bluuebunny/crossref_metadata_2025 huggingface dataset:
Retinoic acid drives hair follicle stem cell activation via Wnt/β‐catenin signalling in androgenetic alopecia
Authors: Wen Lihong , Fan Zhexiang , Huang Weichang , Miao Yong , Zhang Jiarui , Liu Bingcheng , Zhu Decong , Dai Damao , Zhang Jiaxian , Le Demengjie , Zhang Yufan , Qu Qian , Hu Zhiqi , Chen Ruosi
Published: April 2024

Background

Depletion or permanent quiescence of the hair follicle stem cell (HFSC) pool underlies pathogenesis in androgenetic alopecia (AGA). Reactivation of quiescent HFSCs is considered an efficient treatment strategy for hair loss. The retinoic acid (RA) is critical to ensure stem cell homeostasis and function. However, little is known about whether RA regulates HFSC homeostasis. We aimed to investigate the impact of RA on HFSC homeostasis and the underlying mechanisms, in order to provide new potential targets for medical therapies of AGA.

Methods

Microdissected hair follicles from the occipital and frontal scalp in AGA were obtained for RNA sequencing analysis and test. The C57BL/6 mice model in telogen was established to investigate the effect of exogenous RA. Miniaturized hair follicles from frontal scalp were incubated with or without RA in hair follicle organ culture to test the effects on hair shaft elongation, hair cycling and HFSC activities. A strategy to characterize the effect of RA on HFSC in primary culture was developed to identify novel mechanisms that control HFSC activation. A clinical study was performed to test the efficacy of RA treatment in AGA patients.

Results

RA signalling was inhibited in the course of AGA pathogenesis along with HFSC dysfunction. Hair regeneration was retarded in AGA miniaturized hair follicles with RA deficiency, but they tended to recover after treatment with RA. In addition, RA treatment during the telogen phase facilitated HFSC anagen entry and accelerated hair growth. Mechanistically, RA promoted hair growth by stimulating stem cells via Wnt/β‐catenin signalling and accelerating the transition from a dormant to an activated state. Furthermore, a clinical study suggested that RA has obvious advantages in the early intervention of AGA by reactivating HFSCs.

Conclusions

Our study provides insights into the reactivation of HFSCs in AGA and provides potential targets for medical therapies.
Deciphering metabolic dysfunction‐associated steatotic liver disease: insights from predictive modeling and clustering analysis
Authors: Mori Kazuma , Akiyama Yukinori , Tanaka Marenao , Sato Tatsuya , Endo Keisuke , Hosaka Itaru , Hanawa Nagisa , Sakamoto Naoya , Furuhashi Masato
Published: April 2024

Background and Aim

New nomenclature of steatotic liver disease (SLD) including metabolic dysfunction‐associated SLD (MASLD), MASLD and increased alcohol intake (MetALD), and alcohol‐associated liver disease (ALD) has recently been proposed. We investigated clustering analyses to decipher the complex landscape of SLD pathologies including the former nomenclature of nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction‐associated fatty liver disease (MAFLD).

Methods

Japanese individuals who received annual health checkups including abdominal ultrasonography (n = 15 788, men/women: 10 250/5538, mean age: 49 years) were recruited.

Results

The numbers of individuals with SLD, MASLD, MetALD, ALD, NAFLD, and MAFLD were 5603 (35.5%), 4227 (26.8%), 795 (5.0%), 324 (2.1%), 3982 (25.8%), and 4946 (31.3%), respectively. Clustering analyses using t‐distributed stochastic neighbor embedding and K‐means to visually represent interconnections in SLDs uncovered five cluster formations. MASLD and NAFLD mainly shared three clusters including (i) low alcohol intake with relatively low‐grade obesity; (ii) obesity with dyslipidemia; and (iii) dysfunction of glucose metabolism. Both MetALD and ALD displayed one distinct cluster intertwined with alcohol consumption. MAFLD widely shared all of the five clusters. In machine learning‐based analyses using algorithms of random forest and extreme gradient boosting and receiver operating characteristic curve analyses, fatty liver index (FLI), calculated by body mass index, waist circumference, and levels of γ‐glutamyl transferase and triglycerides, was selected as a useful feature for SLDs.

Conclusions

The new nomenclature of SLDs is useful for obtaining a better understanding of liver pathologies and for providing valuable insights into predictive factors and the dynamic interplay of diseases. FLI may be a noninvasive predictive marker for detection of SLDs.
Efficacy of pharmacologic interventions on magnetic resonance imaging biomarkers in patients with nonalcoholic fatty liver disease: systematic review and network meta‐analysis
Authors: Malandris Konstantinos , Papandreou Stylianos , Vasilakou Despoina , Kakotrichi Panagiota , Sarakapina Anna , Kalopitas Georgios , Karagiannis Thomas , Giouleme Olga , Bekiari Eleni , Liakos Aris , Iatridi Fotini , Paschos Paschalis , Sinakos Emmanouil , Tsapas Apostolos
Published: April 2024

Background and Aim

Several agents are under investigation for nonalcoholic fatty liver disease (NAFLD). We assessed the comparative efficacy of pharmacologic interventions for patients with NAFLD focusing on magnetic resonance imaging (MRI) biomarkers.

Methods

We searched Medline, Embase, and CENTRAL. We included randomized controlled trials of more than 12 weeks of intervention that recruited patients with biopsy‐confirmed or MRI‐confirmed NAFLD and assessed the efficacy of interventions on liver fat content (LFC) and fibrosis by means of MRI. We performed random‐effects frequentist network meta‐analyses and assessed confidence in our estimates using the CINeMA (Confidence in Network Meta‐Analysis) approach.

