bluuebunny/crossref_metadata_2025 huggingface dataset:
Cross‐talk of four types of RNA modification writers defines the immune microenvironment in severe asthma
Authors: Lin Qibin , Ni Haiyang , Zheng Zhishui , Zhong Jieying , Nie Hanxiang
Published: May 2022

Adenine modifications, including m6A, m1A, APA, and A‐to‐I modifications, are the most impactful RNA modifications. These modifications are primarily produced by enzymes called writers. The main purpose of this study was to explore the cross‐talk and potential roles of these writers in severe asthma. We found 13 RNA writers potentially related to severe asthma and three RNA modification patterns. Cluster 3 showed predominant neutrophil infiltration and C‐type lectin receptor signaling; cluster 1 showed predominant innate immune cell infiltration and ubiquitin–proteasome system activation; and cluster 2 did not show obvious immune infiltration characteristics. We found that RNA modification writers modified immune cell–related genes and led to both accumulation of different immune cells in the airways and activation of a series of biological processes, which ultimately leads to severe asthma. TRMT6, WTAP, and TRMT6A were included in a random forest model as predictors. Cromoglicic acid, thioperamide, and fluvastatin were potential drugs for clusters 1, 2, and 3, respectively. We found that cross‐talk of RNA modifications is significant in severe asthma, which provides insight into severe asthma pathogenesis and possible treatment avenues.
A novel approach to radiographic detection of growth development period with hand‐wrist radiographs: A preliminary study with ImageJ imaging software
Authors: Şatir Samed , Büyükçavuş Muhammed Hilmi , Sari Ömer Faruk , Çimen Tansu
Published: May 2022

Objective

The purpose of this study is to determine whether or not the ImageJ program can be used to automatically determine the growth period of the hand and wrist which have different growth‐development periods according to the density values in the phalanges in radiographs.

Setting and sample population

Our study included hands‐wrist radiographs of 270 individuals aged 8–17 years.

Material and Methods

The study’s participants were classified into 7 groups according to their skeletal maturation stage (PP2=, MP3=, MP3cap, DP3u, PP3u, MP3u, and Ru) which included pre‐peak, peak, and post‐peak periods. The total density values (TDV) and pure density values (PDV) in the distal, medial, and proximal phalanges were calculated using each radiograph in the ImageJ program. Analysis of variance (ANOVA) was used to evaluate the density values and chronological age, and pairwise comparisons were made using the post‐hoc LSD test.

Results

The total density value was graphically zigzagged in the mesial, distal, and proximal phalanges. However, the pure density value increased continuously until the post‐peak period and decreased after the DP3u period until the Ru period. While no significant difference in total density values was observed between the growth periods for all three phalanges, a significant difference in pure density values was observed.

Conclusion

It has been demonstrated in the ImageJ program that the peak growth period can be distinguished using the pure density values obtained from all phalanges of the third finger and that this method can be used as an alternative to the growth period detection through artificial intelligence.
Factors associated with the healing time of pemphigus vulgaris oral lesions: A prospective study
Authors: Nili Ali , Karimi Shakiba , Salehi Farid Ali , Molhem Azar Pedram , Farimani Zeinab , Shahbazian Haneyeh , Balighi Kamran , Tavakolpour Soheil , Mahmoudi Hamidreza , Daneshpazhooh Maryam
Published: May 2022

Objectives

This study determines the healing time of lesions on different locations and the contributing factors to the healing time in patients with pemphigus.

Methods

In this prospective study, newly diagnosed patients with mucosal lesions were included. A dermatologist evaluated the lesions, disease status, side effects and assigned the PDAI. Follow‐up visits were conducted monthly until the patient reached complete remission and every three months thereafter. A Tzanck smear was performed on lesions clinically suspected to be herpetic in origin.

Results

Sixty patients enrolled in the study with a mean age of 45.9 ± 11.7 years. The buccal lesions took the longest to resolve (73[33.5–105.5] days). However, the posterior pharynx lesions showed the shortest healing time (20[13.0–25.5] days). The likelihood of improvement in buccal and soft palate lesions decreased by 5% and 3% with each additional year of age, respectively. Also, the resolution duration of soft palate lesions was significantly shorter in female patients than males (median of 24.0 days vs. 38.5 days). In contrast, lower gingival lesions resolve significantly faster in male patients by a median of 9 days. Herpes simplex virus infection increases the healing time of lesions by 26 days (median of 55 days vs. 29 days, hazard ratio 2.62, 95% CI: 1.04–5.92).

