bluuebunny/crossref_metadata_2025 huggingface dataset:
Alloy modification for additive manufactured Ni alloy components—part I: effect on microstructure and hardness of Invar alloy
Authors: Eissel Antonia , Engelking Lorenz , Gustus René , Treutler Kai , Wesling Volker , Schroepfer Dirk , Kannengiesser Thomas
Published: March 2023

Alloy 36 (1.3912), also known as “Invar,” is an alloy with 36% nickel. The alloy has a remarkably low thermal expansion coefficient in certain temperature ranges. This peculiarity is called the invar effect, which was discovered in 1896 by the Swiss physicist Charles Édouard Guillaume Sahoo and Medicherla Mater today Proc 43:2242-2244, (2021). Therefore, it is used in applications in which dimensional stability is critical, such as molding tools for composite materials in aerospace, automotive applications, or liquified natural gas (LNG) cargo tanks. Moreover, increasingly complex structures and the optimization of resource efficiency also require additive manufacturing steps for the production or repair of components Frazier J Mater Eng Perform 23:1917-1928, (2014); Treutler and Westling, (2021). Additively manufactured components have a heterogeneous microstructure and anisotropic mechanical properties Guévenoux et al. (2020). In addition, the manufactured components require subsequent machining surface finishing, like finish milling, to achieve their final contour. Nickel iron alloys are difficult to machine Zheng et al. Adv Mater Res 988:296–299, (2014). Additionally, inhomogeneous microstructure may lead to unstable cutting forces and conditions. In part I of this investigation, the initial alloy 36 is modified with the elements Ti, Zr, and Hf up to a maximum of 0.33 wt.-%. The influence of the modification elements on the microstructure as well as on the hardness of the AM components is examined. Furthermore, one modification is applied to metal arc welding process and investigated. Part II focuses on the effect of the alloy modifications on machinability as well as on the surface integrity of plasma-transferred-arc-welded (PTA) and finish milled invar components.
Lived Experiences of Low-Income Unmarried Women in Rural Botswana: A Narrative Approach
Authors: Malinga Tumani , Modie-Moroka Tirelo
Published: March 2023

The research explored the lived experiences of low-income single mothers, to understand the psychosocial life course pathways that might expose them to chains of risks. Studies have found a high prevalence of co-occurring poverty, single parenthood, unemployment, violence, and multiple life traumas among rural unmarried women. It is important to explore how single mothers are vulnerable to poverty and its many effects and how these factors heighten adverse experiences of unmarried rural women. Fifteen low-income unmarried Botswana mothers were purposively sampled. A narrative approach was used to collect data, allowing participants to share detailed lived experiences from childhood to adulthood. The study used a life course framework to explore the lived experiences, transitions, events, and trajectories of the women’s lives. Women’s narratives conveyed exposure to emotional, physical abuse and neglect in childhood; teenage pregnancy and the poverty connection; exposure to intimate partner violence; and multiple pregnancies and promised and suspended marriage. The study suggests that several life events and experiences have negatively influenced and skewed transitions and trajectories in the lives of low-income women. There is need for establishment of family policy and safety net programmes to cater for low-income mothers’ families.
Virtual Tools to Enable Management of Knee Osteoarthritis
Authors: Hinman Rana S. , Lawford Belinda J. , Nelligan Rachel K. , Bennell Kim L.
Published: March 2023

Purpose of review

There is increasing recognition that virtual tools, enabled by the internet and telecommunications technology, can increase access to health care. We review evidence about the clinical effectiveness and acceptability of telephone-delivered and videoconferencing clinician consultations, websites and internet-delivered programs, and SMS and mobile applications in enabling the management of people with knee osteoarthritis (OA). We discuss barriers to using virtual tools and suggest strategies to facilitate implementation in clinical settings.

Recent findings

An increasing number of systematic reviews, meta-analyses, and clinical trials provide evidence showing the effectiveness of virtual tools for improving knee OA management. Qualitative research shows that virtual tools increase patient access to knee OA care, are generally acceptable and convenient for patients, but can be associated with barriers to use from patient and clinician perspectives.

Virtual tools offer new opportunities to enable people with knee OA to manage their condition and receive care that may otherwise be difficult or not possible to access. Telephone calls and videoconferencing can be used for real-time synchronous consultations between clinicians and patients, increasing the geographic reach of health services. Websites and internet-based programs can be used to educate patients about their condition, as well as deliver exercise, weight management, and psychological interventions. Mobile apps can monitor and track OA symptoms, exercise, and physical activity, while SMS can facilitate positive behaviour changes for self-management over the long-term when sustained clinician contact may not be possible.
Are there gender differences in aspirations formation in rural Ethiopia?
Authors: Mekonnen Daniel Ayalew
Published: March 2023

