforming and fused filament fabrication. The former is carried out on an industrial-grade machine, while a desktop printer is used for the latter. This allows for observing the impact of the redesign in two quite distinct scenarios. Findings demonstrate that, since environmental impacts are mainly driven by building time, the adoption of automated design algorithms can be detrimental to the sustainability of the process. On the other hand, relevant benefits on environmental impacts were achieved by reducing the infill percentage of parts. The results of this work highlight the most relevant aspects which must be considered to limit environmental impacts when designing parts for deposition-based additive manufacturing. This information can be used by designers to drive weight reduction towards sustainability.
Overcoming vaccine hesitancy by multiplex social network targeting: an analysis of targeting algorithms and implications
Authors: Fügenschuh Marzena , Fu Feng
Published: September 2023

Incorporating social factors into disease prevention and control efforts is an important undertaking of behavioral epidemiology. The interplay between disease transmission and human health behaviors, such as vaccine uptake, results in complex dynamics of biological and social contagions. Maximizing intervention adoptions via network-based targeting algorithms by harnessing the power of social contagion for behavior and attitude changes largely remains a challenge. Here we address this issue by considering a multiplex network setting. Individuals are situated on two layers of networks: the disease transmission network layer and the peer influence network layer. The disease spreads through direct close contacts while vaccine views and uptake behaviors spread interpersonally within a potentially virtual network. The results of our comprehensive simulations show that network-based targeting with pro-vaccine supporters as initial seeds significantly influences vaccine adoption rates and reduces the extent of an epidemic outbreak. Network targeting interventions are much more effective by selecting individuals with a central position in the opinion network as compared to those grouped in a community or connected professionally. Our findings provide insight into network-based interventions to increase vaccine confidence and demand during an ongoing epidemic.
Contribution of the SOS response and the DNA repair systems to norfloxacin induced mutations in E. coli
Authors: Lin Tongtong , Pan Jiao , Gregory Colin , Wang Yaohai , Tincher Clayton , Rivera Caitlyn , Lynch Michael , Long Hongan , Zhang Yu
Published: September 2023

Antibiotic-resistant bacteria severely threaten human health. Besides spontaneous mutations generated by endogenous factors, the resistance might also originate from mutations induced by certain antibiotics, such as the fluoroquinolones. Such antibiotics increase the genome-wide mutation rate by introducing replication errors from the SOS response pathway or decreasing the efficiency of the DNA repair systems. However, the relative contributions of these molecular mechanisms remain unclear, hindering understanding of the generation of resistant pathogens. Here, using newly-accumulated mutations of wild-type and SOS-uninducible Escherichia coli strains, as well as those of the strains deficient for the mismatch repair (MMR) and the oxidative damage repair pathways, we find that the SOS response is the major mutagenesis contributor in mutation elevation, responsible for ~ 30–50% of the total base-pair substitution (BPS) mutation-rate elevation upon treatment with sublethal levels of norfloxacin (0 ~ 50 ng/mL). We further estimate the significance of the effects on other mutational features of these mechanisms (i.e., transversions, structural variations, and mutation spectrum) in E. coli using linear models. The SOS response plays a positive role in all three mutational features (mutation rates of BPSs, transversions, structural variations) and affects the mutational spectrum. The repair systems significantly reduce the BPS mutation rate and the transversion rate, regardless of whether antibiotics are present, while significantly increasing the structural variation rate in E. coli. Our results quantitatively disentangle the contributions of the SOS response and DNA repair systems in antibiotic-induced mutagenesis.
Sheffield Shield Cricketers Live Longer than the Age-Matched General Australian Male Population
Authors: Luies Nathan , Orchard Jessica J. , Driscoll Tim , Sahdra Saaz Kaur , Cheng Jonathan , Davis Angus J. , Orchard John W.
Published: September 2023

Background/objectives

Previous studies have shown a trend that elite athletes tend to live longer than the general population, which has been attributed to the “healthy worker hire effect” and the health benefits of exercise. There have not been any previous studies looking at survival of elite cricketers with the general population as a reference cohort. This study aimed to compare the annual mortality rates of current and retired elite male Australian cricket players to that of the age-matched general Australian male population.

Methods

Analysis of publicly accessible dates of birth, death, and cricket debut data for male Australian Sheffield Shield cricket players who played before 2022 and had not died before 1971. Included persons were Sheffield Shield players who lived primarily in Australia during and after their cricket careers. Death rates from 1971 to 2021 (inclusive) were compared to the general Australian male population.

Results

1824 Sheffield Shield players had not died prior to 1971 (798 had played before the 1971 season, 1026 debuting subsequently). There were 586 deaths in the 51 years of observations, compared to 825 expected deaths, giving a Standardized Mortality Ratio of 0.71 (95% CI 0.63–0.80).

Conclusion

Elite Australian male Sheffield Shield cricket players outlive the general male population with lower death rates. This is probably due to a combination of the healthy worker hire effect and the health benefits of exercise. This study provides evidence that in terms of longevity, it is safe to play elite-level cricket in Australia.

