bluuebunny/crossref_metadata_2025 huggingface dataset:
A mathematical theory of relational generalization in transitive inference
Authors: Lippl Samuel , Kay Kenneth , Jensen Greg , Ferrera Vincent P. , Abbott L.F.
Published: August 2023

Humans and animals routinely infer relations between different items or events and generalize these relations to novel combinations of items. This allows them to respond appropriately to radically novel circumstances and is fundamental to advanced cognition. However, how learning systems (including the brain) can implement the necessary inductive biases has been unclear. Here we investigated transitive inference (TI), a classic relational task paradigm in which subjects must learn a relation (A>BandB>C) and generalize it to new combinations of items (A>C). Through mathematical analysis, we found that a broad range of biologically relevant learning models (e.g. gradient flow or ridge regression) perform TI successfully and recapitulate signature behavioral patterns long observed in living subjects. First, we found that models with item-wise additive representations automatically encode transitive relations. Second, for more general representations, a single scalar “conjunctivity factor” determines model behavior on TI and, further, the principle of norm minimization (a standard statistical inductive bias) enables models with fixed, partly conjunctive representations to generalize transitively. Finally, neural networks in the “rich regime,” which enables representation learning and has been found to improve generalization, unexpectedly show poor generalization and anomalous behavior. We find that such networks implement a form of norm minimization (over hidden weights) that yields a local encoding mechanism lacking transitivity. Our findings show how minimal statistical learning principles give rise to a classical relational inductive bias (transitivity), explain empirically observed behaviors, and establish a formal approach to understanding the neural basis of relational abstraction.
A chromosome-scale assembly for ‘d’Anjou’ pear
Authors: Yocca Alan , Akinyuwa Mary , Bailey Nick , Cliver Brannan , Estes Harrison , Guillemette Abigail , Hasannin Omar , Hutchison Jennifer , Jenkins Wren , Kaur Ishveen , Khanna Risheek Rahul , Loftin Madelene , Lopes Lauren , Moore-Pollard Erika , Olofintila Oluwakemisola , Oyebode Gideon Oluwaseye , Patel Jinesh , Thapa Parbati , Waldinger Martin , Zhang Jie , Zhang Qiong , Goertzen Leslie , Carey Sarah B. , Hargarten Heidi , Mattheis James , Zhang Huiting , Jones Teresa , Boston LoriBeth , Grimwood Jane , Ficklin Stephen , Honaas Loren , Harkess Alex
Published: August 2023

Cultivated pear consists of severalPyrusspecies withP. communis(European pear) representing a large fraction of worldwide production. As a relatively recently domesticated crop and perennial tree, pear can benefit from genome-assisted breeding. Additionally, comparative genomics within Rosaceae promises greater understanding of evolution within this economically important family. Here, we generate a fully-phased chromosome-scale genome assembly ofP. communiscv. ‘d’Anjou’. Using PacBio HiFi and Dovetail Omni-C reads, the genome is resolved into the expected 17 chromosomes, with each haplotype totalling nearly 540 Megabases and a contig N50 of nearly 14 Mb. Both haplotypes are highly syntenic to each other, and to theMalus domestica‘Honeycrisp’ apple genome. Nearly 45,000 genes were annotated in each haplotype, over 90% of which have direct RNA-seq expression evidence. We detect signatures of the known whole-genome duplication shared between apple and pear, and we estimate 57% of d’Anjou genes are retained in duplicate derived from this event. This genome highlights the value of generating phased diploid assemblies for recovering the full allelic complement in highly heterozygous crop species.
C5aR1 antagonism suppresses inflammatory glial gene expression and alters cellular signaling in an aggressive Alzheimer’s model
Authors: Schartz Nicole D. , Liang Heidi Y. , Carvalho Klebea , Chu Shu-Hui , Mendoza-Arvilla Adrian , Petrisko Tiffany J. , Gomez-Arboledas Angela , Mortazavi Ali , Tenner Andrea J.
Published: August 2023

Alzheimer’s disease (AD) is the leading cause of dementia in older adults, and the need for effective, sustainable therapeutic targets is imperative. Pharmacologic inhibition of C5aR1 reduces plaque load, gliosis and memory deficits in animal models. However, the cellular basis underlying this neuroprotection and which processes were the consequence of amyloid reduction vs alteration of the response to amyloid were unclear. In the Arctic model, the C5aR1 antagonist PMX205 did not reduce plaque load, but deficits in short-term memory in female mice were prevented. Hippocampal single cell and single nucleus RNA-seq clusters revealed C5aR1 dependent and independent gene expression and cell-cell communication. Microglial clusters containing neurotoxic disease-associated microglial genes were robustly upregulated in Arctic mice and drastically reduced with PMX205 treatment, while genes in microglia clusters that were overrepresented in the Arctic-PMX205 vs Arctic group were associated with synapse organization and transmission and learning. PMX205 treatment also reduced some A-1 astrocyte genes. In spite of changes in transcript levels, overall protein levels of some reactive glial markers were relatively unchanged by C5aR1 antagonism, as were clusters associated with protective responses to injury. C5aR1 inhibition promoted signaling pathways associated with cell growth and repair, such as TGFβ and FGF, in Arctic mice, while suppressing inflammatory pathways including PROS, Pecam1, and EPHA. In conclusion, pharmacologic C5aR1 inhibition prevents cognitive loss, limits microglial polarization to a detrimental inflammatory state and permits neuroprotective responses, as well as leaving protective functions of complement intact, making C5aR1 antagonism an attractive therapeutic strategy for individuals with AD.