Conclusions

Buccal and lower gingival lesions are more recalcitrant to treatment, while posterior pharynx lesions heal most rapidly. Furthermore, older age was also associated with a lower rate of lesion improvement.
Wittgenstein's New Way of Talking to Himself
Authors: Higgins CJ
Published: May 2022

A lack of consensus persists as to whom exactly the dialogues of Wittgenstein'sPhilosophical Investigationsare between: Wittgenstein and an interlocutor? Or perhaps a variety of interlocutors, none of whom can be identified with Wittgenstein himself? I argue here that this lack of consensus is possibly due to an ambiguity in the ordinary concept of “talking to oneself,” and that a new concept of “talking to oneself” appropriate to Wittgenstein's dialogues is needed to properly understand them. Wittgenstein is talking to himself—but he is doing so in the way we talk to other people.
Importance of repeated sampling: vegetation analyses after 10 years revealed different restoration trends in formerly extracted peatlands
Authors: Pospíšilová Petra , Vítovcová Kamila , Prach Karel
Published: May 2022

The chronosequence approach, that is, analyses of several stages differing in age since disturbance or restoration but more or less comparable in site conditions, may well demonstrate, despite some limitations, a long‐term ecosystem development. Earlier, we described spontaneous vegetation succession in 11 differently aged industrially harvested raised bogs and suggested that spontaneous recovery of plant cover gradually proceeds toward the reference state of natural raised bogs. We repeated the analyses after 10 years and asked: (1) Are the successional trajectories of spontaneous restoration really directing toward reference natural sites? and (2) How do typical peatland plant species participate in re‐vegetation? Artificially afforested extracted peatland sites were used for comparison. We concluded that spontaneous recovery of plants does not proceed toward the reference sites. Instead it directs more toward the artificially afforested sites. Despite this, the spontaneously developed vegetation harbored many more peatland species. To turn the development toward the natural reference sites would require a substantial rise of the water table after ceasing peat extraction. The study demonstrates the importance of repeated analyses, which may give more reliable signs of the re‐vegetation direction than one‐time analyses.
Recognition and three‐dimensional characteristics of ancient supercritical flow bedforms on a submarine slope: An example from the South China Sea
Authors: Fongngern Rattanaporn , Chi Wu‐Cheng , Berndt Christian , Mohrig David
Published: May 2022

Supercritical flow bedforms are important elements of sedimentary environments, but their internal three‐dimensional structure has been elusive due to seismic imaging limitations. This article presents high‐resolution three‐dimensional seismic reflection data from Formosa Ridge – a ridge between two canyons that incise into the north‐eastern South China Sea margin. The ridge consists of 300 m thick submarine deposits including sediment waves that are manifested as crescentic depressions surrounded by elevated walls on the palaeo‐seafloor. Cross‐sectional profiles display scour fills that turn into step‐like sediment waves further downstream. These bedforms are 470 to 1370 m long and 30 to 140 m high. The three‐dimensional seismic data clearly show the step‐like bedforms that may be misinterpreted as faults or slumps on data with lower resolution. Despite exhibiting negative palaeo‐seafloor relief, they are overall depositional structures and have constructed at least part of the Formosa Ridge. The bedforms’ morphology and upslope migration suggest that they are the continuum of partially depositional to fully depositional cyclic steps formed by bottom currents travelling, based on a series of simple calculations, at least 2 m s−1. These currents are able to transport sediments with grain size up to coarse sand, and such dynamic processes might impact seafloor infrastructure safety, oil and gas reservoir systems, and the functioning of benthic ecosystems in similar settings.
A Task‐Based Approach to Teaching Literary Texts in Advanced Language Classes
Authors: Brandl Klaus K.
Published: May 2022

Many scholars have repeatedly argued that the goals of achieving advanced language skills and understanding literary texts are not to be seen as mutually exclusive and cannot be considered separately. Nevertheless, no general consensus on the approach or how to go about it exists. What is still missing are principled and comprehensive ways of linking language learning with literary‐cultural content. This article argues that a task‐based approach has such a potential. It demonstrates how task‐based principles such as the meaningful principle, goal‐orientedness, and language use for authentic communicative purposes can be effectively applied to the teaching of literary texts in order to gain access to literary‐cultural content and at the same time foster the development of advanced linguistic skills. Based on Judith Hermann's short story “Sonja” (1998), a variety of different task types and designs are presented demonstrating these principles in action.
Leaf anatomical alterations reduce cotton's mesophyll conductance under dynamic drought stress conditions
Authors: Zou Jie , Hu Wei , Li Yuxia , Zhu Honghai , He Jiaqi , Wang Youhua , Meng Yali , Chen Binglin , Zhao Wenqing , Wang Shanshan , Zhou Zhiguo
Published: May 2022

Drought stress significantly affects cotton's net photosynthetic rate (A) by restraining stomatal (gs) and mesophyll conductance (gm) as well as perturbing its biochemical process, resulting in yield reductions. Despite the significant progress in dissecting effects of drought on photosynthesis, the variability observed in cotton's gm, and the mechanisms contributing to that variability under dynamic drought stress conditions are poorly understood. For that reason, a controlled‐environment experiment with two cotton genotypes (Dexiamian 1, Yuzaomian 9110), three water levels (soil relative water content: control [75 ± 5]%, moderate drought [60 ± 5]%, severe drought [45 ± 5]%), and two drought durations (10 and 31 days) were conducted. The results indicated that the cotton boll biomass was significantly decreased under 10‐day severe drought and 31‐day moderate and severe drought. Decreases in gs were later accompanied by decreases in gm and further combined with reductions in electron transport rate, as drought stress progressed in duration and severity, ultimately resulting in significant reductions in A of subtending leaf. Stomatal and mesophyll conductance constraints were the primary factors limiting photosynthesis, while biochemical constraints decreased, as drought stress progressed. Considering gm, its decline was ascribed to increases in the diffusion resistance of CO2 through cytoplasm (rcyt), under short‐ or long‐term drought, as well as to increases in leaf dry mass (LMA), and decreases in the chloroplast surface area exposed to intercellular air space (Sc/S), under long‐term drought. It was concluded that A could be enhanced, under dynamic drought stress conditions, by increasing gm through increasing Sc/S and reducing LMA and rcyt.
How does TRIPs compliance affect the economic growth of developing countries? Application of the Synthetic Control method
Authors: Smith Pamela J. , Anti Sebastian J.
Published: May 2022