This paper examines gender differences in aspirations formation (with respect to income, wealth, and children’s education) using survey data collected from sample households in rural Ethiopia. Results show evidence of upward looking income aspirations for both men and women, and upward looking wealth aspirations only for women, while the social effect of aspirations to children’s education appears to be weak for both sexes. Even though men (in general) appear to have higher aspirations than women, the differences in parameter estimates across gender are not statistically significant, suggesting that the gender-differentiated effect of social drivers on aspirations is limited. The results imply that policies and interventions that raise incomes in the village may increase income aspirations of both men and women, while efforts to enhance women’s wealth aspirations may be more effective if they improve wealth of women in the village. Since our sample is relatively small with limited geographic coverage, findings of this study could be context specific. Hence, further study using more recent and more representative data is necessary to draw fairly generalizable conclusions.
The ion flotation of copper, nickel, and cobalt using the biosurfactant surfactin
Authors: Schlebusch Izak , Pott Robert William McClelland , Tadie Margreth
Published: March 2023

Heavy metal contaminated waters are a significant environmental hazard, which require novel treatment methodologies. Further, the metals which might be recovered from these streams have significant intrinsic value, if they can be collected and concentrated. This work demonstrates, for the first time, the use of surfactin, an environmentally benign biosurfactant, for the flotation of metal ions (Cu2+, Ni2+, and Co2+). Surfactin, at a molar ratio of 1:3, has been shown to float 75.2%, 94.7%, and 98.2% of initial 100 $$\mu$$
μ
M solutions of copper nickel and cobalt, respectively. Increasing the gas flow rate modifies the float by increasing the carryover of water into the overflow. A pH of 5 was found to be ineffective (due to surfactin precipitation), while a pH of 10 was less effective than pH 7, likely due to the ionic speciation of the metals in solution tending to hydroxyl precipitates at a high pH. This work demonstrates an opportunity for the recovery of metals (at low concentrations) using biosurfactant-based froth flotation.
Closed for Democracy
Authors: Nuamah Sally A.
Published: March 2023

Every year, over 1,000 public schools are permanently closed across the United States. And yet, little is known about their impacts on American democracy. Closed for Democracy is the ﬁrst book to systematically study the political causes and democratic consequences of mass public school closures in the United States. The book investigates the declining presence of public schools in large cities and their impacts on the Americans most directly affected – poor Black citizens. It documents how these mass school closure policies target minority communities, making them feel excluded from the public goods afforded to equal citizens. In response, targeted communities become superlative participators to make their voices heard. Nevertheless, the high costs and low responsiveness associated with the policy process undermines their faith in the power of political participation. Ultimately, the book reveals that when schools shut down, so too does Black citizens' access to, and belief in, American democracy.
Erik Chisholm, Scottish Modernist (1904-1965)
Authors: Purser John
Published: March 2023

A study of the life and works of Erik Chisholm, one of the most influential figures in twentieth-century Scottish music.
Summary Catalogue of the Additional Medieval Manuscripts in Cambridge University Library Acquired before 1940
Authors: Ringrose Jayne S.
Published: March 2023

This volume provides a summary description of over three hundred western medieval manuscripts acquired by Cambridge University Library since the publication of the mid-nineteenth century printed catalogue; no published descriptions have hitherto existed.
Cuba and the New Origenismo
Authors: Buckwalter-Arias James
Published: March 2023

1990s' Cuban literature, caught between a beleaguered socialism and an encroaching global capitalism.
The Effect of Currents on Large Surface Gravity Waves Under Cyclonic Conditions in the South/Southeastern Brazil
Authors: Lauton Gustavo , Marta‐Almeida Martinho , Lentini Carlos A. D.
Published: March 2023

Although ocean surface currents are not accounted for in most wave modeling studies, recent works have demonstrated that ocean circulation features may have a great impact on surface gravity waves. In this case study, we coupled in a one‐way mode the hydrodynamic model Regional Ocean Modeling System (ROMS) and the wave model Simulating WAves Nearshore (SWAN) to study the effect of currents on large wave events (LWEs) produced under the influence of cyclones in south/southeastern Brazil. For the five LWEs studied, chosen due to the distinct importance that current‐to‐wave effects had for the period, the results indicate that the addition of currents on the wave model improved the accuracy of the peaks of significant wave height, generally increasing them (by as much as 27%). The increase in wave height occurred mainly near the shelf edge and slope, where the southwestward‐flowing Brazil Current opposes the dominant direction of cyclone‐generated waves (usually from S/SE to S/SW). Modulation of wave height by currents in the subinertial band explained up to 95% of the total variance of the difference between results with and without ocean currents, and this band was largely related to the Brazil Current. Its near‐inertial counterpart explained up to 22% of the total variance and was primarily due to near‐inertial currents in the region. This study provides, for the first time, conclusive evidence that wave‐current interaction can impact LWEs in south/southeastern Brazil.
Assimilation of GRACE Follow‐On Inter‐Satellite Laser Ranging Measurements Into Land Surface Models
Authors: Khaki Mehdi , Han Shin‐Chan , Ghobadi‐Far Khosro , Yeo In‐Young , Tangdamrongsub Natthachet
Published: March 2023