Graphical Abstract
Formal Ontology
Authors: Hakkarainen Jani , Keinänen Markku
Published: September 2023

Formal ontology as a main branch of metaphysics investigates categories of being. In the formal ontological approach to metaphysics, these ontological categories are analysed by ontological forms. This analysis, which the Element illustrates by some category systems, provides a tool to assess the clarity, exactness and intelligibility of different category systems or formal ontologies. It discusses critically different accounts of ontological form in the literature. Of ontological form, the authors propose a character-neutral relational account. In this metatheory, ontological forms of entities are their standings in internal relations whose holding is neutral on the character of their relata. These relations are 'formal ontological relations'. The Element concludes by showing that our metatheory is useful for understanding categorial fundamentality/non-fundamentality, different formal ontologies, and for unifying metaphysical questions. This title is also available as Open Access on Cambridge Core.
Hijacked
Authors: Anderson Elizabeth
Published: September 2023

What is the work ethic? Does it justify policies that promote the wealth and power of the One Percent at workers' expense? Or does it advance policies that promote workers' dignity and standing? Hijacked explores how the history of political economy has been a contest between these two ideas about whom the work ethic is supposed to serve. Today's neoliberal ideology deploys the work ethic on behalf of the One Percent. However, workers and their advocates have long used the work ethic on behalf of ordinary people. By exposing the ideological roots of contemporary neoliberalism as a perversion of the seventeenth-century Protestant work ethic, Elizabeth Anderson shows how we can reclaim the original goals of the work ethic, and uplift ourselves again. Hijacked persuasively and powerfully demonstrates how ideas inspired by the work ethic informed debates among leading political economists of the past, and how these ideas can help us today.
Ethiopia’s ‘Developmental State’
Authors: Lavers Tom
Published: September 2023

Ethiopia stands out as a leading example of state-led development in Africa. Tom Lavers offers in this book a comprehensive, multi-sector analysis of Ethiopia's development project, examining how regimes maintain power during the extended periods required to bring about economic transformation. Specifically, Lavers explores how the Ethiopian Peoples' Revolutionary Democratic Front (EPRDF, 1991-2019) sought to maintain political order through economic transformation, and why the party collapsed, leading to the outbreak of civil war in 2020. The book argues that the EPRDF sought to secure mass acquiescence through distribution of land and employment. However, rapid population growth and the limits of industrial policy in the contemporary global economy led to a distributive crisis that was a central factor in the regime's collapse. This Ethiopian experience raises important questions about the prospects for economic transformation elsewhere on the continent. This title is also available as Open Access on Cambridge Core at doi.org/9781009428316.
Network Analysis
Authors: Rawlings Craig M. , Smith Jeffrey A. , Moody James , McFarland Daniel A.
Published: September 2023

The size and availability of network information has exploded over the last decade. Social scientists now share the stage of network analysis with computer scientists, physicists, and statisticians. While a number of introductions to network analysis are now available, most focus on theory, methods, or application alone. This book integrates all three. Network Analysis is an introduction to both the why and how of Social Network Analysis (SNA). It presents a broad theoretical overview rooted in social scientific approaches and guides users in how network analysis can answer core theoretical questions. It provides a comprehensive overview of descriptive and analytical approaches, including practical tutorials in R with sample data sets. Using an integrated approach, this book aims to quickly bring novice network researchers up to speed while avoiding common programming and analysis mistakes so that they might gain insight into the fundamental theories, key concepts, and methodological application of SNA.
Nonlinear surface Ekman effects on cyclonic and anticyclonic vortices
Authors: Zavala Sansón L. , García-Martínez I.M. , Sheinbaum J.
Published: September 2023

The transfer of momentum between the atmosphere and oceanic motions affected by the Earth's rotation occurs through the thin surface Ekman layer. The exchange depends on the surface wind stress, which produces the Ekman pumping of fluid to the ocean upper layer. The Ekman pumping mainly depends on: (i) the curl of the wind stress and (ii) the advection of vorticity due to the Ekman transport. The wind stress is usually parametrised as a quadratic function of the relative speed between the wind and the ocean currents, providing a feedback mechanism between the two fluids. Under steady and spatially uniform wind conditions over mesoscale vortices, the first mechanism generates vertical motions that induce the vortex decay (top drag), while the second promotes the horizontal advection of vorticity in the Ekman transport direction. This study examines the nonlinear effects of both mechanisms in cyclonic and anticyclonic vortices. The analyses consist of simple analytical approximations and nonlinear numerical simulations of quasi-two-dimensional vortices. When considering only the top drag mechanism, it is found that anticyclones decay faster than cyclones. By considering only the vorticity-advection effect, the vortices acquire horizontal momentum and drift; furthermore, anticyclones are reinforced while cyclones are weakened. The joint action of both mechanisms and the possible consequences on vertical transport properties are also discussed.
Ground penetrating radar in temperate ice: englacial water inclusions as limiting factor for data interpretation
Authors: Ogier Christophe , van Manen Dirk-Jan , Maurer Hansruedi , Räss Ludovic , Hertrich Marian , Bauder Andreas , Farinotti Daniel
Published: September 2023