This paper examines the effects of intellectual property rights (IPRs) on the economic growth of countries, with special attention to developing countries. We examine both the strength of countries' IPRs, as well as their compliance with the 1995 Agreement on Trade‐Related Aspects of Intellectual Property Rights (TRIPs) of the World Trade Organization. Our theoretical framework is a growth model which distinguishes capital as physical capital, human capital and intellectual property. Our methods include panel regression techniques, plus a novel Synthetic Control method. The latter is valuable for examining policy effects in research situations where data are limited to small sample sizes; and where reverse causality and heterogeneity are concerns. The Synthetic Control method allows us to assess the impact of TRIPs compliance on economic growth relative to a counterfactual of what would have occurred in the absence of compliance. The results show that while select developing countries experience growth benefits from complying with the TRIPs agreement, others do not, supporting the notion that there is a wide range of heterogeneity in the effects of IPR reforms on growth. These findings are robust when we account for marginal institutional changes in IPRs, enforcement of IPRs, and technological capacity in developing countries.
Miradas que importan: representaciones mediáticas de la población trans en Colombia y Venezuela
Authors: Polo Néstor David
Published: May 2022

El texto tiene como centro articulador la relación representación-cuerpo-autoimagen desde una perspectiva biopolítica. Retoma los fundamentos de autores como Foucault y Butler sobre la identidad como una construcción simbólica y performativamente configurada, pero los cruza con un enfoque interseccional y decolonial. Es decir, contextualiza la perspectiva queer en América Latina, y reconoce el término trans como algo foráneo, que en Colombia y Venezuela está, además, atravesado por unas relaciones hegemónicas de raza, etnia y clase social.
A Mechanistic-Based Data-Driven Approach for General Friction Modeling in Complex Mechanical System
Authors: Peng Haijun , Song Ningning , Li Fei , Tang Shan
Published: May 2022

The effect of friction is widespread around us, and most important projects must consider the friction effect. To better depict the dynamic characteristics of multibody systems with friction, a series of friction models have been proposed by scholars. Due to the complex and changeable working conditions, the contact surface is uncertain, and characterizing the friction properties is a challenging problem. Therefore, in this work, a mechanistic-based data-driven (MBDD) approach is proposed to establish a general friction model. According to the generalization ability of deep neural networks, the proposed strategy can handle the friction in multibody systems with different contact surfaces. Moreover, the proposed mechanistic-based data-driven approach can utilize both numerical data and experimental data, so it can achieve small data for the dynamic behavior prediction of complex mechanical systems. Eventually, the numerical simulation is compared with the experimental test. The results show that the proposed strategy can predict the dynamic behavior of a complex multibody system well and can reflect many important friction phenomena, such as the Stribeck effect, stiction, and viscous friction.
Product Multibody Dynamics Analysis for Low-Carbon Footprint
Authors: He Bin , Wu Jiachi , Zhu Xuanren , Zhang Dong , Cao Jintao
Published: May 2022

With the increasingly serious global climate problem, the low-carbon design of products has gradually become an important direction of sustainable manufacturing. The optimization design of product structure is one of the important means to realize the low-carbon operation of product structure. Therefore, how to carry out the low-carbon optimization design of the product is the focus of this paper. In this paper, a new framework of low-carbon manufacturing is constructed, the load on the crane of the offshore wind power installation platform is analyzed, and the dynamic load generated by the crane during lifting, rotating, and luffing is analyzed in detail. The simulation results are compared with the empirical formula provided by the crane design specification and the dynamic analysis results of the crane, which proves the rationality of the simulation results and the dynamic theoretical analysis. And the wind load on the crane is calculated, which provides support for the rigid-flexible coupling dynamic analysis of other parts of the solution. Based on the dynamic simulation and load analysis of the offshore platform crane, the low-carbon optimization design of the offshore platform pile leg is carried out, the carbon emission of the whole life cycle is optimized, and the feasibility of the scheme is verified.
Reusing and Extending Standards-Based Unit Manufacturing Process Models for Characterizing Sustainability Performance
Authors: Raman Arvind Shankar , Morris K. C. , Haapala Karl R.
Published: May 2022