Results

We included 47 trials (8583 patients). Versus placebo, thiazolidinediones were the most efficacious for the absolute change in LFC, followed by vitamin E, fibroblast growth factor (FGF) analogs, and glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) with mean differences ranging from −7.46% (95% confidence interval [−11.0, −3.9]) to −4.36% (−7.2, −1.5). No differences between drug classes were evident. Patients receiving GLP‐1 RAs or glucose‐dependent insulinotropic polypeptide (GIP)/GLP‐1 RAs were more likely to achieve ≥30% relative reduction in LFC. Among agents, efruxifermin produced the largest reduction in LFC compared to placebo [−13.5% (−18.5, −8.5)], followed by pioglitazone, while being superior to most interventions. The effect of interventions on magnetic resonance elastography assessed fibrosis was small and insignificant. The confidence in our estimates was low to very low.

Conclusions

Several drug classes may reduce LFC in patients with NAFLD without a significant effect on fibrosis; nevertheless, trial duration was small, and confidence in the effect estimates was low.
OsATL32 ubiquitinates the reactive oxygen species‐producing OsRac5–OsRbohB module to suppress rice immunity
Authors: Yan Yuqing , Wang Hui , Bi Yan , Wang Jiajing , Noman Muhammad , Li Dayong , Song Fengming
Published: April 2024

Ubiquitination‐mediated protein degradation is integral to plant immunity, with E3 ubiquitin ligases acting as key factors in this process. Here, we report the functions of OsATL32, a plasma membrane‐localized Arabidopsis Tóxicos En Levadura (ATL)‐type E3 ubiquitin ligase, in rice (Oryza sativa) immunity and its associated regulatory network. We found that the expression of OsATL32 is downregulated in both compatible and incompatible interactions between rice and the rice blast fungus Magnaporthe oryzae. The OsATL32 protein level declines in response to infection by a compatible M. oryzae strain or to chitin treatment. OsATL32 negatively regulates rice resistance to blast and bacterial leaf blight diseases, as well as chitin‐triggered immunity. Biochemical and genetic studies revealed that OsATL32 suppresses pathogen‐induced reactive oxygen species (ROS) accumulation by mediating ubiquitination and degradation of the ROS‐producing OsRac5–OsRbohB module, which enhances rice immunity against M. oryzae. The protein phosphatase PHOSPHATASE AND TENSIN HOMOLOG enhances rice blast resistance by dephosphorylating OsATL32 and promoting its degradation, preventing its negative effect on rice immunity. This study provides insights into the molecular mechanism by which the E3 ligase OsATL32 targets a ROS‐producing module to undermine rice immunity.
Exploring adult inpatients' perceptions, understanding and preferences regarding the term ‘malnutrition’: A qualitative study
Authors: Mackay Sarah , Botero Liliana , Bell Jack , Young Adrienne
Published: April 2024

Aims

To explore adult inpatients' perceptions, understanding and preferences regarding the term ‘malnutrition’ and to identify the terms that adult inpatients report are used by themselves and health workers to describe malnutrition.

Design

This qualitative study was conducted using data collected for a separate qualitative study that investigated factors that influence the dietary intake of long‐stay, acute adult inpatients.

Methods

Semi‐structured interviews were conducted with a purposive sample of current inpatients. Data were analysed using inductive content analysis.

Results

Nineteen interviews were included (mean age 64 years (standard deviation ±17), 10 female (53%), 12 malnourished (63%)). Four categories were identified. ‘Variation in patients' recognition of malnutrition’ represents the differing abilities of patients to understand and identify with the term ‘malnutrition’. ‘Recognising individuals' needs and preferences’ highlights patients' varying beliefs regarding whether ‘malnutrition’ is or is not an appropriate term and participants' suggestion that health workers should tailor the term used to each patient. ‘Inconsistencies in health workers' and patients' practice regarding malnutrition terminology’ encapsulates the multiple terms that were used to describe malnutrition by health workers and patients. ‘Importance of malnutrition education’ summarises patients' views that health workers should provide patient education on malnutrition prevention, management and complications.

Conclusion

Findings highlight variations in patients' perceptions and understanding of the term ‘malnutrition’ and differences in the terms used by patients and health workers to describe malnutrition.

Implications for the Profession and/or Patient Care

The terminology used by health workers to describe malnutrition risk or malnutrition to their patients can influence patients' recognition of their nutritional status and thus the multidisciplinary management of the condition. To ensure that patients receive information about their malnutrition risk or diagnosis in a way that meets their needs, health workers' practices must be revised. To do this, it is imperative to conduct further collaborative research with patients and health workers to identify optimum terms for ‘malnutrition’ and how health workers should communicate this to patients.

Impact

There is a disparity in patients' perceptions, understanding and preferences for the term ‘malnutrition’ and there are inconsistencies in how health workers communicate malnutrition to patients.

To support patients' recognition and understanding of their nutritional status, it is imperative for health workers to consider how they discuss malnutrition with patients.

Reporting Method

Adheres to the Consolidated Criteria for Reporting Qualitative Research (Tong et al., 2007).