One Sentence Summary

Pharmacologic inhibition of C5aR1 suppresses disease-enhancing processes and promotes disease mitigating pathways in an aggressive model of Alzheimer’s disease.
Prebiotic proanthocyanidins inhibit bile reflux-induced esophageal adenocarcinoma through reshaping the gut microbiome and esophageal metabolome
Authors: Weh Katherine M. , Howard Connor L. , Zhang Yun , Tripp Bridget A. , Clarke Jennifer L. , Howell Amy B. , Rubenstein Joel H. , Abrams Julian A. , Westerhoff Maria , Kresty Laura A.
Published: August 2023

The gut and local esophageal microbiome progressively shift from healthy commensal bacteria to inflammatory-linked pathogenic bacteria in patients with gastroesophageal reflux disease, Barrett’s esophagus and esophageal adenocarcinoma (EAC). However, mechanisms by which microbial communities and metabolites contribute to reflux-driven EAC remain incompletely understood and challenging to target. Herein, we utilized a rat reflux-induced EAC model to investigate targeting the gut microbiome-esophageal metabolome axis with cranberry proanthocyanidins (C-PAC) to inhibit EAC progression. Sprague Dawley rats, with or without reflux-induction received water or C-PACad libitum(700 µg/rat/day) for 25 or 40 weeks. C-PAC exerted prebiotic activity abrogating reflux-induced dysbiosis, and mitigating bile acid metabolism and transport, culminating in significant inhibition of EAC through TLR/NF-κB/P53 signaling cascades. At the species level, C-PAC mitigated reflux-induced pathogenic bacteria(Clostridium perfringens, Escherichia coli,andProteus mirabilis).C-PAC specifically reversed reflux-induced bacterial, inflammatory and immune-implicated proteins and genes includingCcl4, Cd14, Crp, Cxcl1, Il6, Il1β, Lbp, Lcn2, Myd88, Nfkb1, Tlr2 and Tlr4aligning with changes in human EAC progression, as confirmed through public databases. C-PAC is a safe promising dietary constituent that may be utilized alone or potentially as an adjuvant to current therapies to prevent EAC progression through ameliorating reflux-induced dysbiosis, inflammation and cellular damage.
Rise in frequency oflasRmutantPseudomonas aeruginosaamong keratitis isolates between 1993 and 2021
Authors: Shanks Robert M. Q. , Atta Sarah , Stella Nicholas A. , Sundar-Raj Chollapadi V. , Romanowski John E. , Grewel Arman S. , Shanks Hazel Q. , Mumper Sonya M. , Dhaliwal Deepinder K. , Mammen Alex , Callaghan Jake D. , Calvario Rachel C. , Romanowski Eric G. , Kowalski Regis P. , Zegans Michael E. , Jhanji Vishal
Published: August 2023

Pseudomonas aeruginosacauses severe vision threatening keratitis. LasR is a transcription factor that regulates virulence associated genes in response to the quorum sensing molecule N-3-oxo-dodecanoyl-L-homoserine lactone.P. aeruginosaisolates withlasRmutations are characterized by an iridescent high sheen phenotype caused by a build-up of 2-heptyl-4-quinolone. A previous study indicated a high proportion (22 out of 101) ofP. aeruginosakeratitis isolates from India between 2010 and 2016 were sheen positive and had mutations in thelasRgene, and the sheen phenotype correlated with worse clinical outcomes for patients. In this study, a longitudinal collection ofP. aeruginosakeratitis isolates from Eastern North America were screened forlasRmutations by the sheen phenotype and sequencing of thelasRgene. A significant increase in the frequency of isolates with the sheen positive phenotype was observed in isolates between 1993 and 2021. Extracellular protease activity was lower among the sheen positive isolates and a definedlasRmutant. ClonedlasRalleles from the sheen positive isolates were loss of function or dominant negative and differed in sequence from previously reported ocularlasRmutant alleles. Insertion elements were present in a subset of independent isolates and may represent an endemic source from some of the isolates. Retrospective analysis of patient information suggested significantly better visual outcomes for patients with infected by sheen positive isolates. Together, these results indicate an increasing trend towardslasRmutations among keratitis isolates at a tertiary eye care hospital in the United States.
Insight into the emerging insect to human pathogenPhotorhabdusrevealing geographic differences in immune cell tropism
Authors: Addison Max L. , Hapeshi Alexia , Carter Elena , Wong Zi Xin , Connally John E. , Waterfield Nicholas R.
Published: August 2023