Ground penetrating radar (GPR) has been extensively used in glaciology to infer glacier's ice thickness, liquid water content, water drainage pathways, and other properties. The interpretation of such GPR data is not always straightforward and for temperate glaciers, the signal is often affected by strong scattering and attenuation. It has often been suggested that such effects originate from englacial water inclusions, since water and ice have a large contrast in their di-electric permittivity. To investigate such effects quantitatively, we perform an extensive numerical modeling study of GPR signals. By exploring how different liquid water contents (LWC) and water-inclusions size affect the GPR signal, we show that their effects are much larger than the potential presence of a wet snowpack or a heterogeneous distribution of ice permittivity. In particularly, we show that the presence of such water inclusions is a necessary and sufficient condition for reproducing the typical characteristics of GPR data acquired in the field. Further, we find that for 25 MHz GPR antennas, a bulk LWC

$\gtrsim$

0.2%, associated with decimeters-scale water inclusions already limits bedrock detectability for ice thicknesses

$\gtrsim 100$

m. Since these values are typical for Alpine glaciers, they clarify why the quality of GPR data is often poor in such environments.
More than just ambivalence: the perception of emotionally ambiguous words on the spaces of origin and activation indexed by behavioural and webcam-based eye-tracking correlates
Authors: Wielgopolan Adrianna , Imbir Kamil K.
Published: September 2023

When we think about emotional ambiguity, we usually think about the feeling of ambivalence. However, in a recently proposed model, ambiguity might also be present in different emotional spaces, such as origin (dimensions of automaticity and reflectiveness) and activation (arousal and subjective significance) as proposed in the basics of dual-process theories. In two experiments, we checked for behavioural and psychophysical differences in processing words of origin and activation ambiguities while completing an emotionality rating task. In Experiment 1, we assessed emotionality ratings and reaction times; in Experiment 2, we used a webcam-based eye-tracking measurement to assess the number and mean duration of fixations. We found significant effects for words differing in origin and activation: the emotionality ratings increased within the intensity of origin ambiguity but decreased within the intensity of activation ambiguity; more and longer fixations were registered for words of higher origin ambiguity; and gradually fewer and shorter fixations were registered within increases in activation ambiguity. We found that the ambiguities on spaces of origin and activation produced their own main effects, but they also factored significantly into the interaction, modifying each other’s results. Our study is the first to show specifics of the perception of ambiguous stimuli on spaces other than valence.
Effects of epicatechin on cardiovascular function in middle-aged diet-induced obese rat models of metabolic syndrome
Authors: Connolly Kylie , Batacan Romeo , Jackson Douglas , Fenning Andrew Stuart
Published: September 2023

The current study aimed to investigate the cardiovascular effects of epicatechin, a flavonoid found in green tea and cocoa, in attenuating complications associated with metabolic syndrome in diet-induced obese rats. Male Wistar-Kyoto (WKY) rats aged 16 weeks were fed either standard rat chow or given a high-fat-high-carbohydrate (HFHC) diet for 20 weeks. Epicatechin treatment (5 mg/kg/d) was administered to a subset of WKY rats commencing at week 8 of the 20 week HFHC feeding period. Body weights, food, water and energy intakes, blood pressure, heart rate and glucose tolerance were measured throughout the treatment period. Oxidative stress and inflammatory markers, lipid levels, cardiac collagen deposition, cardiac electrical function, aortic and mesenteric vessel reactivity were examined after the treatment. Twenty weeks of HFHC feeding in WKY rats resulted in the development of metabolic syndrome indicated by the presence of abdominal obesity, dyslipidaemia, glucose intolerance and increased blood pressure. Epicatechin treatment was found to enhance the oxidative stress status in HFHC groups through an increase in serum nitric oxide levels and a decrease in 8-isoprostane concentrations. Furthermore, WKY-HFHC rats displayed a decrease in IL-6 levels. The lipid profiles in HFHC groups showed improvement, with a decrease in LDL-cholesterol and TAG and an increase in HDL-cholesterol levels observed in WKY-HFHC rats. However, epicatechin was not effective in preventing weight gain, glucose intolerance or hypertension in HFHC fed rats. Overall, the results of this study suggest that epicatechin has the potential to improve the underlying mechanisms associated with metabolic syndrome in obese rats.
Development and evaluation of a predictive algorithm and telehealth intervention to reduce suicidal behavior among university students
Authors: Hasking Penelope A. , Robinson Kealagh , McEvoy Peter , Melvin Glenn , Bruffaerts Ronny , Boyes Mark E. , Auerbach Randy P. , Hendrie Delia , Nock Matthew K. , Preece David A. , Rees Clare , Kessler Ronald C.
Published: September 2023

Background

Suicidal behaviors are prevalent among college students; however, students remain reluctant to seek support. We developed a predictive algorithm to identify students at risk of suicidal behavior and used telehealth to reduce subsequent risk.