Patient or Public Contribution

No Patient or Public Contribution.
Parental identity and socialization mediate parental racial discrimination's impact on child adjustment
Authors: Zhu Qianyu , Wang Cixin , Cheah Charissa S. L.
Published: April 2024

Objective

The study explored the mediating role of Chinese American parents' ethnic–racial identity (ERI) in linking their discrimination experiences, ethnic–racial socialization (ERS), and their children's mental health, testing whether neighborhood racial diversity and perceived Chinese density moderated these mediation paths.

Background

During COVID‐19, Chinese American families faced increased discrimination, impacting their mental well‐being. However, few studies have examined how parents' discrimination experiences influence their ERI, ERS practice, and ultimately their children's mental health difficulties.

Method

Data from 294 Chinese immigrant parents (Mage = 44.28, 79% female) were collected in two waves, 2020 and 2021. Path analysis tested if parental discrimination affects their ERI and ERS, and children's mental health. Multigroup analysis assessed if mediation models varied for families living in communities with low versus high racial diversity or Chinese density.

Results

Parental racism‐related stress at T1 had significant indirect effects on parental ERS practices (higher use of maintenance of heritage culture and lower use of avoidance of outgroups practice) at T2 via parental ERI (greater private regard) at T2. Parental racial discrimination (perceived sinophobia in the media and racism‐related stress) at T1 had significant indirect effects on children's mental health difficulties at T2 via parental ERS practices (use of maintenance of heritage culture and avoidance of outgroups practices) at T2. The neighborhood racial diversity moderated the mediation model.

Conclusion

These findings advance the understanding of both individual (i.e., parental ERI) and contextual factors (i.e., neighborhood racial diversity) in the complex associations between parents' discrimination experiences and children's mental health difficulties.
Birds of a Feather are Punished Together, or Not? Examining Heterogeneity in Career Advancements of Minority Groups
Authors: Syakhroza Maima Aulia , Lodge Jan
Published: April 2024

In this study we examine the heterogeneous effects of being affiliated with different minority groups on employees’ career advancements in organizations. We draw on the categories literature and its concept of category distance to hypothesize why some minority groups may be more (dis)advantaged than others in their career advancements. To do so, we define category distance in terms of shared identity markers between groups, where identity markers are salient attributes that audiences commonly associate a group with. We test our hypotheses among religious minority groups using employment data from a large Indonesian government organization. Our results indicate that minority groups closer in distance to the organizational majority group are more penalized in their career advancements than minority groups further in distance. These results hold both at the group and at the individual level. Through our study we make contributions to the literatures on careers, categories, and the burgeoning study of religion in organizations. We conclude with implications for practice.
Isotopically nonstationary metabolic flux analysis of plants: recent progress and future opportunities
Authors: Koley Somnath , Jyoti Poonam , Lingwan Maneesh , Allen Doug K.
Published: April 2024

Metabolic flux analysis (MFA) is a valuable tool for quantifying cellular phenotypes and to guide plant metabolic engineering. By introducing stable isotopic tracers and employing mathematical models, MFA can quantify the rates of metabolic reactions through biochemical pathways. Recent applications of isotopically nonstationary MFA (INST‐MFA) to plants have elucidated nonintuitive metabolism in leaves under optimal and stress conditions, described coupled fluxes for fast‐growing algae, and produced a synergistic multi‐organ flux map that is a first in MFA for any biological system. These insights could not be elucidated through other approaches and show the potential of INST‐MFA to correct an oversimplified understanding of plant metabolism.
Positional cloning and characterization reveal the role of TaSRN‐3D and TaBSR1 in the regulation of seminal root number in wheat
Authors: Chen Zhaoyan , Li Xuanshuang , He Fei , Liu Bin , Xu Weiya , Chai Lingling , Cheng Xuejiao , Song Long , Guo Weilong , Hu Zhaorong , Su Zhenqi , Liu Jie , Xin Mingming , Peng Huiru , Yao Yingyin , Sun Qixin , Xing Jiewen , Ni Zhongfu
Published: April 2024

Seminal roots play a critical role in water and nutrient absorption, particularly in the early developmental stages of wheat. However, the genes responsible for controlling SRN in wheat remain largely unknown.

Genetic mapping and functional analyses identified a candidate gene (TraesCS3D01G137200, TaSRN‐3D) encoding a Ser/Thr kinase glycogen synthase kinase 3 (STKc_GSK3) that regulated SRN in wheat. Additionally, experiments involving hormone treatment, nitrate absorption and protein interaction were conducted to explore the regulatory mechanism of TaSRN‐3D.

Results showed that the TaSRN‐3D4332 allele inhibited seminal roots initiation and development, while loss‐of‐function mutants showed significantly higher seminal root number (SRN). Exogenous application of epi‐brassinolide could increase the SRN in a HS2‐allelic background. Furthermore, chlorate sensitivity and 15N uptake assays revealed that a higher number of seminal roots promoted nitrate accumulation. TaBSR1 (BIN2‐related SRN Regulator 1, orthologous to OsGRF4/GL2 in rice) acts as an interactor of TaSRN‐3D and promotes TaBSR1 degradation to reduce SRN.

This study provides valuable insights into understanding the genetic basis and regulatory network of SRN in wheat, highlighting their roles as potential targets for root‐based improvement in wheat breeding.
Ventricular response as a predictor of the termination of sustained paroxysmal atrial fibrillation
Authors: Huang Jen‐Hung , Lin Yung‐Kuo , Hsieh Ming‐Hsiung , Chen Shih‐Ann , Chen Yi‐Jen
Published: April 2024

Background

Atrial fibrillation (AF) is the most common sustained atrial arrhythmia. Accurate detection of the timing and possibility of AF termination is vital for optimizing rhythm and rate control strategies. The present study evaluated whether the ventricular response (VR) in AF offers a distinctive electrocardiographic indicator for predicting AF termination.