Over the past two decades, numerous efforts have characterized manufacturing processes for sustainability performance. These efforts have been pursued primarily by manufacturing researchers in academic and governmental labs, and involve the development of frameworks, methodologies, and standards for characterizing discrete manufacturing processes and their representation as information models. Furthermore, characterization of sustainability performance of manufacturing process flows has been attempted through linking, or composing, these unit manufacturing process (UMP) models. This paper reviews these efforts and identifies existing research gaps that should be addressed by academic, industrial, and governmental researchers. The review includes the relevant sustainable manufacturing standards that have been recently published by ASTM International. A methodology for creating and extending composable models of UMPs that build upon these standards is presented. This research demonstrates how formalization of these prior efforts can address the identified gaps. It is shown that the reuse of UMP models can be enabled by encapsulating specific characteristics of complex processes into information models that can be applied for detailed process analysis and evaluation. This research proposes the concept of a template UMP information model, which can further be abstracted and customized to represent an application-specific, higher-order manufacturing process model. The template model concept is illustrated for manual and computer numerically controlled (CNC) milling processes.
Study of Electroencephalograph-Based Evaluation Method of Car Sound Quality
Authors: Xie Liping , Lu Chihua , Liu Zhien , Zhu Yawei , Xu Tao
Published: May 2022

Those methods that are applied to evaluate car sound quality by means of the scoring mode cannot guarantee the universality of results. Some studies have shown that the sound-induced change of electroencephalograph (EEG) can reflect human cerebral activities and mental perceptions. Thus, EEG is introduced here to evaluate the car sound quality, and a new method is put forward to map the powerful sound quality on account of EEG-based physiological acoustic index (EPAI). Twelve types of EEG features are selected in views of time and frequency domains and entropy feature to establish the feature matrix, and the difference of car sounds with the powerful sound quality are identified by means of five classifiers. Then, the correlation between the powerful sound quality and 12 types of EEG features is further analyzed to screen out the effective EEG features that are strongly related to the powerful car sound quality. Subsequently, seven EPAIs are defined by means of regression model based on three effective EEG features, which are the second-order difference (SOD), power spectral density (PSD) of gamma (PSD_γ), and differential entropy (DE), respectively. Our results show that the support vector machine (SVM) and linear discriminant analysis (LDA) models can be applied to effectively identify the difference of powerful car sounds, and the correlations between SOD, PSD_γ, and DE and the powerful sound quality are high, which are up to 0.86, 0.88, and 0.85, respectively, and our EPAIs 1, 2, and 4 can map the powerful car sound quality where the EPAI 4 results in the best evaluation effect. It is also proved that our EPAIs can reflect the subjective perception of participants under stimulation of the powerful sound quality, and EEG can be used as an evaluation method of car sound quality.
Characterization and Analysis of the Thermal Conductivity of AlSi10Mg Fabricated by Laser Powder Bed Fusion
Authors: Elkholy Ahmed , Quinn Paul , Uí Mhurchadha Sinéad M. , Raghavendra Ramesh , Kempers Roger
Published: May 2022

Laser-based powder bed fusion (L-PBF) of AlSi10Mg can be used to fabricate complex, light-weight structures with high thermal conductivity. Much effort has gone into investigating the mechanical behavior of L-PBF components; however, few studies investigated their thermal properties. This investigation characterizes the effect of process parameters on the relative density and thermal conductivity of L-PBF AlSi10Mg. Exposure time, laser power, pointwise distance, and build orientation were examined. Results show that changing these parameters can affect the thermal conductivity by up to 22%. For example, build orientation and pointwise distance influenced the thermal conductivity by 12.9% and 10%, respectively. As the pointwise distance increased, both the conductivity and the distance between the melt pool boundaries decreased, whereas the laser power had a negligible effect on both. The effect of exposure time was mainly dependent on the pointwise distance. It is shown that thermal conductivity is not only related to the relative density of the samples, but the number of the melt pool boundaries in the microstructure also plays a significant role in interrupting the heat flow. A new factor is introduced to account for the number of melt pool boundaries per unit length in the direction of heat flow, which helps to explain the variation in thermal conductivity for samples manufactured with high energy densities which had almost negligible difference in relative density.
A Novel Asymmetric Face Gear Cut by Duplex Face-Milling With Multiple Auxiliary Flank Modification Motions
Authors: Lee Yi-Hui , Chen Kuan-Hung , Fong Zhang-Hua
Published: May 2022

Face gear sets, comprising a face gear and a cylindrical pinion, are used in the crossed axes transmission with the advantages of easy assembly and a large gear ratio. Based on the geometry of a pinion tooth flank, the tooth surface of the face gear is derived and manufactured by gear hobbing or shaping processes. However, the hobbing and shaping processes to make a face gear require special machine attachments to achieve the spatial relationship between the gear cutter and the workpiece of the face gear. These special machine attachments are not always available in a typical gear-machining factory, so this study develops a manufacturing process that uses a standard spiral bevel gear generator and standard face-milling cutting tools to produce a face gear. The productivity and the gear quality of a face gear that is made using the proposed cutting method are similar to that for a spiral bevel gear that is produced by indexed duplex cutting. The machine settings for the spiral bevel gear generator are derived using the tooth surface of a face gear, which is conjugated to the tooth surface of specific pinion. This study uses a duplex face-milling method with multiple auxiliary flank modification motions to minimize the flank normal deviation between the conjugate and the generated face gear. A numerical example and a cutting experiment are performed to verify the feasibility of the proposed methodology.
High-energy x-ray photoelectron spectroscopy spectra of TiN measured by Cr Kα
Authors: Hoflijk I. , Vanleenhove A. , Zborowski C. , Vaesen I. , Artyushkova K. , Conard T.
Published: May 2022