Methods

Data come from several waves of a prospective cohort study (2016–2022) of college students (n = 5454). All first-year students were invited to participate as volunteers. (Response rates range: 16.00–19.93%). A stepped-care approach was implemented: (i) all students received a comprehensive list of services; (ii) those reporting past 12-month suicidal ideation were directed to a safety planning application; (iii) those identified as high risk of suicidal behavior by the algorithm or reporting 12-month suicide attempt were contacted via telephone within 24-h of survey completion. Intervention focused on support/safety-planning, and referral to services for this high-risk group.

Results

5454 students ranging in age from 17–36 (s.d. = 5.346) participated; 65% female. The algorithm identified 77% of students reporting subsequent suicidal behavior in the top 15% of predicted probabilities (Sensitivity = 26.26 [95% CI 17.93–36.07]; Specificity = 97.46 [95% CI 96.21–98.38], PPV = 53.06 [95% CI 40.16–65.56]; AUC range: 0.895 [95% CIs 0.872–0.917] to 0.966 [95% CIs 0.939–0.994]). High-risk students in the Intervention Cohort showed a 41.7% reduction in probability of suicidal behavior at 12-month follow-up compared to high-risk students in the Control Cohort.

Conclusions

Predictive risk algorithms embedded into universal screening, coupled with telehealth intervention, offer significant potential as a suicide prevention approach for students.
Hospital-based health technology assessment of innovative medical devices: insights from a nationwide survey in France
Authors: Martin Tess , Guercio Alessandra , Besseau Hélène , Huot Laure , Guerre Pascale , Atfeh Jamal , Piazza Laurent , Pineau Judith , Sabatier Brigitte , Borget Isabelle , Martelli Nicolas
Published: September 2023

Objectives

To better understand the process of hospital acquisition of innovative medical devices (MDs) and the hospital-based health technology assessment (HB-HTA) pathways in France, an in-depth study based on a quantitative approach is needed. The aim of the present study was to assess through a national survey how HB-HTA is currently implemented in French hospitals and to identify its level of formalization.

Methods

A quantitative online survey was conducted among hospitals performing HB-HTA in France, with a focus on the acquisition of innovative MDs for individual use. The survey, conducted between March and June 2022, was developed by a scientific board composed of members of the French-speaking Society for HB-HTA.

Results

Sixty-seven out of 131 surveyed hospitals with HB-HTA activities responded, including 29 university hospitals, 24 nonprofit private hospitals, and 14 local hospitals. Sixty-one respondents (91 percent) reported the existence of a process dedicated to evaluating innovative MDs; of these, 16 declared that their hospitals had a formalized unit with HB-HTA activity. These units were more frequently found in larger hospitals with more than 500 inpatient beds (n = 16, p = 0.0160) and in university hospitals (n = 12, p = 0.0158). No hospital reported any collaboration with HAS, the French national HTA agency.

Conclusion

A diverse range of HB-HTA organizations with different structural levels exist in France for MD procurement linked to the category of hospitals. The study highlights the need for recognition of HB-HTA activity at the regulatory level in France and for direct collaboration between HTA activities performed at local and national levels.
Socio-environmental responsibility in Iranian universities: a multidimensional perspective
Authors: Kolahi Mahdi , AzimiSeginSara Rogaieh
Published: September 2023

Universities are expected to play a pivotal role in promoting environmental conservation goals, yet a comprehensive analysis of their actual contributions remains limited. This study delves into the perceptions of socio-environmental responsibility among faculty members within Iran’s top 13 universities. Using random cluster sampling, we collected 410 questionnaires from these institutions, evaluating socio-environmental responsibility through eight distinct variables. The outcomes unveil widespread deficiencies in responsibility across all universities, with 66% exhibiting low levels of engagement. Notably, Gorgan University of Agricultural Sciences and Natural Resources displays the lowest level, while Bu-Ali Sina University ranks highest. The research variables exhibit significant positive correlations, elucidating the interconnectedness of different aspects of socio-environmental responsibility. Furthermore, the study identifies a significant disparity in mean university socio-environmental responsibility concerning gender, although no significant relationships are found with factors such as professors’ academic rank, employment status or age. Sixteen codes are highlighted based on qualitative analysis. These findings underscore the urgency for universities to redefine their roles within the community and prioritize community empowerment, stakeholder engagement, capacity building and environmental education. By addressing these facets, universities can elevate their levels of socio-environmental responsibility and contribute more effectively to environmental conservation efforts.
Rising Coastal Groundwater as a Result of Sea‐Level Rise Will Influence Contaminated Coastal Sites and Underground Infrastructure
Authors: Hill K. , Hirschfeld D. , Lindquist C. , Cook F. , Warner S.
Published: September 2023