Photorhabdus asymbioticais a species of the insect pathogenicPhotorhabdusgenus that has been isolated as an etiological agent in human infections. Since then, multiple isolates have been identified worldwide, however actual clinical infections have so far only been identified in North America, Australia and Nepal. Previous research on the clinical isolates had shown that the strains differed in their behaviour when infecting cultured human cells, based on the geographical site of isolation. In this study we investigate the differences between the pathogenic activities ofP. asymbioticaisolates from different geographic locations. We present findings from the clinical isolates from Australia (Kingscliff) and North America (ATCC43949), and soil borne nematode isolates from Thailand (PB68) and Northern Europe non-clinicalP. asymbioticagenospecies HIT and JUN. We also show the first findings from a new clinical isolate ofP. luminescens(Texas), the first non-asymbioticaspecies to cause a human infection, confirming its ability to infect and survive inside human immune cells. Infection assays were done using both cultured cell lines (THP-1, CHO and HEK cells) and also primary immune cells, Peripheral Blood Mononuclear cells (PBMCs) isolated from human blood. Here for the first time, we show howP. asymbiotica, selectively infects certain immune cells while avoiding others, and that infectivity varies depending on growth temperature. We also show that the infected immune cells vary depending on the geographical location a strain is isolated from, and that the European HIT and JUN strains lack the ability to survive within mammalian cells in tissue culture.
Complex Polyploids: Origins, Genomic Composition, and Role of Introgressed Alleles
Authors: Leal J. Luis , Milesi Pascal , Hodková Eva , Zhou Qiujie , James Jennifer , Eklund D. Magnus , Pyhäjärvi Tanja , Salojärvi Jarkko , Lascoux Martin
Published: August 2023

Abstract

Introgression allows polyploid species to acquire new genomic content from diploid progenitors or from other unrelated diploid or polyploid lineages, contributing to genetic diversity and facilitating adaptive allele discovery. In some cases, high levels of introgression elicit the replacement of large numbers of alleles inherited from the polyploid’s ancestral species, profoundly reshaping the polyploid’s genomic composition. In such complex polyploids it is often difficult to determine which taxa were the progenitor species and which taxa provided additional introgressive blocks through subsequent hybridization. Here, we use population-level genomic data to reconstruct the phylogenetic history ofBetula pubescens(downy birch), a tetraploid species often assumed to be of allopolyploid origin and which is known to hybridize with at least four other birch species. This was achieved by modeling of polyploidization and introgression events under the multispecies coalescent and then using an approximate Bayesian computation (ABC) rejection algorithm to evaluate and compare competing polyploidization models. We provide evidence thatB. pubescensis the outcome of an autoploid genome doubling event in the common ancestor ofB. pendulaand its extant sister species,B. platyphylla, that took place approximately 178,000-188,000 generations ago. Extensive hybridization withB. pendula,B. nana, andB. humilisfollowed in the aftermath of autopolyploidization, with the relative contribution of each of these species to theB. pubescensgenome varying markedly across the species’ range. Functional analysis ofB. pubescensloci containing alleles introgressed fromB. nanaidentified multiple genes involved in climate adaptation, while loci containing alleles derived fromB. humilisrevealed several genes involved in the regulation of meiotic stability and pollen viability in plant species.
Inference of gene regulatory networks using time-series single-cell RNA-seq data with CRISPR perturbations
Authors: Ishikawa Masato , Sugino Seiichi , Masuda Yoshie , Tarumoto Yusuke , Seto Yusuke , Taniyama Nobuko , Wagai Fumi , Yamauchi Yuhei , Kojima Yasuhiro , Kiryu Hisanori , Yusa Kosuke , Eiraku Mototsugu , Mochizuki Atsushi
Published: August 2023

Single-cell RNA-seq analysis coupled with CRISPR-based perturbation (scCRISPR) has enabled the inference of gene regulatory networks (GRNs) with causal relationships. However, a snapshot of scCRISPR data may not lead to an accurate inference, since a gene knockout can influence multi-layered downstream over time. Here, we developed RENGE, a new computational method that infers GRNs using a time-series scCRISPR dataset. RENGE models the propagation process of the effects elicited by a gene knockout on its GRN. It can distinguish between direct and indirect regulations, which allows for the inference of regulations by genes that are not knocked out. RENGE therefore outperforms current methods in the accuracy of inferring GRNs. When used on a dataset we derived from human-induced pluripotent stem cells, RENGE yielded a GRN consistent with multiple databases and literature. Accurate inference of GRNs by RENGE would enable the identification of key factors for various biological systems.
Advancing Protein-DNA Binding Site Prediction: Integrating Sequence Models and Machine Learning Classifiers
Authors: Murad Taslim , Chourasia Prakash , Ali Sarwan , Patterson Murray
Published: August 2023

Predicting protein-DNA binding sites is a challenging computational problem in the field of bioinformatics. Identifying the specific residues where proteins bind to DNA is of paramount importance, as it enables the modeling of their interactions and facilitates downstream studies. Nevertheless, the development of accurate and efficient computational methods for this task remains a persistent challenge. Accurate prediction of protein-DNA binding sites has far-reaching implications for understanding molecular mechanisms, disease processes, drug discovery, and synthetic biology applications. It helps bridge the gap between genomics and functional biology, enabling researchers to uncover the intricacies of cellular processes and advance our knowledge of the biological world. The method used to predict DNA binding residues in this study is a potent combination of conventional bioinformatics tools, protein language models, and cutting-edge machine learning and deep learning classifiers. On a dataset of protein-DNA binding sites, our model is meticulously trained, and it is then rigorously examined using several experiments. As indicated by higher predictive behavior with AUC values on two benchmark datasets, the results show superior performance when compared to existing models. The suggested model has a strong capacity for generalization and shows specificity for DNA-binding sites. We further demonstrated the adaptability of our model as a universal framework for binding site prediction by training it on a variety of protein-ligand binding site datasets. In conclusion, our innovative approach for predicting protein-DNA binding residues holds great promise in advancing our understanding of molecular interactions, thus paving the way for several groundbreaking applications in the field of molecular biology and genetics. Our approach demonstrated efficacy and versatility underscore its potential for driving transformative discoveries in biomolecular research.
Knowledge-sharing attitude and behavior of civil servants: motivations behind rewards
Authors: Lam Kristy , Kong Elaine W.S. , Chiu Dickson K.W. , Ho Kevin K.W.
Published: August 2023