Titanium nitride (TiN) grown by ionized metal plasma on Si was analyzed using high-resolution high-energy x-ray photoelectron spectroscopy (HAXPES). The HAXPES spectra of TiN obtained using monochromatic Cr Kα radiation at 5414.8 eV include two survey scans (Al Kα and Cr Kα) and high-resolution spectra of Ti 1s, Ti2p, Ti 2s, Ti 3p, Ti 3s, N 1s, and O 1s.
Receptor-specific recognition of NPY peptides revealed by structures of NPY receptors
Authors: Tang Tingting , Tan Qiuxiang , Han Shuo , Diemar Anne , Löbner Kristin , Wang Hongyu , Schüß Corinna , Behr Victoria , Mörl Karin , Wang Mu , Chu Xiaojing , Yi Cuiying , Keller Max , Kofoed Jacob , Reedtz-Runge Steffen , Kaiser Anette , Beck-Sickinger Annette G. , Zhao Qiang , Wu Beili
Published: May 2022

In response to three highly conserved neuropeptides, neuropeptide Y (NPY), peptide YY, and pancreatic polypeptide (PP), four G protein–coupled receptors mediate multiple essential physiological processes, such as food intake, vasoconstriction, sedation, and memory retention. Here, we report the structures of the human Y
1
, Y
2
, and Y
4
receptors in complex with NPY or PP, and the G
i1
protein. These structures reveal distinct binding poses of the peptide upon coupling to different receptors, reflecting the importance of the conformational plasticity of the peptide in recognizing the NPY receptors. The N terminus of the peptide forms extensive interactions with the Y
1
receptor, but not with the Y
2
and Y
4
receptors. Supported by mutagenesis and functional studies, subtype-specific interactions between the receptors and peptides were further observed. These findings provide insight into key factors that govern NPY signal recognition and transduction, and would enable development of selective drugs.
Characterization of a vaccine-elicited human antibody with sequence homology to VRC01-class antibodies that binds the C1C2 gp120 domain
Authors: Gray Matthew D. , Feng Junli , Weidle Connor E. , Cohen Kristen W. , Ballweber-Fleming Lamar , MacCamy Anna J. , Huynh Crystal N. , Trichka Josephine J. , Montefiori David , Ferrari Guido , Pancera Marie , McElrath M. Juliana , Stamatatos Leonidas
Published: May 2022

Broadly HIV-1–neutralizing VRC01-class antibodies bind the CD4-binding site of Env and contain V
H
1-2*02–derived heavy chains paired with light chains expressing five–amino acid–long CDRL3s. Their unmutated germline forms do not recognize HIV-1 Env, and their lack of elicitation in human clinical trials could be due to the absence of activation of the corresponding naïve B cells by the vaccine immunogens. To address this point, we examined Env-specific B cell receptor sequences from participants in the HVTN 100 clinical trial. Of all the sequences analyzed, only one displayed homology to VRC01-class antibodies, but the corresponding antibody (FH1) recognized the C1C2 gp120 domain. For FH1 to switch epitope recognition to the CD4-binding site, alterations in the CDRH3 and CDRL3 were necessary. Only germ line–targeting Env immunogens efficiently activated VRC01 B cells, even in the presence of FH1 B cells. Our findings support the use of these immunogens to activate VRC01 B cells in humans.
Genetic physical unclonable functions in human cells
Authors: Li Yi , Bidmeshki Mohammad Mahdi , Kang Taek , Nowak Chance M. , Makris Yiorgos , Bleris Leonidas
Published: May 2022

A physical unclonable function (PUF) is a physical entity that provides a measurable output that can be used as a unique and irreproducible identifier for the artifact wherein it is embedded. Popularized by the electronics industry, silicon PUFs leverage the inherent physical variations of semiconductor manufacturing to establish intrinsic security primitives for attesting integrated circuits. Owing to the stochastic nature of these variations, photolithographically manufactured silicon PUFs are impossible to reproduce (thus unclonable). Inspired by the success of silicon PUFs, we sought to create the first generation of genetic PUFs in human cells. We demonstrate that these PUFs are robust (i.e., they repeatedly produce the same output), unique (i.e., they do not coincide with any other identically produced PUF), and unclonable (i.e., they are virtually impossible to replicate). Furthermore, we demonstrate that CRISPR-engineered PUFs (CRISPR-PUFs) can serve as a foundational principle for establishing provenance attestation protocols.
The effect of mating market dynamics on partner preference and relationship quality among Himba pastoralists
Authors: Prall Sean , Scelza Brooke
Published: May 2022