The monthly mean level‐2 (L2) time‐variable gravity as well as level‐3 (L3) Mass Concentration blocks (mascons) data from Gravity Recovery and Climate Experiment (GRACE) and GRACE Follow‐On (GRACE‐FO) missions are frequently used for improving land surface models. The conventional data assimilation approach requires several pre‐processing steps like filtering (to suppress the random and systematic errors), correction (to reduce the leakage effect) and scaling (to un‐do the attenuation effect by filters) before integrating the data with the models, for example, when computing total water storage (TWS) changes from L2 data. Moreover, due to the monthly sampling of L2 and L3 data, the model estimates are updated only once a month. This confines the applications of the approaches to cases where water storage is slowly varying at seasonal or interannual time‐scales. We present a new methodology based on direct assimilation of along‐orbit Line‐of‐sight Gravity Difference (LGD) measurements from the GRACE‐FO laser ranging interferometer (LRI) which overcomes the limitation of the conventional approach. Inter‐satellite ranging data reflect the gravitational changes at satellite altitude caused by the instantaneous TWS changes at the Earth surface. Therefore, they pose information at wide‐ranging time‐scales from hours to multiple years. The proposed method is applied globally to assimilate LRI data into a land surface model. Evaluation against multiple satellite‐based and ground data shows the superiority of our proposed approach. The new approach also offers better performance in capturing high‐frequency water storage variations imposed by sub‐monthly climatic events due to its higher number of data assimilation cycles within a month.
We (Probably) Can’t Tell Whether Mars Has Life
Authors: Francis Matthew
Published: March 2023

State-of-the-art equipment can’t always identify life inhabiting the most Mars-like spot on Earth, leaving scientists wondering how to do better on the Red Planet.
Impact of two ketogenic diet types in refractory childhood epilepsy
Authors: El-Shafie Ali M. , Bahbah Wael A. , Abd El Naby Sameh A. , Omar Zein A. , Basma Elsayedamr M. , Hegazy Aya A. A. , El Zefzaf Heba M. S.
Published: March 2023

Background

Ketogenic diet (KD) refers to any diet in which food composition induces a ketogenic state of human metabolism.

Objective

To assess short- and long-term efficacy, safety, and tolerability of KD [classic KD and modified Atkins diet (MAD)] in childhood drug-resistant epilepsy (DRE) and to investigate the effect of KD on electroencephalographic (EEG) features of children with DRE.

Methods

Forty patients diagnosed with DRE according to International League Against Epilepsy were included and randomly assigned into classic KD or MAD groups. KD was initiated after clinical, lipid profile and EEG documentation, and regular follow-up was done for 24 months.

Results

Out of 40 patients with DRE, 30 completed this study. Both classic KD and MAD were effective in seizure control as 60% in classic KD group and 53.33% in MAD group became seizure free, and the remaining showed ≥50% seizure reduction. Lipid profile remained within acceptable levels throughout the study period in both groups. Adverse effects were mild and managed medically with an improvement of growth parameters and EEG during the study period.

Conclusions

KD is an effective and safe non-pharmacologic, non-surgical therapy for the management of DRE with a positive impact on growth and EEG.

Impact

Both common types of KD (classic KD and MAD) are effective for DRE, but unfortunately, nonadherence and dropout rates are frequent.

High serum lipid profile (cardiovascular AE) is often suspected in children following a high-fat diet, but lipid profile remained in the acceptable level up to 24 months. Therefore, KD constitutes a safe treatment.

KD had a positive impact on growth, despite inconsistent results of the KD’s effect on growth.

In addition to showing strong clinical effectiveness, KD also considerably decreased the frequency of interictal epileptiform discharges and enhanced the EEG background rhythm.
The genetic architecture of human amygdala volumes and their overlap with common brain disorders
Authors: Ou Ya-Nan , Wu Bang-Sheng , Ge Yi-Jun , Zhang Yi , Jiang Yu-Chao , Kuo Kevin , Yang Liu , Tan Lan , Feng Jian-Feng , Cheng Wei , Yu Jin-Tai
Published: March 2023

The amygdala is a crucial interconnecting structure in the brain that performs several regulatory functions, yet its genetic architectures and involvement in brain disorders remain largely unknown. We carried out the first multivariate genome-wide association study (GWAS) of amygdala subfield volumes in 27,866 UK Biobank individuals. The whole amygdala was segmented into nine nuclei groups using Bayesian amygdala segmentation. The post-GWAS analysis allowed us to identify causal genetic variants in phenotypes at the SNP, locus, and gene levels, as well as genetic overlap with brain health-related traits. We further generalized our GWAS in Adolescent Brain Cognitive Development (ABCD) cohort. The multivariate GWAS identified 98 independent significant variants within 32 genomic loci associated (P < 5 × 10−8) with amygdala volume and its nine nuclei. The univariate GWAS identified significant hits for eight of the ten volumes, tagging 14 independent genomic loci. Overall, 13 of the 14 loci identified in the univariate GWAS were replicated in the multivariate GWAS. The generalization in ABCD cohort supported the GWAS results with the 12q23.2 (RNA gene RP11-210L7.1) being discovered. All of these imaging phenotypes are heritable, with heritability ranging from 15% to 27%. Gene-based analyses revealed pathways relating to cell differentiation/development and ion transporter/homeostasis, with the astrocytes found to be significantly enriched. Pleiotropy analyses revealed shared variants with neurological and psychiatric disorders under the conjFDR threshold of 0.05. These findings advance our understanding of the complex genetic architectures of amygdala and their relevance in neurological and psychiatric disorders.
Oral care considerations for people with cystic fibrosis: a cross-sectional qualitative study
Authors: Coffey Niamh , O’ Leary Fiona , Burke Francis , Plant Barry , Roberts Anthony , Hayes Martina
Published: March 2023

Objectives

To investigate the attitudes of adults with Cystic Fibrosis (CF) towards dental attendance and any perceived barriers to treatment.