Purpose

To a large extent, knowledge in government workplaces resides within the hierarchy as it provides unique services to the public. Governments should preserve and pass on valuable and irreplaceable knowledge in providing their services through learning by sharing. Yet, sharing requires time and effort. This study examines the motivations of civil servants to share knowledge and their knowledge-sharing behaviors.

Design/methodology/approach

The authors conducted an online survey to collect quantitative data from civil servants in the Hong Kong Government and obtained 104 useable responses to test the eight hypotheses comprising six constructs by structural equation modeling to explore the participants' knowledge-sharing behaviors.

Findings

Results indicated that (1) expected contribution was the primary source of motivation behind knowledge sharing; (2) participants engaged more frequently in informal than formal knowledge-sharing activities; and (3) there was a dire need for knowledge sharing focusing on explicit knowledge of work procedures.

Originality/value

The research focuses on motivational factors for knowledge sharing. Despite abundant literature about knowledge sharing in public or governmental organizations, scant studies focus on the motivations behind why expected rewards and expected associations have less significant impacts on the attitude toward knowledge sharing than expected contribution.
The system for distributed energy resources testing according to the IEEE 1547-2018 standard
Authors: Dimitrijević Marko A. , Petronijević Milutin
Published: August 2023

Purpose

This paper aims to propose a new approach to testing distributed energy resources (DERs) in compliance with the IEEE 1547-2018 standard and describes a new, integrated testing and validation system.

Design/methodology/approach

The system is built on the virtual instrumentation paradigm, using acquisition modules to measure physical quantities, while signal processing, including intensive calculations of required parameters, data processing, manipulation and reporting are performed on a computing device.

Findings

Intensive laboratory measurements were performed on a laboratory prototype of a microgrid that emulates DERs. The results obtained using the system described were compared with the measurements obtained by the reference instruments. As all the results match, the usability of the system was verified.

Practical implications

This approach to the realization of the testing and validation system has obvious advantages compared to the classical instruments and provides significant flexibility in multiple aspects. First, the system described integrates all the functions of different instruments into one measuring system, making the entire testing and validation process significantly cheaper and faster. Second, the implementation of the system is possible on different computing platforms depending on specific needs. Third, the software implementation of the system functions enables simple upgrading and the introduction of new functions or changes to existing ones according to changes in the standard. Finally, the system described is designed to automatically provide reports on compliance with the standard.

Originality/value

This paper emphasizes the advantages of the proposed approach over classical testing. The value of the paper is reflected in the applicability and practical implications of the proposed and described hardware and software technical solutions.
Taming wicked problems through international business policy: recommendations for addressing modern slavery
Authors: Rašković Matevž (Matt)
Published: August 2023

Purpose

The paper frames modern slavery as a global wicked problem and aims to provide a set of international business (IB) policy recommendations for taming it. The outlined approach can also guide IB policymaking to address other kinds of wicked problems.

Design/methodology/approach

This is a conceptual paper that reviews existing literature on wicked problems and integrates it with an IB policy double helix framework. The paper focuseses on the role multinational enterprises (MNEs) play in moderl slavery globally, either through global value chains or within global factory modes of operation.

Findings

As a global wicked problem, modern slavery will never be solved, but it can be re-solved time and time over. Understanding the social reproduction of modern slavery can help shift the focus from labor governance and a narrow supply chain focus toward the role of transnational governance and the need to address institutional, market and organizational failures.

Originality/value

The paper contributes to the gap in an overarching theory of modern slavery and systematically applies the concept of wicked problems and wickedness theory to modern slavery. Drawing on an IB policy double helix framework, the paper addresses the governance nexus between modern slavery, IB and policymaking which can in turn advance IB policy research and theory.
ESG and share price volatility in energy sector firms: does the development phase of countries matter?
Authors: Singh Kuldeep , Jaiwani Megha
Published: August 2023

Purpose

The global energy sector draws significant stakeholder attention due to never-ending controversies surrounding its environmental impacts. Investors’ response to such controversies causes direct financial implications for these firms. Furthermore, environmental, social and governance (ESG) sensitivity, which is likely to safeguard the energy sector firms from such controversies, is itself conditional to the development stage of a country and its regulatory environment. Therefore, this study aims to investigate if the influence of ESG on the share price volatility (SPV) of energy sector firms is subject to the development stage of the countries.

Design/methodology/approach

The study investigates nine years of panel data of 93 global energy sector firms from developing and developed nations. Using dynamic two-way fixed effects estimation and computing robust standard errors to obtain the econometric results.

Findings

The main finding reveals that the impact of ESG on SPV is, indeed, subject to the development stage of the nations. Similar results are observed for the effects of the social dimension of ESG on SPV. While ESG impacts the SPV negatively for firms in developing economies, the impact is the opposite for firms in developed nations. In other words, strong ESG propositions induce share price stability for developing countries while destabilizing the firms in developed nations.