Relative mate value has long been believed to be a critical component of mate choice in humans. However, most empirical work focuses on preferences rather than actual pair formation, and data connecting partner preferences, partnership formation, and relationship quality remain rare. Here, we estimate mate value using >12,000 ratings by opposite-sex, in-group members to understand both hypothetical partnership preferences and actualized relationship dynamics. When evaluating hypothetical partnerships, people generally prefer individuals whose mate value is higher than their own, indicating an aspirational matching strategy. However, mate value comparisons of individuals in marital and nonmarital relationships show a positive correlation, suggesting that individuals tend to pair up with similarly desirable individuals. Furthermore, despite aspirational preferences, couples who are more closely matched reported greater relationship quality, measured through frequency of interactions, reported sexual histories, and partnership length.
Structural mapping of antibody landscapes to human betacoronavirus spike proteins
Authors: Bangaru Sandhya , Antanasijevic Aleksandar , Kose Nurgun , Sewall Leigh M. , Jackson Abigail M. , Suryadevara Naveenchandra , Zhan Xiaoyan , Torres Jonathan L. , Copps Jeffrey , de la Peña Alba Torrents , Crowe James E. , Ward Andrew B.
Published: May 2022

Preexisting immunity against seasonal coronaviruses (CoVs) represents an important variable in predicting antibody responses and disease severity to severe acute respiratory syndrome CoV-2 (SARS-CoV-2) infections. We used electron microscopy–based polyclonal epitope mapping (EMPEM) to characterize the antibody specificities against β-CoV spike proteins in prepandemic (PP) sera or SARS-CoV-2 convalescent (SC) sera. We observed that most PP sera had antibodies specific to seasonal human CoVs (HCoVs) OC43 and HKU1 spike proteins while the SC sera showed reactivity across all human β-CoVs. Detailed molecular mapping of spike-antibody complexes revealed epitopes that were differentially targeted by preexisting antibodies and SC serum antibodies. Our studies provide an antigenic landscape to β-HCoV spikes in the general population serving as a basis for cross-reactive epitope analyses in SARS-CoV-2–infected individuals.
Allelic shift in cis-elements of the transcription factor
RAP2.12
underlies adaptation associated with humidity in
Arabidopsis thaliana
Authors: Lou Shangling , Guo Xiang , Liu Lian , Song Yan , Zhang Lei , Jiang Yuanzhong , Zhang Lushui , Sun Pengchuan , Liu Bao , Tong Shaofei , Chen Ningning , Liu Meng , Zhang Han , Liang Ruyun , Feng Xiaoqin , Zheng Yudan , Liu Huanhuan , Holdsworth Michael J. , Liu Jianquan
Published: May 2022

Populations of widespread species are usually geographically distributed through contrasting stresses, but underlying genetic mechanisms controlling this adaptation remain largely unknown. Here, we show that in
Arabidopsis thaliana
, allelic changes in the cis-regulatory elements, WT box and W box, in the promoter of a key transcription factor associated with oxygen sensing, RELATED TO AP 2.12 (RAP2.12), are responsible for differentially regulating tolerance to drought and flooding. These two cis-elements are regulated by different transcription factors that downstream of
RAP2.12
results in differential accumulation of hypoxia-responsive transcripts. The evolution from one cis-element haplotype to the other is associated with the colonization of humid environments from arid habitats. This gene thus promotes both drought and flooding adaptation via an adaptive mechanism that diversifies its regulation through noncoding alleles.
A bivalent Epstein-Barr virus vaccine induces neutralizing antibodies that block infection and confer immunity in humanized mice
Authors: Wei Chih-Jen , Bu Wei , Nguyen Laura A. , Batchelor Joseph D. , Kim JungHyun , Pittaluga Stefania , Fuller James R. , Nguyen Hanh , Chou Te-Hui , Cohen Jeffrey I. , Nabel Gary J.
Published: May 2022

Epstein-Barr virus (EBV) is the major cause of infectious mononucleosis and is associated with several human cancers and, more recently, multiple sclerosis. Despite its prevalence and health impact, there are currently no vaccines or treatments. Four viral glycoproteins (gp), gp350 and gH/gL/gp42, mediate entry into the major sites of viral replication, B cells, and epithelial cells. Here, we designed a nanoparticle vaccine displaying these proteins and showed that it elicits potent neutralizing antibodies that protect against infection in vivo. We designed single-chain gH/gL and gH/gL/gp42 proteins that were each fused to bacterial ferritin to form a self-assembling nanoparticle. Structural analysis revealed that single-chain gH/gL and gH/gL/gp42 adopted a similar conformation to the wild-type proteins, and the protein spikes were observed by electron microscopy. Single-chain gH/gL or gH/gL/gp42 nanoparticle vaccines were constructed to ensure product homogeneity needed for clinical development. These vaccines elicited neutralizing antibodies in mice, ferrets, and nonhuman primates that inhibited EBV entry into both B cells and epithelial cells. When mixed with a previously reported gp350 nanoparticle vaccine, gp350D
123
, no immune competition was observed. To confirm its efficacy in vivo, humanized mice were challenged with EBV after passive transfer of IgG from mice vaccinated with control, gH/gL/gp42+gp350D
123
, or gH/gL+gp350D
123
nanoparticles. Although all control animals were infected, only one mouse in each vaccine group that received immune IgG had detectable transient viremia. Furthermore, no EBV lymphomas were detected in immune animals. This bivalent EBV nanoparticle vaccine represents a promising candidate to prevent EBV infection and EBV-related malignancies in humans.
JAGGED-NOTCH3 signaling in vascular remodeling in pulmonary arterial hypertension
Authors: Zhang Yu , Hernandez Moises , Gower Jonathan , Winicki Nolan , Morataya Xena , Alvarez Sebastian , Yuan Jason X.-J. , Shyy John , Thistlethwaite Patricia A.
Published: May 2022