Methods

Patients experiencing sustained paroxysmal AF for more than 3 h were observed using 24‐h ambulatory Holter monitoring. VR within 5 min before AF termination (VR 0–5 min, BAFT) was compared with VR observed during the 60th to 65th min (VR 60–65 min, BAFT) and the 120th to 125th min (VR 120–125 min, BAFT) before AF termination. Maximum and minimum VRs were calculated on the basis of the average of the highest and lowest VRs across 10 consecutive heartbeats.

Results

Data from 37 episodes of paroxysmal AF revealed that the minimum VR0–5 min, BAFT (64 ± 20 bpm) was significantly faster than both the minimum VR120–125 min, BAFT (56 ± 15 bpm) and the minimum VR60–65 min, BAFT (57 ± 16 bpm, p < .05). Similarly, the maximum VR0–5 min, BAFT (158 ± 49 bpm) was significantly faster than the maximum VR120–125 min, BAFT (148 ± 45 bpm, p < .05). In the daytime, the minimum VR0–5 min, BAFT (66 ± 20 bpm) was significantly faster than both the minimum VR60–65 min, BAFT (58 ± 17 bpm) and minimum VR120–125 min, BAFT (57 ± 15 bpm, p < .05). However, the mean and maximum VR0–5 min, BAFT in the daytime were similar to the mean and maximum VR120–125 min in the daytime, respectively. At night, the minimum, mean, and maximum VR0–5 min, BAFT were similar to the minimum, mean, and maximum VR120–125 min, respectively.

Conclusions

Elevated VR rates during AF episodes may be predictors for the termination of AF, especially during the daytime and in patients with nondilated left atria. These findings may guide the development of clinical approaches to rhythm control in AF.
Far‐red light enrichment affects gene expression and architecture as well as growth and photosynthesis in rice
Authors: Huber Martina , de Boer Hugo Jan , Romanowski Andrés , van Veen Hans , Buti Sara , Kahlon Parvinderdeep S. , van der Meijden Jannes , Koch Jeroen , Pierik Ronald
Published: April 2024

Plants use light as a resource and signal. Photons within the 400–700 nm waveband are considered photosynthetically active. Far‐red photons (FR, 700–800 nm) are used by plants to detect nearby vegetation and elicit the shade avoidance syndrome. In addition, FR photons have also been shown to contribute to photosynthesis, but knowledge about these dual effects remains scarce. Here, we study shoot‐architectural and photosynthetic responses to supplemental FR light during the photoperiod in several rice varieties. We observed that FR enrichment only mildly affected the rice transcriptome and shoot architecture as compared to established model species, whereas leaf formation, tillering and biomass accumulation were clearly promoted. Consistent with this growth promotion, we found that CO2‐fixation in supplemental FR was strongly enhanced, especially in plants acclimated to FR‐enriched conditions as compared to control conditions. This growth promotion dominates the effects of FR photons on shoot development and architecture. When substituting FR enrichment with an end‐of‐day FR pulse, this prevented photosynthesis‐promoting effects and elicited shade avoidance responses. We conclude that FR photons can have a dual role, where effects depend on the environmental context: in addition to being an environmental signal, they are also a potent source of harvestable energy.
Dupilumab treatment of trichothiodystrophy in a child
Authors: Magnaterra Elisabetta , Giovannini Mattia , Filippeschi Cesare , Pedaci Fausto Andrea , Tronconi Greta , Callea Michele , Ricci Silvia , Mori Francesca , Parpagnoli Maria , Oranges Teresa
Published: April 2024

Trichothiodystrophy (TTD) is a rare congenital disorder caused by genetic mutations, leading to hair and skin abnormalities. We report successful treatment of a TTD case using dupilumab, a monoclonal antibody targeting IL‐4Rα. The patient, a 7‐year‐old boy, exhibited significant improvement in skin and hair conditions, suggesting the potential of dupilumab as a therapeutic option for TTD. Further research is needed to elucidate its mechanism and efficacy in TTD treatment.
A disparity‐aware Siamese network for building change detection in bi‐temporal remote sensing images
Authors: Li Yansheng , Li Xinwei , Chen Wei , Zhang Yongjun
Published: April 2024

Building change detection has various applications, such as urban management and disaster assessment. Along with the exponential growth of remote sensing data and computing power, an increasing number of deep‐learning‐based remote sensing building change detection methods have been proposed in recent years. Objectively, the overwhelming majority of existing methods can perfectly deal with the change detection of low‐rise buildings. By contrast, high‐rise buildings often present a large disparity in multitemporal high‐resolution remote sensing images, which degrades the performance of existing methods dramatically. To alleviate this problem, we propose a disparity‐aware Siamese network for detecting building changes in bi‐temporal high‐resolution remote sensing images. The proposed network utilises a cycle‐alignment module to address the disparity problem at both the image and feature levels. A multi‐task learning framework with joint semantic segmentation and change detection loss is used to train the entire deep network, including the cycle‐alignment module in an end‐to‐end manner. Extensive experiments on three publicly open building change detection datasets demonstrate that our method achieves significant improvements on datasets with severe building disparity and state‐of‐the‐art performance on datasets with minimal building disparity simultaneously.
Examining emotional belief expressions of advocacy coalitions in Arkansas' gender identity politics
Authors: Fullerton Allegra H. , Weible Christopher M.
Published: April 2024