Sea‐level rise (SLR) will cause coastal groundwater to rise in many coastal urban environments. Inundation of contaminated soils by groundwater rise (GWR) will alter the physical, biological, and geochemical conditions that influence the fate and transport of existing contaminants. These transformed products can be more toxic and/or more mobile under future conditions driven by SLR and GWR. We reviewed the vulnerability of contaminated sites to GWR in a US national database and in a case comparison with the San Francisco Bay region to estimate the risk of rising groundwater to human and ecosystem health. The results show that 326 sites in the US Superfund program may be vulnerable to changes in groundwater depth or flow direction as a result of SLR, representing 18.1 million hectares of contaminated land. In the San Francisco Bay Area, we found that GWR is predicted to impact twice as much land area as inundation from SLR, and 5,282 additional state‐managed sites of contamination may be vulnerable to inundation from GWR in a 1.0 m SLR scenario. Increases of only a few centimeters of elevation can mobilize soil contaminants, alter flow directions in a heterogeneous urban environment with underground pipes and utility trenches, and result in new exposure pathways. Pumping for flood protection will elevate the saltwater interface, changing groundwater salinity and mobilizing metals in soil. Socially vulnerable communities are disproportionately exposed to this risk at both the national scale and in a regional comparison with the San Francisco Bay Area.
Impact of Giant Iceberg A68A on the Physical Conditions of the Surface South Atlantic, Derived Using Remote Sensing
Authors: Smith R. M. , Bigg G. R.
Published: September 2023

Giant icebergs release cold, fresh meltwater as they drift, perturbing the physical conditions of the surface ocean. This study uses satellite‐derived sea surface salinity and temperature measurements to explore the physical impact of supergiant iceberg A68A between September 2020 and June 2021. During A68A's drift through the Scotia Sea in austral spring, gradual but persistent edge‐wasting contributed to a freshening of several psu extending hundreds of kilometers ahead of the iceberg, whilst the cooling signal was more pronounced in the iceberg's wake. The magnitude of the physical perturbation intensified during A68A's breakup near South Georgia. Several large meltwater lenses surrounding the descendant icebergs displayed temperature anomalies of up to −4.5°C, whilst the salinity measurements indicated a surface (skin‐depth) anomaly regularly exceeding order −10 psu. The perturbations stretched at times >1,000 km and persisted for >2 months following A68A's melt in April 2021.
Quantitative Analysis of Paleomagnetic Sampling Strategies
Authors: Sapienza F. , Gallo L. C. , Zhang Y. , Vaes B. , Domeier M. , Swanson‐Hysell N. L.
Published: September 2023

Sampling strategies used in paleomagnetic studies play a crucial role in dictating the accuracy of our estimates of properties of the ancient geomagnetic field. However, there has been little quantitative analysis of optimal paleomagnetic sampling strategies and the community has instead defaulted to traditional practices that vary between laboratories. In this paper, we quantitatively evaluate the accuracy of alternative paleomagnetic sampling strategies through numerical experiments and an associated analytical framework. Our findings demonstrate a strong correspondence between the accuracy of an estimated paleopole position and the number of sites or independent readings of the time‐varying paleomagnetic field, whereas larger numbers of in‐site samples have a dwindling effect. This remains true even when a large proportion of the sample directions are spurious. This approach can be readily achieved in sedimentary sequences by distributing samples stratigraphically, considering each sample as an individual site. However, where the number of potential independent sites is inherently limited the collection of additional in‐site samples can improve the accuracy of the paleopole estimate (although with diminishing returns with increasing samples per site). Where an estimate of the magnitude of paleosecular variation is sought, multiple in‐site samples should be taken, but the optimal number is dependent on the expected fraction of outliers. The use of filters based on angular distance helps the accuracy of paleopole estimation, but leads to inaccurate estimates of paleosecular variation. We provide both analytical formulas and a series of interactive Jupyter notebooks allowing optimal sampling strategies to be developed from user‐informed expectations.
The cGAS-STING pathway-dependent sensing of mitochondrial DNA mediates ocular surface inflammation
Authors: Ouyang Weijie , Wang Shoubi , Yan Dan , Wu Jieli , Zhang Yunuo , Li Wei , Hu Jiaoyue , Liu Zuguo
Published: September 2023