Within the pulmonary arterial tree, the NOTCH3 pathway is crucial in controlling vascular smooth muscle cell proliferation and maintaining smooth muscle cells in an undifferentiated state. Pulmonary arterial hypertension (PAH) is a fatal disease without cure, characterized by elevated pulmonary vascular resistance due to vascular smooth muscle cell proliferation in precapillary arteries, perivascular inflammation, and asymmetric neointimal hyperplasia. Here, we show that human PAH is characterized by overexpression of the NOTCH ligand JAGGED-1 (JAG-1) in small pulmonary artery smooth muscle cells and that JAG-1 selectively controls NOTCH3 signaling and cellular proliferation in an autocrine fashion. In contrast, the NOTCH ligand DELTA-LIKE 4 is minimally expressed in small pulmonary artery smooth muscle cells from individuals with PAH, inhibits NOTCH3 cleavage and signaling, and retards vascular smooth muscle cell proliferation. A new monoclonal antibody for the treatment of PAH, which blocks JAG-1 cis- and trans-induced cleavage of the NOTCH3 receptor in the pulmonary vasculature, was developed. Inhibition of JAG-1–induced NOTCH3 signaling in the lung reverses clinical and pathologic pulmonary hypertension in two rodent models of disease, without toxic side effects associated with nonspecific NOTCH inhibitors. Our data suggest opposing roles of NOTCH ligands in the pulmonary vasculature in pulmonary hypertension. We propose that selectively targeting JAG-1 activation of NOTCH3 may be an effective, safe strategy to treat PAH.
Pharmacokinetics and Dose Optimization Strategies of Para-Aminosalicylic Acid in Children with Rifampicin-Resistant Tuberculosis
Authors: van der Laan Louvina E. , Garcia-Prats Anthony J. , Schaaf H. Simon , Chirehwa Maxwell , Winckler Jana L. , Mao Jun , Draper Heather R. , Wiesner Lubbe , Norman Jennifer , McIlleron Helen , Donald Peter R. , Hesseling Anneke C. , Denti Paolo
Published: May 2022

Treatment options for children with Rifampicin-resistant tuberculosis (RR-TB) remain limited, and para-aminosalicylic acid (PAS) is still a relevant component of treatment regimens. Prevention of resistance to companion drugs by PAS is dose related, and at higher concentrations, PAS may exhibit significant bactericidal activity in addition to its bacteriostatic properties.
RefZ and Noc Act Synthetically to Prevent Aberrant Divisions during Bacillus subtilis Sporulation
Authors: Miller Allyssa K. , Herman Jennifer K.
Published: May 2022

The DNA-binding protein RefZ and its binding sites (
RBM
s) are conserved in sequence and location on the chromosome across the
Bacillus
genus and contribute to the timing of polar FtsZ-ring assembly during sporulation. Only a small number of noncoding and nonregulatory DNA motifs are known to be conserved in chromosomal position in bacteria, suggesting there is strong selective pressure for their maintenance; however, a
refZ
deletion mutant sporulates efficiently, providing no clues as to their functional significance.
Retraction ATPase Motors from Three Orthologous Type IVa Pilus Systems Support Promiscuous Retraction of the Vibrio cholerae Competence Pilus
Authors: Couser Evan , Chlebek Jennifer L. , Dalia Ankur B.
Published: May 2022

One way in which bacteria interact with their environments is via hair-like appendages called type IVa pili (T4aP). These appendages dynamically extend and retract from the cell surface via the action of distinct ATPase motors.
The 27th Annual Midwest Microbial Pathogenesis Conference in the Age of COVID
Authors: Hammer Neal D. , Waters Christopher M.
Published: May 2022

Michigan State University was honored to host in-person the 27th Annual Midwest Microbial Pathogenesis Conference from 17 to 19 September 2021 in East Lansing, MI. Here, we report the precautions that were used to host a safe, in-person meeting during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) pandemic and the research on microbial pathogenesis that was presented at the meeting.
‘History obligates us to do it’: political capabilities of Indigenous grassroots leaders of health accountability initiatives in rural Guatemala
Authors: Hernandez Alison , Hurtig Anna-Karin , San Sebastian Miguel , Jerez Fernando , Flores Walter
Published: May 2022