Methods

A cross sectional survey in the form of a structured, anonymous questionnaire was used to obtain information regarding adults with CF’s feelings towards dentists and dental treatment. The final version of the questionnaire was based on a collaborative effort between researchers at Cork University Dental School and Hospital and Cystic Fibrosis (CF) patient advocates from CF Ireland. Participants were recruited via CF Ireland’s mailing list and social media channels. The responses underwent descriptive statistical analysis and inductive thematic analysis.

Results

A total of 71 people (33 Male: 38 Female) over the age of 18 living with CF in the Republic of Ireland responded to the survey. 54.9% of respondents were unhappy with their teeth. 63.4% felt that CF had an impact on oral health. 33.8% were anxious about attending their dentist. Respondents believed that CF has impacted on their oral health due to the medications and dietary requirements involved, as well as tiredness and other side effects of CF. Reasons for being anxious about attending the dentist included cross infection concerns, issues with the dentist, with tolerating treatment, and with the teeth themselves. Respondents wanted dentists to be aware of the practicalities of dental treatment for people with CF, especially their discomfort with lying back. They also want the dentist to be aware of the impact that their medication, treatment and diet has on their oral health.

Conclusions

Over one third of adults with CF reported anxiety about attending the dentist. Reasons for this included fear, embarrassment, cross infection concerns and problems with treatment, especially being in the supine position. Adults with CF want dentists to be aware of the impact that CF can have upon dental treatment and oral health care.
Smartphone-based platforms implementing microfluidic detection with image-based artificial intelligence
Authors: Wang Bangfeng , Li Yiwei , Zhou Mengfan , Han Yulong , Zhang Mingyu , Gao Zhaolong , Liu Zetai , Chen Peng , Du Wei , Zhang Xingcai , Feng Xiaojun , Liu Bi-Feng
Published: March 2023

The frequent outbreak of global infectious diseases has prompted the development of rapid and effective diagnostic tools for the early screening of potential patients in point-of-care testing scenarios. With advances in mobile computing power and microfluidic technology, the smartphone-based mobile health platform has drawn significant attention from researchers developing point-of-care testing devices that integrate microfluidic optical detection with artificial intelligence analysis. In this article, we summarize recent progress in these mobile health platforms, including the aspects of microfluidic chips, imaging modalities, supporting components, and the development of software algorithms. We document the application of mobile health platforms in terms of the detection objects, including molecules, viruses, cells, and parasites. Finally, we discuss the prospects for future development of mobile health platforms.
Autocatalytic base editing for RNA-responsive translational control
Authors: Gayet Raphaël V. , Ilia Katherine , Razavi Shiva , Tippens Nathaniel D. , Lalwani Makoto A. , Zhang Kehan , Chen Jack X. , Chen Jonathan C. , Vargas-Asencio Jose , Collins James J.
Published: March 2023

Genetic circuits that control transgene expression in response to pre-defined transcriptional cues would enable the development of smart therapeutics. To this end, here we engineer programmable single-transcript RNA sensors in which adenosine deaminases acting on RNA (ADARs) autocatalytically convert target hybridization into a translational output. Dubbed DART VADAR (Detection and Amplification of RNA Triggers via ADAR), our system amplifies the signal from editing by endogenous ADAR through a positive feedback loop. Amplification is mediated by the expression of a hyperactive, minimal ADAR variant and its recruitment to the edit site via an orthogonal RNA targeting mechanism. This topology confers high dynamic range, low background, minimal off-target effects, and a small genetic footprint. We leverage DART VADAR to detect single nucleotide polymorphisms and modulate translation in response to endogenous transcript levels in mammalian cells.
A cybergenetic framework for engineering intein-mediated integral feedback control systems
Authors: Anastassov Stanislav , Filo Maurice , Chang Ching-Hsiang , Khammash Mustafa
Published: March 2023

The ability of biological systems to tightly regulate targeted variables, despite external and internal disturbances, is known as Robust Perfect Adaptation (RPA). Achieved frequently through biomolecular integral feedback controllers at the cellular level, RPA has important implications for biotechnology and its various applications. In this study, we identify inteins as a versatile class of genetic components suitable for implementing these controllers and present a systematic approach for their design. We develop a theoretical foundation for screening intein-based RPA-achieving controllers and a simplified approach for modeling them. We then genetically engineer and test intein-based controllers using commonly used transcription factors in mammalian cells and demonstrate their exceptional adaptation properties over a wide dynamic range. The small size, flexibility, and applicability of inteins across life forms allow us to create a diversity of genetic RPA-achieving integral feedback control systems that can be used in various applications, including metabolic engineering and cell-based therapy.
Interpretable and context-free deconvolution of multi-scale whole transcriptomic data with UniCell deconvolve
Authors: Charytonowicz Daniel , Brody Rachel , Sebra Robert
Published: March 2023