Many theories and approaches to policy studies have recently begun to question and research how emotions interact with peoples' understanding and behaviors, especially in policy and politics. This paper builds on and contributes to studying emotions in policy and politics via the advocacy coalition framework (ACF). In applying Emotional‐Belief Analysis, this paper examines the legislative testimony on one of the US' first gender‐affirming care (GAC) bans. It shows that those testifying can be organized in competing advocacy coalitions with distinct emotion‐belief expressions in combination with deep core and policy core beliefs. Moreover, expressions of negative emotions and policy core beliefs display significant and the largest effects in explaining coalition affiliation and shared views of the bill banning GAC. The conclusion summarizes the paper's empirical themes with suggestions for incorporating emotions more into the ACF and the broader policy studies field.
Recent advances in early pregnancy loss diagnosis in dairy cows: New approaches
Authors: Gui Lin‐Sen , Dai Tian‐Shu , Guo Xing‐Ru , Wei Shi‐Hao , Ma Zi‐Ming , Yang Di , Ding Bao‐Long , Xiang Hui , Yu Yong‐Tao , Dan Xin‐Gang
Published: April 2024

Early pregnancy loss is a primary cause of low reproductive rates in dairy cows, posing severe economic losses to dairy farming. The accurate diagnosis of dairy cows with early pregnancy loss allows for oestrus synchronization, shortening day open, and increasing the overall conception rate of the herd. Several techniques are available for detecting early pregnancy loss in dairy cows, including rectal ultrasound, circulating blood progesterone, and pregnancy‐associated glycoproteins (PAGs). Yet, there is a need to improve on existing techniques and develop novel strategies to identify cows with early pregnancy loss accurately. This manuscript reviews the applications of rectal ultrasound, circulating blood progesterone concentration, and PAGs in the diagnosis of pregnancy loss in dairy cows. The manuscript also discusses the recent progress of new technologies, including colour Doppler ultrasound (CDUS), interferon tau‐induced genes (ISGs), and exosomal miRNA in diagnosing pregnancy loss in dairy cows. This study will provide an option for producers to re‐breed cows with pregnancy loss, thereby reducing the calving interval and economic costs. Meanwhile, this manuscript might also act as a reference for exploring more economical and precise diagnostic technologies for early pregnancy loss in dairy cows.
Measuring Households' Financial Fragilities: An analysis at the intersection of income, financial wealth, and debt†
Authors: Loschiavo David , Tullio Federico , di Salvatore Antonietta
Published: April 2024

We provide an analysis of the financial fragilities of Italian households in the 2000–2020 period, using data from the Survey on Household Income and Wealth. We comment on the recent trends of financial ill‐being, using different poverty measures, and we provide a descriptive analysis of the fragile households' characteristics. Then, we model persistence in the dynamics of the poverty statuses using different specifications of the dynamic random‐effects probit model to account for observed and latent individual heterogeneity and endogeneity of the initial conditions. A strong state dependence is found in all the considered poverty statuses, with financial and liquidity poverty being the most persistent.
Characterisation of the novel HLA‐B*58:02:04 allele by next‐generation sequencing
Authors: Lion Julien , Larivière Sylvie , Desoutter Judith , Guillaume Nicolas
Published: April 2024

HLA‐B*58:02:04 differs from HLA‐B*58:02:01 by one synonymous nucleotide in codon 215 in exon 4.
SUPG-Based Finite Element Method for Direct Material Property Determination Utilizing Full-Field Deformation Measurements
Authors: Rajan Kattil Sreehari , Bazilevs Yuri , Sutton Michael , Sockalingam Subramani , Kodagali Karan , Weerasooriya Tusit , Alexander Stephen
Published: April 2024

A direct approach is developed using Streamline Upwind Petrov Galerkin (SUPG) concepts to determine the spatially varying property distribution in a nominally heterogeneous material. The approach is based on successful development of a SUPG-stabilized inverse finite element approach to solve the differential equations of equilibrium in terms of material properties, resulting in a matrix form [A] {E} = {R}, where [A] is a known function of measured axial strains (e.g., from StereoDIC) and axial positions, {R} is a known function of axial body forces, applied loads and reactions, and {E} is a vector of unknown material properties at discrete axial locations. Theoretical and computational developments for the SUPG-stabilized approach are described in detail for one-dimensional applications (e.g., heterogeneous tensile/compression specimens, tensile/compressive surfaces of beams). Property predictions using the SUPG method with analytic strains and additive Gaussian noise are shown to be in excellent agreement with known property values, whereas predictions using the classical Bubnov–Galerkin method exhibit large, spurious oscillations in the predicted material properties. To demonstrate the methodology using experimental measurements, a 3D-printed heterogeneous tensile specimen with independently measured material properties is tested and full-field strains measured at several load levels. Results confirm that SUPG finite element property predictions are in very good agreement with independently determined values at each load level along the specimen length, providing confidence that the SUPG FE analysis framework developed in this work is stable and extendable to multiple dimensions.
A Flexible and Accurate Additive Manufacturing Data Retrieval Method Based on Probabilistic Modeling and Transformation-Invariant Feature Learning
Authors: Fang Qihang , Xiong Gang , Wang Weixing , Shen Zhen , Dong Xisong , Wang Fei-Yue
Published: April 2024