Practical implications

The policymakers should further streamline the regulations and policies related to ESG adoption and adherence. In practice, the energy sectors should streamline their operations. Firm managers, especially in the energy sector, should devise strategies with ESG as an essential component to safeguard their firms against environmental and market volatility and adversatives. The firms in developing nations should further strengthen their social dimension of ESG to foster social equity and harmony.

Originality/value

The study contributes through its niche investigations on the energy sector, which is very important for the world economy. The study is relevant in the current scenario when the world faces a severe energy crisis due to global supply chain issues.
Enhancing supply chain resilience in SMEs: a deep Learning-based approach to managing Covid-19 disruption risks
Authors: Sun Kai-Xiang , Ooi Keng-Boon , Tan Garry Wei-Han , Lee Voon-Hsien
Published: August 2023

Purpose

This research examines the relationships between the components of supply chain integration (SCI) (i.e. internal integration (INI), customer integration (CI) and supplier integration (SI)), supply chain risk management (SCRM) and supply chain resilience (SCRE), with disruption impact (DI) as the moderator, among small and medium-sized enterprises (SMEs).

Design/methodology/approach

271 useable data were collected from Chinese SMEs to test the research model with two statistical approaches of PLS-SEM and ANN analysis.

Findings

Results show that SCI (i.e. INI, CI and SI) positively affects SCRM, and subsequently affects SCRE. Moreover, SCRM has also been found to fully mediate the relationship between INI, CI and SI with SCRE. Additionally, DI was also found to moderate the relationship between SCRM and SCRE.

Research limitations/implications

This study expands the supply chain management-related knowledge by empirically validating the mediating role of SCRM between the elements of SCI and SCRE, as well as empirically identifying DI as the moderator between SCRM and SCRE.

Practical implications

The findings offer valuable understanding that can guide SME managers, owners and stakeholders in developing strategies for integrating with customers, suppliers and internal departments, as well as implementing SCRM practices to enhance SCRE performance.

Originality/value

The research expands the existing literature on the elements of SCI and SCRM in maintaining SCRE from an Asian developing country's perspective.
The state of embedded librarianship in the university research processes in selected African academic libraries
Authors: Leonard Anna , Chigwada Josiline , Mushi Gilbert
Published: August 2023

Purpose

This study aims to examine the state of embedded librarianship in African academic libraries by exploring the extent of librarian embedment in research processes in selected academic libraries in Africa.

Design/methodology/approach

A survey was conducted to collect data using an online questionnaire. The study population was comprised of librarians who directly support researchers throughout the research process in the scholarly communication and information services sections. Purposive sampling was used to select librarians, and 63 responses were received from the target of 100. The collected data were analysed using the statistical package for the social sciences (SPSS) software, and content analysis was used to analyse open-ended questions.

Findings

The study results showed that the extent and nature of librarians' embeddedness in the research process vary across different university contexts in Africa. Challenges and areas of research skill gaps among librarians were identified, and propositions to address the research skill gaps were provided.

Practical implications

The study findings can be used as a framework for libraries to embed librarians in the research process. The study made recommendations with practical implications for library practitioners in academia, and institutions offering library and information science education, and the library management responsible for the research process.

Originality/value

A study brings a novel perspective by examining the state of embedded librarianship in the African context. Its contribution generates knowledge and insights that inform the development of effective embedded librarianship practices in African academic libraries to enhance research support services and advancement of scholarly research in the region.
Determination of the elastoplastic properties of Ti-6Al-4V alloy manufactured by electron beam melting
Authors: Yılmaz Fatih , Gürses Ercan , Şahin Melin
Published: August 2023

Purpose

This study aims to evaluate and assess the elastoplastic properties of Ti-6Al-4V alloy manufactured by Arcam Q20 Plus electron beam melting (EBM) machine by a tensile test campaign and micro computerized tomography (microCT) imaging.

Design/methodology/approach

ASTM E8 tensile test specimens are designed and manufactured by EBM at an Arcam Q20 Plus machine. Surface quality is improved by machining to discard the effect of surface roughness. After surface machining, hot isostatic pressing (HIP) post-treatment is applied to half of the specimens to remove unsolicited internal defects. ASTM E8 tensile test campaign is carried out simultaneously with digital image correlation to acquire strain data for each sample. Finally, build direction and HIP post-treatment dependencies of elastoplastic properties are analyzed by F-test and t-test statistical analyses methods.

Findings

Modulus of elasticity presents isotropic behavior for each build direction according to F-test and t-test analysis. Yield and ultimate strengths vary according to build direction and post-treatment. Stiffness and strength properties are superior to conventional Ti-6Al-4V material; however, ductility turns out to be poor for aerospace structures compared to conventional Ti-6Al-4V alloy. In addition, micro CT images show that support structure leads to dense internal defects and pores at applied surfaces. However, HIP post-treatment diminishes those internal defects and pores thoroughly.