We introduce UniCell: Deconvolve Base (UCDBase), a pre-trained, interpretable, deep learning model to deconvolve cell type fractions and predict cell identity across Spatial, bulk-RNA-Seq, and scRNA-Seq datasets without contextualized reference data. UCD is trained on 10 million pseudo-mixtures from a fully-integrated scRNA-Seq training database comprising over 28 million annotated single cells spanning 840 unique cell types from 898 studies. We show that our UCDBase and transfer-learning models achieve comparable or superior performance on in-silico mixture deconvolution to existing, reference-based, state-of-the-art methods. Feature attribute analysis uncovers gene signatures associated with cell-type specific inflammatory-fibrotic responses in ischemic kidney injury, discerns cancer subtypes, and accurately deconvolves tumor microenvironments. UCD identifies pathologic changes in cell fractions among bulk-RNA-Seq data for several disease states. Applied to lung cancer scRNA-Seq data, UCD annotates and distinguishes normal from cancerous cells. Overall, UCD enhances transcriptomic data analysis, aiding in assessment of cellular and spatial context.
Interface synergism and engineering of Pd/Co@N-C for direct ethanol fuel cells
Authors: Chang Jinfa , Wang Guanzhi , Chang Xiaoxia , Yang Zhenzhong , Wang Han , Li Boyang , Zhang Wei , Kovarik Libor , Du Yingge , Orlovskaya Nina , Xu Bingjun , Wang Guofeng , Yang Yang
Published: March 2023

Direct ethanol fuel cells have been widely investigated as nontoxic and low-corrosive energy conversion devices with high energy and power densities. It is still challenging to develop high-activity and durable catalysts for a complete ethanol oxidation reaction on the anode and accelerated oxygen reduction reaction on the cathode. The materials’ physics and chemistry at the catalytic interface play a vital role in determining the overall performance of the catalysts. Herein, we propose a Pd/Co@N-C catalyst that can be used as a model system to study the synergism and engineering at the solid-solid interface. Particularly, the transformation of amorphous carbon to highly graphitic carbon promoted by cobalt nanoparticles helps achieve the spatial confinement effect, which prevents structural degradation of the catalysts. The strong catalyst-support and electronic effects at the interface between palladium and Co@N-C endow the electron-deficient state of palladium, which enhances the electron transfer and improved activity/durability. The Pd/Co@N-C delivers a maximum power density of 438 mW cm−2 in direct ethanol fuel cells and can be operated stably for more than 1000 hours. This work presents a strategy for the ingenious catalyst structural design that will promote the development of fuel cells and other sustainable energy-related technologies.
Clinical and biomarker analyses of sintilimab plus gemcitabine and cisplatin as first-line treatment for patients with advanced biliary tract cancer
Authors: Zeng Tian-mei , Yang Guang , Lou Cheng , Wei Wei , Tao Chen-jie , Chen Xi-yun , Han Qin , Cheng Zhuo , Shang Pei-pei , Dong Yu-long , Xu He-ming , Guo Lie-ping , Chen Dong-sheng , Song Yun-jie , Qi Chuang , Deng Wang-long , Yuan Zhen-gang
Published: March 2023

The prognosis of biliary tract cancer (BTC) remains unsatisfactory. This single-arm, phase II clinical trial (ChiCTR2000036652) investigated the efficacy, safety, and predictive biomarkers of sintilimab plus gemcitabine and cisplatin as the first-line treatment for patients with advanced BTCs. The primary endpoint was overall survival (OS). Secondary endpoints included toxicities, progression-free survival (PFS), and objective response rate (ORR); multi-omics biomarkers were assessed as exploratory objective. Thirty patients were enrolled and received treatment, the median OS and PFS were 15.9 months and 5.1 months, the ORR was 36.7%. The most common grade 3 or 4 treatment-related adverse events were thrombocytopenia (33.3%), with no reported deaths nor unexpected safety events. Predefined biomarker analysis indicated that patients with homologous recombination repair pathway gene alterations or loss-of-function mutations in chromatin remodeling genes presented better tumor response and survival outcomes. Furthermore, transcriptome analysis revealed a markedly longer PFS and tumor response were associated with higher expression of a 3-gene effector T cell signature or an 18-gene inflamed T cell signature. Sintilimab plus gemcitabine and cisplatin meets pre-specified endpoints and displays acceptable safety profile, multiomics potential predictive biomarkers are identified and warrant further verification.
Molecular mechanism of biased signaling at the kappa opioid receptor
Authors: El Daibani Amal , Paggi Joseph M. , Kim Kuglae , Laloudakis Yianni D. , Popov Petr , Bernhard Sarah M. , Krumm Brian E. , Olsen Reid H. J. , Diberto Jeffrey , Carroll F. Ivy , Katritch Vsevolod , Wünsch Bernhard , Dror Ron O. , Che Tao
Published: March 2023