Additive manufacturing (AM) is gaining prominence across numerous fields, which involves the generation of extensive data at each process stage. A relational database is a useful tool to store such AM data and streamline data retrieval. Users can specify the value of one AM variable or attribute and retrieve the corresponding record values of another attribute. This establishes the correlations between AM variables, and supports applications such as process planning. Nonetheless, such an operation is a “hard” query, which lacks reasoning capabilities and fails to provide useful information when required records are missing. It is urgent to develop a more powerful AM database to handle AM data better, which should support “soft” queries, be scalable to high-dimensional data, and maintain flexible query functionality among multiple attributes. In this paper, we construct an AM database with probabilistic modeling and transformation-invariant feature learning, which is termed as a probabilistic AM database (PAMDB). The PAMDB allows the selection of any AM attribute as a query attribute, or even multiple attributes as query attributes, to retrieve the values of other attributes, which is adapted to unseen, high-dimensional, and multimodal AM data. Two case studies were conducted for laser powder bed fusion (LPBF) and vat photopolymerization (VP). Compared with existing methods, experimental results underscore the efficacy of the PAMDBs, both qualitatively and quantitatively, in tasks that includes melt pool size prediction and scan parameter estimation in LPBF, and defect detection for the resin deposition process in VP.
Phase Transition Heat Transfer Enhancement of a Graphene-Coated Microporous Copper Surface Using Two-Step Electrodeposition Method
Authors: Kalita Sanjib , Sen Pulak , Sen Dipak , Das Sudev , Saha Bidyut Baran
Published: April 2024

Owing to their exceptionally high thermal conductivity, there is a growing demand for graphene nanoparticles in phase transition heat transfer applications. This research delves into the exploration of various critical phenomena within the realm of surface science, specifically focusing on interactions at solid-liquid and liquid-liquid interfaces. In this work, graphene nanoparticles at varying concentrations are subject to electrochemical deposition on a microporous copper substrate to form graphene coated over microporous copper (GCOMC). The study encompasses a comprehensive analysis of surface characteristics, such as porosity, roughness, and wettability. Furthermore, the study involves the calculation of two key heat transfer metrics, the critical heat flux (CHF) and the boiling heat transfer coefficient (BHTC), through the execution of pool boiling experiments. The findings of this research underscore the remarkable superiority of GCOMC surfaces over their uncoated copper counterparts in terms of boiling performance. Particularly, the GCOMC surface showcases an impressive 87.5% enhancement in CHF and a 233% increase in BHTC compared to the bare copper surface. Furthermore, this investigation delves into a detailed quantitative analysis of bubble behavior, encompassing parameters such as bubble departure diameter, bubble departure frequency, and nucleation site density, employing high-speed camera techniques to comprehensively understand the underlying processes.
Click detection rate variability of central North Pacific sperm whales from passive acoustic towed arrays
Authors: Barkley Yvonne M. , Merkens Karlina P. B. , Wood Megan , Oleson Erin M. , Marques Tiago A.
Published: April 2024

Passive acoustic monitoring (PAM) is an optimal method for detecting and monitoring cetaceans as they frequently produce sound while underwater. Cue counting, counting acoustic cues of deep-diving cetaceans instead of animals, is an alternative method for density estimation, but requires an average cue production rate to convert cue density to animal density. Limited information about click rates exists for sperm whales in the central North Pacific Ocean. In the absence of acoustic tag data, we used towed hydrophone array data to calculate the first sperm whale click rates from this region and examined their variability based on click type, location, distance of whales from the array, and group size estimated by visual observers. Our findings show click type to be the most important variable, with groups that include codas yielding the highest click rates. We also found a positive relationship between group size and click detection rates that may be useful for acoustic predictions of group size in future studies. Echolocation clicks detected using PAM methods are often the only indicator of deep-diving cetacean presence. Understanding the factors affecting their click rates provides important information for acoustic density estimation.
RIPK3 deficiency blocks R-2-hydroxyglutarate–induced necroptosis in IDH-mutated AML cells
Authors: Zhu Shuanghong , Luo Yingwan , Li Kongfei , Mei Chen , Wang Yuxia , Jiang Lingxu , Wang Wei , Zhang Qi , Yang Wenli , Lang Wei , Zhou Xinping , Wang Lu , Ren Yanling , Ma Liya , Ye Li , Huang Xin , Chen Jianjun , Sun Jie , Tong Hongyan
Published: April 2024

Mutant isocitrate dehydrogenases (IDHs) produce R-2-hydroxyglutarate (R-2HG), which inhibits the growth of most acute myeloid leukemia (AML) cells. Here, we showed that necroptosis, a form of programmed cell death, contributed to the antileukemia activity of R-2HG. Mechanistically, R-2HG competitively inhibited the activity of lysine demethylase 2B (KDM2B), an α-ketoglutarate–dependent dioxygenase. KDM2B inhibition increased histone 3 lysine 4 trimethylation levels and promoted the expression of receptor-interacting protein kinase 1 (RIPK1), which consequently caused necroptosis in AML cells. The expression of RIPK3 was silenced because of DNA methylation in IDH-mutant (mIDH) AML cells, resulting in R-2HG resistance. Decitabine up-regulated RIPK3 expression and repaired endogenous R-2HG–induced necroptosis pathway in mIDH AML cells. Together, R-2HG induced RIPK1-dependent necroptosis via KDM2B inhibition in AML cells. The loss of RIPK3 protected mIDH AML cells from necroptosis. Restoring RIPK3 expression to exert R-2HG’s intrinsic antileukemia effect will be a potential therapeutic strategy in patients with AML.
Perturbation-induced granular fluidization as a model for remote earthquake triggering
Authors: Farain Kasra , Bonn Daniel
Published: April 2024