Originality/value

As a novel scientific contribution, this study investigates the effects of three orthogonal build directions on elastoplastic properties, while many studies focus on only two-build directions. Evaluation of Poisson’s ratio is the other originality of this study. Furthermore, another finding through micro CT imaging is that temporary support structures result in intense defects closer to applied surfaces; hence high-stress regions of structures should be avoided to use support structures.
Flexible and multi-material intrinsically conductive polymer devices fabricated via DLP and DIW additive manufacturing techniques
Authors: Engel Kyle , Kilmartin Paul Andrew , Diegel Olaf
Published: August 2023

Purpose

The purpose of this study is to explore the synthesis of novel conductive photo-resins to produce flexible conducting composites for use in additive manufacturing. By using direct ink writing (DIW) additive manufacturing, this study aims to explore the fabrication of multimaterial devices with conductive and insulating components. Using digital light processing (DLP) additive manufacturing, this study aims to fabricate detailed objects with higher resolution than material extrusion 3D printing systems.

Design/methodology/approach

In this paper, several photocurable conducting resins were prepared for DIW and DLP additive manufacturing. These resins were then cured using 405 nm near UV light to create intrinsically conductive polymer (ICP) composites. The electrochemical properties of these composites were analysed, and the effect of co-monomer choice and crosslinking density was determined. These results determined a suitable resin for subsequent additive manufacture using DIW and DLP. These 3D printing techniques were used to develop flexible conducting devices of submillimetre resolution that were fabricated with unmodified, commercially available 3D printers.

Findings

Cyclic voltammetry and volume conductivity analysis of the conducting resins determined the most conductive resin formula for 3D printing. Conductive devices were fabricated using the two 3D printing techniques. A multimaterial soft conducting device was fabricated using DIW, and each conducting component was insulated from its neighbours. DLP was used to fabricate a soft conducting device with good XY resolution with a minimum feature size of 0.2 mm. All devices were prepared in unmodified commercially available 3D printers.

Practical implications

These findings have value in the development of soft robotics, artificial muscles and wearable sensors. In addition, this work highlights techniques for DIW and DLP additive manufacturing.

Originality/value

Several original conducting resin formulae were developed for use in two 3D printing systems. The resulting 3D-printed composites are soft and flexible while maintaining their conductive properties. These findings are of value to both polymer chemists and to the field of additive manufacturing.
Evaluation of right atrium structure and function in a rat model of monocrotaline‐induced pulmonary hypertension: Exploring the possible antiarrhythmic properties of amiodarone
Authors: Teixeira‐Fonseca Jorge Lucas , Joviano‐Santos Julliane Vasconcelos , da Silva Alcântara Fabiana , de Lima Conceição Michael Ramon , Leal‐Silva Polyana , Roman‐Campos Danilo
Published: August 2023

Atrial arrhythmias (AA) are common in pulmonary hypertension (PH) and are closely associated with poor clinical outcomes. One of the most studied models to investigate PH is the rat model of monocrotaline (MCT) induced PH (MCT‐PH). To date, little is known about right atrium (RA) function in the MCT‐PH model and the propensity of RA to develop arrhythmias. Therefore, the aim of the study was to evaluate the function of the RA of control (CTRL) and MCT treated rats, and the ability of amiodarone, a classical antiarrhythmic, to prevent the occurrence of AA in the RA in MCT‐PH rats. RA function was studied in MCT‐PH rats 20 days after a single subcutaneous injection of MCT 50 mg/kg. The histological results indicated the presence of RA and right ventricular hypertrophy. Surface electrocardiogram demonstrated increased P wave duration, PR wave duration and QT interval in MCT rats. RA from MCT rats were more susceptible to develop ex vivo burst pacing arrhythmias when compared to CTRL. Intriguingly, amiodarone in clinical relevant concentration was not able to prevent the occurrence arrhythmias in RA from MCT‐PH animals. Hence, we conclude that the rat model of MCT‐PH impairs RA structure and function, and acute exposure of RA to amiodarone in clinical relevant concentration is not able to attenuate the onset of arrhythmias in the ex vivo RA preparation.
Effects of temperature on the fecundity and longevity of Zeugodacus cucurbitae (Coquillet) (Diptera: Tephritidae) on artificial diet
Authors: Ahn Jeong Joon , Choi Kyung San , Huang Yu‐Bing
Published: August 2023

The melon fruit fly, Zeugodacus cucurbitae (Coquillett), is an important polyphagous pest that damages to various agricultural crops, whose distribution has become global as a result of human activity. In this study, we investigated the fecundity, pre‐oviposition and oviposition periods, and the longevity of adult Z. cucurbitae at various constant temperatures ranging from 15 to 35.2°C. One newly emerged one virgin female and two males of Z. cucurbitae were used, and the longevity of both sexes and the fecundity of the females were examined daily. The longevity of female Z. cucurbitae ranged from 183.8 days at 15.0°C to 30.8 days at 35.2°C, and the maximum fecundity per female was 1204 eggs at 24.5°C. The lower development threshold (LDT) and thermal constant (K) of females were estimated as 14.8°C and 781.13 degree‐days, respectively. Female reproduction was modeled using a two‐phase oviposition model. Oviposition was estimated using females in the oviposition phase, which had a complete pre‐oviposition phase. The oviposition model consisted of two reproductive components (total fecundity and age‐specific cumulative oviposition rate during oviposition) and a survival component (age‐specific survival rate). The daily egg production of Z. cucurbitae was estimated in relation to adult age and temperature.
A randomized phase III study of docetaxel alone versus docetaxel plus S‐1 in patients with previously treated non‐small cell lung cancer: JMTO LC09‐01
Authors: Atagi Shinji , Daimon Takashi , Okishio Kyoichi , Komuta Kiyoshi , Okano Yoshio , Minato Koichi , Kim Young Hak , Usui Ryo , Tabata Chiharu , Tamura Atsuhisa , Kawahara Masaaki
Published: August 2023

Background

This study evaluated the efficacy and safety of the combination chemotherapy of docetaxel plus S‐1 in patients with previously treated non‐small cell lung cancer (NSCLC) compared to docetaxel alone.