The innate immune response is the main pathophysiological process of ocular surface diseases exposed to multiple environmental stresses. The epithelium is central to the innate immune response, but whether and how innate immunity is initiated by ocular epithelial cells in response to various environmental stresses in ocular surface diseases, such as dry eye, is still unclear. By utilizing two classic experimental dry eye models—a mouse ocular surface treated with benzalkonium chloride (BAC) and a mouse model with surgically removed extraorbital lachrymal glands, as well as dry eye patient samples—along with human corneal epithelial cells (HCE) exposed to hyperosmolarity, we have discovered a novel innate immune pathway in ocular surface epithelial cells. Under stress, mitochondrial DNA (mtDNA) was released into the cytoplasm through the mitochondrial permeability transition pore (mPTP) and further activated the cyclic GMP-AMP synthase (cGAS)—stimulator of interferon genes (STING) pathway, aggravating downstream inflammatory responses and ocular surface damage. Genetic deletion or pharmacological suppression of STING and inhibition of mtDNA release reduced inflammatory responses, whereas mtDNA transfection supported cytoplasmic mtDNA-induced inflammatory responses by activating the cGAS-STING pathway. Our study clarified the cGAS-STING pathway-dependent sensing of mitochondrial DNA-mediated ocular surface inflammation, which elucidated a new mechanism of ocular surface diseases in response to multiple environmental stresses.
Hepatic T-cell senescence and exhaustion are implicated in the progression of fatty liver disease in patients with type 2 diabetes and mouse model with nonalcoholic steatohepatitis
Authors: Sim Byeong Chang , Kang Yea Eun , You Sun Kyoung , Lee Seong Eun , Nga Ha Thi , Lee Ho Yeop , Nguyen Thi Linh , Moon Ji Sun , Tian Jingwen , Jang Hyo Ju , Lee Jeong Eun , Yi Hyon-Seung
Published: September 2023

Immunosenescence and exhaustion are involved in the development and progression of type 2 diabetes (T2D) and metabolic liver diseases, including fatty liver, fibrosis, and cirrhosis, in humans. However, the relationships of the senescence and exhaustion of T cells with insulin resistance-associated liver diseases remain incompletely understood. To better define the relationship of T2D with nonalcoholic fatty liver disease, 59 patients (mean age 58.7 ± 11.0 years; 47.5% male) with T2D were studied. To characterize their systemic immunophenotypes, peripheral blood mononuclear cells were analyzed using flow cytometry. Magnetic resonance imaging (MRI)-based proton density fat fraction and MRI-based elastography were performed using an open-bore, vertical-field 3.0 T scanner to quantify liver fat and fibrosis, respectively. The participants with insulin resistance had a significantly larger population of CD28 − CD57+ senescent T cells among the CD4+ and CD8 + T cells than those with lower Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) values. The abundances of senescent CD4+ and CD8 + T cells and the HOMA-IR positively correlated with the severity of liver fibrosis, assessed using MRI-based elastography. Interleukin 15 from hepatic monocytes was found to be an inducer of bystander activation of T cells, which is associated with progression of liver disease in the participants with T2D. Furthermore, high expression of genes related to senescence and exhaustion was identified in CD4+ and CD8 + T cells from the participants with nonalcoholic steatohepatitis or liver cirrhosis. Finally, we have also demonstrated that hepatic T-cell senescence and exhaustion are induced in a diet or chemical-induced mouse model with nonalcoholic steatohepatitis. In conclusion, we have shown that T-cell senescence is associated with insulin resistance and metabolic liver disease in patients with T2D.
The arginase 1/ornithine decarboxylase pathway suppresses HDAC3 to ameliorate the myeloid cell inflammatory response: implications for retinal ischemic injury
Authors: Shosha Esraa , Shahror Rami A. , Morris Carol A. , Xu Zhimin , Lucas Rudolf , McGee-Lawrence Meghan E. , Rusch Nancy J. , Caldwell Ruth B. , Fouda Abdelrahman Y.
Published: September 2023

The enzyme arginase 1 (A1) hydrolyzes the amino acid arginine to form L-ornithine and urea. Ornithine is further converted to polyamines by the ornithine decarboxylase (ODC) enzyme. We previously reported that deletion of myeloid A1 in mice exacerbates retinal damage after ischemia/reperfusion (IR) injury. Furthermore, treatment with A1 protects against retinal IR injury in wild-type mice. PEG-A1 also mitigates the exaggerated inflammatory response of A1 knockout (KO) macrophages in vitro. Here, we sought to identify the anti-inflammatory pathway that confers macrophage A1-mediated protection against retinal IR injury. Acute elevation of intraocular pressure was used to induce retinal IR injury in mice. A multiplex cytokine assay revealed a marked increase in the inflammatory cytokines interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) in the retina at day 5 after IR injury. In vitro, blocking the A1/ODC pathway augmented IL-1β and TNF-α production in stimulated macrophages. Furthermore, A1 treatment attenuated the stimulated macrophage metabolic switch to a pro-inflammatory glycolytic phenotype, whereas A1 deletion had the opposite effect. Screening for histone deacetylases (HDACs) which play a role in macrophage inflammatory response showed that A1 deletion or ODC inhibition increased the expression of HDAC3. We further showed the involvement of HDAC3 in the upregulation of TNF-α but not IL-1β in stimulated macrophages deficient in the A1/ODC pathway. Investigating HDAC3 KO macrophages showed a reduced inflammatory response and a less glycolytic phenotype upon stimulation. In vivo, HDAC3 co-localized with microglia/macrophages at day 2 after IR in WT retinas and was further increased in A1-deficient retinas. Collectively, our data provide initial evidence that A1 exerts its anti-inflammatory effect in macrophages via ODC-mediated suppression of HDAC3 and IL-1β. Collectively we propose that interventions that augment the A1/ODC pathway and inhibit HDAC3 may confer therapeutic benefits for the treatment of retinal ischemic diseases.
Creating speech zones with self-distributing acoustic swarms
Authors: Itani Malek , Chen Tuochao , Yoshioka Takuya , Gollakota Shyamnath
Published: September 2023