Studying the effect of mechanical perturbations on granular systems is crucial for understanding soil stability, avalanches, and earthquakes. We investigate a granular system as a laboratory proxy for fault gouge. When subjected to a slow shear, granular materials typically exhibit a stress overshoot before reaching a steady state. We find that short seismic pulses can reset a granular system flowing in steady state so that the stress overshoot is regenerated. This feature is shown to determine the stability of the granular system under different applied stresses in the wake of a perturbation pulse and the resulting dynamics when it fails. Using an analytical aging-rejuvenation model for describing the overshoot response, we show that our laboratory-derived theoretical framework can quantitatively explain data from two fault slip events triggered by seismic waves.
Formation of extraterrestrial peptides and their derivatives
Authors: Krasnokutski Serge A. , Jäger Cornelia , Henning Thomas , Geffroy Claude , Remaury Quentin B. , Poinot Pauline
Published: April 2024

The formation of protein precursors, due to the condensation of atomic carbon under the low-temperature conditions of the molecular phases of the interstellar medium, opens alternative pathways for the origin of life. We perform peptide synthesis under conditions prevailing in space and provide a comprehensive analytic characterization of its products. The application of
13
C allowed us to confirm the suggested pathway of peptide formation that proceeds due to the polymerization of aminoketene molecules that are formed in the C + CO + NH
3
reaction. Here, we address the question of how the efficiency of peptide production is modified by the presence of water molecules. We demonstrate that although water slightly reduces the efficiency of polymerization of aminoketene, it does not prevent the formation of peptides.
Dispersive nonreciprocity between a qubit and a cavity
Authors: Wang Ying-Ying , Wang Yu-Xin , van Geldern Sean , Connolly Thomas , Clerk Aashish A. , Wang Chen
Published: April 2024

The dispersive interaction between a qubit and a cavity is ubiquitous in circuit and cavity quantum electrodynamics. It describes the frequency shift of one quantum mode in response to excitations in the other and, in closed systems, is necessarily bidirectional, i.e., reciprocal. Here, we present an experimental study of a nonreciprocal dispersive-type interaction between a transmon qubit and a superconducting cavity, arising from a common coupling to dissipative intermediary modes with broken time reversal symmetry. We characterize the qubit-cavity dynamics, including asymmetric frequency pulls and photon shot noise dephasing, under varying degrees of nonreciprocity by tuning the magnetic field bias of a ferrite component in situ. We introduce a general master equation model for nonreciprocal interactions in the dispersive regime, providing a compact description of the observed qubit-cavity dynamics agnostic to the intermediary system. Our result provides an example of quantum nonreciprocal phenomena beyond the typical paradigms of non-Hermitian Hamiltonians and cascaded systems.
Topology-guided polar ordering of collective cell migration
Authors: Lång Emma , Lång Anna , Blicher Pernille , Rognes Torbjørn , Dommersnes Paul Gunnar , Bøe Stig Ove
Published: April 2024

The ability of epithelial monolayers to self-organize into a dynamic polarized state, where cells migrate in a uniform direction, is essential for tissue regeneration, development, and tumor progression. However, the mechanisms governing long-range polar ordering of motility direction in biological tissues remain unclear. Here, we investigate the self-organizing behavior of quiescent epithelial monolayers that transit to a dynamic state with long-range polar order upon growth factor exposure. We demonstrate that the heightened self-propelled activity of monolayer cells leads to formation of vortex-antivortex pairs that undergo sequential annihilation, ultimately driving the spread of long-range polar order throughout the system. A computational model, which treats the monolayer as an active elastic solid, accurately replicates this behavior, and weakening of cell-to-cell interactions impedes vortex-antivortex annihilation and polar ordering. Our findings uncover a mechanism in epithelia, where elastic solid material characteristics, activated self-propulsion, and topology-mediated guidance converge to fuel a highly efficient polar self-ordering activity.
Dual-responsive nanocarriers for efficient cytosolic protein delivery and CRISPR-Cas9 gene therapy of inflammatory skin disorders
Authors: Tan Echuan , Wan Tao , Pan Qi , Duan Jianan , Zhang Song , Wang Ruijue , Gao Peng , Lv Jia , Wang Hui , Li Dali , Ping Yuan , Cheng Yiyun
Published: April 2024

Developing protein drugs that can target intracellular sites remains a challenge due to their inadequate membrane permeability. Efficient carriers for cytosolic protein delivery are required for protein-based drugs, cancer vaccines, and CRISPR-Cas9 gene therapies. Here, we report a screening process to identify highly efficient materials for cytosolic protein delivery from a library of dual-functionalized polymers bearing both boronate and lipoic acid moieties. Both ligands were found to be crucial for protein binding, endosomal escape, and intracellular protein release. Polymers with higher grafting ratios exhibit remarkable efficacies in cytosolic protein delivery including enzymes, monoclonal antibodies, and Cas9 ribonucleoprotein while preserving their activity. Optimal polymer successfully delivered Cas9 ribonucleoprotein targeting
NLRP3
to disrupt NLRP3 inflammasomes in vivo and ameliorate inflammation in a mouse model of psoriasis. Our study presents a promising option for the discovery of highly efficient materials tailored for cytosolic delivery of specific proteins and complexes such as Cas9 ribonucleoprotein.
A unified theory of tunneling times promoted by Ramsey clocks
Authors: Schach Patrik , Giese Enno
Published: April 2024