Methods

Patients with previously treated NSCLC were randomly assigned to docetaxel alone (arm A) or a combination of docetaxel and S‐1 (arm B) for a maximum of four cycles. The primary endpoint was overall survival (OS).

Results

The study was terminated early because of poor accrual. The number of patients evaluated were 74 and 77 in arm A and arm B, respectively. The median OS was 9.8 months (95% confidence interval [CI]: 6.8–15.2) and 12.3 months (95% CI: 9.2–14.5) in arms A and B, respectively. In arms A and B, the median progression‐free survival was 3.5 months (95% CI: 2.7–4.0) and 4.1 months (95% CI: 3.2–4.7), respectively. No statistically significant difference was observed in OS (hazard ratio [HR]: 0.984, 95% CI: 0.682–1.419, p = 0.4569) or progression‐free survival (HR: 0.823, 95% CI: 0.528–1.282, p = 0.0953). The major toxicity was myelosuppression. The incidence of grade 3 or more neutropenia was higher in arm A than in arm B (44.6% vs. 35.1%). However, the incidence of grade 3 or more febrile neutropenia and infection with neutropenia (12.2% vs. 22.1%) was more frequently observed in arm B.

Conclusions

The prematurely terminated study did not show the benefit of two cytotoxic agents over single‐agent therapy for previously treated NSCLC patients.
Accelerated aging in mice with astrocytic redox imbalance as a consequence of SOD2 deletion
Authors: Tsesmelis Konstantinos , Maity‐Kumar Gandhari , Croner Dana , Sprissler Jasmin , Tsesmelis Miltiadis , Hein Tabea , Baumann Bernd , Wirth Thomas
Published: August 2023

Aging of the central nervous system (CNS) leads to motoric and cognitive decline and increases the probability for neurodegenerative disease development. Astrocytes fulfill central homeostatic functions in the CNS including regulation of immune responses and metabolic support of neurons and oligodendrocytes. In this study, we investigated the effect of redox imbalance in astrocytes by using a conditional astrocyte‐specific SOD2‐deficient mouse model (SOD2ako) and analyzed these animals at different stages of their life. SOD2ako mice did not exhibit any overt phenotype within the first postnatal weeks. However, already as young adults, they displayed progressive motoric impairments. Moreover, as these mice grew older, they exhibited signs of a progeroid phenotype and early death. Histological analysis in moribund SOD2ako mice revealed the presence of age‐related brain alterations, neuroinflammation, neuronal damage and myelin impairment in brain and spinal cord. Additionally, transcriptome analysis of primary astrocytes revealed that SOD2 deletion triggered a hypometabolic state and promoted polarization toward A1‐neurotoxic status, possibly underlying the neuronal and myelin deficits. Conclusively, our study identifies maintenance of ROS homeostasis in astrocytes as a critical prerequisite for physiological CNS aging.
The impact of the cardiovascular component and somatic mutations on ageing
Authors: Garger Daniel , Meinel Martin , Dietl Tamina , Hillig Christina , Garzorz‐Stark Natalie , Eyerich Kilian , de Angelis Martin Hrabě , Eyerich Stefanie , Menden Michael P.
Published: August 2023

Mechanistic insight into ageing may empower prolonging the lifespan of humans; however, a complete understanding of this process is still lacking despite a plethora of ageing theories. In order to address this, we investigated the association of lifespan with eight phenotypic traits, that is, litter size, body mass, female and male sexual maturity, somatic mutation, heart, respiratory, and metabolic rate. In support of the somatic mutation theory, we analysed 15 mammalian species and their whole‐genome sequencing deriving somatic mutation rate, which displayed the strongest negative correlation with lifespan. All remaining phenotypic traits showed almost equivalent strong associations across this mammalian cohort, however, resting heart rate explained additional variance in lifespan. Integrating somatic mutation and resting heart rate boosted the prediction of lifespan, thus highlighting that resting heart rate may either directly influence lifespan, or represents an epiphenomenon for additional lower‐level mechanisms, for example, metabolic rate, that are associated with lifespan.
A Meta‐Analytic Assessment of the Effects of Emotions on Political Information Search and Decision‐Making
Authors: Funck Amy S. , Lau Richard R.
Published: August 2023

With increasing interest in the role of emotions in politics across the discipline, we review theoretical and methodological approaches utilized by political psychologists. Although theorists have been highlighting the role of emotions in politics for thousands of years, modern political psychologists primarily employ Marcus, Neuman, and MacKuen's (2000) affective intelligence theory to grapple with the consequences of emotions for political attitudes and behavior. We present results from a formal meta‐analytic assessment exploring the strength of the empirical evidence for the relationship between emotions and political information search and decision strategies. Overall, we find weak but statistically reliable evidence linking anger, anxiety, and enthusiasm to information search when search is self‐reported, but when information search is objectively measured, we find no link between it and anxiety or enthusiasm. Surprisingly, we also find little reliable evidence linking emotions to differential reliance on heuristics or more evidence‐based criteria in voter decision‐making.
Damaged Relations: How Treaty Withdrawal Impacts International Cooperation
Authors: Schmidt Averell
Published: August 2023