The κ-opioid receptor (KOR) has emerged as an attractive drug target for pain management without addiction, and biased signaling through particular pathways of KOR may be key to maintaining this benefit while minimizing side-effect liabilities. As for most G protein-coupled receptors (GPCRs), however, the molecular mechanisms of ligand-specific signaling at KOR have remained unclear. To better understand the molecular determinants of KOR signaling bias, we apply structure determination, atomic-level molecular dynamics (MD) simulations, and functional assays. We determine a crystal structure of KOR bound to the G protein-biased agonist nalfurafine, the first approved KOR-targeting drug. We also identify an arrestin-biased KOR agonist, WMS-X600. Using MD simulations of KOR bound to nalfurafine, WMS-X600, and a balanced agonist U50,488, we identify three active-state receptor conformations, including one that appears to favor arrestin signaling over G protein signaling and another that appears to favor G protein signaling over arrestin signaling. These results, combined with mutagenesis validation, provide a molecular explanation of how agonists achieve biased signaling at KOR.
Microbiota alters the metabolome in an age- and sex- dependent manner in mice
Authors: Brown Kirsty , Thomson Carolyn A. , Wacker Soren , Drikic Marija , Groves Ryan , Fan Vina , Lewis Ian A. , McCoy Kathy D.
Published: March 2023

Commensal bacteria are major contributors to mammalian metabolism. We used liquid chromatography mass spectrometry to study the metabolomes of germ-free, gnotobiotic, and specific-pathogen-free mice, while also evaluating the influence of age and sex on metabolite profiles. Microbiota modified the metabolome of all body sites and accounted for the highest proportion of variation within the gastrointestinal tract. Microbiota and age explained similar amounts of variation the metabolome of urine, serum, and peritoneal fluid, while age was the primary driver of variation in the liver and spleen. Although sex explained the least amount of variation at all sites, it had a significant impact on all sites except the ileum. Collectively, these data illustrate the interplay between microbiota, age, and sex in the metabolic phenotypes of diverse body sites. This provides a framework for interpreting complex metabolic phenotypes and will help guide future studies into the role that the microbiome plays in disease.
The collective burst mechanism of angular jumps in liquid water
Authors: Offei-Danso Adu , Morzan Uriel N. , Rodriguez Alex , Hassanali Ali , Jelic Asja
Published: March 2023

Understanding the microscopic origins of collective reorientational motions in aqueous systems requires techniques that allow us to reach beyond our chemical imagination. Herein, we elucidate a mechanism using a protocol that automatically detects abrupt motions in reorientational dynamics, showing that large angular jumps in liquid water involve highly cooperative orchestrated motions. Our automatized detection of angular fluctuations, unravels a heterogeneity in the type of angular jumps occurring concertedly in the system. We show that large orientational motions require a highly collective dynamical process involving correlated motion of many water molecules in the hydrogen-bond network that form spatially connected clusters going beyond the local angular jump mechanism. This phenomenon is rooted in the collective fluctuations of the network topology which results in the creation of defects in waves on the THz timescale. The mechanism we propose involves a cascade of hydrogen-bond fluctuations underlying angular jumps and provides new insights into the current localized picture of angular jumps, and its wide use in the interpretations of numerous spectroscopies as well in reorientational dynamics of water near biological and inorganic systems. The role of finite size effects, as well as of the chosen water model, on the collective reorientation is also elucidated.
Short-term molecular consequences of chromosome mis-segregation for genome stability
Authors: Garribba Lorenza , De Feudis Giuseppina , Martis Valentino , Galli Martina , Dumont Marie , Eliezer Yonatan , Wardenaar René , Ippolito Marica Rosaria , Iyer Divya Ramalingam , Tijhuis Andréa E. , Spierings Diana C. J. , Schubert Michael , Taglietti Silvia , Soriani Chiara , Gemble Simon , Basto Renata , Rhind Nick , Foijer Floris , Ben-David Uri , Fachinetti Daniele , Doksani Ylli , Santaguida Stefano
Published: March 2023

Chromosome instability (CIN) is the most common form of genome instability and is a hallmark of cancer. CIN invariably leads to aneuploidy, a state of karyotype imbalance. Here, we show that aneuploidy can also trigger CIN. We found that aneuploid cells experience DNA replication stress in their first S-phase and precipitate in a state of continuous CIN. This generates a repertoire of genetically diverse cells with structural chromosomal abnormalities that can either continue proliferating or stop dividing. Cycling aneuploid cells display lower karyotype complexity compared to the arrested ones and increased expression of DNA repair signatures. Interestingly, the same signatures are upregulated in highly-proliferative cancer cells, which might enable them to proliferate despite the disadvantage conferred by aneuploidy-induced CIN. Altogether, our study reveals the short-term origins of CIN following aneuploidy and indicates the aneuploid state of cancer cells as a point mutation-independent source of genome instability, providing an explanation for aneuploidy occurrence in tumors.
An effective way to control the radical reaction and its mechanism in EPDM under γ-ray irradiation
Authors: Zhou Yiyang , Meng Qiuyue , Chen Ming , Wang Chenxi , Jiang Tao , Zhou Jingsong , Wang Ping , Xia Lei , You Yezi , Wei Haibing , Ding Yunsheng
Published: March 2023