What time does a clock tell after quantum tunneling? Predictions and indirect measurements range from superluminal or instantaneous tunneling to finite durations, depending on the specific experiment and the precise definition of the elapsed time. Proposals and implementations use the atomic motion to define this delay, although the inherent quantum nature of atoms implies a delocalization and is in sharp contrast to classical trajectories. Here, we rely on an operational approach: We prepare atoms in a coherent superposition of internal states and study the time read-off via a Ramsey sequence after the tunneling process without the notion of classical trajectories or velocities. Our operational framework (i) unifies definitions of tunneling delay within one approach, (ii) connects the time to a frequency standard given by a conventional atomic clock that can be boosted by differential light shifts, and (iii) highlights that there exists no superluminal or instantaneous tunneling.
Locomotion as manipulation with ReachBot
Authors: Chen Tony G. , Newdick Stephanie , Di Julia , Bosio Carlo , Ongole Nitin , Lapôtre Mathieu , Pavone Marco , Cutkosky Mark R.
Published: April 2024

Caves and lava tubes on the Moon and Mars are sites of geological and astrobiological interest but consist of terrain that is inaccessible with traditional robot locomotion. To support the exploration of these sites, we present ReachBot, a robot that uses extendable booms as appendages to manipulate itself with respect to irregular rock surfaces. The booms terminate in grippers equipped with microspines and provide ReachBot with a large workspace, allowing it to achieve force closure in enclosed spaces, such as the walls of a lava tube. To propel ReachBot, we present a contact-before-motion planner for nongaited legged locomotion that uses internal force control, similar to a multifingered hand, to keep its long, slender booms in tension. Motion planning also depends on finding and executing secure grips on rock features. We used a Monte Carlo simulation to inform gripper design and predict grasp strength and variability. In addition, we used a two-step perception system to identify possible grasp locations. To validate our approach and mechanisms under realistic conditions, we deployed a single ReachBot arm and gripper in a lava tube in the Mojave Desert. The field test confirmed that ReachBot will find many targets for secure grasps with the proposed kinematic design.
The prostaglandin D2 antagonist asapiprant ameliorates clinical severity in young hosts infected with invasive
Streptococcus pneumoniae
Authors: Bhalla Manmeet , Herring Sydney , Lenhard Alexsandra , Wheeler Joshua R. , Aswad Fred , Klumpp Klaus , Rebo Justin , Wang Yan , Wilhelmsen Kevin , Fortney Kristen , Bou Ghanem Elsa N.
Published: April 2024

Streptococcus pneumoniae
(pneumococcus) remains a serious cause of pulmonary and systemic infections globally, and host-directed therapies are lacking. The aim of this study was to test the therapeutic efficacy of asapiprant, an inhibitor of prostaglandin D2 signaling, against pneumococcal infection. Treatment of young mice with asapiprant after pulmonary infection with invasive pneumococci significantly reduced systemic spread, disease severity, and host death. Protection was specific against bacterial dissemination from the lung to the blood but had no effect on pulmonary bacterial burden. Asapiprant-treated mice had enhanced antimicrobial activity in circulating neutrophils, elevated levels of reactive oxygen species (ROS) in lung macrophages/monocytes, and improved pulmonary barrier integrity indicated by significantly reduced diffusion of fluorescein isothiocyanate (FITC)-dextran from lungs into the circulation. These findings suggest that asapiprant protects the host against pneumococcal dissemination by enhancing the antimicrobial activity of immune cells and maintaining epithelial/endothelial barrier integrity in the lungs.
Development of advanced control material for reverse transcription-mediated bacterial nucleic acid amplification tests
Authors: Lewis Janessa D. , Salipante Stephen J.
Published: April 2024

Detection of bacterial RNA by nucleic acid amplification tests (NAATs), such as reverse transcription PCR (RT-PCR) and reverse transcription loop-mediated isothermal amplification (RT-LAMP), offers distinct advantages over DNA-based methods. However, such assays also present challenges in ascertaining positive and internal control material that can reliably monitor success over all phases of testing (bacterial lysis, nucleic acid recovery, reverse transcription, amplification, and signal detection): since they are unable to distinguish between amplification of bacterial RNA transcripts and the DNA templates that encode them, using intact organisms as controls can inform cell lysis but not successful detection of RNA. We developed a control strategy for RNA-based bacterial NAATs that allows ready discrimination of RNA from DNA templates using self-splicing bacterial introns, such that those nucleic acids ultimately encode different sequences. We engineered two vectors encoding synthetic transgenes based on this principle, one that is active in the Gram-negative bacterium
Escherichia coli
and one that functions in both
E. coli
and the Gram-positive organism
Staphylococcus aureus
. We subsequently designed RT-LAMP assays that either target RNA and DNA from transgenic organisms or target RNA exclusively and demonstrated the specificity of amplification using purified nucleic acids. Using multiplex fluorescent RT-LAMP of heat-lysed specimens, we showed the practicality of deploying such transgenic organisms as an internal control to ascertain sample integrity and assay performance during clinical diagnostic testing. Our approach has broad utility for RNA-based bacterial NAATs, especially point-of-care assays and other applications where nucleic acids are nonspecifically liberated for testing.