Imagine being in a crowded room with a cacophony of speakers and having the ability to focus on or remove speech from a specific 2D region. This would require understanding and manipulating an acoustic scene, isolating each speaker, and associating a 2D spatial context with each constituent speech. However, separating speech from a large number of concurrent speakers in a room into individual streams and identifying their precise 2D locations is challenging, even for the human brain. Here, we present the first acoustic swarm that demonstrates cooperative navigation with centimeter-resolution using sound, eliminating the need for cameras or external infrastructure. Our acoustic swarm forms a self-distributing wireless microphone array, which, along with our attention-based neural network framework, lets us separate and localize concurrent human speakers in the 2D space, enabling speech zones. Our evaluations showed that the acoustic swarm could localize and separate 3-5 concurrent speech sources in real-world unseen reverberant environments with median and 90-percentile 2D errors of 15 cm and 50 cm, respectively. Our system enables applications like mute zones (parts of the room where sounds are muted), active zones (regions where sounds are captured), multi-conversation separation and location-aware interaction.
The NCOR-HDAC3 co-repressive complex modulates the leukemogenic potential of the transcription factor ERG
Authors: Kugler Eitan , Madiwale Shreyas , Yong Darren , Thoms Julie A. I. , Birger Yehudit , Sykes David B. , Schmoellerl Johannes , Drakul Aneta , Priebe Valdemar , Yassin Muhammad , Aqaqe Nasma , Rein Avigail , Fishman Hila , Geron Ifat , Chen Chun-Wei , Raught Brian , Liu Qiao , Ogana Heather , Liedke Elisabeth , Bourquin Jean-Pierre , Zuber Johannes , Milyavsky Michael , Pimanda John , Privé Gilbert G. , Izraeli Shai
Published: September 2023

The ERG (ETS-related gene) transcription factor is linked to various types of cancer, including leukemia. However, the specific ERG domains and co-factors contributing to leukemogenesis are poorly understood. Drug targeting a transcription factor such as ERG is challenging. Our study reveals the critical role of a conserved amino acid, proline, at position 199, located at the 3’ end of the PNT (pointed) domain, in ERG’s ability to induce leukemia. P199 is necessary for ERG to promote self-renewal, prevent myeloid differentiation in hematopoietic progenitor cells, and initiate leukemia in mouse models. Here we show that P199 facilitates ERG’s interaction with the NCoR-HDAC3 co-repressor complex. Inhibiting HDAC3 reduces the growth of ERG-dependent leukemic and prostate cancer cells, indicating that the interaction between ERG and the NCoR-HDAC3 co-repressor complex is crucial for its oncogenic activity. Thus, targeting this interaction may offer a potential therapeutic intervention.
Reassessing chain tilt in the lamellar crystals of polyethylene
Authors: Kanomi Shusuke , Marubayashi Hironori , Miyata Tomohiro , Jinnai Hiroshi
Published: September 2023

Semicrystalline polymers are extensively used in various forms, including fibres, films, and bottles. They exhibit remarkable properties, e.g., mechanical and thermal, that are governed by hierarchical structures comprising 10–20-nm-thick lamellar crystals. In 1957, Keller deduced that long polyethylene (PE) chains fold to form thin single lamellar crystals, with the molecular chains perpendicular to the flat faces of the crystals (the chain-folding model). Chains inclining to the perpendicular orientation in single crystals have since been reported, along with their effects on the physical properties of PE. For bulk specimens, the chain tilt angle (φ) has been investigated only for model samples with well-annealed internal structures. However, for briefly annealed specimens, the φ values of lamellae and their origins are controversial owing to the disordered lamellar morphology and orientation. Herein, we report the direct determination of molecular-chain orientations in the lamellar crystals of high-density PE using a state-of-the-art electron-diffraction-based imaging technique with nanometre-scale positional resolution and provide compelling evidence for the existence of lamellar crystals with different inner-chain orientations. Clarifying the nanoscale variation in lamellar crystals in PE can allow precise tuning of properties and expedite resource-saving material design.
Signal-noise metrics for RNA binding protein identification reveal broad spectrum protein-RNA interaction frequencies and dynamics
Authors: Kristofich JohnCarlo , Nicchitta Christopher V.
Published: September 2023