The effects of a compound that contains a xanthate group named DIP on the radical reactions and structural evolution of the ethylene propylene diene monomer (EPDM) were investigated. It was found that the structural evolution and long-term stability of the EPDM can be realized by controlling the radical reaction in the matrixes of EPDM during γ-ray irradiation. The results show that the DIP can prevent EPDM deterioration, when the γ-ray irradiation dose reaches 450 kGy, the retention rate of the elongation at break and tensile strength of the EPDM samples containing 1 wt% DIP could remain about 90% and 160%, while those of additive-free EPDM are only about 33% and 70%. On the other hand, the thermal stability of the EPDM samples decreases markedly with the dose increasing under γ-ray irradiation. However, the thermal decomposition temperature of the EPDM samples containing DIP remains basically unchanged after irradiation, and DIP can also improve the oxidation resistance of the EPDM. Electron spin resonance studies reveal that DIP can effectively control the radical reactions inside the EPDM during γ-ray irradiation. Rheology results show that the structural evolution of the EPDM can be well controlled under γ-ray irradiation owing to the presence of DIP in the EPDM matrixes. Density functional theory calculations indicate that the reversible radical reactions inside EPDM/DIP systems are crucial in realizing the long-term stability and controllable structural evolution of the EPDM under γ-ray irradiation.
Inflammatory CSF profiles and longitudinal development of cognitive decline in sporadic and GBA-associated PD
Authors: Lerche Stefanie , Zimmermann Milan , Roeben Benjamin , Wurster Isabel , Fries Franca Laura , Deuschle Christian , Waniek Katharina , Lachmann Ingolf , Jakobi Meike , Joos Thomas O. , Knorpp Thomas , Schneiderhan-Marra Nicole , Brockmann Kathrin
Published: March 2023

Inflammation modifies the incidence and progression of Parkinson’s disease (PD). By using 30 inflammatory markers in CSF in 498 people with PD and 67 people with dementia with Lewy bodies (DLB) we show that: (1) levels of ICAM-1, Interleukin-8, MCP-1, MIP-1 beta, SCF and VEGF were associated with clinical scores and neurodegenerative CSF biomarkers (Aβ1-42, t-Tau, p181-Tau, NFL and α-synuclein). (2) PD patients with GBA mutations show similar levels of inflammatory markers compared to PD patients without GBA mutations, even when stratified by mutation severity. (3) PD patients who longitudinally developed cognitive impairment during the study had higher levels of TNF-alpha at baseline compared to patients without the development of cognitive impairment. (4) Higher levels of VEGF and MIP-1 beta were associated with a longer duration until the development of cognitive impairment. We conclude that the majority of inflammatory markers is limited in robustly predicting longitudinal trajectories of developing cognitive impairment.
Urinary exosomal microRNAs as predictive biomarkers for persistent psychotic-like experiences
Authors: Tomita Yasufumi , Suzuki Kazuhiro , Yamasaki Syudo , Toriumi Kazuya , Miyashita Mitsuhiro , Ando Shuntaro , Endo Kaori , Yoshikawa Akane , Tabata Koichi , Usami Satoshi , Hiraiwa-Hasegawa Mariko , Itokawa Masanari , Kawaji Hideya , Kasai Kiyoto , Nishida Atsushi , Arai Makoto
Published: March 2023

Psychotic-like experiences (PLEs) occur occasionally in adolescence and mostly disappear with increasing age. Their presence, if persistent, is considered a robust risk factor for subsequent psychiatric disorders. To date, only a few biological markers have been investigated for persistent PLE prediction. This study identified urinary exosomal microRNAs that can serve as predictive biomarkers for persistent PLEs. This study was part of a population-based biomarker subsample study of the Tokyo Teen Cohort Study. A total of 345 participants aged 13 (baseline) and 14 (follow-up) years underwent PLE assessments by experienced psychiatrists using semi-structured interviews. We defined remitted and persistent PLEs based on longitudinal profiles. We obtained urine at baseline and the expression levels of urinary exosomal miRNAs were compared between 15 individuals with persistent PLEs and 15 age- and sex-matched individuals with remitted PLEs. We constructed a logistic regression model to examine whether miRNA expression levels could predict persistent PLEs. We identified six significant differentially expressed microRNAs, namely hsa-miR-486-5p, hsa-miR-199a-3p, hsa-miR-144-5p, hsa-miR-451a, hsa-miR-143-3p, and hsa-miR-142-3p. The predictive model showed an area under the curve of 0.860 (95% confidence interval: 0.713–0.993) for five-fold cross-validation. We found a subset of urinary exosomal microRNAs that were differentially expressed in persistent PLEs and presented the likelihood that a microRNA-based statistical model could predict them with high accuracy. Therefore, urine exosomal miRNAs may serve as novel biomarkers for the risk of psychiatric disorders.
Dust flow analysis by low coherence Doppler lidar
Authors: Okubo Kosuke , Lagrosas Nofel , Shiina Tatsuo
Published: March 2023

Visualization of dust flow and wind dynamics near the ground surface are essential for understanding the mixing and interaction between geosphere and atmosphere near the surface. Knowing the temporal dust flow is beneficial in dealing with air pollution and health issues. Dust flows near the ground surface are difficult to monitor because of their small temporal and spatial scale. In this study, we propose a low-coherence Doppler lidar (LCDL) for measuring dust flow near the ground with high temporal and spatial resolutions of 5 ms and 1 m, respectively. We demonstrate the performance of LCDL in laboratory experiments using flour and calcium carbonate particles released into the wind tunnel. LCDL experiment results show a good agreement with anemometer measurement in wind speeds ranging from 0 to 5 m/s. The LCDL technique can reveal dust’s speed distribution, which is affected by mass and particle size. As a result, different speed distribution profiles can be used to determine dust type. The simulation results of dust flow coincide well with the experimental results.
Larval rockfish growth and survival in response to anomalous ocean conditions
Authors: Fennie H. William , Grorud-Colvert Kirsten , Sponaugle Su
Published: March 2023