Growing interest in how marginalised citizens can leverage countervailing power to make health systems more inclusive and equitable points to the need for politicised frameworks for examining bottom-up accountability initiatives. This study explores how political capabilities are manifested in the actions and strategies of Indigenous grassroots leaders of health accountability initiatives in rural Guatemala. Qualitative data were gathered through group discussions and interviews with initiative leaders (called defenders of the right to health) and initiative collaborators in three municipalities. Analysis was oriented by three dimensions of political capabilities proposed for evaluating the longer-term value of participatory development initiatives: political learning, reshaping networks and patterns of representation. Our findings indicated that the defenders’ political learning began with actionable knowledge about defending the right to health and citizen participation. The defenders used their understanding of local norms to build trust with remote Indigenous communities and influence them to participate in monitoring to attempt to hold the state accountable for the discriminatory and deficient healthcare they received. Network reshaping was focused on broadening their base of support. Their leadership strategies enabled them to work with other grassroots leaders and access resources that would expand their reach in collective action and lend them more influence representing their problems beyond the local level. Patterns of representing their interests with a range of local and regional authorities indicated they had gained confidence and credibility through their evolving capability to navigate the political landscape and seek the right authority based on the situation. Our results affirm the critical importance of sustained, long-term processes of engagement with marginalised communities and representatives of the state to enable grassroots leaders of accountability initiatives to develop the capabilities needed to mobilise collective action, shift the terms of interaction with the state and build more equitable health systems.
Cancer patients’ needs assessment in primary care: study protocol for a cluster randomised controlled trial (cRCT), economic evaluation and normalisation process theory evaluation of the needs assessment tool cancer (CANAssess)
Authors: Clark Joseph , Copsey Bethan , Wright-Hughes Alexandra , McNaught Emma , Bijsterveld Petra , McCormack Terry , Foy Robbie , Wilkes Scott , Dickson Jon Mark , Meads David , Farrin Amanda , Johnson Miriam
Published: May 2022

Introduction

Unmet needs in patients with cancer and their carers are common but poorly identified and addressed. The Needs Assessment Tool-Cancer (NAT-C) is a structured consultation guide to identify and triage patient and carer unmet needs. The NAT-C is validated, but its effectiveness in reducing unmet patient and carer needs in primary care is unknown.

Methods and analysis

Cluster randomised controlled trial with internal pilot and embedded process evaluation to test the clinical and cost effectiveness of the NAT-C in primary care for people with active cancer in reducing unmet patient and carer need, compared with usual care. We will recruit 1080 patients with active cancer (and carers if relevant) from 54 general practices in England.

Participating practices will be randomised 1:1 to either deliver an NAT-guided clinical consultation plus usual care or to usual care alone. Consenting participants with active cancer and their carers (if nominated) will be asked to complete study questionnaires at baseline, 1 and 3 months for all, 6 months except for those recruited outside of the last 3 months of recruitment, and attend an NAT-C appointment if allocated to an intervention practice. An internal pilot will assess: site and participant recruitment, intervention uptake and follow-up rates. The primary outcome, the proportion of patients with an unmet need on the Supportive Care Needs Survey Short Form 34 at 3 months postregistration, will be analysed using a multilevel logistic regression. Mixed-methods process evaluation informed by Normalisation Process Theory will use quantitative survey and interview data from clinicians and key stakeholders in cancer care to develop an implementation strategy for nationwide rollout of the NAT-C if the intervention is cost-effective.

Ethics and dissemination

Ethical approval from London-Surrey REC (20/LO/0312). Results will be peer-reviewed, published and made available to research participants.

Trial registration number

ISRCTN15497400.
Impact of an e-cigarette tax on cigarette and e-cigarette use in a middle-income country: a study from Indonesia using a pre–post design
Authors: Kowitt Sarah D , Anshari Dien , Orlan Elizabeth N , Kim KyungSu , Ranney Leah M , Goldstein Adam O , Byron M Justin
Published: May 2022

Objectives

Indonesia implemented its first e-cigarette regulation in 2018, a 57% tax on the retail price of e-cigarette liquid (e-liquid), exceeding the 40% average tax on cigarettes. Economic research suggests that this tax could unintentionally increase cigarette smoking among dual users, but this has not been examined in a low-income or middle-income country. We therefore investigated the effects of the e-liquid tax among adults in Indonesia.

Design

Pre–post study.

Setting

Indonesia.

Participants

Adults who currently used e-cigarettes and either currently or occasionally smoked cigarettes or recently quit were recruited using Facebook and Instagram ads. Our follow-up response rate was 79%. A final sample of 1039 adults participated.

Primary outcome measures

E-cigarette and cigarette use.

Results

Following the e-liquid tax, participants reported paying a 4.4% higher price for e-liquid (p=0.02). Participants also reported an average 0.5-day decrease in the number of days they used e-cigarettes in the past week (p<0.001), and the proportion of daily e-cigarette users decreased (75.9% to 63.6%; p<0.001). Overall, reported use of cigarettes also declined, on average, by nine cigarettes per week. Participants who reported decreasing their e-cigarette use had higher odds of reporting increasing their cigarette use rather than reporting no change (adjusted OR: 2.99; 95% CI: 1.95 to 4.59). Further, as participants reported using e-cigarettes less frequently, they reported using cigarettes more frequently (β=−2.41, p=0.007).

Conclusions

Following an e-liquid tax in Indonesia, prices of e-liquid increased slightly, e-cigarette and cigarette use declined, and people who reported decreasing their e-cigarette use reported increasing their cigarette use. To avoid encouraging cigarette use, a prudent approach would be to raise cigarette taxes concurrently with e-cigarette taxes.