Recent efforts towards the comprehensive identification of RNA-bound proteomes have revealed a large, surprisingly diverse family of candidate RNA-binding proteins (RBPs). Quantitative metrics for characterization and validation of protein-RNA interactions and their dynamic interactions have, however, proven analytically challenging and prone to error. Here we report a method termed LEAP-RBP (Liquid-Emulsion-Assisted-Purification of RNA-Bound Protein) for the selective, quantitative recovery of UV-crosslinked RNA-protein complexes. By virtue of its high specificity and yield, LEAP-RBP distinguishes RNA-bound and RNA-free protein levels and reveals common sources of experimental noise in RNA-centric RBP enrichment methods. We introduce strategies for accurate RBP identification and signal-based metrics for quantifying protein-RNA complex enrichment, relative RNA occupancy, and method specificity. In this work, the utility of our approach is validated by comprehensive identification of RBPs whose association with mRNA is modulated in response to global mRNA translation state changes and through in-depth benchmark comparisons with current methodologies.
Accelerated discovery of multi-elemental reverse water-gas shift catalysts using extrapolative machine learning approach
Authors: Wang Gang , Mine Shinya , Chen Duotian , Jing Yuan , Ting Kah Wei , Yamaguchi Taichi , Takao Motoshi , Maeno Zen , Takigawa Ichigaku , Matsushita Koichi , Shimizu Ken-ichi , Toyao Takashi
Published: September 2023

Designing novel catalysts is key to solving many energy and environmental challenges. Despite the promise that data science approaches, including machine learning (ML), can accelerate the development of catalysts, truly novel catalysts have rarely been discovered through ML approaches because of one of its most common limitations and criticisms—the assumed inability to extrapolate and identify extraordinary materials. Herein, we demonstrate an extrapolative ML approach to develop new multi-elemental reverse water-gas shift catalysts. Using 45 catalysts as the initial data points and performing 44 cycles of the closed loop discovery system (ML prediction + experiment), we experimentally tested a total of 300 catalysts and identified more than 100 catalysts with superior activity compared to those of the previously reported high-performance catalysts. The composition of the optimal catalyst discovered was Pt(3)/Rb(1)-Ba(1)-Mo(0.6)-Nb(0.2)/TiO2. Notably, niobium (Nb) was not included in the original dataset, and the catalyst composition identified was not predictable even by human experts.
mRNA vaccine quality analysis using RNA sequencing
Authors: Gunter Helen M. , Idrisoglu Senel , Singh Swati , Han Dae Jong , Ariens Emily , Peters Jonathan R. , Wong Ted , Cheetham Seth W. , Xu Jun , Rai Subash Kumar , Feldman Robert , Herbert Andy , Marcellin Esteban , Tropee Romain , Munro Trent , Mercer Tim R.
Published: September 2023

The success of mRNA vaccines has been realised, in part, by advances in manufacturing that enabled billions of doses to be produced at sufficient quality and safety. However, mRNA vaccines must be rigorously analysed to measure their integrity and detect contaminants that reduce their effectiveness and induce side-effects. Currently, mRNA vaccines and therapies are analysed using a range of time-consuming and costly methods. Here we describe a streamlined method to analyse mRNA vaccines and therapies using long-read nanopore sequencing. Compared to other industry-standard techniques, VAX-seq can comprehensively measure key mRNA vaccine quality attributes, including sequence, length, integrity, and purity. We also show how direct RNA sequencing can analyse mRNA chemistry, including the detection of nucleoside modifications. To support this approach, we provide supporting software to automatically report on mRNA and plasmid template quality and integrity. Given these advantages, we anticipate that RNA sequencing methods, such as VAX-seq, will become central to the development and manufacture of mRNA drugs.
Strained few-layer MoS2 with atomic copper and selectively exposed in-plane sulfur vacancies for CO2 hydrogenation to methanol
Authors: Zhou Shenghui , Ma Wenrui , Anjum Uzma , Kosari Mohammadreza , Xi Shibo , Kozlov Sergey M. , Zeng Hua Chun
Published: September 2023

In-plane sulfur vacancies (Sv) in molybdenum disulfide (MoS2) were newly unveiled for CO2 hydrogenation to methanol, whereas edge Sv were found to facilitate methane formation. Thus, selective exposure and activation of basal plane is crucial for methanol synthesis. Here, we report a mesoporous silica-encapsulated MoS2 catalysts with fullerene-like structure and atomic copper (Cu/MoS2@SiO2). The main approach is based on a physically constrained topologic conversion of molybdenum dioxide (MoO2) to MoS2 within silica. The spherical curvature enables the generation of strain and Sv in inert basal plane. More importantly, fullerene-like structure of few-layer MoS2 can selectively expose in-plane Sv and reduce the exposure of edge Sv. After promotion by atomic copper, the resultant Cu/MoS2@SiO2 exhibits stable specific methanol yield of 6.11 molMeOH molMo–1 h–1 with methanol selectivity of 72.5% at 260 °C, much superior to its counterparts lacking the fullerene-like structure and copper decoration. The reaction mechanism and promoting role of copper are investigated by in-situ DRIFTS and in-situ XAS. Theoretical calculations demonstrate that the compressive strain facilitates Sv formation and CO2 hydrogenation, while tensile strain accelerates the regeneration of active sites, rationalizing the critical role of strain.