Understanding how future ocean conditions will affect populations of marine species is integral to predicting how climate change will impact both ecosystem function and fisheries management. Fish population dynamics are driven by variable survival of the early life stages, which are highly sensitive to environmental conditions. As global warming generates extreme ocean conditions (i.e., marine heatwaves) we can gain insight into how larval fish growth and mortality will change in warmer conditions. The California Current Large Marine Ecosystem experienced anomalous ocean warming from 2014 to 2016, creating novel conditions. We examined the otolith microstructure of juveniles of the economically and ecologically important black rockfish (Sebastes melanops) collected from 2013 to 2019 to quantify the implications of changing ocean conditions on early growth and survival. Our results demonstrated that fish growth and development were positively related to temperature, but survival to settlement was not directly related to ocean conditions. Instead, settlement had a dome-shaped relationship with growth, suggesting an optimal growth window. Our results demonstrated that the dramatic change in water temperature caused by such extreme warm water anomalies increased black rockfish growth in the larval stage; however, without sufficient prey or with high predator abundance these extreme conditions contributed to reduced survival.
Cyanobacteria blooms induced precipitation of calcium carbonate and dissolution of silica in a subtropical lagoon, Florida Bay, USA
Authors: Zhang Jia-Zhong
Published: March 2023

In recent decades, annual cyanobacteria blooms in Florida Bay displayed spatial and temporal patterns that are consistent with changes in alkalinity and dissolved silicon in water. In early summer, the blooms developed in the north–central bay and spread southward in fall. The blooms drew down dissolved inorganic carbon and increased water pH, causing in situ precipitation of calcium carbonate. Dissolved silicon concentrations in these waters were at minimum in spring (20–60 µM), increased during summer, and reached an annual maximum (100–200 µM) during late summer. The dissolution of silica as a result of high pH in bloom water was first observed in this study. During the peak of blooms, silica dissolution in Florida Bay varied from 0.9 × 107 to 6.9 × 107 mol per month over the study period, depending on the extent of cyanobacteria blooms in a given year. Concurrent calcium carbonate precipitations in the cyanobacteria bloom region are between 0.9 × 108 and 2.6 × 108 mol per month. It is estimated that 30–70% of atmospheric CO2 uptake in bloom waters was precipitated as calcium carbonate mineral and remainders of CO2 influx were used for the production of biomass.
Understanding the effect of component proportions on disease control in two-component cultivar cereal mixtures using a pathogen dispersal scaling hypothesis
Authors: Newton Adrian C. , Skelsey Peter
Published: March 2023

A field experiment was carried out to determine the importance of component cultivar proportions to spring barley mixture efficacy against rhynchosporium or scald symptoms caused by the splash-dispersed pathogen Rhynchosporium commune. A larger effect than expected was observed of small amounts of one component on another for reducing disease overall, but relative insensitivity to proportion as amounts of each component become more similar. An established theoretical framework, the ‘Dispersal scaling hypothesis’, was used to model the expected effect of mixing proportions on the spatiotemporal spread of disease. The model captured the unequal effect of mixing different proportions on disease spread and there was good agreement between predictions and observations. The dispersal scaling hypothesis therefore provides a conceptual framework to explain the observed phenomenon, and a tool to predict the proportion of mixing at which mixture performance is maximized.
Uranium oxides structural transformation in human body liquids
Authors: Poliakova Tatiana , Krot Anna , Trigub Alexander , Nevolin Iurii , Averin Alexey , Yapaskurt Vasiliy , Vlasova Irina , Matveev Petr , Kalmykov Stepan
Published: March 2023

Uranium oxide microparticles ingestion is one of the potential sources of internal radiation doses to the humans at accidental or undesirable releases of radioactive materials. It is important to predict the obtained dose and possible biological effect of these microparticles by studying uranium oxides transformations in case of their ingestion or inhalation. Using a combination of methods, a complex examination of structural changes of uranium oxides in the range from UO2 to U4O9, U3O8 and UO3 as well as before and after exposure of uranium oxides in simulated biological fluids: gastro-intestinal and lung—was carried out. Oxides were thoroughly characterized by Raman and XAFS spectroscopy. It was determined that the duration of expose has more influence on all oxides transformations. The greatest changes occurred in U4O9, that transformed into U4O9-y. UO2.05 and U3O8 structures became more ordered and UO3 did not undergo significant transformation.
Numerical simulation of laser-produced plasma expansion on a droplet surface
Authors: Zhao Zhenyu , Li Weizhong
Published: March 2023

In this study, a numerical model of the plasma expansion on a droplet surface based on the initial plasma method was proposed. The initial plasma was obtained through the pressure inlet boundary condition, and the effect of ambient pressure on the initial plasma and adiabatic expansion of the plasma on the droplet surface, including the effect on the velocity and temperature distribution, were investigated. The simulation results showed that the ambient pressure decreased, leading to an increase in the expansion rate and temperature, and therefore a larger plasma size was formed. Plasma expansion creates a backward driving force and eventually envelops the entire droplet, indicating a significant difference compared to planar targets.