This article examines how treaty withdrawal affects international cooperation. By terminating its treaty commitments, the exiting state could earn a reputation for unreliability, making other states less willing to cooperate with it. However, states’ reactions to withdrawal vary markedly, even though it is public behavior. I develop an experiential theory of international cooperation that explains this variation. I argue that withdrawal damages the exiting state's relations with other treaty members, causing them to ratify fewer agreements with it in the future. I test this theory using an original data set of all treaties registered with the United Nations and a case study of France's exit from NATO's Status of Forces Agreement. I find that withdrawal reduces treaty members’ ratification of agreements with the exiting state by 7.9% in the 7 years after exit. This effect increases with the salience and material cost of withdrawal and can spill across issue areas.
Cryopreservation of equine spermatozoa reduces plasma membrane integrity and phospholipase C zeta 1 content as associated with oocyte activation
Authors: Gonzalez‐Castro Raul A. , Whitcomb Luke A. , Pinsinski Emma C. , Carnevale Elaine M.
Published: August 2023

Background

Phospholipase C zeta (PLCZ1) is considered the major sperm‐borne oocyte activation factor. Cryopreserved stallion spermatozoa are commonly used for intracytoplasmic sperm injection (ICSI). However, plasma membrane damage and protein modifications caused by cryopreservation could impair sperm structure and function, leading to a reduction of PLCZ1 and oocyte activation after ICSI.

Objectives

We compared membrane integrity and PLCZ1 abundance in populations for fresh, frozen, and refrozen stallion spermatozoa, either thawed and refrozen at room or low temperature; and examined the effect of relative PLCZ1 content on cleavage after ICSI.

Materials and methods

Western blotting, ELISA, and immunofluorescence were conducted in stallion spermatozoa, freezing extenders, and detergent‐extracted sperm fractions to detect and quantify PLCZ1. Retrospectively, PLCZ1 content and cleavage rate were analyzed. Fresh, frozen, and refrozen at room and low temperatures spermatozoa were evaluated for acrosomal and plasma membrane integrity and PLCZ1 content using flow cytometry.

Results

Western blotting, ELISA, and immunofluorescence revealed significant reduction of PLCZ1 in spermatozoa after cryopreservation and confirmed PLCZ1 detection in extenders. After detergent extraction, a PLCZ1‐nonextractable fraction remained in the postacrosomal region of spermatozoa. Plasma membrane integrity was significantly reduced after freezing. Acrosomal and plasma membrane integrity were similar between frozen and refrozen samples at low temperature, but both were significantly higher than samples refrozen at room temperature. Acrosomal and plasma membrane integrity significantly correlated to PLCZ1 content. Percentages of PLCZ1‐labeled spermatozoa and PLCZ1 content were reduced after freezing but not after refreezing. Relative content and localization of PLCZ1 were associated with cleavage rates after ICSI.

Discussion and conclusion

Sperm PLCZ1 content associates with cleavage rates after ICSI. Cryopreservation is detrimental to sperm plasma membrane integrity and PLCZ1 retention. However, refreezing did not result in additional PLCZ1 loss. Refreezing stallion spermatozoa at a low temperature resulted in better survival but did not improve PLCZ1 retention.
Prevalence, molecular markers, and outcome of bronchial squamous carcinoma in situ in high‐risk subjects
Authors: Jonsson Steinn , Franklin Wilbur A. , Varella‐Garcia Marileila , Kennedy Timothy C. , Merrick Daniel , Matney Kathryn D. , Oskarsdottir Gudrun N. , Saemundsson Arni , Keith Robert L. , Bunn Paul A. , Miller York E.
Published: August 2023

Bronchial squamous carcinoma in situ (CIS) is a preinvasive lesion that is thought to precede invasive carcinoma. We conducted prospective autofluorescence and white light bronchoscopy trials between 1992 and 2016 to assess the prevalence, molecular markers, and outcome of individuals with CIS and other preneoplastic bronchial lesions. Biopsies were evaluated at multiple levels and selected biopsies were tested for aneuploidy and DNA sequenced for TP53 mutation. Thirty‐one individuals with CIS were identified. Twenty‐two cases of CIS occurred in association with concurrent invasive carcinomas. Seven of the invasive tumors were radiographically occult. In two cases, CIS spread from the focus of invasive carcinoma into contralateral lung lobes, forming secondary invasive tumors. In nine cases, CIS occurred as isolated lesions and one progressed to invasive squamous carcinoma at the same site 40 months after discovery. In a second case, CIS was a precursor of carcinoma at a separate site in a different lobe. In seven cases CIS regressed to a lower grade or disappeared. High level chromosomal aneusomy was often associated with TP53 mutation and with invasive carcinoma. CIS most often occurs in association with invasive squamous carcinoma and may extend along the airways into distant lobes. In rare cases, CIS may be observed to directly transform into invasive carcinoma. CIS may be indicative of invasive tumor at a separate distant site. Isolated CIS may regress. Molecular changes parallel histological changes in CIS and may be used to map clonal expansion in the airways.